Datasets:

hazyresearch

/

based-fda

like 3

idK150144_s0_e2000

K150144.txt

applicant

Affinity Biologicals Inc.

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K150144 B. Purpose for Submission: Clearance of a new device C. Measurand: Fibrinogen D. Type of Test: Quality Control Material, Assayed E. Applicant: Affinity Biologicals Inc. F. Proprietary and Established Names: VisuCon-F Low Fibrinogen Control Plasma G. Regulatory Information: 1. Regulation section: 21 CFR §864.5425, Multipurpose system for in vitro coagulation studies 2. Classification: Class II 3. Product code: GGN, Plasma, Coagulation Control 4. Panel: 81 (Hematology) 2 H. Intended Use: 1. Intended use(s): The VisuCon-F Low Fibrinogen Control Plasma is an assayed control plasma prepared from de-fibrinated human plasma intended for use in the quality control of quantitative fibrinogen assays in the low abnormal range. The VisuCon-F Low Fibrinogen Control Plasma may be used with mechanical instruments in conjunction with appropriate commercial reagents for determining fibrinogen levels in plasma by the clotting method of Clauss. This plasma is intended “For In Vitro Diagnostic Use”. The intended users of the VisuCon-F Low Fibrinogen Control Plasma are trained laboratory personnel working in clinical laboratories. 2. Indication(s) for use: Same as intended use 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Not applicable I. Device Description: The VisuCon-F Low Fibrinogen Control Plasma is a pool of de-fibrinated citrated human plasma collected from a minimum of 10 donors, buffered with 0.02 M HEPES buffer. The VisuCon-F Low Fibrinogen Control Plasma is packaged frozen in boxes containing: 5 x 1mL vials, 25 x 1mL vials or 81 x 1mL vials. J. Substantial Equivalence Information: 1. Predicate device name(s): Precision Biologic Inc., Cryocheck Low Fibrinogen Control 2. Predicate 510(k) number(s): K951823 3 3. Comparison with predicate: Similarities Item Device VisuCon-F Low Fibrinogen Control Plasma Predicate Cryo Check Low Fibrinogen Control Intended Use The VisuCon-F Low Fibrinogen Control Plasma is an assayed control plasma prepared from de-fibrinated human plasma intended for use in the quality control of quantitative fibrinogen assays in the low abnormal range. The VisuCon-F Low Fibrinogen Control Plasma may be used with mechanical instruments in conjunction with appropriate commercial reagents for determining fibrinogen levels in plasma by the clotting method of Clauss. This plasma is intended “For In Vitro Diagnostic Use”. The intended users of the VisuCon-F Low Fibrinogen Control Plasma are trained laboratory personnel working in clinical laboratories. The Cryo√ CheckTM Low Fibrinogen Control is a citrated normal human source plasma recommended for use as an abnormal control in monitoring the precision and accuracy of quantitative clottable fibrinogen assays. Analyte Fibrinogen Same Matrix Citrated human plasma Same Differences Item Device Predicate Storage ≤ -60°C -40°C to -80°C Open-Vial Stability 72 hours at 2–8°C or 8 hours on-board instrument (19–22° C) 72 hours at 2–8°C Packaging 5 x 1.0 mL 25 x 1.0 mL 81 x 1.0 mL 25 vials x 1.0 mL 80 vials x 1.0 mL K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A2; Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline, 2nd Edition L. Test Principle: The VisuCon-F Low Fibrinogen control is to be utilized to monitor the performance of 4 fibrinogen assays in the low abnormal range using the Clauss clotting method in mechanical instruments. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility/Precision Study: A reproducibility study was conducted at three sites (one internal and two external), testing three individual lots at each site, two runs per day in triplicate for five non- consecutive days. At each testing site, each of the three VisuCon Low Control lots were tested by one operator using one lot of Diagnostica STA-Fibrinogen Assay (K840211) on STA Compact Analyzer (K093167). All data points from the study were pooled and analyzed in a mixed effect model with lot, test site, day and run treated as random effects. The coefficient of variation (CV) and the standard deviation (SD) for each of the random effects (variance): lot-to-lot, site-to-site, between-day, between-run, within-run and total reproducibility precision was calculated. Results show that data met pre-determined acceptance criteria and demonstrated reproducibility of the VisuCon Low Control under tested conditions. Results of the pooled data are presented below: Instrument: STA Compact Analyzer Source of Variance Standard Deviation (SD) %CV (SD/mean)*100 Lot-to-lot 0.059 7.2% Site-to-site 0.013 1.5% Between-Day 0.006 0.7% Between-Run 0 0% Within-Run (Repeatability) 0.025 3.0% Total Variability 0.07 8.0% Repeatability study/Within-Laboratory Precision Study: Three lots of VisuCon-F Low Fibrinogen Control Plasma were tested on two different Diagnostica Stago STA- Compact Analyzers using the Diagnostica Stago STA-Fibrinogen 5 assay. Testing was conducted in duplicate, two runs per day over a period of 20 days. Data from the repeatability study was pooled (n=480) and analyzed in a mixed effect model with the lot, instrument, day and run treated as random effects. Results show the data met pre-determined acceptance criteria, and are summarized below: 5 Instrument: Diagnostica Stago STA Compact Analyzer Source of Variance SD %CV Lot-to-Lot 0.066 7.8% Instrument-to-Instrument 0.004 0.5% Between-Day 0.005 0.5% Between-Run 0.00 0% Within-Run (Repeatability) 0.027 3.2% Within-Device (total) 0.072 8.4% b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Stability Study: Open Vial Stability Study: The open vial stability study was conducted at the refrigerated temperature of 2°C to 8°C and on-board temperature of 19°C to 22°C, on two lots of VisuCon-F Low Fibrinogen Control plasma. The study demonstrated the VisuCon-F Low Fibrinogen Control Plasma is stable up to 72 hours when stored at 2- 8°C and up to 8 hours at 19-22°C. The study met the pre-determined acceptance criteria. Closed Vial Stability Study: The closed vial stability study was conducted at the storage temperature of ≤ -60°C using three lots of the VisuCon-F Low Fibrinogen Control Plasma. The study demonstrated that the VisuCon-F Low Fibrinogen Control Plasma is stable up to 36 months when stored at or below -60°C. The study met the pre-determined acceptance criteria. Value Assignment: The value assignment for VisuCon-F Low Fibrinogen Control Plasmas were assigned to fibrinogen by testing 20 vials, 5 vials per day over 4 days (n=20). The ranges for the controls were assigned to fibrinogen by calculating and applying ± 2 standard deviations (SD) from the mean. Three lots were tested using the Diagnostica Stago Fibrinogen-5 Assay, which was calibrated against SSC/ISTH Secondary Coagulation Standard. The mean values assigned to each lot met the acceptance criteria and is as follows: 6 Lot 1 Vial Day 1 (g/L) Day 2 (g/L) Day 3 (g/L) Day 4 (g/L) 1 0.81 0.81 0.81 0.80 2 0.78 0.78 0.77 0.77 3 0.82 0.80 0.77 0.76 4 0.79 0.78 0.77 0.82 5 0.77 0.81 0.79 0.81 Overall Mean 0.79 g/L Overall SD 0.019 Overall %CV 2.41% Assigned range 0.75 – 0.83 g/L Lot 2 Vial Day 1 (g/L) Day 2 (g/L) Day 3 (g/L) Day 4 (g/L) 1 0.82 0.82 0.82 0.83 2 0.82 0.84 0. Applicant:

idK150144_s0_e2000

K150144.txt

proprietary and established names

VisuCon-F Low Fibrinogen Control Plasma

IAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K150144 B. Purpose for Submission: Clearance of a new device C. Measurand: Fibrinogen D. Type of Test: Quality Control Material, Assayed E. Applicant: Affinity Biologicals Inc. F. Proprietary and Established Names: VisuCon-F Low Fibrinogen Control Plasma G. Regulatory Information: 1. Regulation section: 21 CFR §864.5425, Multipurpose system for in vitro coagulation studies 2. Classification: Class II 3. Product code: GGN, Plasma, Coagulation Control 4. Panel: 81 (Hematology) 2 H. Intended Use: 1. Intended use(s): The VisuCon-F Low Fibrinogen Control Plasma is an assayed control plasma prepared from de-fibrinated human plasma intended for use in the quality control of quantitative fibrinogen assays in the low abnormal range. The VisuCon-F Low Fibrinogen Control Plasma may be used with mechanical instruments in conjunction with appropriate commercial reagents for determining fibrinogen levels in plasma by the clotting method of Clauss. This plasma is intended “For In Vitro Diagnostic Use”. The intended users of the VisuCon-F Low Fibrinogen Control Plasma are trained laboratory personnel working in clinical laboratories. 2. Indication(s) for use: Same as intended use 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Not applicable I. Device Description: The VisuCon-F Low Fibrinogen Control Plasma is a pool of de-fibrinated citrated human plasma collected from a minimum of 10 donors, buffered with 0.02 M HEPES buffer. The VisuCon-F Low Fibrinogen Control Plasma is packaged frozen in boxes containing: 5 x 1mL vials, 25 x 1mL vials or 81 x 1mL vials. J. Substantial Equivalence Information: 1. Predicate device name(s): Precision Biologic Inc., Cryocheck Low Fibrinogen Control 2. Predicate 510(k) number(s): K951823 3 3. Comparison with predicate: Similarities Item Device VisuCon-F Low Fibrinogen Control Plasma Predicate Cryo Check Low Fibrinogen Control Intended Use The VisuCon-F Low Fibrinogen Control Plasma is an assayed control plasma prepared from de-fibrinated human plasma intended for use in the quality control of quantitative fibrinogen assays in the low abnormal range. The VisuCon-F Low Fibrinogen Control Plasma may be used with mechanical instruments in conjunction with appropriate commercial reagents for determining fibrinogen levels in plasma by the clotting method of Clauss. This plasma is intended “For In Vitro Diagnostic Use”. The intended users of the VisuCon-F Low Fibrinogen Control Plasma are trained laboratory personnel working in clinical laboratories. The Cryo√ CheckTM Low Fibrinogen Control is a citrated normal human source plasma recommended for use as an abnormal control in monitoring the precision and accuracy of quantitative clottable fibrinogen assays. Analyte Fibrinogen Same Matrix Citrated human plasma Same Differences Item Device Predicate Storage ≤ -60°C -40°C to -80°C Open-Vial Stability 72 hours at 2–8°C or 8 hours on-board instrument (19–22° C) 72 hours at 2–8°C Packaging 5 x 1.0 mL 25 x 1.0 mL 81 x 1.0 mL 25 vials x 1.0 mL 80 vials x 1.0 mL K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A2; Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline, 2nd Edition L. Test Principle: The VisuCon-F Low Fibrinogen control is to be utilized to monitor the performance of 4 fibrinogen assays in the low abnormal range using the Clauss clotting method in mechanical instruments. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility/Precision Study: A reproducibility study was conducted at three sites (one internal and two external), testing three individual lots at each site, two runs per day in triplicate for five non- consecutive days. At each testing site, each of the three VisuCon Low Control lots were tested by one operator using one lot of Diagnostica STA-Fibrinogen Assay (K840211) on STA Compact Analyzer (K093167). All data points from the study were pooled and analyzed in a mixed effect model with lot, test site, day and run treated as random effects. The coefficient of variation (CV) and the standard deviation (SD) for each of the random effects (variance): lot-to-lot, site-to-site, between-day, between-run, within-run and total reproducibility precision was calculated. Results show that data met pre-determined acceptance criteria and demonstrated reproducibility of the VisuCon Low Control under tested conditions. Results of the pooled data are presented below: Instrument: STA Compact Analyzer Source of Variance Standard Deviation (SD) %CV (SD/mean)*100 Lot-to-lot 0.059 7.2% Site-to-site 0.013 1.5% Between-Day 0.006 0.7% Between-Run 0 0% Within-Run (Repeatability) 0.025 3.0% Total Variability 0.07 8.0% Repeatability study/Within-Laboratory Precision Study: Three lots of VisuCon-F Low Fibrinogen Control Plasma were tested on two different Diagnostica Stago STA- Compact Analyzers using the Diagnostica Stago STA-Fibrinogen 5 assay. Testing was conducted in duplicate, two runs per day over a period of 20 days. Data from the repeatability study was pooled (n=480) and analyzed in a mixed effect model with the lot, instrument, day and run treated as random effects. Results show the data met pre-determined acceptance criteria, and are summarized below: 5 Instrument: Diagnostica Stago STA Compact Analyzer Source of Variance SD %CV Lot-to-Lot 0.066 7.8% Instrument-to-Instrument 0.004 0.5% Between-Day 0.005 0.5% Between-Run 0.00 0% Within-Run (Repeatability) 0.027 3.2% Within-Device (total) 0.072 8.4% b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Stability Study: Open Vial Stability Study: The open vial stability study was conducted at the refrigerated temperature of 2°C to 8°C and on-board temperature of 19°C to 22°C, on two lots of VisuCon-F Low Fibrinogen Control plasma. The study demonstrated the VisuCon-F Low Fibrinogen Control Plasma is stable up to 72 hours when stored at 2- 8°C and up to 8 hours at 19-22°C. The study met the pre-determined acceptance criteria. Closed Vial Stability Study: The closed vial stability study was conducted at the storage temperature of ≤ -60°C using three lots of the VisuCon-F Low Fibrinogen Control Plasma. The study demonstrated that the VisuCon-F Low Fibrinogen Control Plasma is stable up to 36 months when stored at or below -60°C. The study met the pre-determined acceptance criteria. Value Assignment: The value assignment for VisuCon-F Low Fibrinogen Control Plasmas were assigned to fibrinogen by testing 20 vials, 5 vials per day over 4 days (n=20). The ranges for the controls were assigned to fibrinogen by calculating and applying ± 2 standard deviations (SD) from the mean. Three lots were tested using the Diagnostica Stago Fibrinogen-5 Assay, which was calibrated against SSC/ISTH Secondary Coagulation Standard. The mean values assigned to each lot met the acceptance criteria and is as follows: 6 Lot 1 Vial Day 1 (g/L) Day 2 (g/L) Day 3 (g/L) Day 4 (g/L) 1 0.81 0.81 0.81 0.80 2 0.78 0.78 0.77 0.77 3 0.82 0.80 0.77 0.76 4 0.79 0.78 0.77 0.82 5 0.77 0.81 0.79 0.81 Overall Mean 0.79 g/L Overall SD 0.019 Overall %CV 2.41% Assigned range 0.75 – 0.83 g/L Lot 2 Vial Day 1 (g/L) Day 2 (g/L) Day 3 (g/L) Day 4 (g/L) 1 0.82 0.82 0.82 0.83 2 0.82 0.84 0. Proprietary and established names:

idK150144_s0_e2000

K150144.txt

regulation section

21 CFR §864.5425, Multipurpose system for in vitro coagulation studies

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K150144 B. Purpose for Submission: Clearance of a new device C. Measurand: Fibrinogen D. Type of Test: Quality Control Material, Assayed E. Applicant: Affinity Biologicals Inc. F. Proprietary and Established Names: VisuCon-F Low Fibrinogen Control Plasma G. Regulatory Information: 1. Regulation section: 21 CFR §864.5425, Multipurpose system for in vitro coagulation studies 2. Classification: Class II 3. Product code: GGN, Plasma, Coagulation Control 4. Panel: 81 (Hematology) 2 H. Intended Use: 1. Intended use(s): The VisuCon-F Low Fibrinogen Control Plasma is an assayed control plasma prepared from de-fibrinated human plasma intended for use in the quality control of quantitative fibrinogen assays in the low abnormal range. The VisuCon-F Low Fibrinogen Control Plasma may be used with mechanical instruments in conjunction with appropriate commercial reagents for determining fibrinogen levels in plasma by the clotting method of Clauss. This plasma is intended “For In Vitro Diagnostic Use”. The intended users of the VisuCon-F Low Fibrinogen Control Plasma are trained laboratory personnel working in clinical laboratories. 2. Indication(s) for use: Same as intended use 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Not applicable I. Device Description: The VisuCon-F Low Fibrinogen Control Plasma is a pool of de-fibrinated citrated human plasma collected from a minimum of 10 donors, buffered with 0.02 M HEPES buffer. The VisuCon-F Low Fibrinogen Control Plasma is packaged frozen in boxes containing: 5 x 1mL vials, 25 x 1mL vials or 81 x 1mL vials. J. Substantial Equivalence Information: 1. Predicate device name(s): Precision Biologic Inc., Cryocheck Low Fibrinogen Control 2. Predicate 510(k) number(s): K951823 3 3. Comparison with predicate: Similarities Item Device VisuCon-F Low Fibrinogen Control Plasma Predicate Cryo Check Low Fibrinogen Control Intended Use The VisuCon-F Low Fibrinogen Control Plasma is an assayed control plasma prepared from de-fibrinated human plasma intended for use in the quality control of quantitative fibrinogen assays in the low abnormal range. The VisuCon-F Low Fibrinogen Control Plasma may be used with mechanical instruments in conjunction with appropriate commercial reagents for determining fibrinogen levels in plasma by the clotting method of Clauss. This plasma is intended “For In Vitro Diagnostic Use”. The intended users of the VisuCon-F Low Fibrinogen Control Plasma are trained laboratory personnel working in clinical laboratories. The Cryo√ CheckTM Low Fibrinogen Control is a citrated normal human source plasma recommended for use as an abnormal control in monitoring the precision and accuracy of quantitative clottable fibrinogen assays. Analyte Fibrinogen Same Matrix Citrated human plasma Same Differences Item Device Predicate Storage ≤ -60°C -40°C to -80°C Open-Vial Stability 72 hours at 2–8°C or 8 hours on-board instrument (19–22° C) 72 hours at 2–8°C Packaging 5 x 1.0 mL 25 x 1.0 mL 81 x 1.0 mL 25 vials x 1.0 mL 80 vials x 1.0 mL K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A2; Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline, 2nd Edition L. Test Principle: The VisuCon-F Low Fibrinogen control is to be utilized to monitor the performance of 4 fibrinogen assays in the low abnormal range using the Clauss clotting method in mechanical instruments. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility/Precision Study: A reproducibility study was conducted at three sites (one internal and two external), testing three individual lots at each site, two runs per day in triplicate for five non- consecutive days. At each testing site, each of the three VisuCon Low Control lots were tested by one operator using one lot of Diagnostica STA-Fibrinogen Assay (K840211) on STA Compact Analyzer (K093167). All data points from the study were pooled and analyzed in a mixed effect model with lot, test site, day and run treated as random effects. The coefficient of variation (CV) and the standard deviation (SD) for each of the random effects (variance): lot-to-lot, site-to-site, between-day, between-run, within-run and total reproducibility precision was calculated. Results show that data met pre-determined acceptance criteria and demonstrated reproducibility of the VisuCon Low Control under tested conditions. Results of the pooled data are presented below: Instrument: STA Compact Analyzer Source of Variance Standard Deviation (SD) %CV (SD/mean)*100 Lot-to-lot 0.059 7.2% Site-to-site 0.013 1.5% Between-Day 0.006 0.7% Between-Run 0 0% Within-Run (Repeatability) 0.025 3.0% Total Variability 0.07 8.0% Repeatability study/Within-Laboratory Precision Study: Three lots of VisuCon-F Low Fibrinogen Control Plasma were tested on two different Diagnostica Stago STA- Compact Analyzers using the Diagnostica Stago STA-Fibrinogen 5 assay. Testing was conducted in duplicate, two runs per day over a period of 20 days. Data from the repeatability study was pooled (n=480) and analyzed in a mixed effect model with the lot, instrument, day and run treated as random effects. Results show the data met pre-determined acceptance criteria, and are summarized below: 5 Instrument: Diagnostica Stago STA Compact Analyzer Source of Variance SD %CV Lot-to-Lot 0.066 7.8% Instrument-to-Instrument 0.004 0.5% Between-Day 0.005 0.5% Between-Run 0.00 0% Within-Run (Repeatability) 0.027 3.2% Within-Device (total) 0.072 8.4% b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Stability Study: Open Vial Stability Study: The open vial stability study was conducted at the refrigerated temperature of 2°C to 8°C and on-board temperature of 19°C to 22°C, on two lots of VisuCon-F Low Fibrinogen Control plasma. The study demonstrated the VisuCon-F Low Fibrinogen Control Plasma is stable up to 72 hours when stored at 2- 8°C and up to 8 hours at 19-22°C. The study met the pre-determined acceptance criteria. Closed Vial Stability Study: The closed vial stability study was conducted at the storage temperature of ≤ -60°C using three lots of the VisuCon-F Low Fibrinogen Control Plasma. The study demonstrated that the VisuCon-F Low Fibrinogen Control Plasma is stable up to 36 months when stored at or below -60°C. The study met the pre-determined acceptance criteria. Value Assignment: The value assignment for VisuCon-F Low Fibrinogen Control Plasmas were assigned to fibrinogen by testing 20 vials, 5 vials per day over 4 days (n=20). The ranges for the controls were assigned to fibrinogen by calculating and applying ± 2 standard deviations (SD) from the mean. Three lots were tested using the Diagnostica Stago Fibrinogen-5 Assay, which was calibrated against SSC/ISTH Secondary Coagulation Standard. The mean values assigned to each lot met the acceptance criteria and is as follows: 6 Lot 1 Vial Day 1 (g/L) Day 2 (g/L) Day 3 (g/L) Day 4 (g/L) 1 0.81 0.81 0.81 0.80 2 0.78 0.78 0.77 0.77 3 0.82 0.80 0.77 0.76 4 0.79 0.78 0.77 0.82 5 0.77 0.81 0.79 0.81 Overall Mean 0.79 g/L Overall SD 0.019 Overall %CV 2.41% Assigned range 0.75 – 0.83 g/L Lot 2 Vial Day 1 (g/L) Day 2 (g/L) Day 3 (g/L) Day 4 (g/L) 1 0.82 0.82 0.82 0.83 2 0.82 0.84 0. Regulation section:

idK150144_s2000_e4000

K150144.txt

proposed labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

0.80 0.80 0.77 0.79 4 0.80 0.86 0.79 0.78 5 0.82 0.82 0.82 0.81 Overall Mean 0.81 g/L Overall SD 0.022 Overall %CV 2.72% Assigned range 0.77 – 0.85 g/L Lot 3 Vial Day 1 (g/L) Day 2 (g/L) Day 3 (g/L) Day 4 (g/L) 1 0.93 0.92 0.93 0.93 2 0.96 0.92 0.85 0.91 3 0.80 0.90 0.90 0.87 4 0.87 0.91 0.88 0.90 5 0.96 0.91 0.92 0.88 Overall Mean 0.90 g/L Overall SD 0.037 Overall %CV 4.11% Assigned range 0.83 – 0.97 g/L d. Detection limit: Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: 7 Not applicable 2. Comparison studies: a. Method comparison with predicate device: Not Applicable b. Matrix comparison: Not Applicable 3. Clinical studies: a. Clinical Sensitivity: Not applicable b. Clinical specificity: Not applicable c. Other clinical supportive data (when a. and b. are not applicable): Not applicable 4. Clinical cut-off: Not applicable 5. Expected values/Reference range: A lot-specific Certificate of Analysis with an assigned reference value is provided in the package insert accompanying the product. N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK150144_s2000_e4000

K150144.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

78 3 0.80 0.80 0.77 0.79 4 0.80 0.86 0.79 0.78 5 0.82 0.82 0.82 0.81 Overall Mean 0.81 g/L Overall SD 0.022 Overall %CV 2.72% Assigned range 0.77 – 0.85 g/L Lot 3 Vial Day 1 (g/L) Day 2 (g/L) Day 3 (g/L) Day 4 (g/L) 1 0.93 0.92 0.93 0.93 2 0.96 0.92 0.85 0.91 3 0.80 0.90 0.90 0.87 4 0.87 0.91 0.88 0.90 5 0.96 0.91 0.92 0.88 Overall Mean 0.90 g/L Overall SD 0.037 Overall %CV 4.11% Assigned range 0.83 – 0.97 g/L d. Detection limit: Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: 7 Not applicable 2. Comparison studies: a. Method comparison with predicate device: Not Applicable b. Matrix comparison: Not Applicable 3. Clinical studies: a. Clinical Sensitivity: Not applicable b. Clinical specificity: Not applicable c. Other clinical supportive data (when a. and b. are not applicable): Not applicable 4. Clinical cut-off: Not applicable 5. Expected values/Reference range: A lot-specific Certificate of Analysis with an assigned reference value is provided in the package insert accompanying the product. N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK172333_s0_e2000

K172333.txt

purpose for submission

To expand the use of previously cleared assay reagents for Factor V Leiden; Coagulation Factor VIII Deficient Plasma; Coagulation Factor IX Deficient Plasma; Lupus Anticoagulant with LA 1 Screening Reagent; Lupus Anticoagulant with LA 2 Confirmation Reagent and Lupus Anticoagulant with LA 1 / LA 2 Ratio to the Sysmex® Automated Blood Coagulation Analyzer CS-5100.

ANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172333 B. Purpose for Submission: To expand the use of previously cleared assay reagents for Factor V Leiden; Coagulation Factor VIII Deficient Plasma; Coagulation Factor IX Deficient Plasma; Lupus Anticoagulant with LA 1 Screening Reagent; Lupus Anticoagulant with LA 2 Confirmation Reagent and Lupus Anticoagulant with LA 1 / LA 2 Ratio to the Sysmex® Automated Blood Coagulation Analyzer CS-5100. C. Measurand: Factor V Leiden activity with Factor V Leiden Assay; Factor VIII activity with Dade® Actin® FSL Activated PTT Reagent; Factor IX activity with Dade® Actin® FSL Activated PTT Reagent; Lupus Anticoagulant with LA 1 Screening Reagent; Lupus Anticoagulant with LA 2 Confirmation Reagent and Lupus Anticoagulant with LA Ratio. Factor V Leiden Assay and Lupus Anticoagulant LA1/LA2 Ratio are reported as ratio; Factor VIII and Factor IX are reported as percent (%) of normal; Lupus Anticoagulant with LA 1 Screening Reagent and Lupus Anticoagulant with LA2 Confirmation Reagent are reported as clotting time in seconds. D. Type of Test: Quantitative clot-based applications E. Applicant: Siemens Healthcare Diagnostics Product GmbH F. Proprietary and Established Names: Sysmex® Automated Blood Coagulation Analyzer CS-5100 Factor V Leiden Assay Coagulation Factor VIII, IX, XI and XII Deficient Plasmas LA 1 Screening Reagent, LA 2 Confirmation Reagent, and LA Ratio Note: The performance of Coagulation Factor XI Deficient Plasma and Coagulation Factor XII Deficient Plasma was not evaluated in this premarket notification. G. Regulatory Information: 1. Regulation section: Device Regulation Section Sysmex CS-5100 21 CFR 864.5425, Multipurpose system for in vitro coagulation studies Factor V Leiden Assay 21 CFR 864.7925, Partial thromboplastin time test Coagulation Factor VIII Deficient Plasma 21 CFR 864.7290, Factor deficiency test Coagulation Factor IX Deficient Plasma LA 1 Screening Reagent, LA 2 Confirmation Reagent, and LA Ratio 21 CFR 864.8950, Russell viper venom reagent 2. Classification: Class II: Factor V Leiden Assay; Coagulation Factor VIII Deficient Plasma; Coagulation Factor IX Deficient Plasma Class I: LA 1 Screening Reagent, LA 2 Confirmation Reagent, and LA Ratio 3. Product code: Device Product Code Sysmex CS-5100 JPA, System, multipurpose for in vitro coagulation studies Factor V Leiden Assay GGW, Test, Time, Partial Thromboplastin Coagulation Factor VIII Deficient Plasma GJT, Plasma, coagulation factor deficient Coagulation Factor IX Deficient Plasma LA 1 Screening Reagent, LA 2 Confirmation Reagent, and LA Ratio GIR, Reagent, Russell Viper Venom 4. Panel: Hematology (81) H. Intended Use: 1. Intended use(s): Sysmex CS-5100 The Sysmex® Automated Blood Coagulation Analyzer CS-5100 is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of: • Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® • Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL • Fibrinogen (Fbg) with Dade® Thrombin Reagent • Coagulation Factor V with Dade® Innovin® • Coagulation Factor VII with Dade® Innovin® • Coagulation Factor VIII with Dade® Actin® FSL • Coagulation Factor IX with Dade® Actin® FSL • Lupus Anticoagulant with LA1 Screening and LA2 Confirmation Reagent • Factor V Leiden with Factor V Leiden Assay • Protein C with Protein C Reagent • Antithrombin (AT) with INNOVANCE® Antithrombin • Protein C with Berichrom® Protein C • D-dimer with INNOVANCE® D-Dimer The performance of this device has not been established in neonate and pediatric patient populations. Factor V Leiden Assay The Siemens Healthcare Diagnostics Factor V Leiden Assay is a simple functional clotting test system intended for screening of resistance to Activated Protein C (APC) in plasma from individuals with Factor V (Leiden) defect. For in vitro diagnostic use. Coagulation Factor VIII and IX Deficient Plasma In vitro diagnostic reagents for the determination of the activity of coagulation factors VIII, IX, XI and XII in human plasma by coagulation methods. LA1 Screening and LA2 Confirmation Reagents LA1 Screening Reagent and LA2 Confirmation Reagent are simplified DRVVT reagents for detection of Lupus Anticoagulants (LA) in one-stage clotting tests. LA1 Screening Reagent: Simplified DRVV reagent to screen for the presence of Lupus Anticoagulants. LA2 Confirmation Reagent: Phospholipid-rich DRVV reagent for the specific correction of Lupus Anticoagulants. 2. Indication(s) for use: Same as Intended Use(s) above 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Sysmex® CS-5100 I. Device Description: Sysmex CS-5100 The Sysmex Automated Blood Coagulation Analyzer CS-5100 (hereafter Sysmex CS-5100) is an automated blood coagulation instrument which analyzes venous plasma samples collected in 3.2% sodium citrate using clotting, chromogenic and immunoassay methods. Results are displayed on the Information Processing Unit (IPU) screen and can be printed on external printers or transmitted to a host computer. The instrument is capable of analyzing samples in a normal mode and a micro-sample mode. Factor V Leiden with Factor V Leiden Assay The Factor V Leiden Assay is based on the activation of endogenous Protein C by incubation of plasma with Agkistrodon contortrix contortrix (Southern Copperhead) venom. The kit contains the venom activator in stabilizing-buffer solution and the PR3V Reagent: dilute phospholipid rich Vipera Russelli venom, calcium and heparin inhibitor. Both reagents contain sodium azide as preservative. Coagulation Factor VIII and IX Deficient Plasmas Coagulation Factor Deficient Plasmas are lyophilized human plasmas with a residual Factor VIII, IX, XI or XII activity of ≤ 1 %. The deficient plasmas are manufactured by immunoadsorption from normal plasma and are free from antigen of the respective factor. Fibrinogen is present in a quantity of at least 1 g/L, and the remaining coagulation factors are present in an activity greater than 40 % of the norm. The plasmas contain mannitol (20 g/L) as a stabilizer. Lupus Anticoagulant with LA1 Screening and LA2 Confirmation Reagent LA 1 Screening Reagent and LA 2 Confirmation Reagent contain Russell’s viper venom, phospholipids, antiheparin agents, calcium, buffers, stabilizers, sodium azide and dyes. J. Substantial Equivalence Information: 1. Predicate device name(s): Sysmex® CA-1500 2. Predicate 510(k) number(s): K011235 (Sysmex CA-1500) The performance of the Factor V Leiden Assay on the Sysmex CA-1500 was evaluated in K992456. The performance of Coagulation Factor VIII Deficient Plasma and Coagulation Factor IX Deficient Plasma in combination with the Sysmex CA-1500 was evaluated in K924396. The performance of LA 1 Screening Reagent,LA 2 Confirmation Reagent, and LA Ratio on the Sysmex CA-1500 was evaluated in K993299. 3. Comparison with predicate: Similarities Item Device Sysmex CS-5100 Predicate Sysmex CA-1500 Intended use The Sysmex CS-5100 is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of: For determination of: • Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® • Activated Partial Thromboplastin Time Purpose for submission:

idK172333_s0_e2000

K172333.txt

measurand

Factor V Leiden activity with Factor V Leiden Assay; Factor VIII activity with Dade® Actin® FSL Activated PTT Reagent; Factor IX activity with Dade® Actin® FSL Activated PTT Reagent; Lupus Anticoagulant with LA 1 Screening Reagent; Lupus Anticoagulant with LA 2 Confirmation Reagent and Lupus Anticoagulant with LA Ratio. Factor V Leiden Assay and Lupus Anticoagulant LA1/LA2 Ratio are reported as ratio; Factor VIII and Factor IX are reported as percent (%) of normal; Lupus Anticoagulant with LA 1 Screening Reagent and Lupus Anticoagulant with LA2 Confirmation Reagent are reported as clotting time in seconds.

ANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172333 B. Purpose for Submission: To expand the use of previously cleared assay reagents for Factor V Leiden; Coagulation Factor VIII Deficient Plasma; Coagulation Factor IX Deficient Plasma; Lupus Anticoagulant with LA 1 Screening Reagent; Lupus Anticoagulant with LA 2 Confirmation Reagent and Lupus Anticoagulant with LA 1 / LA 2 Ratio to the Sysmex® Automated Blood Coagulation Analyzer CS-5100. C. Measurand: Factor V Leiden activity with Factor V Leiden Assay; Factor VIII activity with Dade® Actin® FSL Activated PTT Reagent; Factor IX activity with Dade® Actin® FSL Activated PTT Reagent; Lupus Anticoagulant with LA 1 Screening Reagent; Lupus Anticoagulant with LA 2 Confirmation Reagent and Lupus Anticoagulant with LA Ratio. Factor V Leiden Assay and Lupus Anticoagulant LA1/LA2 Ratio are reported as ratio; Factor VIII and Factor IX are reported as percent (%) of normal; Lupus Anticoagulant with LA 1 Screening Reagent and Lupus Anticoagulant with LA2 Confirmation Reagent are reported as clotting time in seconds. D. Type of Test: Quantitative clot-based applications E. Applicant: Siemens Healthcare Diagnostics Product GmbH F. Proprietary and Established Names: Sysmex® Automated Blood Coagulation Analyzer CS-5100 Factor V Leiden Assay Coagulation Factor VIII, IX, XI and XII Deficient Plasmas LA 1 Screening Reagent, LA 2 Confirmation Reagent, and LA Ratio Note: The performance of Coagulation Factor XI Deficient Plasma and Coagulation Factor XII Deficient Plasma was not evaluated in this premarket notification. G. Regulatory Information: 1. Regulation section: Device Regulation Section Sysmex CS-5100 21 CFR 864.5425, Multipurpose system for in vitro coagulation studies Factor V Leiden Assay 21 CFR 864.7925, Partial thromboplastin time test Coagulation Factor VIII Deficient Plasma 21 CFR 864.7290, Factor deficiency test Coagulation Factor IX Deficient Plasma LA 1 Screening Reagent, LA 2 Confirmation Reagent, and LA Ratio 21 CFR 864.8950, Russell viper venom reagent 2. Classification: Class II: Factor V Leiden Assay; Coagulation Factor VIII Deficient Plasma; Coagulation Factor IX Deficient Plasma Class I: LA 1 Screening Reagent, LA 2 Confirmation Reagent, and LA Ratio 3. Product code: Device Product Code Sysmex CS-5100 JPA, System, multipurpose for in vitro coagulation studies Factor V Leiden Assay GGW, Test, Time, Partial Thromboplastin Coagulation Factor VIII Deficient Plasma GJT, Plasma, coagulation factor deficient Coagulation Factor IX Deficient Plasma LA 1 Screening Reagent, LA 2 Confirmation Reagent, and LA Ratio GIR, Reagent, Russell Viper Venom 4. Panel: Hematology (81) H. Intended Use: 1. Intended use(s): Sysmex CS-5100 The Sysmex® Automated Blood Coagulation Analyzer CS-5100 is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of: • Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® • Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL • Fibrinogen (Fbg) with Dade® Thrombin Reagent • Coagulation Factor V with Dade® Innovin® • Coagulation Factor VII with Dade® Innovin® • Coagulation Factor VIII with Dade® Actin® FSL • Coagulation Factor IX with Dade® Actin® FSL • Lupus Anticoagulant with LA1 Screening and LA2 Confirmation Reagent • Factor V Leiden with Factor V Leiden Assay • Protein C with Protein C Reagent • Antithrombin (AT) with INNOVANCE® Antithrombin • Protein C with Berichrom® Protein C • D-dimer with INNOVANCE® D-Dimer The performance of this device has not been established in neonate and pediatric patient populations. Factor V Leiden Assay The Siemens Healthcare Diagnostics Factor V Leiden Assay is a simple functional clotting test system intended for screening of resistance to Activated Protein C (APC) in plasma from individuals with Factor V (Leiden) defect. For in vitro diagnostic use. Coagulation Factor VIII and IX Deficient Plasma In vitro diagnostic reagents for the determination of the activity of coagulation factors VIII, IX, XI and XII in human plasma by coagulation methods. LA1 Screening and LA2 Confirmation Reagents LA1 Screening Reagent and LA2 Confirmation Reagent are simplified DRVVT reagents for detection of Lupus Anticoagulants (LA) in one-stage clotting tests. LA1 Screening Reagent: Simplified DRVV reagent to screen for the presence of Lupus Anticoagulants. LA2 Confirmation Reagent: Phospholipid-rich DRVV reagent for the specific correction of Lupus Anticoagulants. 2. Indication(s) for use: Same as Intended Use(s) above 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Sysmex® CS-5100 I. Device Description: Sysmex CS-5100 The Sysmex Automated Blood Coagulation Analyzer CS-5100 (hereafter Sysmex CS-5100) is an automated blood coagulation instrument which analyzes venous plasma samples collected in 3.2% sodium citrate using clotting, chromogenic and immunoassay methods. Results are displayed on the Information Processing Unit (IPU) screen and can be printed on external printers or transmitted to a host computer. The instrument is capable of analyzing samples in a normal mode and a micro-sample mode. Factor V Leiden with Factor V Leiden Assay The Factor V Leiden Assay is based on the activation of endogenous Protein C by incubation of plasma with Agkistrodon contortrix contortrix (Southern Copperhead) venom. The kit contains the venom activator in stabilizing-buffer solution and the PR3V Reagent: dilute phospholipid rich Vipera Russelli venom, calcium and heparin inhibitor. Both reagents contain sodium azide as preservative. Coagulation Factor VIII and IX Deficient Plasmas Coagulation Factor Deficient Plasmas are lyophilized human plasmas with a residual Factor VIII, IX, XI or XII activity of ≤ 1 %. The deficient plasmas are manufactured by immunoadsorption from normal plasma and are free from antigen of the respective factor. Fibrinogen is present in a quantity of at least 1 g/L, and the remaining coagulation factors are present in an activity greater than 40 % of the norm. The plasmas contain mannitol (20 g/L) as a stabilizer. Lupus Anticoagulant with LA1 Screening and LA2 Confirmation Reagent LA 1 Screening Reagent and LA 2 Confirmation Reagent contain Russell’s viper venom, phospholipids, antiheparin agents, calcium, buffers, stabilizers, sodium azide and dyes. J. Substantial Equivalence Information: 1. Predicate device name(s): Sysmex® CA-1500 2. Predicate 510(k) number(s): K011235 (Sysmex CA-1500) The performance of the Factor V Leiden Assay on the Sysmex CA-1500 was evaluated in K992456. The performance of Coagulation Factor VIII Deficient Plasma and Coagulation Factor IX Deficient Plasma in combination with the Sysmex CA-1500 was evaluated in K924396. The performance of LA 1 Screening Reagent,LA 2 Confirmation Reagent, and LA Ratio on the Sysmex CA-1500 was evaluated in K993299. 3. Comparison with predicate: Similarities Item Device Sysmex CS-5100 Predicate Sysmex CA-1500 Intended use The Sysmex CS-5100 is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of: For determination of: • Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® • Activated Partial Thromboplastin Time Measurand:

idK172333_s0_e2000

K172333.txt

type of test

Quantitative clot-based applications

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172333 B. Purpose for Submission: To expand the use of previously cleared assay reagents for Factor V Leiden; Coagulation Factor VIII Deficient Plasma; Coagulation Factor IX Deficient Plasma; Lupus Anticoagulant with LA 1 Screening Reagent; Lupus Anticoagulant with LA 2 Confirmation Reagent and Lupus Anticoagulant with LA 1 / LA 2 Ratio to the Sysmex® Automated Blood Coagulation Analyzer CS-5100. C. Measurand: Factor V Leiden activity with Factor V Leiden Assay; Factor VIII activity with Dade® Actin® FSL Activated PTT Reagent; Factor IX activity with Dade® Actin® FSL Activated PTT Reagent; Lupus Anticoagulant with LA 1 Screening Reagent; Lupus Anticoagulant with LA 2 Confirmation Reagent and Lupus Anticoagulant with LA Ratio. Factor V Leiden Assay and Lupus Anticoagulant LA1/LA2 Ratio are reported as ratio; Factor VIII and Factor IX are reported as percent (%) of normal; Lupus Anticoagulant with LA 1 Screening Reagent and Lupus Anticoagulant with LA2 Confirmation Reagent are reported as clotting time in seconds. D. Type of Test: Quantitative clot-based applications E. Applicant: Siemens Healthcare Diagnostics Product GmbH F. Proprietary and Established Names: Sysmex® Automated Blood Coagulation Analyzer CS-5100 Factor V Leiden Assay Coagulation Factor VIII, IX, XI and XII Deficient Plasmas LA 1 Screening Reagent, LA 2 Confirmation Reagent, and LA Ratio Note: The performance of Coagulation Factor XI Deficient Plasma and Coagulation Factor XII Deficient Plasma was not evaluated in this premarket notification. G. Regulatory Information: 1. Regulation section: Device Regulation Section Sysmex CS-5100 21 CFR 864.5425, Multipurpose system for in vitro coagulation studies Factor V Leiden Assay 21 CFR 864.7925, Partial thromboplastin time test Coagulation Factor VIII Deficient Plasma 21 CFR 864.7290, Factor deficiency test Coagulation Factor IX Deficient Plasma LA 1 Screening Reagent, LA 2 Confirmation Reagent, and LA Ratio 21 CFR 864.8950, Russell viper venom reagent 2. Classification: Class II: Factor V Leiden Assay; Coagulation Factor VIII Deficient Plasma; Coagulation Factor IX Deficient Plasma Class I: LA 1 Screening Reagent, LA 2 Confirmation Reagent, and LA Ratio 3. Product code: Device Product Code Sysmex CS-5100 JPA, System, multipurpose for in vitro coagulation studies Factor V Leiden Assay GGW, Test, Time, Partial Thromboplastin Coagulation Factor VIII Deficient Plasma GJT, Plasma, coagulation factor deficient Coagulation Factor IX Deficient Plasma LA 1 Screening Reagent, LA 2 Confirmation Reagent, and LA Ratio GIR, Reagent, Russell Viper Venom 4. Panel: Hematology (81) H. Intended Use: 1. Intended use(s): Sysmex CS-5100 The Sysmex® Automated Blood Coagulation Analyzer CS-5100 is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of: • Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® • Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL • Fibrinogen (Fbg) with Dade® Thrombin Reagent • Coagulation Factor V with Dade® Innovin® • Coagulation Factor VII with Dade® Innovin® • Coagulation Factor VIII with Dade® Actin® FSL • Coagulation Factor IX with Dade® Actin® FSL • Lupus Anticoagulant with LA1 Screening and LA2 Confirmation Reagent • Factor V Leiden with Factor V Leiden Assay • Protein C with Protein C Reagent • Antithrombin (AT) with INNOVANCE® Antithrombin • Protein C with Berichrom® Protein C • D-dimer with INNOVANCE® D-Dimer The performance of this device has not been established in neonate and pediatric patient populations. Factor V Leiden Assay The Siemens Healthcare Diagnostics Factor V Leiden Assay is a simple functional clotting test system intended for screening of resistance to Activated Protein C (APC) in plasma from individuals with Factor V (Leiden) defect. For in vitro diagnostic use. Coagulation Factor VIII and IX Deficient Plasma In vitro diagnostic reagents for the determination of the activity of coagulation factors VIII, IX, XI and XII in human plasma by coagulation methods. LA1 Screening and LA2 Confirmation Reagents LA1 Screening Reagent and LA2 Confirmation Reagent are simplified DRVVT reagents for detection of Lupus Anticoagulants (LA) in one-stage clotting tests. LA1 Screening Reagent: Simplified DRVV reagent to screen for the presence of Lupus Anticoagulants. LA2 Confirmation Reagent: Phospholipid-rich DRVV reagent for the specific correction of Lupus Anticoagulants. 2. Indication(s) for use: Same as Intended Use(s) above 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Sysmex® CS-5100 I. Device Description: Sysmex CS-5100 The Sysmex Automated Blood Coagulation Analyzer CS-5100 (hereafter Sysmex CS-5100) is an automated blood coagulation instrument which analyzes venous plasma samples collected in 3.2% sodium citrate using clotting, chromogenic and immunoassay methods. Results are displayed on the Information Processing Unit (IPU) screen and can be printed on external printers or transmitted to a host computer. The instrument is capable of analyzing samples in a normal mode and a micro-sample mode. Factor V Leiden with Factor V Leiden Assay The Factor V Leiden Assay is based on the activation of endogenous Protein C by incubation of plasma with Agkistrodon contortrix contortrix (Southern Copperhead) venom. The kit contains the venom activator in stabilizing-buffer solution and the PR3V Reagent: dilute phospholipid rich Vipera Russelli venom, calcium and heparin inhibitor. Both reagents contain sodium azide as preservative. Coagulation Factor VIII and IX Deficient Plasmas Coagulation Factor Deficient Plasmas are lyophilized human plasmas with a residual Factor VIII, IX, XI or XII activity of ≤ 1 %. The deficient plasmas are manufactured by immunoadsorption from normal plasma and are free from antigen of the respective factor. Fibrinogen is present in a quantity of at least 1 g/L, and the remaining coagulation factors are present in an activity greater than 40 % of the norm. The plasmas contain mannitol (20 g/L) as a stabilizer. Lupus Anticoagulant with LA1 Screening and LA2 Confirmation Reagent LA 1 Screening Reagent and LA 2 Confirmation Reagent contain Russell’s viper venom, phospholipids, antiheparin agents, calcium, buffers, stabilizers, sodium azide and dyes. J. Substantial Equivalence Information: 1. Predicate device name(s): Sysmex® CA-1500 2. Predicate 510(k) number(s): K011235 (Sysmex CA-1500) The performance of the Factor V Leiden Assay on the Sysmex CA-1500 was evaluated in K992456. The performance of Coagulation Factor VIII Deficient Plasma and Coagulation Factor IX Deficient Plasma in combination with the Sysmex CA-1500 was evaluated in K924396. The performance of LA 1 Screening Reagent,LA 2 Confirmation Reagent, and LA Ratio on the Sysmex CA-1500 was evaluated in K993299. 3. Comparison with predicate: Similarities Item Device Sysmex CS-5100 Predicate Sysmex CA-1500 Intended use The Sysmex CS-5100 is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of: For determination of: • Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® • Activated Partial Thromboplastin Time Type of test:

idK172333_s0_e2000

K172333.txt

panel

Hematology (81)

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172333 B. Purpose for Submission: To expand the use of previously cleared assay reagents for Factor V Leiden; Coagulation Factor VIII Deficient Plasma; Coagulation Factor IX Deficient Plasma; Lupus Anticoagulant with LA 1 Screening Reagent; Lupus Anticoagulant with LA 2 Confirmation Reagent and Lupus Anticoagulant with LA 1 / LA 2 Ratio to the Sysmex® Automated Blood Coagulation Analyzer CS-5100. C. Measurand: Factor V Leiden activity with Factor V Leiden Assay; Factor VIII activity with Dade® Actin® FSL Activated PTT Reagent; Factor IX activity with Dade® Actin® FSL Activated PTT Reagent; Lupus Anticoagulant with LA 1 Screening Reagent; Lupus Anticoagulant with LA 2 Confirmation Reagent and Lupus Anticoagulant with LA Ratio. Factor V Leiden Assay and Lupus Anticoagulant LA1/LA2 Ratio are reported as ratio; Factor VIII and Factor IX are reported as percent (%) of normal; Lupus Anticoagulant with LA 1 Screening Reagent and Lupus Anticoagulant with LA2 Confirmation Reagent are reported as clotting time in seconds. D. Type of Test: Quantitative clot-based applications E. Applicant: Siemens Healthcare Diagnostics Product GmbH F. Proprietary and Established Names: Sysmex® Automated Blood Coagulation Analyzer CS-5100 Factor V Leiden Assay Coagulation Factor VIII, IX, XI and XII Deficient Plasmas LA 1 Screening Reagent, LA 2 Confirmation Reagent, and LA Ratio Note: The performance of Coagulation Factor XI Deficient Plasma and Coagulation Factor XII Deficient Plasma was not evaluated in this premarket notification. G. Regulatory Information: 1. Regulation section: Device Regulation Section Sysmex CS-5100 21 CFR 864.5425, Multipurpose system for in vitro coagulation studies Factor V Leiden Assay 21 CFR 864.7925, Partial thromboplastin time test Coagulation Factor VIII Deficient Plasma 21 CFR 864.7290, Factor deficiency test Coagulation Factor IX Deficient Plasma LA 1 Screening Reagent, LA 2 Confirmation Reagent, and LA Ratio 21 CFR 864.8950, Russell viper venom reagent 2. Classification: Class II: Factor V Leiden Assay; Coagulation Factor VIII Deficient Plasma; Coagulation Factor IX Deficient Plasma Class I: LA 1 Screening Reagent, LA 2 Confirmation Reagent, and LA Ratio 3. Product code: Device Product Code Sysmex CS-5100 JPA, System, multipurpose for in vitro coagulation studies Factor V Leiden Assay GGW, Test, Time, Partial Thromboplastin Coagulation Factor VIII Deficient Plasma GJT, Plasma, coagulation factor deficient Coagulation Factor IX Deficient Plasma LA 1 Screening Reagent, LA 2 Confirmation Reagent, and LA Ratio GIR, Reagent, Russell Viper Venom 4. Panel: Hematology (81) H. Intended Use: 1. Intended use(s): Sysmex CS-5100 The Sysmex® Automated Blood Coagulation Analyzer CS-5100 is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of: • Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® • Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL • Fibrinogen (Fbg) with Dade® Thrombin Reagent • Coagulation Factor V with Dade® Innovin® • Coagulation Factor VII with Dade® Innovin® • Coagulation Factor VIII with Dade® Actin® FSL • Coagulation Factor IX with Dade® Actin® FSL • Lupus Anticoagulant with LA1 Screening and LA2 Confirmation Reagent • Factor V Leiden with Factor V Leiden Assay • Protein C with Protein C Reagent • Antithrombin (AT) with INNOVANCE® Antithrombin • Protein C with Berichrom® Protein C • D-dimer with INNOVANCE® D-Dimer The performance of this device has not been established in neonate and pediatric patient populations. Factor V Leiden Assay The Siemens Healthcare Diagnostics Factor V Leiden Assay is a simple functional clotting test system intended for screening of resistance to Activated Protein C (APC) in plasma from individuals with Factor V (Leiden) defect. For in vitro diagnostic use. Coagulation Factor VIII and IX Deficient Plasma In vitro diagnostic reagents for the determination of the activity of coagulation factors VIII, IX, XI and XII in human plasma by coagulation methods. LA1 Screening and LA2 Confirmation Reagents LA1 Screening Reagent and LA2 Confirmation Reagent are simplified DRVVT reagents for detection of Lupus Anticoagulants (LA) in one-stage clotting tests. LA1 Screening Reagent: Simplified DRVV reagent to screen for the presence of Lupus Anticoagulants. LA2 Confirmation Reagent: Phospholipid-rich DRVV reagent for the specific correction of Lupus Anticoagulants. 2. Indication(s) for use: Same as Intended Use(s) above 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Sysmex® CS-5100 I. Device Description: Sysmex CS-5100 The Sysmex Automated Blood Coagulation Analyzer CS-5100 (hereafter Sysmex CS-5100) is an automated blood coagulation instrument which analyzes venous plasma samples collected in 3.2% sodium citrate using clotting, chromogenic and immunoassay methods. Results are displayed on the Information Processing Unit (IPU) screen and can be printed on external printers or transmitted to a host computer. The instrument is capable of analyzing samples in a normal mode and a micro-sample mode. Factor V Leiden with Factor V Leiden Assay The Factor V Leiden Assay is based on the activation of endogenous Protein C by incubation of plasma with Agkistrodon contortrix contortrix (Southern Copperhead) venom. The kit contains the venom activator in stabilizing-buffer solution and the PR3V Reagent: dilute phospholipid rich Vipera Russelli venom, calcium and heparin inhibitor. Both reagents contain sodium azide as preservative. Coagulation Factor VIII and IX Deficient Plasmas Coagulation Factor Deficient Plasmas are lyophilized human plasmas with a residual Factor VIII, IX, XI or XII activity of ≤ 1 %. The deficient plasmas are manufactured by immunoadsorption from normal plasma and are free from antigen of the respective factor. Fibrinogen is present in a quantity of at least 1 g/L, and the remaining coagulation factors are present in an activity greater than 40 % of the norm. The plasmas contain mannitol (20 g/L) as a stabilizer. Lupus Anticoagulant with LA1 Screening and LA2 Confirmation Reagent LA 1 Screening Reagent and LA 2 Confirmation Reagent contain Russell’s viper venom, phospholipids, antiheparin agents, calcium, buffers, stabilizers, sodium azide and dyes. J. Substantial Equivalence Information: 1. Predicate device name(s): Sysmex® CA-1500 2. Predicate 510(k) number(s): K011235 (Sysmex CA-1500) The performance of the Factor V Leiden Assay on the Sysmex CA-1500 was evaluated in K992456. The performance of Coagulation Factor VIII Deficient Plasma and Coagulation Factor IX Deficient Plasma in combination with the Sysmex CA-1500 was evaluated in K924396. The performance of LA 1 Screening Reagent,LA 2 Confirmation Reagent, and LA Ratio on the Sysmex CA-1500 was evaluated in K993299. 3. Comparison with predicate: Similarities Item Device Sysmex CS-5100 Predicate Sysmex CA-1500 Intended use The Sysmex CS-5100 is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of: For determination of: • Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® • Activated Partial Thromboplastin Time Panel:

idK172333_s0_e2000

K172333.txt

predicate device name

Sysmex® CA-1500

ANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172333 B. Purpose for Submission: To expand the use of previously cleared assay reagents for Factor V Leiden; Coagulation Factor VIII Deficient Plasma; Coagulation Factor IX Deficient Plasma; Lupus Anticoagulant with LA 1 Screening Reagent; Lupus Anticoagulant with LA 2 Confirmation Reagent and Lupus Anticoagulant with LA 1 / LA 2 Ratio to the Sysmex® Automated Blood Coagulation Analyzer CS-5100. C. Measurand: Factor V Leiden activity with Factor V Leiden Assay; Factor VIII activity with Dade® Actin® FSL Activated PTT Reagent; Factor IX activity with Dade® Actin® FSL Activated PTT Reagent; Lupus Anticoagulant with LA 1 Screening Reagent; Lupus Anticoagulant with LA 2 Confirmation Reagent and Lupus Anticoagulant with LA Ratio. Factor V Leiden Assay and Lupus Anticoagulant LA1/LA2 Ratio are reported as ratio; Factor VIII and Factor IX are reported as percent (%) of normal; Lupus Anticoagulant with LA 1 Screening Reagent and Lupus Anticoagulant with LA2 Confirmation Reagent are reported as clotting time in seconds. D. Type of Test: Quantitative clot-based applications E. Applicant: Siemens Healthcare Diagnostics Product GmbH F. Proprietary and Established Names: Sysmex® Automated Blood Coagulation Analyzer CS-5100 Factor V Leiden Assay Coagulation Factor VIII, IX, XI and XII Deficient Plasmas LA 1 Screening Reagent, LA 2 Confirmation Reagent, and LA Ratio Note: The performance of Coagulation Factor XI Deficient Plasma and Coagulation Factor XII Deficient Plasma was not evaluated in this premarket notification. G. Regulatory Information: 1. Regulation section: Device Regulation Section Sysmex CS-5100 21 CFR 864.5425, Multipurpose system for in vitro coagulation studies Factor V Leiden Assay 21 CFR 864.7925, Partial thromboplastin time test Coagulation Factor VIII Deficient Plasma 21 CFR 864.7290, Factor deficiency test Coagulation Factor IX Deficient Plasma LA 1 Screening Reagent, LA 2 Confirmation Reagent, and LA Ratio 21 CFR 864.8950, Russell viper venom reagent 2. Classification: Class II: Factor V Leiden Assay; Coagulation Factor VIII Deficient Plasma; Coagulation Factor IX Deficient Plasma Class I: LA 1 Screening Reagent, LA 2 Confirmation Reagent, and LA Ratio 3. Product code: Device Product Code Sysmex CS-5100 JPA, System, multipurpose for in vitro coagulation studies Factor V Leiden Assay GGW, Test, Time, Partial Thromboplastin Coagulation Factor VIII Deficient Plasma GJT, Plasma, coagulation factor deficient Coagulation Factor IX Deficient Plasma LA 1 Screening Reagent, LA 2 Confirmation Reagent, and LA Ratio GIR, Reagent, Russell Viper Venom 4. Panel: Hematology (81) H. Intended Use: 1. Intended use(s): Sysmex CS-5100 The Sysmex® Automated Blood Coagulation Analyzer CS-5100 is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of: • Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® • Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL • Fibrinogen (Fbg) with Dade® Thrombin Reagent • Coagulation Factor V with Dade® Innovin® • Coagulation Factor VII with Dade® Innovin® • Coagulation Factor VIII with Dade® Actin® FSL • Coagulation Factor IX with Dade® Actin® FSL • Lupus Anticoagulant with LA1 Screening and LA2 Confirmation Reagent • Factor V Leiden with Factor V Leiden Assay • Protein C with Protein C Reagent • Antithrombin (AT) with INNOVANCE® Antithrombin • Protein C with Berichrom® Protein C • D-dimer with INNOVANCE® D-Dimer The performance of this device has not been established in neonate and pediatric patient populations. Factor V Leiden Assay The Siemens Healthcare Diagnostics Factor V Leiden Assay is a simple functional clotting test system intended for screening of resistance to Activated Protein C (APC) in plasma from individuals with Factor V (Leiden) defect. For in vitro diagnostic use. Coagulation Factor VIII and IX Deficient Plasma In vitro diagnostic reagents for the determination of the activity of coagulation factors VIII, IX, XI and XII in human plasma by coagulation methods. LA1 Screening and LA2 Confirmation Reagents LA1 Screening Reagent and LA2 Confirmation Reagent are simplified DRVVT reagents for detection of Lupus Anticoagulants (LA) in one-stage clotting tests. LA1 Screening Reagent: Simplified DRVV reagent to screen for the presence of Lupus Anticoagulants. LA2 Confirmation Reagent: Phospholipid-rich DRVV reagent for the specific correction of Lupus Anticoagulants. 2. Indication(s) for use: Same as Intended Use(s) above 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Sysmex® CS-5100 I. Device Description: Sysmex CS-5100 The Sysmex Automated Blood Coagulation Analyzer CS-5100 (hereafter Sysmex CS-5100) is an automated blood coagulation instrument which analyzes venous plasma samples collected in 3.2% sodium citrate using clotting, chromogenic and immunoassay methods. Results are displayed on the Information Processing Unit (IPU) screen and can be printed on external printers or transmitted to a host computer. The instrument is capable of analyzing samples in a normal mode and a micro-sample mode. Factor V Leiden with Factor V Leiden Assay The Factor V Leiden Assay is based on the activation of endogenous Protein C by incubation of plasma with Agkistrodon contortrix contortrix (Southern Copperhead) venom. The kit contains the venom activator in stabilizing-buffer solution and the PR3V Reagent: dilute phospholipid rich Vipera Russelli venom, calcium and heparin inhibitor. Both reagents contain sodium azide as preservative. Coagulation Factor VIII and IX Deficient Plasmas Coagulation Factor Deficient Plasmas are lyophilized human plasmas with a residual Factor VIII, IX, XI or XII activity of ≤ 1 %. The deficient plasmas are manufactured by immunoadsorption from normal plasma and are free from antigen of the respective factor. Fibrinogen is present in a quantity of at least 1 g/L, and the remaining coagulation factors are present in an activity greater than 40 % of the norm. The plasmas contain mannitol (20 g/L) as a stabilizer. Lupus Anticoagulant with LA1 Screening and LA2 Confirmation Reagent LA 1 Screening Reagent and LA 2 Confirmation Reagent contain Russell’s viper venom, phospholipids, antiheparin agents, calcium, buffers, stabilizers, sodium azide and dyes. J. Substantial Equivalence Information: 1. Predicate device name(s): Sysmex® CA-1500 2. Predicate 510(k) number(s): K011235 (Sysmex CA-1500) The performance of the Factor V Leiden Assay on the Sysmex CA-1500 was evaluated in K992456. The performance of Coagulation Factor VIII Deficient Plasma and Coagulation Factor IX Deficient Plasma in combination with the Sysmex CA-1500 was evaluated in K924396. The performance of LA 1 Screening Reagent,LA 2 Confirmation Reagent, and LA Ratio on the Sysmex CA-1500 was evaluated in K993299. 3. Comparison with predicate: Similarities Item Device Sysmex CS-5100 Predicate Sysmex CA-1500 Intended use The Sysmex CS-5100 is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of: For determination of: • Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® • Activated Partial Thromboplastin Time Predicate device name:

idK172333_s0_e2000

K172333.txt

applicant

Siemens Healthcare Diagnostics Product GmbH

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172333 B. Purpose for Submission: To expand the use of previously cleared assay reagents for Factor V Leiden; Coagulation Factor VIII Deficient Plasma; Coagulation Factor IX Deficient Plasma; Lupus Anticoagulant with LA 1 Screening Reagent; Lupus Anticoagulant with LA 2 Confirmation Reagent and Lupus Anticoagulant with LA 1 / LA 2 Ratio to the Sysmex® Automated Blood Coagulation Analyzer CS-5100. C. Measurand: Factor V Leiden activity with Factor V Leiden Assay; Factor VIII activity with Dade® Actin® FSL Activated PTT Reagent; Factor IX activity with Dade® Actin® FSL Activated PTT Reagent; Lupus Anticoagulant with LA 1 Screening Reagent; Lupus Anticoagulant with LA 2 Confirmation Reagent and Lupus Anticoagulant with LA Ratio. Factor V Leiden Assay and Lupus Anticoagulant LA1/LA2 Ratio are reported as ratio; Factor VIII and Factor IX are reported as percent (%) of normal; Lupus Anticoagulant with LA 1 Screening Reagent and Lupus Anticoagulant with LA2 Confirmation Reagent are reported as clotting time in seconds. D. Type of Test: Quantitative clot-based applications E. Applicant: Siemens Healthcare Diagnostics Product GmbH F. Proprietary and Established Names: Sysmex® Automated Blood Coagulation Analyzer CS-5100 Factor V Leiden Assay Coagulation Factor VIII, IX, XI and XII Deficient Plasmas LA 1 Screening Reagent, LA 2 Confirmation Reagent, and LA Ratio Note: The performance of Coagulation Factor XI Deficient Plasma and Coagulation Factor XII Deficient Plasma was not evaluated in this premarket notification. G. Regulatory Information: 1. Regulation section: Device Regulation Section Sysmex CS-5100 21 CFR 864.5425, Multipurpose system for in vitro coagulation studies Factor V Leiden Assay 21 CFR 864.7925, Partial thromboplastin time test Coagulation Factor VIII Deficient Plasma 21 CFR 864.7290, Factor deficiency test Coagulation Factor IX Deficient Plasma LA 1 Screening Reagent, LA 2 Confirmation Reagent, and LA Ratio 21 CFR 864.8950, Russell viper venom reagent 2. Classification: Class II: Factor V Leiden Assay; Coagulation Factor VIII Deficient Plasma; Coagulation Factor IX Deficient Plasma Class I: LA 1 Screening Reagent, LA 2 Confirmation Reagent, and LA Ratio 3. Product code: Device Product Code Sysmex CS-5100 JPA, System, multipurpose for in vitro coagulation studies Factor V Leiden Assay GGW, Test, Time, Partial Thromboplastin Coagulation Factor VIII Deficient Plasma GJT, Plasma, coagulation factor deficient Coagulation Factor IX Deficient Plasma LA 1 Screening Reagent, LA 2 Confirmation Reagent, and LA Ratio GIR, Reagent, Russell Viper Venom 4. Panel: Hematology (81) H. Intended Use: 1. Intended use(s): Sysmex CS-5100 The Sysmex® Automated Blood Coagulation Analyzer CS-5100 is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of: • Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® • Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL • Fibrinogen (Fbg) with Dade® Thrombin Reagent • Coagulation Factor V with Dade® Innovin® • Coagulation Factor VII with Dade® Innovin® • Coagulation Factor VIII with Dade® Actin® FSL • Coagulation Factor IX with Dade® Actin® FSL • Lupus Anticoagulant with LA1 Screening and LA2 Confirmation Reagent • Factor V Leiden with Factor V Leiden Assay • Protein C with Protein C Reagent • Antithrombin (AT) with INNOVANCE® Antithrombin • Protein C with Berichrom® Protein C • D-dimer with INNOVANCE® D-Dimer The performance of this device has not been established in neonate and pediatric patient populations. Factor V Leiden Assay The Siemens Healthcare Diagnostics Factor V Leiden Assay is a simple functional clotting test system intended for screening of resistance to Activated Protein C (APC) in plasma from individuals with Factor V (Leiden) defect. For in vitro diagnostic use. Coagulation Factor VIII and IX Deficient Plasma In vitro diagnostic reagents for the determination of the activity of coagulation factors VIII, IX, XI and XII in human plasma by coagulation methods. LA1 Screening and LA2 Confirmation Reagents LA1 Screening Reagent and LA2 Confirmation Reagent are simplified DRVVT reagents for detection of Lupus Anticoagulants (LA) in one-stage clotting tests. LA1 Screening Reagent: Simplified DRVV reagent to screen for the presence of Lupus Anticoagulants. LA2 Confirmation Reagent: Phospholipid-rich DRVV reagent for the specific correction of Lupus Anticoagulants. 2. Indication(s) for use: Same as Intended Use(s) above 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Sysmex® CS-5100 I. Device Description: Sysmex CS-5100 The Sysmex Automated Blood Coagulation Analyzer CS-5100 (hereafter Sysmex CS-5100) is an automated blood coagulation instrument which analyzes venous plasma samples collected in 3.2% sodium citrate using clotting, chromogenic and immunoassay methods. Results are displayed on the Information Processing Unit (IPU) screen and can be printed on external printers or transmitted to a host computer. The instrument is capable of analyzing samples in a normal mode and a micro-sample mode. Factor V Leiden with Factor V Leiden Assay The Factor V Leiden Assay is based on the activation of endogenous Protein C by incubation of plasma with Agkistrodon contortrix contortrix (Southern Copperhead) venom. The kit contains the venom activator in stabilizing-buffer solution and the PR3V Reagent: dilute phospholipid rich Vipera Russelli venom, calcium and heparin inhibitor. Both reagents contain sodium azide as preservative. Coagulation Factor VIII and IX Deficient Plasmas Coagulation Factor Deficient Plasmas are lyophilized human plasmas with a residual Factor VIII, IX, XI or XII activity of ≤ 1 %. The deficient plasmas are manufactured by immunoadsorption from normal plasma and are free from antigen of the respective factor. Fibrinogen is present in a quantity of at least 1 g/L, and the remaining coagulation factors are present in an activity greater than 40 % of the norm. The plasmas contain mannitol (20 g/L) as a stabilizer. Lupus Anticoagulant with LA1 Screening and LA2 Confirmation Reagent LA 1 Screening Reagent and LA 2 Confirmation Reagent contain Russell’s viper venom, phospholipids, antiheparin agents, calcium, buffers, stabilizers, sodium azide and dyes. J. Substantial Equivalence Information: 1. Predicate device name(s): Sysmex® CA-1500 2. Predicate 510(k) number(s): K011235 (Sysmex CA-1500) The performance of the Factor V Leiden Assay on the Sysmex CA-1500 was evaluated in K992456. The performance of Coagulation Factor VIII Deficient Plasma and Coagulation Factor IX Deficient Plasma in combination with the Sysmex CA-1500 was evaluated in K924396. The performance of LA 1 Screening Reagent,LA 2 Confirmation Reagent, and LA Ratio on the Sysmex CA-1500 was evaluated in K993299. 3. Comparison with predicate: Similarities Item Device Sysmex CS-5100 Predicate Sysmex CA-1500 Intended use The Sysmex CS-5100 is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of: For determination of: • Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® • Activated Partial Thromboplastin Time Applicant:

idK172333_s12000_e14000

K172333.txt

proposed labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

51.7 (2.5th to 97.5th percentile) Lupus Anticoagulant with LA 2 Confirmation Reagent (seconds) Fresh samples 185 34.7–42.6 (2.5th to 97.5th percentile) Frozen samples 191 35.7–43.6 (2.5th to 97.5th percentile) Lupus Anticoagulant with LA 1 / LA 2 Ratio (no units) Fresh samples 184 0.89–1.25 (2.5th to 97.5th percentile) Frozen samples 191 0.91–1.26 (2.5th to 97.5th percentile) N. Instrument Name: Sysmex® Automated Blood Coagulation Analyzer CS-5100 (Sysmex CS-5100) O. System Descriptions: 1. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes ___X_____ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No ____X____ 2. Software: FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: Yes ____X____ or No ________ 3. Specimen Identification: Manual entry and barcode reader 4. Specimen Sampling and Handling: The Sysmex CS-5100 supports two different analysis modes; normal mode for capped (closed) and uncapped (open) sampling from collection tubes, and the micro-sample mode for open (uncapped) sampling. In the normal mode, capped and uncapped samples may be loaded into the same sample rack for analysis. Automatic reanalysis is also an exclusive function of the normal mode. In the micro-sample mode, uncapped samples may be loaded in the sampler or STAT holder. 5. Calibration: Calibration is performed using Standard Human Plasma (SHP) as an automated function of the Sysmex CS-5100. A new standard curve must be established when changing a reagent lot, post-major maintenance or service, if indicated by quality control results, and when required according to laboratory control procedures and government regulations. 6. Quality Control: Quality control testing using Control Plasma N, Control Plasma P and ProC Control Plasma should be performed at least every 8 hours during intervals of patient testing. Controls should be run after a new standard curve is established and after each change of reagent. Patient test results should not be reported if controls are out of range. P. Other Supportive Instrument Performance Characteristics Data Not Covered In The “Performance Characteristics” Section above: 1. Dilution Study The Sysmex CS-5100 analyzer offers additional dilution options for each application carried out by an auto-dilution mode when measurement results are observed outside the analytical measuring range (AMR): auto-dilution mode 1:4 for Factor VIII with Dade Actin FSL results above 120% of norm, and auto-dilution mode 1:2 for Factor IX with Dade Actin FSL results above 120% of norm. The Sysmex CS-5100 analyzer also provides the 2:1 processing mode for results below the AMR. In addition to automatic dilution settings, the Sysmex CS-5100 analyzer provides an on- demand ‘dilution analysis.’ The application is programmed with a list of pre-defined dilutions that may be selected for such purposes. The following options are provided by the Sysmex CS-5100 analyzer to the customer for ‘dilution analysis’: 1/2, 1/4, 1/8 dilution and processing modes 3/2, 2/1 on demand. The dilutions that may be selected are application-specific and are listed in the application sheets. The auto-dilution study was carried out with one analyzer and one reagent lot with three different plasma samples covering the range outside the calibration curve between the end of the analytical measurement range (AMR) and the clinically reportable range (CRR), for each of the applicable reagent applications. Three test samples were analyzed for each dilution, in five replicates. The same samples, but undiluted, were measured upon auto-dilution by the instrument. All observed maximum deviations in the dilution analysis study were below the pre-defined acceptance criteria. 2. Normal Mode versus Micro Mode The Sysmex CS-5100 has two analysis modes: normal and micro. In the normal-sample mode, samples for all the analyses including re-analyses are taken into the instrument at the same time and analyzed using capped sample tube analysis. In the normal mode, a capped sample tube analysis can be performed. Automatic re-analysis can also be performed. In the micro-sample mode, the sample volume from samples set in the sampler or STAT holder is taken into the instrument through a secondary dispensing sample probe and analyzed. This analysis mode can also be performed with less sample volume than normal mode. However, in the micro-sample mode, capped sample tube analysis as well as automatic re-analysis cannot be performed. The comparison study between micro versus normal mode was conducted for each application using 60 samples covering the clinical reportable ranges. The study was conducted with one reagent lot on one Sysmex CS-5100 analyzer and the predicate instrument. The study results met the pre-defined acceptance criteria and demonstrated acceptable comparability between micro versus normal mode. 3. Carryover Studies Reagent Carryover The reagent carryover study investigated whether a reagent or a test component of a donor application may affect an acceptor application. A combination of donor and acceptor applications was tested in a defined sequence. One normal plasma pool and one pathological plasma pool were used as test samples. The reagent carryover studies data showed no cross-contamination caused between one application into another. Sample Carryover A donor, was defined as a test sample with the highest possible analyte concentration that might interfere in the subsequent assay. Whereas an acceptor, was defined as a low analyte concentration test sample measured after the measurements of the donor assay. If sample carryover occurs the results of the acceptor assay show interference. Samples were prepared by dilution or spiking of a normal plasma pool with the respective application-specific deficient plasma or respective analyte concentrate. The donor and acceptor assay measurements were performed in a defined sequence. The data showed no sample carryover. 4. Ambient Temperature Testing The study investigated the influence of environmental temperatures on test results. Each study was carried out with one Sysmex CS-5100 analyzer, one reagent lot, and one calibrator lot. The samples were chosen to represent the respective entire clinical reportable range (CRR) and the medical decision points (MDPs): in addition to pooled plasma, ProC Global Control, Control Plasma N and P were tested in a minimum of five replicates on three different days, each day representing a different ambient temperature (15°C, 22°C, and 30°C). The mean values were calculated for each sample and the relative (percent) or absolute differences were calculated for each application and found to be within the pre-defined acceptance criteria. The data confirmed that the correctness of the measured results is assured within the operating range temperatures of the Sysmex CS-5100 analyzer (15°C–30°C). Q. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. R. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK172333_s12000_e14000

K172333.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

8–51.7 (2.5th to 97.5th percentile) Lupus Anticoagulant with LA 2 Confirmation Reagent (seconds) Fresh samples 185 34.7–42.6 (2.5th to 97.5th percentile) Frozen samples 191 35.7–43.6 (2.5th to 97.5th percentile) Lupus Anticoagulant with LA 1 / LA 2 Ratio (no units) Fresh samples 184 0.89–1.25 (2.5th to 97.5th percentile) Frozen samples 191 0.91–1.26 (2.5th to 97.5th percentile) N. Instrument Name: Sysmex® Automated Blood Coagulation Analyzer CS-5100 (Sysmex CS-5100) O. System Descriptions: 1. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes ___X_____ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No ____X____ 2. Software: FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: Yes ____X____ or No ________ 3. Specimen Identification: Manual entry and barcode reader 4. Specimen Sampling and Handling: The Sysmex CS-5100 supports two different analysis modes; normal mode for capped (closed) and uncapped (open) sampling from collection tubes, and the micro-sample mode for open (uncapped) sampling. In the normal mode, capped and uncapped samples may be loaded into the same sample rack for analysis. Automatic reanalysis is also an exclusive function of the normal mode. In the micro-sample mode, uncapped samples may be loaded in the sampler or STAT holder. 5. Calibration: Calibration is performed using Standard Human Plasma (SHP) as an automated function of the Sysmex CS-5100. A new standard curve must be established when changing a reagent lot, post-major maintenance or service, if indicated by quality control results, and when required according to laboratory control procedures and government regulations. 6. Quality Control: Quality control testing using Control Plasma N, Control Plasma P and ProC Control Plasma should be performed at least every 8 hours during intervals of patient testing. Controls should be run after a new standard curve is established and after each change of reagent. Patient test results should not be reported if controls are out of range. P. Other Supportive Instrument Performance Characteristics Data Not Covered In The “Performance Characteristics” Section above: 1. Dilution Study The Sysmex CS-5100 analyzer offers additional dilution options for each application carried out by an auto-dilution mode when measurement results are observed outside the analytical measuring range (AMR): auto-dilution mode 1:4 for Factor VIII with Dade Actin FSL results above 120% of norm, and auto-dilution mode 1:2 for Factor IX with Dade Actin FSL results above 120% of norm. The Sysmex CS-5100 analyzer also provides the 2:1 processing mode for results below the AMR. In addition to automatic dilution settings, the Sysmex CS-5100 analyzer provides an on- demand ‘dilution analysis.’ The application is programmed with a list of pre-defined dilutions that may be selected for such purposes. The following options are provided by the Sysmex CS-5100 analyzer to the customer for ‘dilution analysis’: 1/2, 1/4, 1/8 dilution and processing modes 3/2, 2/1 on demand. The dilutions that may be selected are application-specific and are listed in the application sheets. The auto-dilution study was carried out with one analyzer and one reagent lot with three different plasma samples covering the range outside the calibration curve between the end of the analytical measurement range (AMR) and the clinically reportable range (CRR), for each of the applicable reagent applications. Three test samples were analyzed for each dilution, in five replicates. The same samples, but undiluted, were measured upon auto-dilution by the instrument. All observed maximum deviations in the dilution analysis study were below the pre-defined acceptance criteria. 2. Normal Mode versus Micro Mode The Sysmex CS-5100 has two analysis modes: normal and micro. In the normal-sample mode, samples for all the analyses including re-analyses are taken into the instrument at the same time and analyzed using capped sample tube analysis. In the normal mode, a capped sample tube analysis can be performed. Automatic re-analysis can also be performed. In the micro-sample mode, the sample volume from samples set in the sampler or STAT holder is taken into the instrument through a secondary dispensing sample probe and analyzed. This analysis mode can also be performed with less sample volume than normal mode. However, in the micro-sample mode, capped sample tube analysis as well as automatic re-analysis cannot be performed. The comparison study between micro versus normal mode was conducted for each application using 60 samples covering the clinical reportable ranges. The study was conducted with one reagent lot on one Sysmex CS-5100 analyzer and the predicate instrument. The study results met the pre-defined acceptance criteria and demonstrated acceptable comparability between micro versus normal mode. 3. Carryover Studies Reagent Carryover The reagent carryover study investigated whether a reagent or a test component of a donor application may affect an acceptor application. A combination of donor and acceptor applications was tested in a defined sequence. One normal plasma pool and one pathological plasma pool were used as test samples. The reagent carryover studies data showed no cross-contamination caused between one application into another. Sample Carryover A donor, was defined as a test sample with the highest possible analyte concentration that might interfere in the subsequent assay. Whereas an acceptor, was defined as a low analyte concentration test sample measured after the measurements of the donor assay. If sample carryover occurs the results of the acceptor assay show interference. Samples were prepared by dilution or spiking of a normal plasma pool with the respective application-specific deficient plasma or respective analyte concentrate. The donor and acceptor assay measurements were performed in a defined sequence. The data showed no sample carryover. 4. Ambient Temperature Testing The study investigated the influence of environmental temperatures on test results. Each study was carried out with one Sysmex CS-5100 analyzer, one reagent lot, and one calibrator lot. The samples were chosen to represent the respective entire clinical reportable range (CRR) and the medical decision points (MDPs): in addition to pooled plasma, ProC Global Control, Control Plasma N and P were tested in a minimum of five replicates on three different days, each day representing a different ambient temperature (15°C, 22°C, and 30°C). The mean values were calculated for each sample and the relative (percent) or absolute differences were calculated for each application and found to be within the pre-defined acceptance criteria. The data confirmed that the correctness of the measured results is assured within the operating range temperatures of the Sysmex CS-5100 analyzer (15°C–30°C). Q. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. R. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK190332_s0_e2000

K190332.txt

purpose for submission

New Whole Slide Imaging (WSI) system

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K190332 B. Purpose for Submission: New Whole Slide Imaging (WSI) system C. Measurand: Not applicable D. Type of Test: Digital pathology whole slide imaging E. Applicant: Leica Biosystems Imaging, Inc. F. Proprietary and Established Names: Aperio AT2 DX System G. Regulatory Information: 1. Regulation section: 21 CFR 864.3700 2. Classification: Class II (special controls) 3. Product code: PSY 4. Panel: 88 - Pathology 2 H. Intended Use: 1. Intended use(s): The Aperio AT2 DX System is an automated digital slide creation and viewing system. The Aperio AT2 DX System is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The Aperio AT2 DX System is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The Aperio AT2 DX System is composed of the Aperio AT2 DX scanner, the ImageScope DX review application and Display. The Aperio AT2 DX System is for creation and viewing of digital images of scanned glass slides that would otherwise be appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using the Aperio AT2 DX System. 2. Indication(s) for use: Same as Intended Use. 3. Special conditions for use statement(s): For in vitro diagnostic (IVD) use only For prescription use only 4. Special instrument requirements: Aperio AT2 DX digital slide scanner (for software Aperio Console DX 102.0.4.46 and Aperio Controller DX 102.0.4.85_x64) Viewing Workstation executing ImageScope DX viewer software (version 1.0.0.5018) Display (MR2416) I. Device Description: The Aperio AT2 DX System is an automated digital slide creation and viewing system. The system is composed of the following components: • Aperio AT2 DX digital slide scanner • Viewing Workstation executing ImageScope DX viewer software 3 • Display (MR2416) The Aperio AT2 DX digital slide scanner digitizes microscope slides at diagnostic resolutions: 0.5 µm/pixel (20x objective equivalent) and 0.25 µm/pixel (40x objective equivalent), to create digital WSI images. The Aperio AT2 DX scanner has a capacity of 400 1x3 inch glass slides. After the slides are loaded the scanning process begins when the operator starts the Aperio AT2 DX scanner and finishes when the scanner has completed scanning of all loaded slides. The image acquisition components include a white LED light source, Olympus Plan Apo 20x lens with a Numeric Aperture (NA) of 0.75, a 10/90 beam splitter, a 2D area-scan camera and a 1D line-scan camera which is the primary image capture device. The 10/90 bean splitter sends 10% of the photons toward the 2D area-scan camera and remaining 90% of the photons toward the 1D line- scan camera. Two motorized stages are used with one stage for moving the slide to be scanned and the other stage for moving the objective lens for focusing purposes. During scanning with a 20x objective lens, the motion of the slide stage combined with the speed of the 1D line-scan camera, the field of view of the objective lens and the number of pixels of the camera result in a resolution of 0.5 µm/pixel for 20x magnification. 40x magnification is achieved with a magnification doubler, with 0.25 μm/pixel resolution. Focus during the scan is maintained using a triangulated focus map built from individual focus points determined in a separate step before scanning is started. Proprietary software is used for image processing during acquisition. Leica’s proprietary format, SVS, is used to store and transmit the images between the Aperio AT2 DX digital slide scanner and the ImageScope DX viewer on viewing station. Software Aperio Controller DX runs on the AT2 DX workstation as a system service and controls the operations of the scanner. Software Aperio Console DX is a desktop program that runs on the AT2 DX workstation with a display monitor (Dell MR2416) and provides user interface for an operator to control operations of AT2 DX scanner. The ImageScope DX application is a software only subsystem to be used with the display monitor (Dell MR2416) and runs on a separate viewing workstation PC. The ImageScope DX software opens the WSI images acquired with Aperio AT2 DX scanner from the image storage attached to local network and uses the color profile to render the image data to the calibrated display monitor to deliver the image view at the appropriate magnification and color. Functionalities of ImageScope DX include navigating the slide similar to using an optical microscope, panning across the slide to examine all tissue regions, zooming in and out to allow review at different magnification levels, and allowing pathologist annotations during review. The different subsystems of the Aperio AT2 DX System are connected over an IT network at the user site. The IT hardware/software that supports the ImageScope DX Application Server & Storage software is not provided as part of the Aperio AT2 DX System, but may be located in a central server room separate from the workstation with the ImageScope DX viewing software and Display. The communication of data between Aperio AT2 DX scanner and ImageScope DX application is via a customer provided wired network or a direct connected cable between these subsystems. Aperio AT2 DX System includes a display that has been validated as part of the pivotal clinical study. 4 The Aperio AT2 DX System allows pathologists to view and evaluate digital images of formalin-fixed, paraffin-embedded (FFPE) tissue slides that would otherwise be appropriate for manual visualization by conventional brightfield (light) microscopy. The Aperio AT2 DX System does not include any automated image analysis applications that would constitute computer aided detection or diagnosis. J. Substantial Equivalence Information: 1. Predicate device name(s): Philips IntelliSite Pathology Solution (PIPS) 2. Predicate 510(k) number(s): DEN160056 3. Comparison with predicate: Similarities Item Device Predicate Intended Use The Aperio AT2 DX System is an automated digital slide creation and viewing system. The Aperio AT2 DX System is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The Aperio AT2 DX System is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The Aperio AT2 DX System is composed of the Aperio AT2 DX scanner, the ImageScope DX review application and Display. The Aperio AT2 DX System is for creation and viewing of digital images of scanned glass slides that would otherwise be appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified The Philips IntelliSite Pathology Solution (PIPS) is an automated digital slide creation, viewing, and management system. The PIPS is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The PIPS is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The PIPS comprises the Image Management System (IMS), the Ultra Fast Scanner (UFS) and Display. The PIPS is for creation and viewing of digital images of scanned glass slides that would otherwise be 5 Similarities Item Device Predicate pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using the Aperio AT2 DX System. appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using PIPS. Specimen type Surgical pathology slides prepared from FFPE tissue Same Principle of operation After conducting Quality Control (QC) on the glass slides per laboratory standards (e.g., staining, cover- slipping, barcode placement, etc.), the technician loads the slides into the Aperio AT2 DX scanner. The scanner scans the slides and generates WSI image for each slide. The technician performs QC on scanned WSI images by checking image data and image quality. When QC is failed, the slide will be re-scanned. The acquired WSI images are stored in an end user provided image storage attached to the local network. During review, the pathologist opens WSI images acquired with the Aperio AT2 DX scanner from the image storage, performs further QC to ensure image quality and reads WSI images of the slides to make a diagnosis. Same Device Components WSI scanner (Aperio AT2 DX scanner), Image Management System (ImageScope DX application), and color monitor display Same (PIPS Ultra Fast Scanner, Image Management System Purpose for submission:

idK190332_s0_e2000

K190332.txt

measurand

Not applicable

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K190332 B. Purpose for Submission: New Whole Slide Imaging (WSI) system C. Measurand: Not applicable D. Type of Test: Digital pathology whole slide imaging E. Applicant: Leica Biosystems Imaging, Inc. F. Proprietary and Established Names: Aperio AT2 DX System G. Regulatory Information: 1. Regulation section: 21 CFR 864.3700 2. Classification: Class II (special controls) 3. Product code: PSY 4. Panel: 88 - Pathology 2 H. Intended Use: 1. Intended use(s): The Aperio AT2 DX System is an automated digital slide creation and viewing system. The Aperio AT2 DX System is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The Aperio AT2 DX System is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The Aperio AT2 DX System is composed of the Aperio AT2 DX scanner, the ImageScope DX review application and Display. The Aperio AT2 DX System is for creation and viewing of digital images of scanned glass slides that would otherwise be appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using the Aperio AT2 DX System. 2. Indication(s) for use: Same as Intended Use. 3. Special conditions for use statement(s): For in vitro diagnostic (IVD) use only For prescription use only 4. Special instrument requirements: Aperio AT2 DX digital slide scanner (for software Aperio Console DX 102.0.4.46 and Aperio Controller DX 102.0.4.85_x64) Viewing Workstation executing ImageScope DX viewer software (version 1.0.0.5018) Display (MR2416) I. Device Description: The Aperio AT2 DX System is an automated digital slide creation and viewing system. The system is composed of the following components: • Aperio AT2 DX digital slide scanner • Viewing Workstation executing ImageScope DX viewer software 3 • Display (MR2416) The Aperio AT2 DX digital slide scanner digitizes microscope slides at diagnostic resolutions: 0.5 µm/pixel (20x objective equivalent) and 0.25 µm/pixel (40x objective equivalent), to create digital WSI images. The Aperio AT2 DX scanner has a capacity of 400 1x3 inch glass slides. After the slides are loaded the scanning process begins when the operator starts the Aperio AT2 DX scanner and finishes when the scanner has completed scanning of all loaded slides. The image acquisition components include a white LED light source, Olympus Plan Apo 20x lens with a Numeric Aperture (NA) of 0.75, a 10/90 beam splitter, a 2D area-scan camera and a 1D line-scan camera which is the primary image capture device. The 10/90 bean splitter sends 10% of the photons toward the 2D area-scan camera and remaining 90% of the photons toward the 1D line- scan camera. Two motorized stages are used with one stage for moving the slide to be scanned and the other stage for moving the objective lens for focusing purposes. During scanning with a 20x objective lens, the motion of the slide stage combined with the speed of the 1D line-scan camera, the field of view of the objective lens and the number of pixels of the camera result in a resolution of 0.5 µm/pixel for 20x magnification. 40x magnification is achieved with a magnification doubler, with 0.25 μm/pixel resolution. Focus during the scan is maintained using a triangulated focus map built from individual focus points determined in a separate step before scanning is started. Proprietary software is used for image processing during acquisition. Leica’s proprietary format, SVS, is used to store and transmit the images between the Aperio AT2 DX digital slide scanner and the ImageScope DX viewer on viewing station. Software Aperio Controller DX runs on the AT2 DX workstation as a system service and controls the operations of the scanner. Software Aperio Console DX is a desktop program that runs on the AT2 DX workstation with a display monitor (Dell MR2416) and provides user interface for an operator to control operations of AT2 DX scanner. The ImageScope DX application is a software only subsystem to be used with the display monitor (Dell MR2416) and runs on a separate viewing workstation PC. The ImageScope DX software opens the WSI images acquired with Aperio AT2 DX scanner from the image storage attached to local network and uses the color profile to render the image data to the calibrated display monitor to deliver the image view at the appropriate magnification and color. Functionalities of ImageScope DX include navigating the slide similar to using an optical microscope, panning across the slide to examine all tissue regions, zooming in and out to allow review at different magnification levels, and allowing pathologist annotations during review. The different subsystems of the Aperio AT2 DX System are connected over an IT network at the user site. The IT hardware/software that supports the ImageScope DX Application Server & Storage software is not provided as part of the Aperio AT2 DX System, but may be located in a central server room separate from the workstation with the ImageScope DX viewing software and Display. The communication of data between Aperio AT2 DX scanner and ImageScope DX application is via a customer provided wired network or a direct connected cable between these subsystems. Aperio AT2 DX System includes a display that has been validated as part of the pivotal clinical study. 4 The Aperio AT2 DX System allows pathologists to view and evaluate digital images of formalin-fixed, paraffin-embedded (FFPE) tissue slides that would otherwise be appropriate for manual visualization by conventional brightfield (light) microscopy. The Aperio AT2 DX System does not include any automated image analysis applications that would constitute computer aided detection or diagnosis. J. Substantial Equivalence Information: 1. Predicate device name(s): Philips IntelliSite Pathology Solution (PIPS) 2. Predicate 510(k) number(s): DEN160056 3. Comparison with predicate: Similarities Item Device Predicate Intended Use The Aperio AT2 DX System is an automated digital slide creation and viewing system. The Aperio AT2 DX System is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The Aperio AT2 DX System is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The Aperio AT2 DX System is composed of the Aperio AT2 DX scanner, the ImageScope DX review application and Display. The Aperio AT2 DX System is for creation and viewing of digital images of scanned glass slides that would otherwise be appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified The Philips IntelliSite Pathology Solution (PIPS) is an automated digital slide creation, viewing, and management system. The PIPS is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The PIPS is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The PIPS comprises the Image Management System (IMS), the Ultra Fast Scanner (UFS) and Display. The PIPS is for creation and viewing of digital images of scanned glass slides that would otherwise be 5 Similarities Item Device Predicate pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using the Aperio AT2 DX System. appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using PIPS. Specimen type Surgical pathology slides prepared from FFPE tissue Same Principle of operation After conducting Quality Control (QC) on the glass slides per laboratory standards (e.g., staining, cover- slipping, barcode placement, etc.), the technician loads the slides into the Aperio AT2 DX scanner. The scanner scans the slides and generates WSI image for each slide. The technician performs QC on scanned WSI images by checking image data and image quality. When QC is failed, the slide will be re-scanned. The acquired WSI images are stored in an end user provided image storage attached to the local network. During review, the pathologist opens WSI images acquired with the Aperio AT2 DX scanner from the image storage, performs further QC to ensure image quality and reads WSI images of the slides to make a diagnosis. Same Device Components WSI scanner (Aperio AT2 DX scanner), Image Management System (ImageScope DX application), and color monitor display Same (PIPS Ultra Fast Scanner, Image Management System Measurand:

idK190332_s0_e2000

K190332.txt

type of test

Digital pathology whole slide imaging

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K190332 B. Purpose for Submission: New Whole Slide Imaging (WSI) system C. Measurand: Not applicable D. Type of Test: Digital pathology whole slide imaging E. Applicant: Leica Biosystems Imaging, Inc. F. Proprietary and Established Names: Aperio AT2 DX System G. Regulatory Information: 1. Regulation section: 21 CFR 864.3700 2. Classification: Class II (special controls) 3. Product code: PSY 4. Panel: 88 - Pathology 2 H. Intended Use: 1. Intended use(s): The Aperio AT2 DX System is an automated digital slide creation and viewing system. The Aperio AT2 DX System is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The Aperio AT2 DX System is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The Aperio AT2 DX System is composed of the Aperio AT2 DX scanner, the ImageScope DX review application and Display. The Aperio AT2 DX System is for creation and viewing of digital images of scanned glass slides that would otherwise be appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using the Aperio AT2 DX System. 2. Indication(s) for use: Same as Intended Use. 3. Special conditions for use statement(s): For in vitro diagnostic (IVD) use only For prescription use only 4. Special instrument requirements: Aperio AT2 DX digital slide scanner (for software Aperio Console DX 102.0.4.46 and Aperio Controller DX 102.0.4.85_x64) Viewing Workstation executing ImageScope DX viewer software (version 1.0.0.5018) Display (MR2416) I. Device Description: The Aperio AT2 DX System is an automated digital slide creation and viewing system. The system is composed of the following components: • Aperio AT2 DX digital slide scanner • Viewing Workstation executing ImageScope DX viewer software 3 • Display (MR2416) The Aperio AT2 DX digital slide scanner digitizes microscope slides at diagnostic resolutions: 0.5 µm/pixel (20x objective equivalent) and 0.25 µm/pixel (40x objective equivalent), to create digital WSI images. The Aperio AT2 DX scanner has a capacity of 400 1x3 inch glass slides. After the slides are loaded the scanning process begins when the operator starts the Aperio AT2 DX scanner and finishes when the scanner has completed scanning of all loaded slides. The image acquisition components include a white LED light source, Olympus Plan Apo 20x lens with a Numeric Aperture (NA) of 0.75, a 10/90 beam splitter, a 2D area-scan camera and a 1D line-scan camera which is the primary image capture device. The 10/90 bean splitter sends 10% of the photons toward the 2D area-scan camera and remaining 90% of the photons toward the 1D line- scan camera. Two motorized stages are used with one stage for moving the slide to be scanned and the other stage for moving the objective lens for focusing purposes. During scanning with a 20x objective lens, the motion of the slide stage combined with the speed of the 1D line-scan camera, the field of view of the objective lens and the number of pixels of the camera result in a resolution of 0.5 µm/pixel for 20x magnification. 40x magnification is achieved with a magnification doubler, with 0.25 μm/pixel resolution. Focus during the scan is maintained using a triangulated focus map built from individual focus points determined in a separate step before scanning is started. Proprietary software is used for image processing during acquisition. Leica’s proprietary format, SVS, is used to store and transmit the images between the Aperio AT2 DX digital slide scanner and the ImageScope DX viewer on viewing station. Software Aperio Controller DX runs on the AT2 DX workstation as a system service and controls the operations of the scanner. Software Aperio Console DX is a desktop program that runs on the AT2 DX workstation with a display monitor (Dell MR2416) and provides user interface for an operator to control operations of AT2 DX scanner. The ImageScope DX application is a software only subsystem to be used with the display monitor (Dell MR2416) and runs on a separate viewing workstation PC. The ImageScope DX software opens the WSI images acquired with Aperio AT2 DX scanner from the image storage attached to local network and uses the color profile to render the image data to the calibrated display monitor to deliver the image view at the appropriate magnification and color. Functionalities of ImageScope DX include navigating the slide similar to using an optical microscope, panning across the slide to examine all tissue regions, zooming in and out to allow review at different magnification levels, and allowing pathologist annotations during review. The different subsystems of the Aperio AT2 DX System are connected over an IT network at the user site. The IT hardware/software that supports the ImageScope DX Application Server & Storage software is not provided as part of the Aperio AT2 DX System, but may be located in a central server room separate from the workstation with the ImageScope DX viewing software and Display. The communication of data between Aperio AT2 DX scanner and ImageScope DX application is via a customer provided wired network or a direct connected cable between these subsystems. Aperio AT2 DX System includes a display that has been validated as part of the pivotal clinical study. 4 The Aperio AT2 DX System allows pathologists to view and evaluate digital images of formalin-fixed, paraffin-embedded (FFPE) tissue slides that would otherwise be appropriate for manual visualization by conventional brightfield (light) microscopy. The Aperio AT2 DX System does not include any automated image analysis applications that would constitute computer aided detection or diagnosis. J. Substantial Equivalence Information: 1. Predicate device name(s): Philips IntelliSite Pathology Solution (PIPS) 2. Predicate 510(k) number(s): DEN160056 3. Comparison with predicate: Similarities Item Device Predicate Intended Use The Aperio AT2 DX System is an automated digital slide creation and viewing system. The Aperio AT2 DX System is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The Aperio AT2 DX System is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The Aperio AT2 DX System is composed of the Aperio AT2 DX scanner, the ImageScope DX review application and Display. The Aperio AT2 DX System is for creation and viewing of digital images of scanned glass slides that would otherwise be appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified The Philips IntelliSite Pathology Solution (PIPS) is an automated digital slide creation, viewing, and management system. The PIPS is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The PIPS is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The PIPS comprises the Image Management System (IMS), the Ultra Fast Scanner (UFS) and Display. The PIPS is for creation and viewing of digital images of scanned glass slides that would otherwise be 5 Similarities Item Device Predicate pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using the Aperio AT2 DX System. appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using PIPS. Specimen type Surgical pathology slides prepared from FFPE tissue Same Principle of operation After conducting Quality Control (QC) on the glass slides per laboratory standards (e.g., staining, cover- slipping, barcode placement, etc.), the technician loads the slides into the Aperio AT2 DX scanner. The scanner scans the slides and generates WSI image for each slide. The technician performs QC on scanned WSI images by checking image data and image quality. When QC is failed, the slide will be re-scanned. The acquired WSI images are stored in an end user provided image storage attached to the local network. During review, the pathologist opens WSI images acquired with the Aperio AT2 DX scanner from the image storage, performs further QC to ensure image quality and reads WSI images of the slides to make a diagnosis. Same Device Components WSI scanner (Aperio AT2 DX scanner), Image Management System (ImageScope DX application), and color monitor display Same (PIPS Ultra Fast Scanner, Image Management System Type of test:

idK190332_s0_e2000

K190332.txt

classification

Class II

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K190332 B. Purpose for Submission: New Whole Slide Imaging (WSI) system C. Measurand: Not applicable D. Type of Test: Digital pathology whole slide imaging E. Applicant: Leica Biosystems Imaging, Inc. F. Proprietary and Established Names: Aperio AT2 DX System G. Regulatory Information: 1. Regulation section: 21 CFR 864.3700 2. Classification: Class II (special controls) 3. Product code: PSY 4. Panel: 88 - Pathology 2 H. Intended Use: 1. Intended use(s): The Aperio AT2 DX System is an automated digital slide creation and viewing system. The Aperio AT2 DX System is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The Aperio AT2 DX System is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The Aperio AT2 DX System is composed of the Aperio AT2 DX scanner, the ImageScope DX review application and Display. The Aperio AT2 DX System is for creation and viewing of digital images of scanned glass slides that would otherwise be appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using the Aperio AT2 DX System. 2. Indication(s) for use: Same as Intended Use. 3. Special conditions for use statement(s): For in vitro diagnostic (IVD) use only For prescription use only 4. Special instrument requirements: Aperio AT2 DX digital slide scanner (for software Aperio Console DX 102.0.4.46 and Aperio Controller DX 102.0.4.85_x64) Viewing Workstation executing ImageScope DX viewer software (version 1.0.0.5018) Display (MR2416) I. Device Description: The Aperio AT2 DX System is an automated digital slide creation and viewing system. The system is composed of the following components: • Aperio AT2 DX digital slide scanner • Viewing Workstation executing ImageScope DX viewer software 3 • Display (MR2416) The Aperio AT2 DX digital slide scanner digitizes microscope slides at diagnostic resolutions: 0.5 µm/pixel (20x objective equivalent) and 0.25 µm/pixel (40x objective equivalent), to create digital WSI images. The Aperio AT2 DX scanner has a capacity of 400 1x3 inch glass slides. After the slides are loaded the scanning process begins when the operator starts the Aperio AT2 DX scanner and finishes when the scanner has completed scanning of all loaded slides. The image acquisition components include a white LED light source, Olympus Plan Apo 20x lens with a Numeric Aperture (NA) of 0.75, a 10/90 beam splitter, a 2D area-scan camera and a 1D line-scan camera which is the primary image capture device. The 10/90 bean splitter sends 10% of the photons toward the 2D area-scan camera and remaining 90% of the photons toward the 1D line- scan camera. Two motorized stages are used with one stage for moving the slide to be scanned and the other stage for moving the objective lens for focusing purposes. During scanning with a 20x objective lens, the motion of the slide stage combined with the speed of the 1D line-scan camera, the field of view of the objective lens and the number of pixels of the camera result in a resolution of 0.5 µm/pixel for 20x magnification. 40x magnification is achieved with a magnification doubler, with 0.25 μm/pixel resolution. Focus during the scan is maintained using a triangulated focus map built from individual focus points determined in a separate step before scanning is started. Proprietary software is used for image processing during acquisition. Leica’s proprietary format, SVS, is used to store and transmit the images between the Aperio AT2 DX digital slide scanner and the ImageScope DX viewer on viewing station. Software Aperio Controller DX runs on the AT2 DX workstation as a system service and controls the operations of the scanner. Software Aperio Console DX is a desktop program that runs on the AT2 DX workstation with a display monitor (Dell MR2416) and provides user interface for an operator to control operations of AT2 DX scanner. The ImageScope DX application is a software only subsystem to be used with the display monitor (Dell MR2416) and runs on a separate viewing workstation PC. The ImageScope DX software opens the WSI images acquired with Aperio AT2 DX scanner from the image storage attached to local network and uses the color profile to render the image data to the calibrated display monitor to deliver the image view at the appropriate magnification and color. Functionalities of ImageScope DX include navigating the slide similar to using an optical microscope, panning across the slide to examine all tissue regions, zooming in and out to allow review at different magnification levels, and allowing pathologist annotations during review. The different subsystems of the Aperio AT2 DX System are connected over an IT network at the user site. The IT hardware/software that supports the ImageScope DX Application Server & Storage software is not provided as part of the Aperio AT2 DX System, but may be located in a central server room separate from the workstation with the ImageScope DX viewing software and Display. The communication of data between Aperio AT2 DX scanner and ImageScope DX application is via a customer provided wired network or a direct connected cable between these subsystems. Aperio AT2 DX System includes a display that has been validated as part of the pivotal clinical study. 4 The Aperio AT2 DX System allows pathologists to view and evaluate digital images of formalin-fixed, paraffin-embedded (FFPE) tissue slides that would otherwise be appropriate for manual visualization by conventional brightfield (light) microscopy. The Aperio AT2 DX System does not include any automated image analysis applications that would constitute computer aided detection or diagnosis. J. Substantial Equivalence Information: 1. Predicate device name(s): Philips IntelliSite Pathology Solution (PIPS) 2. Predicate 510(k) number(s): DEN160056 3. Comparison with predicate: Similarities Item Device Predicate Intended Use The Aperio AT2 DX System is an automated digital slide creation and viewing system. The Aperio AT2 DX System is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The Aperio AT2 DX System is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The Aperio AT2 DX System is composed of the Aperio AT2 DX scanner, the ImageScope DX review application and Display. The Aperio AT2 DX System is for creation and viewing of digital images of scanned glass slides that would otherwise be appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified The Philips IntelliSite Pathology Solution (PIPS) is an automated digital slide creation, viewing, and management system. The PIPS is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The PIPS is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The PIPS comprises the Image Management System (IMS), the Ultra Fast Scanner (UFS) and Display. The PIPS is for creation and viewing of digital images of scanned glass slides that would otherwise be 5 Similarities Item Device Predicate pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using the Aperio AT2 DX System. appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using PIPS. Specimen type Surgical pathology slides prepared from FFPE tissue Same Principle of operation After conducting Quality Control (QC) on the glass slides per laboratory standards (e.g., staining, cover- slipping, barcode placement, etc.), the technician loads the slides into the Aperio AT2 DX scanner. The scanner scans the slides and generates WSI image for each slide. The technician performs QC on scanned WSI images by checking image data and image quality. When QC is failed, the slide will be re-scanned. The acquired WSI images are stored in an end user provided image storage attached to the local network. During review, the pathologist opens WSI images acquired with the Aperio AT2 DX scanner from the image storage, performs further QC to ensure image quality and reads WSI images of the slides to make a diagnosis. Same Device Components WSI scanner (Aperio AT2 DX scanner), Image Management System (ImageScope DX application), and color monitor display Same (PIPS Ultra Fast Scanner, Image Management System Classification:

idK190332_s0_e2000

K190332.txt

product code

PSY

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K190332 B. Purpose for Submission: New Whole Slide Imaging (WSI) system C. Measurand: Not applicable D. Type of Test: Digital pathology whole slide imaging E. Applicant: Leica Biosystems Imaging, Inc. F. Proprietary and Established Names: Aperio AT2 DX System G. Regulatory Information: 1. Regulation section: 21 CFR 864.3700 2. Classification: Class II (special controls) 3. Product code: PSY 4. Panel: 88 - Pathology 2 H. Intended Use: 1. Intended use(s): The Aperio AT2 DX System is an automated digital slide creation and viewing system. The Aperio AT2 DX System is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The Aperio AT2 DX System is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The Aperio AT2 DX System is composed of the Aperio AT2 DX scanner, the ImageScope DX review application and Display. The Aperio AT2 DX System is for creation and viewing of digital images of scanned glass slides that would otherwise be appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using the Aperio AT2 DX System. 2. Indication(s) for use: Same as Intended Use. 3. Special conditions for use statement(s): For in vitro diagnostic (IVD) use only For prescription use only 4. Special instrument requirements: Aperio AT2 DX digital slide scanner (for software Aperio Console DX 102.0.4.46 and Aperio Controller DX 102.0.4.85_x64) Viewing Workstation executing ImageScope DX viewer software (version 1.0.0.5018) Display (MR2416) I. Device Description: The Aperio AT2 DX System is an automated digital slide creation and viewing system. The system is composed of the following components: • Aperio AT2 DX digital slide scanner • Viewing Workstation executing ImageScope DX viewer software 3 • Display (MR2416) The Aperio AT2 DX digital slide scanner digitizes microscope slides at diagnostic resolutions: 0.5 µm/pixel (20x objective equivalent) and 0.25 µm/pixel (40x objective equivalent), to create digital WSI images. The Aperio AT2 DX scanner has a capacity of 400 1x3 inch glass slides. After the slides are loaded the scanning process begins when the operator starts the Aperio AT2 DX scanner and finishes when the scanner has completed scanning of all loaded slides. The image acquisition components include a white LED light source, Olympus Plan Apo 20x lens with a Numeric Aperture (NA) of 0.75, a 10/90 beam splitter, a 2D area-scan camera and a 1D line-scan camera which is the primary image capture device. The 10/90 bean splitter sends 10% of the photons toward the 2D area-scan camera and remaining 90% of the photons toward the 1D line- scan camera. Two motorized stages are used with one stage for moving the slide to be scanned and the other stage for moving the objective lens for focusing purposes. During scanning with a 20x objective lens, the motion of the slide stage combined with the speed of the 1D line-scan camera, the field of view of the objective lens and the number of pixels of the camera result in a resolution of 0.5 µm/pixel for 20x magnification. 40x magnification is achieved with a magnification doubler, with 0.25 μm/pixel resolution. Focus during the scan is maintained using a triangulated focus map built from individual focus points determined in a separate step before scanning is started. Proprietary software is used for image processing during acquisition. Leica’s proprietary format, SVS, is used to store and transmit the images between the Aperio AT2 DX digital slide scanner and the ImageScope DX viewer on viewing station. Software Aperio Controller DX runs on the AT2 DX workstation as a system service and controls the operations of the scanner. Software Aperio Console DX is a desktop program that runs on the AT2 DX workstation with a display monitor (Dell MR2416) and provides user interface for an operator to control operations of AT2 DX scanner. The ImageScope DX application is a software only subsystem to be used with the display monitor (Dell MR2416) and runs on a separate viewing workstation PC. The ImageScope DX software opens the WSI images acquired with Aperio AT2 DX scanner from the image storage attached to local network and uses the color profile to render the image data to the calibrated display monitor to deliver the image view at the appropriate magnification and color. Functionalities of ImageScope DX include navigating the slide similar to using an optical microscope, panning across the slide to examine all tissue regions, zooming in and out to allow review at different magnification levels, and allowing pathologist annotations during review. The different subsystems of the Aperio AT2 DX System are connected over an IT network at the user site. The IT hardware/software that supports the ImageScope DX Application Server & Storage software is not provided as part of the Aperio AT2 DX System, but may be located in a central server room separate from the workstation with the ImageScope DX viewing software and Display. The communication of data between Aperio AT2 DX scanner and ImageScope DX application is via a customer provided wired network or a direct connected cable between these subsystems. Aperio AT2 DX System includes a display that has been validated as part of the pivotal clinical study. 4 The Aperio AT2 DX System allows pathologists to view and evaluate digital images of formalin-fixed, paraffin-embedded (FFPE) tissue slides that would otherwise be appropriate for manual visualization by conventional brightfield (light) microscopy. The Aperio AT2 DX System does not include any automated image analysis applications that would constitute computer aided detection or diagnosis. J. Substantial Equivalence Information: 1. Predicate device name(s): Philips IntelliSite Pathology Solution (PIPS) 2. Predicate 510(k) number(s): DEN160056 3. Comparison with predicate: Similarities Item Device Predicate Intended Use The Aperio AT2 DX System is an automated digital slide creation and viewing system. The Aperio AT2 DX System is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The Aperio AT2 DX System is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The Aperio AT2 DX System is composed of the Aperio AT2 DX scanner, the ImageScope DX review application and Display. The Aperio AT2 DX System is for creation and viewing of digital images of scanned glass slides that would otherwise be appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified The Philips IntelliSite Pathology Solution (PIPS) is an automated digital slide creation, viewing, and management system. The PIPS is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The PIPS is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The PIPS comprises the Image Management System (IMS), the Ultra Fast Scanner (UFS) and Display. The PIPS is for creation and viewing of digital images of scanned glass slides that would otherwise be 5 Similarities Item Device Predicate pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using the Aperio AT2 DX System. appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using PIPS. Specimen type Surgical pathology slides prepared from FFPE tissue Same Principle of operation After conducting Quality Control (QC) on the glass slides per laboratory standards (e.g., staining, cover- slipping, barcode placement, etc.), the technician loads the slides into the Aperio AT2 DX scanner. The scanner scans the slides and generates WSI image for each slide. The technician performs QC on scanned WSI images by checking image data and image quality. When QC is failed, the slide will be re-scanned. The acquired WSI images are stored in an end user provided image storage attached to the local network. During review, the pathologist opens WSI images acquired with the Aperio AT2 DX scanner from the image storage, performs further QC to ensure image quality and reads WSI images of the slides to make a diagnosis. Same Device Components WSI scanner (Aperio AT2 DX scanner), Image Management System (ImageScope DX application), and color monitor display Same (PIPS Ultra Fast Scanner, Image Management System Product code:

idK190332_s0_e2000

K190332.txt

panel

88 - Pathology

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K190332 B. Purpose for Submission: New Whole Slide Imaging (WSI) system C. Measurand: Not applicable D. Type of Test: Digital pathology whole slide imaging E. Applicant: Leica Biosystems Imaging, Inc. F. Proprietary and Established Names: Aperio AT2 DX System G. Regulatory Information: 1. Regulation section: 21 CFR 864.3700 2. Classification: Class II (special controls) 3. Product code: PSY 4. Panel: 88 - Pathology 2 H. Intended Use: 1. Intended use(s): The Aperio AT2 DX System is an automated digital slide creation and viewing system. The Aperio AT2 DX System is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The Aperio AT2 DX System is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The Aperio AT2 DX System is composed of the Aperio AT2 DX scanner, the ImageScope DX review application and Display. The Aperio AT2 DX System is for creation and viewing of digital images of scanned glass slides that would otherwise be appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using the Aperio AT2 DX System. 2. Indication(s) for use: Same as Intended Use. 3. Special conditions for use statement(s): For in vitro diagnostic (IVD) use only For prescription use only 4. Special instrument requirements: Aperio AT2 DX digital slide scanner (for software Aperio Console DX 102.0.4.46 and Aperio Controller DX 102.0.4.85_x64) Viewing Workstation executing ImageScope DX viewer software (version 1.0.0.5018) Display (MR2416) I. Device Description: The Aperio AT2 DX System is an automated digital slide creation and viewing system. The system is composed of the following components: • Aperio AT2 DX digital slide scanner • Viewing Workstation executing ImageScope DX viewer software 3 • Display (MR2416) The Aperio AT2 DX digital slide scanner digitizes microscope slides at diagnostic resolutions: 0.5 µm/pixel (20x objective equivalent) and 0.25 µm/pixel (40x objective equivalent), to create digital WSI images. The Aperio AT2 DX scanner has a capacity of 400 1x3 inch glass slides. After the slides are loaded the scanning process begins when the operator starts the Aperio AT2 DX scanner and finishes when the scanner has completed scanning of all loaded slides. The image acquisition components include a white LED light source, Olympus Plan Apo 20x lens with a Numeric Aperture (NA) of 0.75, a 10/90 beam splitter, a 2D area-scan camera and a 1D line-scan camera which is the primary image capture device. The 10/90 bean splitter sends 10% of the photons toward the 2D area-scan camera and remaining 90% of the photons toward the 1D line- scan camera. Two motorized stages are used with one stage for moving the slide to be scanned and the other stage for moving the objective lens for focusing purposes. During scanning with a 20x objective lens, the motion of the slide stage combined with the speed of the 1D line-scan camera, the field of view of the objective lens and the number of pixels of the camera result in a resolution of 0.5 µm/pixel for 20x magnification. 40x magnification is achieved with a magnification doubler, with 0.25 μm/pixel resolution. Focus during the scan is maintained using a triangulated focus map built from individual focus points determined in a separate step before scanning is started. Proprietary software is used for image processing during acquisition. Leica’s proprietary format, SVS, is used to store and transmit the images between the Aperio AT2 DX digital slide scanner and the ImageScope DX viewer on viewing station. Software Aperio Controller DX runs on the AT2 DX workstation as a system service and controls the operations of the scanner. Software Aperio Console DX is a desktop program that runs on the AT2 DX workstation with a display monitor (Dell MR2416) and provides user interface for an operator to control operations of AT2 DX scanner. The ImageScope DX application is a software only subsystem to be used with the display monitor (Dell MR2416) and runs on a separate viewing workstation PC. The ImageScope DX software opens the WSI images acquired with Aperio AT2 DX scanner from the image storage attached to local network and uses the color profile to render the image data to the calibrated display monitor to deliver the image view at the appropriate magnification and color. Functionalities of ImageScope DX include navigating the slide similar to using an optical microscope, panning across the slide to examine all tissue regions, zooming in and out to allow review at different magnification levels, and allowing pathologist annotations during review. The different subsystems of the Aperio AT2 DX System are connected over an IT network at the user site. The IT hardware/software that supports the ImageScope DX Application Server & Storage software is not provided as part of the Aperio AT2 DX System, but may be located in a central server room separate from the workstation with the ImageScope DX viewing software and Display. The communication of data between Aperio AT2 DX scanner and ImageScope DX application is via a customer provided wired network or a direct connected cable between these subsystems. Aperio AT2 DX System includes a display that has been validated as part of the pivotal clinical study. 4 The Aperio AT2 DX System allows pathologists to view and evaluate digital images of formalin-fixed, paraffin-embedded (FFPE) tissue slides that would otherwise be appropriate for manual visualization by conventional brightfield (light) microscopy. The Aperio AT2 DX System does not include any automated image analysis applications that would constitute computer aided detection or diagnosis. J. Substantial Equivalence Information: 1. Predicate device name(s): Philips IntelliSite Pathology Solution (PIPS) 2. Predicate 510(k) number(s): DEN160056 3. Comparison with predicate: Similarities Item Device Predicate Intended Use The Aperio AT2 DX System is an automated digital slide creation and viewing system. The Aperio AT2 DX System is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The Aperio AT2 DX System is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The Aperio AT2 DX System is composed of the Aperio AT2 DX scanner, the ImageScope DX review application and Display. The Aperio AT2 DX System is for creation and viewing of digital images of scanned glass slides that would otherwise be appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified The Philips IntelliSite Pathology Solution (PIPS) is an automated digital slide creation, viewing, and management system. The PIPS is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The PIPS is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The PIPS comprises the Image Management System (IMS), the Ultra Fast Scanner (UFS) and Display. The PIPS is for creation and viewing of digital images of scanned glass slides that would otherwise be 5 Similarities Item Device Predicate pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using the Aperio AT2 DX System. appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using PIPS. Specimen type Surgical pathology slides prepared from FFPE tissue Same Principle of operation After conducting Quality Control (QC) on the glass slides per laboratory standards (e.g., staining, cover- slipping, barcode placement, etc.), the technician loads the slides into the Aperio AT2 DX scanner. The scanner scans the slides and generates WSI image for each slide. The technician performs QC on scanned WSI images by checking image data and image quality. When QC is failed, the slide will be re-scanned. The acquired WSI images are stored in an end user provided image storage attached to the local network. During review, the pathologist opens WSI images acquired with the Aperio AT2 DX scanner from the image storage, performs further QC to ensure image quality and reads WSI images of the slides to make a diagnosis. Same Device Components WSI scanner (Aperio AT2 DX scanner), Image Management System (ImageScope DX application), and color monitor display Same (PIPS Ultra Fast Scanner, Image Management System Panel:

idK190332_s0_e2000

K190332.txt

predicate device name

Philips IntelliSite Pathology Solution (PIPS)

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K190332 B. Purpose for Submission: New Whole Slide Imaging (WSI) system C. Measurand: Not applicable D. Type of Test: Digital pathology whole slide imaging E. Applicant: Leica Biosystems Imaging, Inc. F. Proprietary and Established Names: Aperio AT2 DX System G. Regulatory Information: 1. Regulation section: 21 CFR 864.3700 2. Classification: Class II (special controls) 3. Product code: PSY 4. Panel: 88 - Pathology 2 H. Intended Use: 1. Intended use(s): The Aperio AT2 DX System is an automated digital slide creation and viewing system. The Aperio AT2 DX System is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The Aperio AT2 DX System is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The Aperio AT2 DX System is composed of the Aperio AT2 DX scanner, the ImageScope DX review application and Display. The Aperio AT2 DX System is for creation and viewing of digital images of scanned glass slides that would otherwise be appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using the Aperio AT2 DX System. 2. Indication(s) for use: Same as Intended Use. 3. Special conditions for use statement(s): For in vitro diagnostic (IVD) use only For prescription use only 4. Special instrument requirements: Aperio AT2 DX digital slide scanner (for software Aperio Console DX 102.0.4.46 and Aperio Controller DX 102.0.4.85_x64) Viewing Workstation executing ImageScope DX viewer software (version 1.0.0.5018) Display (MR2416) I. Device Description: The Aperio AT2 DX System is an automated digital slide creation and viewing system. The system is composed of the following components: • Aperio AT2 DX digital slide scanner • Viewing Workstation executing ImageScope DX viewer software 3 • Display (MR2416) The Aperio AT2 DX digital slide scanner digitizes microscope slides at diagnostic resolutions: 0.5 µm/pixel (20x objective equivalent) and 0.25 µm/pixel (40x objective equivalent), to create digital WSI images. The Aperio AT2 DX scanner has a capacity of 400 1x3 inch glass slides. After the slides are loaded the scanning process begins when the operator starts the Aperio AT2 DX scanner and finishes when the scanner has completed scanning of all loaded slides. The image acquisition components include a white LED light source, Olympus Plan Apo 20x lens with a Numeric Aperture (NA) of 0.75, a 10/90 beam splitter, a 2D area-scan camera and a 1D line-scan camera which is the primary image capture device. The 10/90 bean splitter sends 10% of the photons toward the 2D area-scan camera and remaining 90% of the photons toward the 1D line- scan camera. Two motorized stages are used with one stage for moving the slide to be scanned and the other stage for moving the objective lens for focusing purposes. During scanning with a 20x objective lens, the motion of the slide stage combined with the speed of the 1D line-scan camera, the field of view of the objective lens and the number of pixels of the camera result in a resolution of 0.5 µm/pixel for 20x magnification. 40x magnification is achieved with a magnification doubler, with 0.25 μm/pixel resolution. Focus during the scan is maintained using a triangulated focus map built from individual focus points determined in a separate step before scanning is started. Proprietary software is used for image processing during acquisition. Leica’s proprietary format, SVS, is used to store and transmit the images between the Aperio AT2 DX digital slide scanner and the ImageScope DX viewer on viewing station. Software Aperio Controller DX runs on the AT2 DX workstation as a system service and controls the operations of the scanner. Software Aperio Console DX is a desktop program that runs on the AT2 DX workstation with a display monitor (Dell MR2416) and provides user interface for an operator to control operations of AT2 DX scanner. The ImageScope DX application is a software only subsystem to be used with the display monitor (Dell MR2416) and runs on a separate viewing workstation PC. The ImageScope DX software opens the WSI images acquired with Aperio AT2 DX scanner from the image storage attached to local network and uses the color profile to render the image data to the calibrated display monitor to deliver the image view at the appropriate magnification and color. Functionalities of ImageScope DX include navigating the slide similar to using an optical microscope, panning across the slide to examine all tissue regions, zooming in and out to allow review at different magnification levels, and allowing pathologist annotations during review. The different subsystems of the Aperio AT2 DX System are connected over an IT network at the user site. The IT hardware/software that supports the ImageScope DX Application Server & Storage software is not provided as part of the Aperio AT2 DX System, but may be located in a central server room separate from the workstation with the ImageScope DX viewing software and Display. The communication of data between Aperio AT2 DX scanner and ImageScope DX application is via a customer provided wired network or a direct connected cable between these subsystems. Aperio AT2 DX System includes a display that has been validated as part of the pivotal clinical study. 4 The Aperio AT2 DX System allows pathologists to view and evaluate digital images of formalin-fixed, paraffin-embedded (FFPE) tissue slides that would otherwise be appropriate for manual visualization by conventional brightfield (light) microscopy. The Aperio AT2 DX System does not include any automated image analysis applications that would constitute computer aided detection or diagnosis. J. Substantial Equivalence Information: 1. Predicate device name(s): Philips IntelliSite Pathology Solution (PIPS) 2. Predicate 510(k) number(s): DEN160056 3. Comparison with predicate: Similarities Item Device Predicate Intended Use The Aperio AT2 DX System is an automated digital slide creation and viewing system. The Aperio AT2 DX System is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The Aperio AT2 DX System is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The Aperio AT2 DX System is composed of the Aperio AT2 DX scanner, the ImageScope DX review application and Display. The Aperio AT2 DX System is for creation and viewing of digital images of scanned glass slides that would otherwise be appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified The Philips IntelliSite Pathology Solution (PIPS) is an automated digital slide creation, viewing, and management system. The PIPS is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The PIPS is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The PIPS comprises the Image Management System (IMS), the Ultra Fast Scanner (UFS) and Display. The PIPS is for creation and viewing of digital images of scanned glass slides that would otherwise be 5 Similarities Item Device Predicate pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using the Aperio AT2 DX System. appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using PIPS. Specimen type Surgical pathology slides prepared from FFPE tissue Same Principle of operation After conducting Quality Control (QC) on the glass slides per laboratory standards (e.g., staining, cover- slipping, barcode placement, etc.), the technician loads the slides into the Aperio AT2 DX scanner. The scanner scans the slides and generates WSI image for each slide. The technician performs QC on scanned WSI images by checking image data and image quality. When QC is failed, the slide will be re-scanned. The acquired WSI images are stored in an end user provided image storage attached to the local network. During review, the pathologist opens WSI images acquired with the Aperio AT2 DX scanner from the image storage, performs further QC to ensure image quality and reads WSI images of the slides to make a diagnosis. Same Device Components WSI scanner (Aperio AT2 DX scanner), Image Management System (ImageScope DX application), and color monitor display Same (PIPS Ultra Fast Scanner, Image Management System Predicate device name:

idK190332_s0_e2000

K190332.txt

applicant

Leica Biosystems Imaging, Inc.

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K190332 B. Purpose for Submission: New Whole Slide Imaging (WSI) system C. Measurand: Not applicable D. Type of Test: Digital pathology whole slide imaging E. Applicant: Leica Biosystems Imaging, Inc. F. Proprietary and Established Names: Aperio AT2 DX System G. Regulatory Information: 1. Regulation section: 21 CFR 864.3700 2. Classification: Class II (special controls) 3. Product code: PSY 4. Panel: 88 - Pathology 2 H. Intended Use: 1. Intended use(s): The Aperio AT2 DX System is an automated digital slide creation and viewing system. The Aperio AT2 DX System is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The Aperio AT2 DX System is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The Aperio AT2 DX System is composed of the Aperio AT2 DX scanner, the ImageScope DX review application and Display. The Aperio AT2 DX System is for creation and viewing of digital images of scanned glass slides that would otherwise be appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using the Aperio AT2 DX System. 2. Indication(s) for use: Same as Intended Use. 3. Special conditions for use statement(s): For in vitro diagnostic (IVD) use only For prescription use only 4. Special instrument requirements: Aperio AT2 DX digital slide scanner (for software Aperio Console DX 102.0.4.46 and Aperio Controller DX 102.0.4.85_x64) Viewing Workstation executing ImageScope DX viewer software (version 1.0.0.5018) Display (MR2416) I. Device Description: The Aperio AT2 DX System is an automated digital slide creation and viewing system. The system is composed of the following components: • Aperio AT2 DX digital slide scanner • Viewing Workstation executing ImageScope DX viewer software 3 • Display (MR2416) The Aperio AT2 DX digital slide scanner digitizes microscope slides at diagnostic resolutions: 0.5 µm/pixel (20x objective equivalent) and 0.25 µm/pixel (40x objective equivalent), to create digital WSI images. The Aperio AT2 DX scanner has a capacity of 400 1x3 inch glass slides. After the slides are loaded the scanning process begins when the operator starts the Aperio AT2 DX scanner and finishes when the scanner has completed scanning of all loaded slides. The image acquisition components include a white LED light source, Olympus Plan Apo 20x lens with a Numeric Aperture (NA) of 0.75, a 10/90 beam splitter, a 2D area-scan camera and a 1D line-scan camera which is the primary image capture device. The 10/90 bean splitter sends 10% of the photons toward the 2D area-scan camera and remaining 90% of the photons toward the 1D line- scan camera. Two motorized stages are used with one stage for moving the slide to be scanned and the other stage for moving the objective lens for focusing purposes. During scanning with a 20x objective lens, the motion of the slide stage combined with the speed of the 1D line-scan camera, the field of view of the objective lens and the number of pixels of the camera result in a resolution of 0.5 µm/pixel for 20x magnification. 40x magnification is achieved with a magnification doubler, with 0.25 μm/pixel resolution. Focus during the scan is maintained using a triangulated focus map built from individual focus points determined in a separate step before scanning is started. Proprietary software is used for image processing during acquisition. Leica’s proprietary format, SVS, is used to store and transmit the images between the Aperio AT2 DX digital slide scanner and the ImageScope DX viewer on viewing station. Software Aperio Controller DX runs on the AT2 DX workstation as a system service and controls the operations of the scanner. Software Aperio Console DX is a desktop program that runs on the AT2 DX workstation with a display monitor (Dell MR2416) and provides user interface for an operator to control operations of AT2 DX scanner. The ImageScope DX application is a software only subsystem to be used with the display monitor (Dell MR2416) and runs on a separate viewing workstation PC. The ImageScope DX software opens the WSI images acquired with Aperio AT2 DX scanner from the image storage attached to local network and uses the color profile to render the image data to the calibrated display monitor to deliver the image view at the appropriate magnification and color. Functionalities of ImageScope DX include navigating the slide similar to using an optical microscope, panning across the slide to examine all tissue regions, zooming in and out to allow review at different magnification levels, and allowing pathologist annotations during review. The different subsystems of the Aperio AT2 DX System are connected over an IT network at the user site. The IT hardware/software that supports the ImageScope DX Application Server & Storage software is not provided as part of the Aperio AT2 DX System, but may be located in a central server room separate from the workstation with the ImageScope DX viewing software and Display. The communication of data between Aperio AT2 DX scanner and ImageScope DX application is via a customer provided wired network or a direct connected cable between these subsystems. Aperio AT2 DX System includes a display that has been validated as part of the pivotal clinical study. 4 The Aperio AT2 DX System allows pathologists to view and evaluate digital images of formalin-fixed, paraffin-embedded (FFPE) tissue slides that would otherwise be appropriate for manual visualization by conventional brightfield (light) microscopy. The Aperio AT2 DX System does not include any automated image analysis applications that would constitute computer aided detection or diagnosis. J. Substantial Equivalence Information: 1. Predicate device name(s): Philips IntelliSite Pathology Solution (PIPS) 2. Predicate 510(k) number(s): DEN160056 3. Comparison with predicate: Similarities Item Device Predicate Intended Use The Aperio AT2 DX System is an automated digital slide creation and viewing system. The Aperio AT2 DX System is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The Aperio AT2 DX System is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The Aperio AT2 DX System is composed of the Aperio AT2 DX scanner, the ImageScope DX review application and Display. The Aperio AT2 DX System is for creation and viewing of digital images of scanned glass slides that would otherwise be appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified The Philips IntelliSite Pathology Solution (PIPS) is an automated digital slide creation, viewing, and management system. The PIPS is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The PIPS is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The PIPS comprises the Image Management System (IMS), the Ultra Fast Scanner (UFS) and Display. The PIPS is for creation and viewing of digital images of scanned glass slides that would otherwise be 5 Similarities Item Device Predicate pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using the Aperio AT2 DX System. appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using PIPS. Specimen type Surgical pathology slides prepared from FFPE tissue Same Principle of operation After conducting Quality Control (QC) on the glass slides per laboratory standards (e.g., staining, cover- slipping, barcode placement, etc.), the technician loads the slides into the Aperio AT2 DX scanner. The scanner scans the slides and generates WSI image for each slide. The technician performs QC on scanned WSI images by checking image data and image quality. When QC is failed, the slide will be re-scanned. The acquired WSI images are stored in an end user provided image storage attached to the local network. During review, the pathologist opens WSI images acquired with the Aperio AT2 DX scanner from the image storage, performs further QC to ensure image quality and reads WSI images of the slides to make a diagnosis. Same Device Components WSI scanner (Aperio AT2 DX scanner), Image Management System (ImageScope DX application), and color monitor display Same (PIPS Ultra Fast Scanner, Image Management System Applicant:

idK190332_s0_e2000

K190332.txt

proprietary and established names

Aperio AT2 DX System

IAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K190332 B. Purpose for Submission: New Whole Slide Imaging (WSI) system C. Measurand: Not applicable D. Type of Test: Digital pathology whole slide imaging E. Applicant: Leica Biosystems Imaging, Inc. F. Proprietary and Established Names: Aperio AT2 DX System G. Regulatory Information: 1. Regulation section: 21 CFR 864.3700 2. Classification: Class II (special controls) 3. Product code: PSY 4. Panel: 88 - Pathology 2 H. Intended Use: 1. Intended use(s): The Aperio AT2 DX System is an automated digital slide creation and viewing system. The Aperio AT2 DX System is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The Aperio AT2 DX System is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The Aperio AT2 DX System is composed of the Aperio AT2 DX scanner, the ImageScope DX review application and Display. The Aperio AT2 DX System is for creation and viewing of digital images of scanned glass slides that would otherwise be appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using the Aperio AT2 DX System. 2. Indication(s) for use: Same as Intended Use. 3. Special conditions for use statement(s): For in vitro diagnostic (IVD) use only For prescription use only 4. Special instrument requirements: Aperio AT2 DX digital slide scanner (for software Aperio Console DX 102.0.4.46 and Aperio Controller DX 102.0.4.85_x64) Viewing Workstation executing ImageScope DX viewer software (version 1.0.0.5018) Display (MR2416) I. Device Description: The Aperio AT2 DX System is an automated digital slide creation and viewing system. The system is composed of the following components: • Aperio AT2 DX digital slide scanner • Viewing Workstation executing ImageScope DX viewer software 3 • Display (MR2416) The Aperio AT2 DX digital slide scanner digitizes microscope slides at diagnostic resolutions: 0.5 µm/pixel (20x objective equivalent) and 0.25 µm/pixel (40x objective equivalent), to create digital WSI images. The Aperio AT2 DX scanner has a capacity of 400 1x3 inch glass slides. After the slides are loaded the scanning process begins when the operator starts the Aperio AT2 DX scanner and finishes when the scanner has completed scanning of all loaded slides. The image acquisition components include a white LED light source, Olympus Plan Apo 20x lens with a Numeric Aperture (NA) of 0.75, a 10/90 beam splitter, a 2D area-scan camera and a 1D line-scan camera which is the primary image capture device. The 10/90 bean splitter sends 10% of the photons toward the 2D area-scan camera and remaining 90% of the photons toward the 1D line- scan camera. Two motorized stages are used with one stage for moving the slide to be scanned and the other stage for moving the objective lens for focusing purposes. During scanning with a 20x objective lens, the motion of the slide stage combined with the speed of the 1D line-scan camera, the field of view of the objective lens and the number of pixels of the camera result in a resolution of 0.5 µm/pixel for 20x magnification. 40x magnification is achieved with a magnification doubler, with 0.25 μm/pixel resolution. Focus during the scan is maintained using a triangulated focus map built from individual focus points determined in a separate step before scanning is started. Proprietary software is used for image processing during acquisition. Leica’s proprietary format, SVS, is used to store and transmit the images between the Aperio AT2 DX digital slide scanner and the ImageScope DX viewer on viewing station. Software Aperio Controller DX runs on the AT2 DX workstation as a system service and controls the operations of the scanner. Software Aperio Console DX is a desktop program that runs on the AT2 DX workstation with a display monitor (Dell MR2416) and provides user interface for an operator to control operations of AT2 DX scanner. The ImageScope DX application is a software only subsystem to be used with the display monitor (Dell MR2416) and runs on a separate viewing workstation PC. The ImageScope DX software opens the WSI images acquired with Aperio AT2 DX scanner from the image storage attached to local network and uses the color profile to render the image data to the calibrated display monitor to deliver the image view at the appropriate magnification and color. Functionalities of ImageScope DX include navigating the slide similar to using an optical microscope, panning across the slide to examine all tissue regions, zooming in and out to allow review at different magnification levels, and allowing pathologist annotations during review. The different subsystems of the Aperio AT2 DX System are connected over an IT network at the user site. The IT hardware/software that supports the ImageScope DX Application Server & Storage software is not provided as part of the Aperio AT2 DX System, but may be located in a central server room separate from the workstation with the ImageScope DX viewing software and Display. The communication of data between Aperio AT2 DX scanner and ImageScope DX application is via a customer provided wired network or a direct connected cable between these subsystems. Aperio AT2 DX System includes a display that has been validated as part of the pivotal clinical study. 4 The Aperio AT2 DX System allows pathologists to view and evaluate digital images of formalin-fixed, paraffin-embedded (FFPE) tissue slides that would otherwise be appropriate for manual visualization by conventional brightfield (light) microscopy. The Aperio AT2 DX System does not include any automated image analysis applications that would constitute computer aided detection or diagnosis. J. Substantial Equivalence Information: 1. Predicate device name(s): Philips IntelliSite Pathology Solution (PIPS) 2. Predicate 510(k) number(s): DEN160056 3. Comparison with predicate: Similarities Item Device Predicate Intended Use The Aperio AT2 DX System is an automated digital slide creation and viewing system. The Aperio AT2 DX System is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The Aperio AT2 DX System is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The Aperio AT2 DX System is composed of the Aperio AT2 DX scanner, the ImageScope DX review application and Display. The Aperio AT2 DX System is for creation and viewing of digital images of scanned glass slides that would otherwise be appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified The Philips IntelliSite Pathology Solution (PIPS) is an automated digital slide creation, viewing, and management system. The PIPS is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The PIPS is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The PIPS comprises the Image Management System (IMS), the Ultra Fast Scanner (UFS) and Display. The PIPS is for creation and viewing of digital images of scanned glass slides that would otherwise be 5 Similarities Item Device Predicate pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using the Aperio AT2 DX System. appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using PIPS. Specimen type Surgical pathology slides prepared from FFPE tissue Same Principle of operation After conducting Quality Control (QC) on the glass slides per laboratory standards (e.g., staining, cover- slipping, barcode placement, etc.), the technician loads the slides into the Aperio AT2 DX scanner. The scanner scans the slides and generates WSI image for each slide. The technician performs QC on scanned WSI images by checking image data and image quality. When QC is failed, the slide will be re-scanned. The acquired WSI images are stored in an end user provided image storage attached to the local network. During review, the pathologist opens WSI images acquired with the Aperio AT2 DX scanner from the image storage, performs further QC to ensure image quality and reads WSI images of the slides to make a diagnosis. Same Device Components WSI scanner (Aperio AT2 DX scanner), Image Management System (ImageScope DX application), and color monitor display Same (PIPS Ultra Fast Scanner, Image Management System Proprietary and established names:

idK190332_s0_e2000

K190332.txt

regulation section

21 CFR 864.3700

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K190332 B. Purpose for Submission: New Whole Slide Imaging (WSI) system C. Measurand: Not applicable D. Type of Test: Digital pathology whole slide imaging E. Applicant: Leica Biosystems Imaging, Inc. F. Proprietary and Established Names: Aperio AT2 DX System G. Regulatory Information: 1. Regulation section: 21 CFR 864.3700 2. Classification: Class II (special controls) 3. Product code: PSY 4. Panel: 88 - Pathology 2 H. Intended Use: 1. Intended use(s): The Aperio AT2 DX System is an automated digital slide creation and viewing system. The Aperio AT2 DX System is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The Aperio AT2 DX System is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The Aperio AT2 DX System is composed of the Aperio AT2 DX scanner, the ImageScope DX review application and Display. The Aperio AT2 DX System is for creation and viewing of digital images of scanned glass slides that would otherwise be appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using the Aperio AT2 DX System. 2. Indication(s) for use: Same as Intended Use. 3. Special conditions for use statement(s): For in vitro diagnostic (IVD) use only For prescription use only 4. Special instrument requirements: Aperio AT2 DX digital slide scanner (for software Aperio Console DX 102.0.4.46 and Aperio Controller DX 102.0.4.85_x64) Viewing Workstation executing ImageScope DX viewer software (version 1.0.0.5018) Display (MR2416) I. Device Description: The Aperio AT2 DX System is an automated digital slide creation and viewing system. The system is composed of the following components: • Aperio AT2 DX digital slide scanner • Viewing Workstation executing ImageScope DX viewer software 3 • Display (MR2416) The Aperio AT2 DX digital slide scanner digitizes microscope slides at diagnostic resolutions: 0.5 µm/pixel (20x objective equivalent) and 0.25 µm/pixel (40x objective equivalent), to create digital WSI images. The Aperio AT2 DX scanner has a capacity of 400 1x3 inch glass slides. After the slides are loaded the scanning process begins when the operator starts the Aperio AT2 DX scanner and finishes when the scanner has completed scanning of all loaded slides. The image acquisition components include a white LED light source, Olympus Plan Apo 20x lens with a Numeric Aperture (NA) of 0.75, a 10/90 beam splitter, a 2D area-scan camera and a 1D line-scan camera which is the primary image capture device. The 10/90 bean splitter sends 10% of the photons toward the 2D area-scan camera and remaining 90% of the photons toward the 1D line- scan camera. Two motorized stages are used with one stage for moving the slide to be scanned and the other stage for moving the objective lens for focusing purposes. During scanning with a 20x objective lens, the motion of the slide stage combined with the speed of the 1D line-scan camera, the field of view of the objective lens and the number of pixels of the camera result in a resolution of 0.5 µm/pixel for 20x magnification. 40x magnification is achieved with a magnification doubler, with 0.25 μm/pixel resolution. Focus during the scan is maintained using a triangulated focus map built from individual focus points determined in a separate step before scanning is started. Proprietary software is used for image processing during acquisition. Leica’s proprietary format, SVS, is used to store and transmit the images between the Aperio AT2 DX digital slide scanner and the ImageScope DX viewer on viewing station. Software Aperio Controller DX runs on the AT2 DX workstation as a system service and controls the operations of the scanner. Software Aperio Console DX is a desktop program that runs on the AT2 DX workstation with a display monitor (Dell MR2416) and provides user interface for an operator to control operations of AT2 DX scanner. The ImageScope DX application is a software only subsystem to be used with the display monitor (Dell MR2416) and runs on a separate viewing workstation PC. The ImageScope DX software opens the WSI images acquired with Aperio AT2 DX scanner from the image storage attached to local network and uses the color profile to render the image data to the calibrated display monitor to deliver the image view at the appropriate magnification and color. Functionalities of ImageScope DX include navigating the slide similar to using an optical microscope, panning across the slide to examine all tissue regions, zooming in and out to allow review at different magnification levels, and allowing pathologist annotations during review. The different subsystems of the Aperio AT2 DX System are connected over an IT network at the user site. The IT hardware/software that supports the ImageScope DX Application Server & Storage software is not provided as part of the Aperio AT2 DX System, but may be located in a central server room separate from the workstation with the ImageScope DX viewing software and Display. The communication of data between Aperio AT2 DX scanner and ImageScope DX application is via a customer provided wired network or a direct connected cable between these subsystems. Aperio AT2 DX System includes a display that has been validated as part of the pivotal clinical study. 4 The Aperio AT2 DX System allows pathologists to view and evaluate digital images of formalin-fixed, paraffin-embedded (FFPE) tissue slides that would otherwise be appropriate for manual visualization by conventional brightfield (light) microscopy. The Aperio AT2 DX System does not include any automated image analysis applications that would constitute computer aided detection or diagnosis. J. Substantial Equivalence Information: 1. Predicate device name(s): Philips IntelliSite Pathology Solution (PIPS) 2. Predicate 510(k) number(s): DEN160056 3. Comparison with predicate: Similarities Item Device Predicate Intended Use The Aperio AT2 DX System is an automated digital slide creation and viewing system. The Aperio AT2 DX System is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The Aperio AT2 DX System is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The Aperio AT2 DX System is composed of the Aperio AT2 DX scanner, the ImageScope DX review application and Display. The Aperio AT2 DX System is for creation and viewing of digital images of scanned glass slides that would otherwise be appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified The Philips IntelliSite Pathology Solution (PIPS) is an automated digital slide creation, viewing, and management system. The PIPS is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The PIPS is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. The PIPS comprises the Image Management System (IMS), the Ultra Fast Scanner (UFS) and Display. The PIPS is for creation and viewing of digital images of scanned glass slides that would otherwise be 5 Similarities Item Device Predicate pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using the Aperio AT2 DX System. appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using PIPS. Specimen type Surgical pathology slides prepared from FFPE tissue Same Principle of operation After conducting Quality Control (QC) on the glass slides per laboratory standards (e.g., staining, cover- slipping, barcode placement, etc.), the technician loads the slides into the Aperio AT2 DX scanner. The scanner scans the slides and generates WSI image for each slide. The technician performs QC on scanned WSI images by checking image data and image quality. When QC is failed, the slide will be re-scanned. The acquired WSI images are stored in an end user provided image storage attached to the local network. During review, the pathologist opens WSI images acquired with the Aperio AT2 DX scanner from the image storage, performs further QC to ensure image quality and reads WSI images of the slides to make a diagnosis. Same Device Components WSI scanner (Aperio AT2 DX scanner), Image Management System (ImageScope DX application), and color monitor display Same (PIPS Ultra Fast Scanner, Image Management System Regulation section:

idK190332_s8000_e10000

K190332.txt

proposed labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809, as applicable, and the special controls for this device type under 21 CFR 864.3700.

3.68 1.55 Lymph node 1.09 1.87 -0.78 Prostate 3.00 3.44 -0.44 Salivary gland 0.55 1.69 -1.14 Skin 4.74 2.72 2.03 Soft tissue 4.23 4.83 -0.60 Stomach 3.15 2.09 1.06 Three (3) organ types, appendix, gallbladder and hernial/peritoneal, had major discordance rates of 0.00% for both modalities. For all organ types, the absolute values of the observed differences in the major discordance rates between WSIR diagnosis and MSR diagnosis (relative to the reference diagnosis) were ≤ 2.03%. When examining the major discordance rates, ‘Bladder’ had the highest major discordance rate of 10.40% for WSIR and 9.47% for MSR. However, statistical model showed that the modality-by- organ interaction was not statistically significant. Secondary analysis of agreement between the WSIR and MSR diagnosis showed that there was also strong agreement between the two modalities. There were 7423 pairs of readings with both adjudication outcomes for WSIR and MSR. Results showed 96.1% of the paired readings resulted in no major discordance for both modalities (94.7%) or major discordance for both modalities (1.47%). The modality-by-organ interaction was not statistically significant. The clinical study was not powered to analyze the results by individual organ site or diagnosis. The number of unbalanced diagnoses in which the WSIR modality had major discordance and the MSR modality had concordance with the reference diagnosis in each tissue/organ type category ranged from 0 cases for kidney to 15 cases in breast, corresponding to 0.0% to 4.9% of the total cases in each organ type group. Similarly, the number of unbalanced diagnoses in which the MSR modality had major discordance and the WSIR modality had concordance with the reference diagnosis in each tissue/organ type category ranged from 0 cases in skin to 13 cases in breast, corresponding to 0.0% to 4.3% of the total cases in each organ type group. Thus, unbalanced diagnoses represented a small percentage of the 19 overall cases and occurred with similar frequency for both modalities. When the specific diagnoses were examined by tissue/organ type, there were no apparent trends in any tissue/organ type that suggested WSIR is more inherently prone to major discrepancies compared to MSR. When examining this data by reading pathologist, none of the reading pathologists showed a tendency to have more types of specific major discrepancies with WSIR as compared to MSR. In every case the observed rates were within the known and established rate of inter-pathologist variation in diagnosis as reported in literature. 4. Clinical cut-off: Not applicable 5. Expected values/Reference range: Not applicable N. Instrument Name: Aperio AT2 DX System O. System Descriptions: 1. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes ____X____ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No ____X____ 2. Software: FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: Yes ____X____ or No ________ 3. Specimen Identification: Glass slides are identified by barcodes on slide label. 20 4. Specimen Sampling and Handling: Glass slides are loaded manually into the slide feeder (Autoloader) which is a component of the Aperio AT2 DX scanner as a batch. With AutoLoader, the scanner automatically loads each slide in the batch to the stage and scans the glass slide to generate WSI image. After the scanning of all slides in the batch is completed, the slides are unloaded from the scanner and stored according to the lab procedure. 5. Calibration: The Aperio AT2 DX scanner is calibrated and verified at the factory before shipment. No further manual calibration or verification is required by the customer. Annual preventive maintenance performed by Leica Biosystems Technical Services is recommended to ensure the scanner is operating correctly. The scanner provides automatic calibration and verification every time a slide is scanned by performing calibration during the scan. The monitors provided with the Aperio AT2 DX System have been calibrated at the factory and may require periodic re-calibration in the field by authorized Leica Biosystems technicians. The user should not attempt to change the monitor settings as doing so may interfere with the monitor calibration. The ImageScope DX application does not require calibration. 6. Quality Control: It is the responsibility of the laboratory staff to conduct and maintain quality control of the slides per their laboratory standards (e.g., staining, cover-slipping, barcode placement) prior to loading the slides into the Aperio AT2 DX scanner. After completing a scan, the lab technician checks image data and image quality using the Aperio ConsoleDX application installed on the scanner workstation per the instructions for use. Before review, the pathologist performs quality control on the WSI images of the slide per instructions for use. P. Other Supportive Instrument Performance Characteristics Data Not Covered In The “Performance Characteristics” Section above: Not applicable Q. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809, as applicable, and the special controls for this device type under 21 CFR 864.3700. R. Conclusion: 21 The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK190332_s8000_e10000

K190332.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

.24 3.68 1.55 Lymph node 1.09 1.87 -0.78 Prostate 3.00 3.44 -0.44 Salivary gland 0.55 1.69 -1.14 Skin 4.74 2.72 2.03 Soft tissue 4.23 4.83 -0.60 Stomach 3.15 2.09 1.06 Three (3) organ types, appendix, gallbladder and hernial/peritoneal, had major discordance rates of 0.00% for both modalities. For all organ types, the absolute values of the observed differences in the major discordance rates between WSIR diagnosis and MSR diagnosis (relative to the reference diagnosis) were ≤ 2.03%. When examining the major discordance rates, ‘Bladder’ had the highest major discordance rate of 10.40% for WSIR and 9.47% for MSR. However, statistical model showed that the modality-by- organ interaction was not statistically significant. Secondary analysis of agreement between the WSIR and MSR diagnosis showed that there was also strong agreement between the two modalities. There were 7423 pairs of readings with both adjudication outcomes for WSIR and MSR. Results showed 96.1% of the paired readings resulted in no major discordance for both modalities (94.7%) or major discordance for both modalities (1.47%). The modality-by-organ interaction was not statistically significant. The clinical study was not powered to analyze the results by individual organ site or diagnosis. The number of unbalanced diagnoses in which the WSIR modality had major discordance and the MSR modality had concordance with the reference diagnosis in each tissue/organ type category ranged from 0 cases for kidney to 15 cases in breast, corresponding to 0.0% to 4.9% of the total cases in each organ type group. Similarly, the number of unbalanced diagnoses in which the MSR modality had major discordance and the WSIR modality had concordance with the reference diagnosis in each tissue/organ type category ranged from 0 cases in skin to 13 cases in breast, corresponding to 0.0% to 4.3% of the total cases in each organ type group. Thus, unbalanced diagnoses represented a small percentage of the 19 overall cases and occurred with similar frequency for both modalities. When the specific diagnoses were examined by tissue/organ type, there were no apparent trends in any tissue/organ type that suggested WSIR is more inherently prone to major discrepancies compared to MSR. When examining this data by reading pathologist, none of the reading pathologists showed a tendency to have more types of specific major discrepancies with WSIR as compared to MSR. In every case the observed rates were within the known and established rate of inter-pathologist variation in diagnosis as reported in literature. 4. Clinical cut-off: Not applicable 5. Expected values/Reference range: Not applicable N. Instrument Name: Aperio AT2 DX System O. System Descriptions: 1. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes ____X____ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No ____X____ 2. Software: FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: Yes ____X____ or No ________ 3. Specimen Identification: Glass slides are identified by barcodes on slide label. 20 4. Specimen Sampling and Handling: Glass slides are loaded manually into the slide feeder (Autoloader) which is a component of the Aperio AT2 DX scanner as a batch. With AutoLoader, the scanner automatically loads each slide in the batch to the stage and scans the glass slide to generate WSI image. After the scanning of all slides in the batch is completed, the slides are unloaded from the scanner and stored according to the lab procedure. 5. Calibration: The Aperio AT2 DX scanner is calibrated and verified at the factory before shipment. No further manual calibration or verification is required by the customer. Annual preventive maintenance performed by Leica Biosystems Technical Services is recommended to ensure the scanner is operating correctly. The scanner provides automatic calibration and verification every time a slide is scanned by performing calibration during the scan. The monitors provided with the Aperio AT2 DX System have been calibrated at the factory and may require periodic re-calibration in the field by authorized Leica Biosystems technicians. The user should not attempt to change the monitor settings as doing so may interfere with the monitor calibration. The ImageScope DX application does not require calibration. 6. Quality Control: It is the responsibility of the laboratory staff to conduct and maintain quality control of the slides per their laboratory standards (e.g., staining, cover-slipping, barcode placement) prior to loading the slides into the Aperio AT2 DX scanner. After completing a scan, the lab technician checks image data and image quality using the Aperio ConsoleDX application installed on the scanner workstation per the instructions for use. Before review, the pathologist performs quality control on the WSI images of the slide per instructions for use. P. Other Supportive Instrument Performance Characteristics Data Not Covered In The “Performance Characteristics” Section above: Not applicable Q. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809, as applicable, and the special controls for this device type under 21 CFR 864.3700. R. Conclusion: 21 The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK170127_s0_e2000

K170127.txt

purpose for submission

Addition of Ceftolozane/Tazobactam Antimicrobial Susceptibility Test Disk for testing Enterobacteriaceae

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K170127 B. Purpose for Submission: Addition of Ceftolozane/Tazobactam Antimicrobial Susceptibility Test Disk for testing Enterobacteriaceae C. Measurand: Ceftolozane/Tazobactam, 30/10µg D. Type of Test: Antimicrobial Susceptibility Test Disks E. Applicant: Hardy Diagnostics F. Proprietary and Established Names: HardyDisk Ceftolozane/Tazobactam, (30/10µg) - C/T40 G. Regulatory Information: 1. Regulation section: 21 CFR 866.1620 Antimicrobial Susceptibility Test Disc 2. Classification: Class II 3. Product code: JTN – Susceptibility Test Disc, Antimicrobial 4. Panel: 83 - Microbiology 2 H. Intended Use: 1. Intended use(s): HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp. including Streptococcus pneumoniae. 2. Indication(s) for use: Use of HardyDisk Ceftolozane/Tazobactam, (30/10µg) - C/T40, for in vitro agar diffusion susceptibility testing is indicated when there is a need to determine the susceptibility of bacteria to Ceftolozane/Tazobactam. The concentration of Ceftolozane/Tazobactam, (30/10µg) - C/T40, has been shown to be active against susceptible isolates of the following microorganisms with in vitro use: Citrobacter koseri, Morganella morganii, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Serratia liquefacians, and Serratia marcescens. The concentration of Ceftolozane/Tazobactam, (30/10µg)-C/T40, has been shown to be active against susceptible isolates of the following microorganisms both in vitro and in clinical infections: Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa. HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp. including Streptococcus pneumoniae. 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Not Applicable 3 I. Device Description: The HardyDisk AST Disks utilize 6-mm diameter white filter paper disks. The disks are prepared by impregnating absorbent paper with a known concentration of 30µg Ceftolozane and 10µg of Tazobactam. The disks are marked with the code C/T40 on both sides. The letters C/T are for the two agents and the number reflects the total content for both agents combined. HardyDisk AST Disks are supplied in plastic cartridges containing 50 disks each. They are also packaged as one cartridge per vial with desiccant or five cartridges per vial with desiccant. J. Substantial Equivalence Information: 1. Predicate device name(s): HardyDisk Tigecycline 15µg 2. Predicate 510(k) number(s): K062245 3. Comparison with predicate: Table 1: Comparison with Predicate Device Similarities Item Device: HardyDisk Ceftolozane/Tazobactam K170127 Predicate: HardyDisk Tigecycline K062245 Test Method Antimicrobial Susceptibility testing using paper discs impregnated with an antimicrobial agent Same Intended Use Antimicrobial Susceptibility Test Disks are used for in vitro susceptibility testing by standardized agar diffusion test procedures. Same Methodology Kirby-Bauer Disk Diffusion Susceptibility Test Protocol require the user to determine categorical interpretations (S/I/R) using the measured zone diameters. Same 4 Similarities Item Device: HardyDisk Ceftolozane/Tazobactam K170127 Predicate: HardyDisk Tigecycline K062245 Inoculum Prepared from pure isolated colonies in a suspension to match the turbidity equivalent of a 0.5 McFarland in Tryptic Soy Broth. Same Inoculum Method A sterile swab is dipped into the prepared inoculum, and applied to the surface of an appropriate agar plate in three directions. Disks impregnated with the antimicrobial agent are added to the surface of the plate. The plate is incubated agar side up in a 35 ± 2°C incubator for 18-24 hours. Same Interpretation The user will interpret the zone diameters according established interpretive criteria for the drug. Same Differences Item Device Predicate Product Name HardyDisk Ceftolozane/Tazobactam (30/10µg)- C/T40 HardyDisk Tigecycline Antibiotic Ceftolozane/Tazobactam Tigecycline Concentration 30µg Ceftolozane/10µg Tazobactam 15µg Tigecycline K. Standard/Guidance Document Referenced (if applicable): CLSI M02-A12, Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard- Twelfth Edition CLSI M100-S25, Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement L. Test Principle: The HardyDisk AST Disks are based on the agar diffusion (Kirby-Bauer) methodology. It utilizes dried filter paper disks impregnated with known concentrations of antimicrobial agents that are placed onto the test medium surface. Mueller Hinton agar is recommended for agar diffusion testing of non-fastidious organisms. Three to five similar colonies are transferred to 4-5 mL of a suitable broth medium. The broth is incubated at 35°C for 2-6 hours to develop a turbidity that exceeds or is equivalent to a 0.5 McFarland standard. 5 Alternatively, a direct broth or saline suspension of colonies may be prepared from an overnight culture. The final inoculum density should be equivalent to a 0.5 McFarland turbidity standard. The inoculum density may also be standardized photometrically. Within 15 minutes of inoculum preparation, the Mueller Hinton agar is streaked with an inoculated swab to obtain an even inoculation. Disks are aseptically placed onto the agar surface with a disk dispenser and the disks are pressed down with a sterile needle or forceps to make contact with the agar surface. Agar plates are incubated in an ambient air incubator at 35 ± 2°C for 16 -18 hours. Fastidious organisms are tested using appropriate media incubated in an atmosphere enriched with 5% CO2, as recommended in the CLSI M02 approved standard document. After incubation the agar medium is examined for zone of inhibition around the disks. The zones of inhibition are measured to the nearest millimeter and compared against recognized zone size ranges for the antimicrobial agent being tested. M. Performance Characteristics (if/when applicable): Descriptive characteristics were sufficient for this Ceftolozane/Tazobactam disk. The studies evaluated by FDA/CDER at the time of Ceftolozane/Tazobactam approval were used for this review. 1. Analytical performance: a. Precision/Reproducibility: Not applicable b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Not applicable d. Detection limit: Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: 6 Not applicable 2. Comparison studies: a. Method comparison with predicate device: Not applicable b. Matrix comparison: Not applicable 3. Clinical studies: a. Clinical Sensitivity: Not applicable b. Clinical specificity: Not applicable c. Other clinical supportive data (when a. and b. are not applicable): Not applicable 4. Clinical cut-off: Not applicable 5 Purpose for submission:

idK170127_s0_e2000

K170127.txt

measurand

Ceftolozane/Tazobactam, 30/10µg

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K170127 B. Purpose for Submission: Addition of Ceftolozane/Tazobactam Antimicrobial Susceptibility Test Disk for testing Enterobacteriaceae C. Measurand: Ceftolozane/Tazobactam, 30/10µg D. Type of Test: Antimicrobial Susceptibility Test Disks E. Applicant: Hardy Diagnostics F. Proprietary and Established Names: HardyDisk Ceftolozane/Tazobactam, (30/10µg) - C/T40 G. Regulatory Information: 1. Regulation section: 21 CFR 866.1620 Antimicrobial Susceptibility Test Disc 2. Classification: Class II 3. Product code: JTN – Susceptibility Test Disc, Antimicrobial 4. Panel: 83 - Microbiology 2 H. Intended Use: 1. Intended use(s): HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp. including Streptococcus pneumoniae. 2. Indication(s) for use: Use of HardyDisk Ceftolozane/Tazobactam, (30/10µg) - C/T40, for in vitro agar diffusion susceptibility testing is indicated when there is a need to determine the susceptibility of bacteria to Ceftolozane/Tazobactam. The concentration of Ceftolozane/Tazobactam, (30/10µg) - C/T40, has been shown to be active against susceptible isolates of the following microorganisms with in vitro use: Citrobacter koseri, Morganella morganii, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Serratia liquefacians, and Serratia marcescens. The concentration of Ceftolozane/Tazobactam, (30/10µg)-C/T40, has been shown to be active against susceptible isolates of the following microorganisms both in vitro and in clinical infections: Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa. HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp. including Streptococcus pneumoniae. 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Not Applicable 3 I. Device Description: The HardyDisk AST Disks utilize 6-mm diameter white filter paper disks. The disks are prepared by impregnating absorbent paper with a known concentration of 30µg Ceftolozane and 10µg of Tazobactam. The disks are marked with the code C/T40 on both sides. The letters C/T are for the two agents and the number reflects the total content for both agents combined. HardyDisk AST Disks are supplied in plastic cartridges containing 50 disks each. They are also packaged as one cartridge per vial with desiccant or five cartridges per vial with desiccant. J. Substantial Equivalence Information: 1. Predicate device name(s): HardyDisk Tigecycline 15µg 2. Predicate 510(k) number(s): K062245 3. Comparison with predicate: Table 1: Comparison with Predicate Device Similarities Item Device: HardyDisk Ceftolozane/Tazobactam K170127 Predicate: HardyDisk Tigecycline K062245 Test Method Antimicrobial Susceptibility testing using paper discs impregnated with an antimicrobial agent Same Intended Use Antimicrobial Susceptibility Test Disks are used for in vitro susceptibility testing by standardized agar diffusion test procedures. Same Methodology Kirby-Bauer Disk Diffusion Susceptibility Test Protocol require the user to determine categorical interpretations (S/I/R) using the measured zone diameters. Same 4 Similarities Item Device: HardyDisk Ceftolozane/Tazobactam K170127 Predicate: HardyDisk Tigecycline K062245 Inoculum Prepared from pure isolated colonies in a suspension to match the turbidity equivalent of a 0.5 McFarland in Tryptic Soy Broth. Same Inoculum Method A sterile swab is dipped into the prepared inoculum, and applied to the surface of an appropriate agar plate in three directions. Disks impregnated with the antimicrobial agent are added to the surface of the plate. The plate is incubated agar side up in a 35 ± 2°C incubator for 18-24 hours. Same Interpretation The user will interpret the zone diameters according established interpretive criteria for the drug. Same Differences Item Device Predicate Product Name HardyDisk Ceftolozane/Tazobactam (30/10µg)- C/T40 HardyDisk Tigecycline Antibiotic Ceftolozane/Tazobactam Tigecycline Concentration 30µg Ceftolozane/10µg Tazobactam 15µg Tigecycline K. Standard/Guidance Document Referenced (if applicable): CLSI M02-A12, Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard- Twelfth Edition CLSI M100-S25, Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement L. Test Principle: The HardyDisk AST Disks are based on the agar diffusion (Kirby-Bauer) methodology. It utilizes dried filter paper disks impregnated with known concentrations of antimicrobial agents that are placed onto the test medium surface. Mueller Hinton agar is recommended for agar diffusion testing of non-fastidious organisms. Three to five similar colonies are transferred to 4-5 mL of a suitable broth medium. The broth is incubated at 35°C for 2-6 hours to develop a turbidity that exceeds or is equivalent to a 0.5 McFarland standard. 5 Alternatively, a direct broth or saline suspension of colonies may be prepared from an overnight culture. The final inoculum density should be equivalent to a 0.5 McFarland turbidity standard. The inoculum density may also be standardized photometrically. Within 15 minutes of inoculum preparation, the Mueller Hinton agar is streaked with an inoculated swab to obtain an even inoculation. Disks are aseptically placed onto the agar surface with a disk dispenser and the disks are pressed down with a sterile needle or forceps to make contact with the agar surface. Agar plates are incubated in an ambient air incubator at 35 ± 2°C for 16 -18 hours. Fastidious organisms are tested using appropriate media incubated in an atmosphere enriched with 5% CO2, as recommended in the CLSI M02 approved standard document. After incubation the agar medium is examined for zone of inhibition around the disks. The zones of inhibition are measured to the nearest millimeter and compared against recognized zone size ranges for the antimicrobial agent being tested. M. Performance Characteristics (if/when applicable): Descriptive characteristics were sufficient for this Ceftolozane/Tazobactam disk. The studies evaluated by FDA/CDER at the time of Ceftolozane/Tazobactam approval were used for this review. 1. Analytical performance: a. Precision/Reproducibility: Not applicable b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Not applicable d. Detection limit: Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: 6 Not applicable 2. Comparison studies: a. Method comparison with predicate device: Not applicable b. Matrix comparison: Not applicable 3. Clinical studies: a. Clinical Sensitivity: Not applicable b. Clinical specificity: Not applicable c. Other clinical supportive data (when a. and b. are not applicable): Not applicable 4. Clinical cut-off: Not applicable 5 Measurand:

idK170127_s0_e2000

K170127.txt

type of test

Antimicrobial Susceptibility Test Disks

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K170127 B. Purpose for Submission: Addition of Ceftolozane/Tazobactam Antimicrobial Susceptibility Test Disk for testing Enterobacteriaceae C. Measurand: Ceftolozane/Tazobactam, 30/10µg D. Type of Test: Antimicrobial Susceptibility Test Disks E. Applicant: Hardy Diagnostics F. Proprietary and Established Names: HardyDisk Ceftolozane/Tazobactam, (30/10µg) - C/T40 G. Regulatory Information: 1. Regulation section: 21 CFR 866.1620 Antimicrobial Susceptibility Test Disc 2. Classification: Class II 3. Product code: JTN – Susceptibility Test Disc, Antimicrobial 4. Panel: 83 - Microbiology 2 H. Intended Use: 1. Intended use(s): HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp. including Streptococcus pneumoniae. 2. Indication(s) for use: Use of HardyDisk Ceftolozane/Tazobactam, (30/10µg) - C/T40, for in vitro agar diffusion susceptibility testing is indicated when there is a need to determine the susceptibility of bacteria to Ceftolozane/Tazobactam. The concentration of Ceftolozane/Tazobactam, (30/10µg) - C/T40, has been shown to be active against susceptible isolates of the following microorganisms with in vitro use: Citrobacter koseri, Morganella morganii, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Serratia liquefacians, and Serratia marcescens. The concentration of Ceftolozane/Tazobactam, (30/10µg)-C/T40, has been shown to be active against susceptible isolates of the following microorganisms both in vitro and in clinical infections: Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa. HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp. including Streptococcus pneumoniae. 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Not Applicable 3 I. Device Description: The HardyDisk AST Disks utilize 6-mm diameter white filter paper disks. The disks are prepared by impregnating absorbent paper with a known concentration of 30µg Ceftolozane and 10µg of Tazobactam. The disks are marked with the code C/T40 on both sides. The letters C/T are for the two agents and the number reflects the total content for both agents combined. HardyDisk AST Disks are supplied in plastic cartridges containing 50 disks each. They are also packaged as one cartridge per vial with desiccant or five cartridges per vial with desiccant. J. Substantial Equivalence Information: 1. Predicate device name(s): HardyDisk Tigecycline 15µg 2. Predicate 510(k) number(s): K062245 3. Comparison with predicate: Table 1: Comparison with Predicate Device Similarities Item Device: HardyDisk Ceftolozane/Tazobactam K170127 Predicate: HardyDisk Tigecycline K062245 Test Method Antimicrobial Susceptibility testing using paper discs impregnated with an antimicrobial agent Same Intended Use Antimicrobial Susceptibility Test Disks are used for in vitro susceptibility testing by standardized agar diffusion test procedures. Same Methodology Kirby-Bauer Disk Diffusion Susceptibility Test Protocol require the user to determine categorical interpretations (S/I/R) using the measured zone diameters. Same 4 Similarities Item Device: HardyDisk Ceftolozane/Tazobactam K170127 Predicate: HardyDisk Tigecycline K062245 Inoculum Prepared from pure isolated colonies in a suspension to match the turbidity equivalent of a 0.5 McFarland in Tryptic Soy Broth. Same Inoculum Method A sterile swab is dipped into the prepared inoculum, and applied to the surface of an appropriate agar plate in three directions. Disks impregnated with the antimicrobial agent are added to the surface of the plate. The plate is incubated agar side up in a 35 ± 2°C incubator for 18-24 hours. Same Interpretation The user will interpret the zone diameters according established interpretive criteria for the drug. Same Differences Item Device Predicate Product Name HardyDisk Ceftolozane/Tazobactam (30/10µg)- C/T40 HardyDisk Tigecycline Antibiotic Ceftolozane/Tazobactam Tigecycline Concentration 30µg Ceftolozane/10µg Tazobactam 15µg Tigecycline K. Standard/Guidance Document Referenced (if applicable): CLSI M02-A12, Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard- Twelfth Edition CLSI M100-S25, Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement L. Test Principle: The HardyDisk AST Disks are based on the agar diffusion (Kirby-Bauer) methodology. It utilizes dried filter paper disks impregnated with known concentrations of antimicrobial agents that are placed onto the test medium surface. Mueller Hinton agar is recommended for agar diffusion testing of non-fastidious organisms. Three to five similar colonies are transferred to 4-5 mL of a suitable broth medium. The broth is incubated at 35°C for 2-6 hours to develop a turbidity that exceeds or is equivalent to a 0.5 McFarland standard. 5 Alternatively, a direct broth or saline suspension of colonies may be prepared from an overnight culture. The final inoculum density should be equivalent to a 0.5 McFarland turbidity standard. The inoculum density may also be standardized photometrically. Within 15 minutes of inoculum preparation, the Mueller Hinton agar is streaked with an inoculated swab to obtain an even inoculation. Disks are aseptically placed onto the agar surface with a disk dispenser and the disks are pressed down with a sterile needle or forceps to make contact with the agar surface. Agar plates are incubated in an ambient air incubator at 35 ± 2°C for 16 -18 hours. Fastidious organisms are tested using appropriate media incubated in an atmosphere enriched with 5% CO2, as recommended in the CLSI M02 approved standard document. After incubation the agar medium is examined for zone of inhibition around the disks. The zones of inhibition are measured to the nearest millimeter and compared against recognized zone size ranges for the antimicrobial agent being tested. M. Performance Characteristics (if/when applicable): Descriptive characteristics were sufficient for this Ceftolozane/Tazobactam disk. The studies evaluated by FDA/CDER at the time of Ceftolozane/Tazobactam approval were used for this review. 1. Analytical performance: a. Precision/Reproducibility: Not applicable b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Not applicable d. Detection limit: Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: 6 Not applicable 2. Comparison studies: a. Method comparison with predicate device: Not applicable b. Matrix comparison: Not applicable 3. Clinical studies: a. Clinical Sensitivity: Not applicable b. Clinical specificity: Not applicable c. Other clinical supportive data (when a. and b. are not applicable): Not applicable 4. Clinical cut-off: Not applicable 5 Type of test:

idK170127_s0_e2000

K170127.txt

classification

Class II

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K170127 B. Purpose for Submission: Addition of Ceftolozane/Tazobactam Antimicrobial Susceptibility Test Disk for testing Enterobacteriaceae C. Measurand: Ceftolozane/Tazobactam, 30/10µg D. Type of Test: Antimicrobial Susceptibility Test Disks E. Applicant: Hardy Diagnostics F. Proprietary and Established Names: HardyDisk Ceftolozane/Tazobactam, (30/10µg) - C/T40 G. Regulatory Information: 1. Regulation section: 21 CFR 866.1620 Antimicrobial Susceptibility Test Disc 2. Classification: Class II 3. Product code: JTN – Susceptibility Test Disc, Antimicrobial 4. Panel: 83 - Microbiology 2 H. Intended Use: 1. Intended use(s): HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp. including Streptococcus pneumoniae. 2. Indication(s) for use: Use of HardyDisk Ceftolozane/Tazobactam, (30/10µg) - C/T40, for in vitro agar diffusion susceptibility testing is indicated when there is a need to determine the susceptibility of bacteria to Ceftolozane/Tazobactam. The concentration of Ceftolozane/Tazobactam, (30/10µg) - C/T40, has been shown to be active against susceptible isolates of the following microorganisms with in vitro use: Citrobacter koseri, Morganella morganii, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Serratia liquefacians, and Serratia marcescens. The concentration of Ceftolozane/Tazobactam, (30/10µg)-C/T40, has been shown to be active against susceptible isolates of the following microorganisms both in vitro and in clinical infections: Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa. HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp. including Streptococcus pneumoniae. 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Not Applicable 3 I. Device Description: The HardyDisk AST Disks utilize 6-mm diameter white filter paper disks. The disks are prepared by impregnating absorbent paper with a known concentration of 30µg Ceftolozane and 10µg of Tazobactam. The disks are marked with the code C/T40 on both sides. The letters C/T are for the two agents and the number reflects the total content for both agents combined. HardyDisk AST Disks are supplied in plastic cartridges containing 50 disks each. They are also packaged as one cartridge per vial with desiccant or five cartridges per vial with desiccant. J. Substantial Equivalence Information: 1. Predicate device name(s): HardyDisk Tigecycline 15µg 2. Predicate 510(k) number(s): K062245 3. Comparison with predicate: Table 1: Comparison with Predicate Device Similarities Item Device: HardyDisk Ceftolozane/Tazobactam K170127 Predicate: HardyDisk Tigecycline K062245 Test Method Antimicrobial Susceptibility testing using paper discs impregnated with an antimicrobial agent Same Intended Use Antimicrobial Susceptibility Test Disks are used for in vitro susceptibility testing by standardized agar diffusion test procedures. Same Methodology Kirby-Bauer Disk Diffusion Susceptibility Test Protocol require the user to determine categorical interpretations (S/I/R) using the measured zone diameters. Same 4 Similarities Item Device: HardyDisk Ceftolozane/Tazobactam K170127 Predicate: HardyDisk Tigecycline K062245 Inoculum Prepared from pure isolated colonies in a suspension to match the turbidity equivalent of a 0.5 McFarland in Tryptic Soy Broth. Same Inoculum Method A sterile swab is dipped into the prepared inoculum, and applied to the surface of an appropriate agar plate in three directions. Disks impregnated with the antimicrobial agent are added to the surface of the plate. The plate is incubated agar side up in a 35 ± 2°C incubator for 18-24 hours. Same Interpretation The user will interpret the zone diameters according established interpretive criteria for the drug. Same Differences Item Device Predicate Product Name HardyDisk Ceftolozane/Tazobactam (30/10µg)- C/T40 HardyDisk Tigecycline Antibiotic Ceftolozane/Tazobactam Tigecycline Concentration 30µg Ceftolozane/10µg Tazobactam 15µg Tigecycline K. Standard/Guidance Document Referenced (if applicable): CLSI M02-A12, Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard- Twelfth Edition CLSI M100-S25, Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement L. Test Principle: The HardyDisk AST Disks are based on the agar diffusion (Kirby-Bauer) methodology. It utilizes dried filter paper disks impregnated with known concentrations of antimicrobial agents that are placed onto the test medium surface. Mueller Hinton agar is recommended for agar diffusion testing of non-fastidious organisms. Three to five similar colonies are transferred to 4-5 mL of a suitable broth medium. The broth is incubated at 35°C for 2-6 hours to develop a turbidity that exceeds or is equivalent to a 0.5 McFarland standard. 5 Alternatively, a direct broth or saline suspension of colonies may be prepared from an overnight culture. The final inoculum density should be equivalent to a 0.5 McFarland turbidity standard. The inoculum density may also be standardized photometrically. Within 15 minutes of inoculum preparation, the Mueller Hinton agar is streaked with an inoculated swab to obtain an even inoculation. Disks are aseptically placed onto the agar surface with a disk dispenser and the disks are pressed down with a sterile needle or forceps to make contact with the agar surface. Agar plates are incubated in an ambient air incubator at 35 ± 2°C for 16 -18 hours. Fastidious organisms are tested using appropriate media incubated in an atmosphere enriched with 5% CO2, as recommended in the CLSI M02 approved standard document. After incubation the agar medium is examined for zone of inhibition around the disks. The zones of inhibition are measured to the nearest millimeter and compared against recognized zone size ranges for the antimicrobial agent being tested. M. Performance Characteristics (if/when applicable): Descriptive characteristics were sufficient for this Ceftolozane/Tazobactam disk. The studies evaluated by FDA/CDER at the time of Ceftolozane/Tazobactam approval were used for this review. 1. Analytical performance: a. Precision/Reproducibility: Not applicable b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Not applicable d. Detection limit: Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: 6 Not applicable 2. Comparison studies: a. Method comparison with predicate device: Not applicable b. Matrix comparison: Not applicable 3. Clinical studies: a. Clinical Sensitivity: Not applicable b. Clinical specificity: Not applicable c. Other clinical supportive data (when a. and b. are not applicable): Not applicable 4. Clinical cut-off: Not applicable 5 Classification:

idK170127_s0_e2000

K170127.txt

product code

JTN – Susceptibility Test Disc, Antimicrobial

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K170127 B. Purpose for Submission: Addition of Ceftolozane/Tazobactam Antimicrobial Susceptibility Test Disk for testing Enterobacteriaceae C. Measurand: Ceftolozane/Tazobactam, 30/10µg D. Type of Test: Antimicrobial Susceptibility Test Disks E. Applicant: Hardy Diagnostics F. Proprietary and Established Names: HardyDisk Ceftolozane/Tazobactam, (30/10µg) - C/T40 G. Regulatory Information: 1. Regulation section: 21 CFR 866.1620 Antimicrobial Susceptibility Test Disc 2. Classification: Class II 3. Product code: JTN – Susceptibility Test Disc, Antimicrobial 4. Panel: 83 - Microbiology 2 H. Intended Use: 1. Intended use(s): HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp. including Streptococcus pneumoniae. 2. Indication(s) for use: Use of HardyDisk Ceftolozane/Tazobactam, (30/10µg) - C/T40, for in vitro agar diffusion susceptibility testing is indicated when there is a need to determine the susceptibility of bacteria to Ceftolozane/Tazobactam. The concentration of Ceftolozane/Tazobactam, (30/10µg) - C/T40, has been shown to be active against susceptible isolates of the following microorganisms with in vitro use: Citrobacter koseri, Morganella morganii, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Serratia liquefacians, and Serratia marcescens. The concentration of Ceftolozane/Tazobactam, (30/10µg)-C/T40, has been shown to be active against susceptible isolates of the following microorganisms both in vitro and in clinical infections: Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa. HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp. including Streptococcus pneumoniae. 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Not Applicable 3 I. Device Description: The HardyDisk AST Disks utilize 6-mm diameter white filter paper disks. The disks are prepared by impregnating absorbent paper with a known concentration of 30µg Ceftolozane and 10µg of Tazobactam. The disks are marked with the code C/T40 on both sides. The letters C/T are for the two agents and the number reflects the total content for both agents combined. HardyDisk AST Disks are supplied in plastic cartridges containing 50 disks each. They are also packaged as one cartridge per vial with desiccant or five cartridges per vial with desiccant. J. Substantial Equivalence Information: 1. Predicate device name(s): HardyDisk Tigecycline 15µg 2. Predicate 510(k) number(s): K062245 3. Comparison with predicate: Table 1: Comparison with Predicate Device Similarities Item Device: HardyDisk Ceftolozane/Tazobactam K170127 Predicate: HardyDisk Tigecycline K062245 Test Method Antimicrobial Susceptibility testing using paper discs impregnated with an antimicrobial agent Same Intended Use Antimicrobial Susceptibility Test Disks are used for in vitro susceptibility testing by standardized agar diffusion test procedures. Same Methodology Kirby-Bauer Disk Diffusion Susceptibility Test Protocol require the user to determine categorical interpretations (S/I/R) using the measured zone diameters. Same 4 Similarities Item Device: HardyDisk Ceftolozane/Tazobactam K170127 Predicate: HardyDisk Tigecycline K062245 Inoculum Prepared from pure isolated colonies in a suspension to match the turbidity equivalent of a 0.5 McFarland in Tryptic Soy Broth. Same Inoculum Method A sterile swab is dipped into the prepared inoculum, and applied to the surface of an appropriate agar plate in three directions. Disks impregnated with the antimicrobial agent are added to the surface of the plate. The plate is incubated agar side up in a 35 ± 2°C incubator for 18-24 hours. Same Interpretation The user will interpret the zone diameters according established interpretive criteria for the drug. Same Differences Item Device Predicate Product Name HardyDisk Ceftolozane/Tazobactam (30/10µg)- C/T40 HardyDisk Tigecycline Antibiotic Ceftolozane/Tazobactam Tigecycline Concentration 30µg Ceftolozane/10µg Tazobactam 15µg Tigecycline K. Standard/Guidance Document Referenced (if applicable): CLSI M02-A12, Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard- Twelfth Edition CLSI M100-S25, Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement L. Test Principle: The HardyDisk AST Disks are based on the agar diffusion (Kirby-Bauer) methodology. It utilizes dried filter paper disks impregnated with known concentrations of antimicrobial agents that are placed onto the test medium surface. Mueller Hinton agar is recommended for agar diffusion testing of non-fastidious organisms. Three to five similar colonies are transferred to 4-5 mL of a suitable broth medium. The broth is incubated at 35°C for 2-6 hours to develop a turbidity that exceeds or is equivalent to a 0.5 McFarland standard. 5 Alternatively, a direct broth or saline suspension of colonies may be prepared from an overnight culture. The final inoculum density should be equivalent to a 0.5 McFarland turbidity standard. The inoculum density may also be standardized photometrically. Within 15 minutes of inoculum preparation, the Mueller Hinton agar is streaked with an inoculated swab to obtain an even inoculation. Disks are aseptically placed onto the agar surface with a disk dispenser and the disks are pressed down with a sterile needle or forceps to make contact with the agar surface. Agar plates are incubated in an ambient air incubator at 35 ± 2°C for 16 -18 hours. Fastidious organisms are tested using appropriate media incubated in an atmosphere enriched with 5% CO2, as recommended in the CLSI M02 approved standard document. After incubation the agar medium is examined for zone of inhibition around the disks. The zones of inhibition are measured to the nearest millimeter and compared against recognized zone size ranges for the antimicrobial agent being tested. M. Performance Characteristics (if/when applicable): Descriptive characteristics were sufficient for this Ceftolozane/Tazobactam disk. The studies evaluated by FDA/CDER at the time of Ceftolozane/Tazobactam approval were used for this review. 1. Analytical performance: a. Precision/Reproducibility: Not applicable b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Not applicable d. Detection limit: Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: 6 Not applicable 2. Comparison studies: a. Method comparison with predicate device: Not applicable b. Matrix comparison: Not applicable 3. Clinical studies: a. Clinical Sensitivity: Not applicable b. Clinical specificity: Not applicable c. Other clinical supportive data (when a. and b. are not applicable): Not applicable 4. Clinical cut-off: Not applicable 5 Product code:

idK170127_s0_e2000

K170127.txt

panel

83 - Microbiology

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K170127 B. Purpose for Submission: Addition of Ceftolozane/Tazobactam Antimicrobial Susceptibility Test Disk for testing Enterobacteriaceae C. Measurand: Ceftolozane/Tazobactam, 30/10µg D. Type of Test: Antimicrobial Susceptibility Test Disks E. Applicant: Hardy Diagnostics F. Proprietary and Established Names: HardyDisk Ceftolozane/Tazobactam, (30/10µg) - C/T40 G. Regulatory Information: 1. Regulation section: 21 CFR 866.1620 Antimicrobial Susceptibility Test Disc 2. Classification: Class II 3. Product code: JTN – Susceptibility Test Disc, Antimicrobial 4. Panel: 83 - Microbiology 2 H. Intended Use: 1. Intended use(s): HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp. including Streptococcus pneumoniae. 2. Indication(s) for use: Use of HardyDisk Ceftolozane/Tazobactam, (30/10µg) - C/T40, for in vitro agar diffusion susceptibility testing is indicated when there is a need to determine the susceptibility of bacteria to Ceftolozane/Tazobactam. The concentration of Ceftolozane/Tazobactam, (30/10µg) - C/T40, has been shown to be active against susceptible isolates of the following microorganisms with in vitro use: Citrobacter koseri, Morganella morganii, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Serratia liquefacians, and Serratia marcescens. The concentration of Ceftolozane/Tazobactam, (30/10µg)-C/T40, has been shown to be active against susceptible isolates of the following microorganisms both in vitro and in clinical infections: Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa. HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp. including Streptococcus pneumoniae. 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Not Applicable 3 I. Device Description: The HardyDisk AST Disks utilize 6-mm diameter white filter paper disks. The disks are prepared by impregnating absorbent paper with a known concentration of 30µg Ceftolozane and 10µg of Tazobactam. The disks are marked with the code C/T40 on both sides. The letters C/T are for the two agents and the number reflects the total content for both agents combined. HardyDisk AST Disks are supplied in plastic cartridges containing 50 disks each. They are also packaged as one cartridge per vial with desiccant or five cartridges per vial with desiccant. J. Substantial Equivalence Information: 1. Predicate device name(s): HardyDisk Tigecycline 15µg 2. Predicate 510(k) number(s): K062245 3. Comparison with predicate: Table 1: Comparison with Predicate Device Similarities Item Device: HardyDisk Ceftolozane/Tazobactam K170127 Predicate: HardyDisk Tigecycline K062245 Test Method Antimicrobial Susceptibility testing using paper discs impregnated with an antimicrobial agent Same Intended Use Antimicrobial Susceptibility Test Disks are used for in vitro susceptibility testing by standardized agar diffusion test procedures. Same Methodology Kirby-Bauer Disk Diffusion Susceptibility Test Protocol require the user to determine categorical interpretations (S/I/R) using the measured zone diameters. Same 4 Similarities Item Device: HardyDisk Ceftolozane/Tazobactam K170127 Predicate: HardyDisk Tigecycline K062245 Inoculum Prepared from pure isolated colonies in a suspension to match the turbidity equivalent of a 0.5 McFarland in Tryptic Soy Broth. Same Inoculum Method A sterile swab is dipped into the prepared inoculum, and applied to the surface of an appropriate agar plate in three directions. Disks impregnated with the antimicrobial agent are added to the surface of the plate. The plate is incubated agar side up in a 35 ± 2°C incubator for 18-24 hours. Same Interpretation The user will interpret the zone diameters according established interpretive criteria for the drug. Same Differences Item Device Predicate Product Name HardyDisk Ceftolozane/Tazobactam (30/10µg)- C/T40 HardyDisk Tigecycline Antibiotic Ceftolozane/Tazobactam Tigecycline Concentration 30µg Ceftolozane/10µg Tazobactam 15µg Tigecycline K. Standard/Guidance Document Referenced (if applicable): CLSI M02-A12, Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard- Twelfth Edition CLSI M100-S25, Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement L. Test Principle: The HardyDisk AST Disks are based on the agar diffusion (Kirby-Bauer) methodology. It utilizes dried filter paper disks impregnated with known concentrations of antimicrobial agents that are placed onto the test medium surface. Mueller Hinton agar is recommended for agar diffusion testing of non-fastidious organisms. Three to five similar colonies are transferred to 4-5 mL of a suitable broth medium. The broth is incubated at 35°C for 2-6 hours to develop a turbidity that exceeds or is equivalent to a 0.5 McFarland standard. 5 Alternatively, a direct broth or saline suspension of colonies may be prepared from an overnight culture. The final inoculum density should be equivalent to a 0.5 McFarland turbidity standard. The inoculum density may also be standardized photometrically. Within 15 minutes of inoculum preparation, the Mueller Hinton agar is streaked with an inoculated swab to obtain an even inoculation. Disks are aseptically placed onto the agar surface with a disk dispenser and the disks are pressed down with a sterile needle or forceps to make contact with the agar surface. Agar plates are incubated in an ambient air incubator at 35 ± 2°C for 16 -18 hours. Fastidious organisms are tested using appropriate media incubated in an atmosphere enriched with 5% CO2, as recommended in the CLSI M02 approved standard document. After incubation the agar medium is examined for zone of inhibition around the disks. The zones of inhibition are measured to the nearest millimeter and compared against recognized zone size ranges for the antimicrobial agent being tested. M. Performance Characteristics (if/when applicable): Descriptive characteristics were sufficient for this Ceftolozane/Tazobactam disk. The studies evaluated by FDA/CDER at the time of Ceftolozane/Tazobactam approval were used for this review. 1. Analytical performance: a. Precision/Reproducibility: Not applicable b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Not applicable d. Detection limit: Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: 6 Not applicable 2. Comparison studies: a. Method comparison with predicate device: Not applicable b. Matrix comparison: Not applicable 3. Clinical studies: a. Clinical Sensitivity: Not applicable b. Clinical specificity: Not applicable c. Other clinical supportive data (when a. and b. are not applicable): Not applicable 4. Clinical cut-off: Not applicable 5 Panel:

idK170127_s0_e2000

K170127.txt

intended use

HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp. including Streptococcus pneumoniae.

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K170127 B. Purpose for Submission: Addition of Ceftolozane/Tazobactam Antimicrobial Susceptibility Test Disk for testing Enterobacteriaceae C. Measurand: Ceftolozane/Tazobactam, 30/10µg D. Type of Test: Antimicrobial Susceptibility Test Disks E. Applicant: Hardy Diagnostics F. Proprietary and Established Names: HardyDisk Ceftolozane/Tazobactam, (30/10µg) - C/T40 G. Regulatory Information: 1. Regulation section: 21 CFR 866.1620 Antimicrobial Susceptibility Test Disc 2. Classification: Class II 3. Product code: JTN – Susceptibility Test Disc, Antimicrobial 4. Panel: 83 - Microbiology 2 H. Intended Use: 1. Intended use(s): HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp. including Streptococcus pneumoniae. 2. Indication(s) for use: Use of HardyDisk Ceftolozane/Tazobactam, (30/10µg) - C/T40, for in vitro agar diffusion susceptibility testing is indicated when there is a need to determine the susceptibility of bacteria to Ceftolozane/Tazobactam. The concentration of Ceftolozane/Tazobactam, (30/10µg) - C/T40, has been shown to be active against susceptible isolates of the following microorganisms with in vitro use: Citrobacter koseri, Morganella morganii, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Serratia liquefacians, and Serratia marcescens. The concentration of Ceftolozane/Tazobactam, (30/10µg)-C/T40, has been shown to be active against susceptible isolates of the following microorganisms both in vitro and in clinical infections: Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa. HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp. including Streptococcus pneumoniae. 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Not Applicable 3 I. Device Description: The HardyDisk AST Disks utilize 6-mm diameter white filter paper disks. The disks are prepared by impregnating absorbent paper with a known concentration of 30µg Ceftolozane and 10µg of Tazobactam. The disks are marked with the code C/T40 on both sides. The letters C/T are for the two agents and the number reflects the total content for both agents combined. HardyDisk AST Disks are supplied in plastic cartridges containing 50 disks each. They are also packaged as one cartridge per vial with desiccant or five cartridges per vial with desiccant. J. Substantial Equivalence Information: 1. Predicate device name(s): HardyDisk Tigecycline 15µg 2. Predicate 510(k) number(s): K062245 3. Comparison with predicate: Table 1: Comparison with Predicate Device Similarities Item Device: HardyDisk Ceftolozane/Tazobactam K170127 Predicate: HardyDisk Tigecycline K062245 Test Method Antimicrobial Susceptibility testing using paper discs impregnated with an antimicrobial agent Same Intended Use Antimicrobial Susceptibility Test Disks are used for in vitro susceptibility testing by standardized agar diffusion test procedures. Same Methodology Kirby-Bauer Disk Diffusion Susceptibility Test Protocol require the user to determine categorical interpretations (S/I/R) using the measured zone diameters. Same 4 Similarities Item Device: HardyDisk Ceftolozane/Tazobactam K170127 Predicate: HardyDisk Tigecycline K062245 Inoculum Prepared from pure isolated colonies in a suspension to match the turbidity equivalent of a 0.5 McFarland in Tryptic Soy Broth. Same Inoculum Method A sterile swab is dipped into the prepared inoculum, and applied to the surface of an appropriate agar plate in three directions. Disks impregnated with the antimicrobial agent are added to the surface of the plate. The plate is incubated agar side up in a 35 ± 2°C incubator for 18-24 hours. Same Interpretation The user will interpret the zone diameters according established interpretive criteria for the drug. Same Differences Item Device Predicate Product Name HardyDisk Ceftolozane/Tazobactam (30/10µg)- C/T40 HardyDisk Tigecycline Antibiotic Ceftolozane/Tazobactam Tigecycline Concentration 30µg Ceftolozane/10µg Tazobactam 15µg Tigecycline K. Standard/Guidance Document Referenced (if applicable): CLSI M02-A12, Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard- Twelfth Edition CLSI M100-S25, Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement L. Test Principle: The HardyDisk AST Disks are based on the agar diffusion (Kirby-Bauer) methodology. It utilizes dried filter paper disks impregnated with known concentrations of antimicrobial agents that are placed onto the test medium surface. Mueller Hinton agar is recommended for agar diffusion testing of non-fastidious organisms. Three to five similar colonies are transferred to 4-5 mL of a suitable broth medium. The broth is incubated at 35°C for 2-6 hours to develop a turbidity that exceeds or is equivalent to a 0.5 McFarland standard. 5 Alternatively, a direct broth or saline suspension of colonies may be prepared from an overnight culture. The final inoculum density should be equivalent to a 0.5 McFarland turbidity standard. The inoculum density may also be standardized photometrically. Within 15 minutes of inoculum preparation, the Mueller Hinton agar is streaked with an inoculated swab to obtain an even inoculation. Disks are aseptically placed onto the agar surface with a disk dispenser and the disks are pressed down with a sterile needle or forceps to make contact with the agar surface. Agar plates are incubated in an ambient air incubator at 35 ± 2°C for 16 -18 hours. Fastidious organisms are tested using appropriate media incubated in an atmosphere enriched with 5% CO2, as recommended in the CLSI M02 approved standard document. After incubation the agar medium is examined for zone of inhibition around the disks. The zones of inhibition are measured to the nearest millimeter and compared against recognized zone size ranges for the antimicrobial agent being tested. M. Performance Characteristics (if/when applicable): Descriptive characteristics were sufficient for this Ceftolozane/Tazobactam disk. The studies evaluated by FDA/CDER at the time of Ceftolozane/Tazobactam approval were used for this review. 1. Analytical performance: a. Precision/Reproducibility: Not applicable b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Not applicable d. Detection limit: Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: 6 Not applicable 2. Comparison studies: a. Method comparison with predicate device: Not applicable b. Matrix comparison: Not applicable 3. Clinical studies: a. Clinical Sensitivity: Not applicable b. Clinical specificity: Not applicable c. Other clinical supportive data (when a. and b. are not applicable): Not applicable 4. Clinical cut-off: Not applicable 5 Intended use:

idK170127_s0_e2000

K170127.txt

predicate device name

HardyDisk Tigecycline 15µg

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K170127 B. Purpose for Submission: Addition of Ceftolozane/Tazobactam Antimicrobial Susceptibility Test Disk for testing Enterobacteriaceae C. Measurand: Ceftolozane/Tazobactam, 30/10µg D. Type of Test: Antimicrobial Susceptibility Test Disks E. Applicant: Hardy Diagnostics F. Proprietary and Established Names: HardyDisk Ceftolozane/Tazobactam, (30/10µg) - C/T40 G. Regulatory Information: 1. Regulation section: 21 CFR 866.1620 Antimicrobial Susceptibility Test Disc 2. Classification: Class II 3. Product code: JTN – Susceptibility Test Disc, Antimicrobial 4. Panel: 83 - Microbiology 2 H. Intended Use: 1. Intended use(s): HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp. including Streptococcus pneumoniae. 2. Indication(s) for use: Use of HardyDisk Ceftolozane/Tazobactam, (30/10µg) - C/T40, for in vitro agar diffusion susceptibility testing is indicated when there is a need to determine the susceptibility of bacteria to Ceftolozane/Tazobactam. The concentration of Ceftolozane/Tazobactam, (30/10µg) - C/T40, has been shown to be active against susceptible isolates of the following microorganisms with in vitro use: Citrobacter koseri, Morganella morganii, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Serratia liquefacians, and Serratia marcescens. The concentration of Ceftolozane/Tazobactam, (30/10µg)-C/T40, has been shown to be active against susceptible isolates of the following microorganisms both in vitro and in clinical infections: Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa. HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp. including Streptococcus pneumoniae. 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Not Applicable 3 I. Device Description: The HardyDisk AST Disks utilize 6-mm diameter white filter paper disks. The disks are prepared by impregnating absorbent paper with a known concentration of 30µg Ceftolozane and 10µg of Tazobactam. The disks are marked with the code C/T40 on both sides. The letters C/T are for the two agents and the number reflects the total content for both agents combined. HardyDisk AST Disks are supplied in plastic cartridges containing 50 disks each. They are also packaged as one cartridge per vial with desiccant or five cartridges per vial with desiccant. J. Substantial Equivalence Information: 1. Predicate device name(s): HardyDisk Tigecycline 15µg 2. Predicate 510(k) number(s): K062245 3. Comparison with predicate: Table 1: Comparison with Predicate Device Similarities Item Device: HardyDisk Ceftolozane/Tazobactam K170127 Predicate: HardyDisk Tigecycline K062245 Test Method Antimicrobial Susceptibility testing using paper discs impregnated with an antimicrobial agent Same Intended Use Antimicrobial Susceptibility Test Disks are used for in vitro susceptibility testing by standardized agar diffusion test procedures. Same Methodology Kirby-Bauer Disk Diffusion Susceptibility Test Protocol require the user to determine categorical interpretations (S/I/R) using the measured zone diameters. Same 4 Similarities Item Device: HardyDisk Ceftolozane/Tazobactam K170127 Predicate: HardyDisk Tigecycline K062245 Inoculum Prepared from pure isolated colonies in a suspension to match the turbidity equivalent of a 0.5 McFarland in Tryptic Soy Broth. Same Inoculum Method A sterile swab is dipped into the prepared inoculum, and applied to the surface of an appropriate agar plate in three directions. Disks impregnated with the antimicrobial agent are added to the surface of the plate. The plate is incubated agar side up in a 35 ± 2°C incubator for 18-24 hours. Same Interpretation The user will interpret the zone diameters according established interpretive criteria for the drug. Same Differences Item Device Predicate Product Name HardyDisk Ceftolozane/Tazobactam (30/10µg)- C/T40 HardyDisk Tigecycline Antibiotic Ceftolozane/Tazobactam Tigecycline Concentration 30µg Ceftolozane/10µg Tazobactam 15µg Tigecycline K. Standard/Guidance Document Referenced (if applicable): CLSI M02-A12, Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard- Twelfth Edition CLSI M100-S25, Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement L. Test Principle: The HardyDisk AST Disks are based on the agar diffusion (Kirby-Bauer) methodology. It utilizes dried filter paper disks impregnated with known concentrations of antimicrobial agents that are placed onto the test medium surface. Mueller Hinton agar is recommended for agar diffusion testing of non-fastidious organisms. Three to five similar colonies are transferred to 4-5 mL of a suitable broth medium. The broth is incubated at 35°C for 2-6 hours to develop a turbidity that exceeds or is equivalent to a 0.5 McFarland standard. 5 Alternatively, a direct broth or saline suspension of colonies may be prepared from an overnight culture. The final inoculum density should be equivalent to a 0.5 McFarland turbidity standard. The inoculum density may also be standardized photometrically. Within 15 minutes of inoculum preparation, the Mueller Hinton agar is streaked with an inoculated swab to obtain an even inoculation. Disks are aseptically placed onto the agar surface with a disk dispenser and the disks are pressed down with a sterile needle or forceps to make contact with the agar surface. Agar plates are incubated in an ambient air incubator at 35 ± 2°C for 16 -18 hours. Fastidious organisms are tested using appropriate media incubated in an atmosphere enriched with 5% CO2, as recommended in the CLSI M02 approved standard document. After incubation the agar medium is examined for zone of inhibition around the disks. The zones of inhibition are measured to the nearest millimeter and compared against recognized zone size ranges for the antimicrobial agent being tested. M. Performance Characteristics (if/when applicable): Descriptive characteristics were sufficient for this Ceftolozane/Tazobactam disk. The studies evaluated by FDA/CDER at the time of Ceftolozane/Tazobactam approval were used for this review. 1. Analytical performance: a. Precision/Reproducibility: Not applicable b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Not applicable d. Detection limit: Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: 6 Not applicable 2. Comparison studies: a. Method comparison with predicate device: Not applicable b. Matrix comparison: Not applicable 3. Clinical studies: a. Clinical Sensitivity: Not applicable b. Clinical specificity: Not applicable c. Other clinical supportive data (when a. and b. are not applicable): Not applicable 4. Clinical cut-off: Not applicable 5 Predicate device name:

idK170127_s0_e2000

K170127.txt

applicant

Hardy Diagnostics

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K170127 B. Purpose for Submission: Addition of Ceftolozane/Tazobactam Antimicrobial Susceptibility Test Disk for testing Enterobacteriaceae C. Measurand: Ceftolozane/Tazobactam, 30/10µg D. Type of Test: Antimicrobial Susceptibility Test Disks E. Applicant: Hardy Diagnostics F. Proprietary and Established Names: HardyDisk Ceftolozane/Tazobactam, (30/10µg) - C/T40 G. Regulatory Information: 1. Regulation section: 21 CFR 866.1620 Antimicrobial Susceptibility Test Disc 2. Classification: Class II 3. Product code: JTN – Susceptibility Test Disc, Antimicrobial 4. Panel: 83 - Microbiology 2 H. Intended Use: 1. Intended use(s): HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp. including Streptococcus pneumoniae. 2. Indication(s) for use: Use of HardyDisk Ceftolozane/Tazobactam, (30/10µg) - C/T40, for in vitro agar diffusion susceptibility testing is indicated when there is a need to determine the susceptibility of bacteria to Ceftolozane/Tazobactam. The concentration of Ceftolozane/Tazobactam, (30/10µg) - C/T40, has been shown to be active against susceptible isolates of the following microorganisms with in vitro use: Citrobacter koseri, Morganella morganii, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Serratia liquefacians, and Serratia marcescens. The concentration of Ceftolozane/Tazobactam, (30/10µg)-C/T40, has been shown to be active against susceptible isolates of the following microorganisms both in vitro and in clinical infections: Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa. HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp. including Streptococcus pneumoniae. 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Not Applicable 3 I. Device Description: The HardyDisk AST Disks utilize 6-mm diameter white filter paper disks. The disks are prepared by impregnating absorbent paper with a known concentration of 30µg Ceftolozane and 10µg of Tazobactam. The disks are marked with the code C/T40 on both sides. The letters C/T are for the two agents and the number reflects the total content for both agents combined. HardyDisk AST Disks are supplied in plastic cartridges containing 50 disks each. They are also packaged as one cartridge per vial with desiccant or five cartridges per vial with desiccant. J. Substantial Equivalence Information: 1. Predicate device name(s): HardyDisk Tigecycline 15µg 2. Predicate 510(k) number(s): K062245 3. Comparison with predicate: Table 1: Comparison with Predicate Device Similarities Item Device: HardyDisk Ceftolozane/Tazobactam K170127 Predicate: HardyDisk Tigecycline K062245 Test Method Antimicrobial Susceptibility testing using paper discs impregnated with an antimicrobial agent Same Intended Use Antimicrobial Susceptibility Test Disks are used for in vitro susceptibility testing by standardized agar diffusion test procedures. Same Methodology Kirby-Bauer Disk Diffusion Susceptibility Test Protocol require the user to determine categorical interpretations (S/I/R) using the measured zone diameters. Same 4 Similarities Item Device: HardyDisk Ceftolozane/Tazobactam K170127 Predicate: HardyDisk Tigecycline K062245 Inoculum Prepared from pure isolated colonies in a suspension to match the turbidity equivalent of a 0.5 McFarland in Tryptic Soy Broth. Same Inoculum Method A sterile swab is dipped into the prepared inoculum, and applied to the surface of an appropriate agar plate in three directions. Disks impregnated with the antimicrobial agent are added to the surface of the plate. The plate is incubated agar side up in a 35 ± 2°C incubator for 18-24 hours. Same Interpretation The user will interpret the zone diameters according established interpretive criteria for the drug. Same Differences Item Device Predicate Product Name HardyDisk Ceftolozane/Tazobactam (30/10µg)- C/T40 HardyDisk Tigecycline Antibiotic Ceftolozane/Tazobactam Tigecycline Concentration 30µg Ceftolozane/10µg Tazobactam 15µg Tigecycline K. Standard/Guidance Document Referenced (if applicable): CLSI M02-A12, Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard- Twelfth Edition CLSI M100-S25, Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement L. Test Principle: The HardyDisk AST Disks are based on the agar diffusion (Kirby-Bauer) methodology. It utilizes dried filter paper disks impregnated with known concentrations of antimicrobial agents that are placed onto the test medium surface. Mueller Hinton agar is recommended for agar diffusion testing of non-fastidious organisms. Three to five similar colonies are transferred to 4-5 mL of a suitable broth medium. The broth is incubated at 35°C for 2-6 hours to develop a turbidity that exceeds or is equivalent to a 0.5 McFarland standard. 5 Alternatively, a direct broth or saline suspension of colonies may be prepared from an overnight culture. The final inoculum density should be equivalent to a 0.5 McFarland turbidity standard. The inoculum density may also be standardized photometrically. Within 15 minutes of inoculum preparation, the Mueller Hinton agar is streaked with an inoculated swab to obtain an even inoculation. Disks are aseptically placed onto the agar surface with a disk dispenser and the disks are pressed down with a sterile needle or forceps to make contact with the agar surface. Agar plates are incubated in an ambient air incubator at 35 ± 2°C for 16 -18 hours. Fastidious organisms are tested using appropriate media incubated in an atmosphere enriched with 5% CO2, as recommended in the CLSI M02 approved standard document. After incubation the agar medium is examined for zone of inhibition around the disks. The zones of inhibition are measured to the nearest millimeter and compared against recognized zone size ranges for the antimicrobial agent being tested. M. Performance Characteristics (if/when applicable): Descriptive characteristics were sufficient for this Ceftolozane/Tazobactam disk. The studies evaluated by FDA/CDER at the time of Ceftolozane/Tazobactam approval were used for this review. 1. Analytical performance: a. Precision/Reproducibility: Not applicable b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Not applicable d. Detection limit: Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: 6 Not applicable 2. Comparison studies: a. Method comparison with predicate device: Not applicable b. Matrix comparison: Not applicable 3. Clinical studies: a. Clinical Sensitivity: Not applicable b. Clinical specificity: Not applicable c. Other clinical supportive data (when a. and b. are not applicable): Not applicable 4. Clinical cut-off: Not applicable 5 Applicant:

idK170127_s0_e2000

K170127.txt

proprietary and established names

HardyDisk Ceftolozane/Tazobactam, (30/10µg) - C/T40

IAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K170127 B. Purpose for Submission: Addition of Ceftolozane/Tazobactam Antimicrobial Susceptibility Test Disk for testing Enterobacteriaceae C. Measurand: Ceftolozane/Tazobactam, 30/10µg D. Type of Test: Antimicrobial Susceptibility Test Disks E. Applicant: Hardy Diagnostics F. Proprietary and Established Names: HardyDisk Ceftolozane/Tazobactam, (30/10µg) - C/T40 G. Regulatory Information: 1. Regulation section: 21 CFR 866.1620 Antimicrobial Susceptibility Test Disc 2. Classification: Class II 3. Product code: JTN – Susceptibility Test Disc, Antimicrobial 4. Panel: 83 - Microbiology 2 H. Intended Use: 1. Intended use(s): HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp. including Streptococcus pneumoniae. 2. Indication(s) for use: Use of HardyDisk Ceftolozane/Tazobactam, (30/10µg) - C/T40, for in vitro agar diffusion susceptibility testing is indicated when there is a need to determine the susceptibility of bacteria to Ceftolozane/Tazobactam. The concentration of Ceftolozane/Tazobactam, (30/10µg) - C/T40, has been shown to be active against susceptible isolates of the following microorganisms with in vitro use: Citrobacter koseri, Morganella morganii, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Serratia liquefacians, and Serratia marcescens. The concentration of Ceftolozane/Tazobactam, (30/10µg)-C/T40, has been shown to be active against susceptible isolates of the following microorganisms both in vitro and in clinical infections: Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa. HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp. including Streptococcus pneumoniae. 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Not Applicable 3 I. Device Description: The HardyDisk AST Disks utilize 6-mm diameter white filter paper disks. The disks are prepared by impregnating absorbent paper with a known concentration of 30µg Ceftolozane and 10µg of Tazobactam. The disks are marked with the code C/T40 on both sides. The letters C/T are for the two agents and the number reflects the total content for both agents combined. HardyDisk AST Disks are supplied in plastic cartridges containing 50 disks each. They are also packaged as one cartridge per vial with desiccant or five cartridges per vial with desiccant. J. Substantial Equivalence Information: 1. Predicate device name(s): HardyDisk Tigecycline 15µg 2. Predicate 510(k) number(s): K062245 3. Comparison with predicate: Table 1: Comparison with Predicate Device Similarities Item Device: HardyDisk Ceftolozane/Tazobactam K170127 Predicate: HardyDisk Tigecycline K062245 Test Method Antimicrobial Susceptibility testing using paper discs impregnated with an antimicrobial agent Same Intended Use Antimicrobial Susceptibility Test Disks are used for in vitro susceptibility testing by standardized agar diffusion test procedures. Same Methodology Kirby-Bauer Disk Diffusion Susceptibility Test Protocol require the user to determine categorical interpretations (S/I/R) using the measured zone diameters. Same 4 Similarities Item Device: HardyDisk Ceftolozane/Tazobactam K170127 Predicate: HardyDisk Tigecycline K062245 Inoculum Prepared from pure isolated colonies in a suspension to match the turbidity equivalent of a 0.5 McFarland in Tryptic Soy Broth. Same Inoculum Method A sterile swab is dipped into the prepared inoculum, and applied to the surface of an appropriate agar plate in three directions. Disks impregnated with the antimicrobial agent are added to the surface of the plate. The plate is incubated agar side up in a 35 ± 2°C incubator for 18-24 hours. Same Interpretation The user will interpret the zone diameters according established interpretive criteria for the drug. Same Differences Item Device Predicate Product Name HardyDisk Ceftolozane/Tazobactam (30/10µg)- C/T40 HardyDisk Tigecycline Antibiotic Ceftolozane/Tazobactam Tigecycline Concentration 30µg Ceftolozane/10µg Tazobactam 15µg Tigecycline K. Standard/Guidance Document Referenced (if applicable): CLSI M02-A12, Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard- Twelfth Edition CLSI M100-S25, Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement L. Test Principle: The HardyDisk AST Disks are based on the agar diffusion (Kirby-Bauer) methodology. It utilizes dried filter paper disks impregnated with known concentrations of antimicrobial agents that are placed onto the test medium surface. Mueller Hinton agar is recommended for agar diffusion testing of non-fastidious organisms. Three to five similar colonies are transferred to 4-5 mL of a suitable broth medium. The broth is incubated at 35°C for 2-6 hours to develop a turbidity that exceeds or is equivalent to a 0.5 McFarland standard. 5 Alternatively, a direct broth or saline suspension of colonies may be prepared from an overnight culture. The final inoculum density should be equivalent to a 0.5 McFarland turbidity standard. The inoculum density may also be standardized photometrically. Within 15 minutes of inoculum preparation, the Mueller Hinton agar is streaked with an inoculated swab to obtain an even inoculation. Disks are aseptically placed onto the agar surface with a disk dispenser and the disks are pressed down with a sterile needle or forceps to make contact with the agar surface. Agar plates are incubated in an ambient air incubator at 35 ± 2°C for 16 -18 hours. Fastidious organisms are tested using appropriate media incubated in an atmosphere enriched with 5% CO2, as recommended in the CLSI M02 approved standard document. After incubation the agar medium is examined for zone of inhibition around the disks. The zones of inhibition are measured to the nearest millimeter and compared against recognized zone size ranges for the antimicrobial agent being tested. M. Performance Characteristics (if/when applicable): Descriptive characteristics were sufficient for this Ceftolozane/Tazobactam disk. The studies evaluated by FDA/CDER at the time of Ceftolozane/Tazobactam approval were used for this review. 1. Analytical performance: a. Precision/Reproducibility: Not applicable b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Not applicable d. Detection limit: Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: 6 Not applicable 2. Comparison studies: a. Method comparison with predicate device: Not applicable b. Matrix comparison: Not applicable 3. Clinical studies: a. Clinical Sensitivity: Not applicable b. Clinical specificity: Not applicable c. Other clinical supportive data (when a. and b. are not applicable): Not applicable 4. Clinical cut-off: Not applicable 5 Proprietary and established names:

idK170127_s0_e2000

K170127.txt

regulation section

21 CFR 866.1620 Antimicrobial Susceptibility Test Disc

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K170127 B. Purpose for Submission: Addition of Ceftolozane/Tazobactam Antimicrobial Susceptibility Test Disk for testing Enterobacteriaceae C. Measurand: Ceftolozane/Tazobactam, 30/10µg D. Type of Test: Antimicrobial Susceptibility Test Disks E. Applicant: Hardy Diagnostics F. Proprietary and Established Names: HardyDisk Ceftolozane/Tazobactam, (30/10µg) - C/T40 G. Regulatory Information: 1. Regulation section: 21 CFR 866.1620 Antimicrobial Susceptibility Test Disc 2. Classification: Class II 3. Product code: JTN – Susceptibility Test Disc, Antimicrobial 4. Panel: 83 - Microbiology 2 H. Intended Use: 1. Intended use(s): HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp. including Streptococcus pneumoniae. 2. Indication(s) for use: Use of HardyDisk Ceftolozane/Tazobactam, (30/10µg) - C/T40, for in vitro agar diffusion susceptibility testing is indicated when there is a need to determine the susceptibility of bacteria to Ceftolozane/Tazobactam. The concentration of Ceftolozane/Tazobactam, (30/10µg) - C/T40, has been shown to be active against susceptible isolates of the following microorganisms with in vitro use: Citrobacter koseri, Morganella morganii, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Serratia liquefacians, and Serratia marcescens. The concentration of Ceftolozane/Tazobactam, (30/10µg)-C/T40, has been shown to be active against susceptible isolates of the following microorganisms both in vitro and in clinical infections: Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa. HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp. including Streptococcus pneumoniae. 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Not Applicable 3 I. Device Description: The HardyDisk AST Disks utilize 6-mm diameter white filter paper disks. The disks are prepared by impregnating absorbent paper with a known concentration of 30µg Ceftolozane and 10µg of Tazobactam. The disks are marked with the code C/T40 on both sides. The letters C/T are for the two agents and the number reflects the total content for both agents combined. HardyDisk AST Disks are supplied in plastic cartridges containing 50 disks each. They are also packaged as one cartridge per vial with desiccant or five cartridges per vial with desiccant. J. Substantial Equivalence Information: 1. Predicate device name(s): HardyDisk Tigecycline 15µg 2. Predicate 510(k) number(s): K062245 3. Comparison with predicate: Table 1: Comparison with Predicate Device Similarities Item Device: HardyDisk Ceftolozane/Tazobactam K170127 Predicate: HardyDisk Tigecycline K062245 Test Method Antimicrobial Susceptibility testing using paper discs impregnated with an antimicrobial agent Same Intended Use Antimicrobial Susceptibility Test Disks are used for in vitro susceptibility testing by standardized agar diffusion test procedures. Same Methodology Kirby-Bauer Disk Diffusion Susceptibility Test Protocol require the user to determine categorical interpretations (S/I/R) using the measured zone diameters. Same 4 Similarities Item Device: HardyDisk Ceftolozane/Tazobactam K170127 Predicate: HardyDisk Tigecycline K062245 Inoculum Prepared from pure isolated colonies in a suspension to match the turbidity equivalent of a 0.5 McFarland in Tryptic Soy Broth. Same Inoculum Method A sterile swab is dipped into the prepared inoculum, and applied to the surface of an appropriate agar plate in three directions. Disks impregnated with the antimicrobial agent are added to the surface of the plate. The plate is incubated agar side up in a 35 ± 2°C incubator for 18-24 hours. Same Interpretation The user will interpret the zone diameters according established interpretive criteria for the drug. Same Differences Item Device Predicate Product Name HardyDisk Ceftolozane/Tazobactam (30/10µg)- C/T40 HardyDisk Tigecycline Antibiotic Ceftolozane/Tazobactam Tigecycline Concentration 30µg Ceftolozane/10µg Tazobactam 15µg Tigecycline K. Standard/Guidance Document Referenced (if applicable): CLSI M02-A12, Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard- Twelfth Edition CLSI M100-S25, Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement L. Test Principle: The HardyDisk AST Disks are based on the agar diffusion (Kirby-Bauer) methodology. It utilizes dried filter paper disks impregnated with known concentrations of antimicrobial agents that are placed onto the test medium surface. Mueller Hinton agar is recommended for agar diffusion testing of non-fastidious organisms. Three to five similar colonies are transferred to 4-5 mL of a suitable broth medium. The broth is incubated at 35°C for 2-6 hours to develop a turbidity that exceeds or is equivalent to a 0.5 McFarland standard. 5 Alternatively, a direct broth or saline suspension of colonies may be prepared from an overnight culture. The final inoculum density should be equivalent to a 0.5 McFarland turbidity standard. The inoculum density may also be standardized photometrically. Within 15 minutes of inoculum preparation, the Mueller Hinton agar is streaked with an inoculated swab to obtain an even inoculation. Disks are aseptically placed onto the agar surface with a disk dispenser and the disks are pressed down with a sterile needle or forceps to make contact with the agar surface. Agar plates are incubated in an ambient air incubator at 35 ± 2°C for 16 -18 hours. Fastidious organisms are tested using appropriate media incubated in an atmosphere enriched with 5% CO2, as recommended in the CLSI M02 approved standard document. After incubation the agar medium is examined for zone of inhibition around the disks. The zones of inhibition are measured to the nearest millimeter and compared against recognized zone size ranges for the antimicrobial agent being tested. M. Performance Characteristics (if/when applicable): Descriptive characteristics were sufficient for this Ceftolozane/Tazobactam disk. The studies evaluated by FDA/CDER at the time of Ceftolozane/Tazobactam approval were used for this review. 1. Analytical performance: a. Precision/Reproducibility: Not applicable b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Not applicable d. Detection limit: Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: 6 Not applicable 2. Comparison studies: a. Method comparison with predicate device: Not applicable b. Matrix comparison: Not applicable 3. Clinical studies: a. Clinical Sensitivity: Not applicable b. Clinical specificity: Not applicable c. Other clinical supportive data (when a. and b. are not applicable): Not applicable 4. Clinical cut-off: Not applicable 5 Regulation section:

idK170127_s2000_e4000

K170127.txt

proposed labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

Reference range: Table 2: FDA Interpretative Criteria for Ceftolozane/Tazobactam Indications For Use Organism(s) Interpretative Criteria Zone Diameter (mm) R I S Enterobacteriaceae ≤17 18-20 ≥21 N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK170127_s2000_e4000

K170127.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

values/Reference range: Table 2: FDA Interpretative Criteria for Ceftolozane/Tazobactam Indications For Use Organism(s) Interpretative Criteria Zone Diameter (mm) R I S Enterobacteriaceae ≤17 18-20 ≥21 N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK181288_s0_e2000

K181288.txt

purpose for submission

Clearance of a new device

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM A. 510(k) Number: K181288 B. Purpose for Submission: Clearance of a new device C. Measurand: White blood cell count (WBC) and percent neutrophil count (NEUT%) D. Type of Test: Enumeration of WBCs and NEUT% E. Applicant: Athelas Inc. F. Proprietary and Established Names: Athelas One G. Regulatory Information: 1. Regulation section: 21 CFR 864.5220, Automated differential cell counter 2. Classification: Class II 3. Product code: GKZ, Counter, differential cell 4. Panel: Hematology (81) 2 H. Intended Use: 1. Intended use(s): Athelas One is indicated for use for quantitative determination of white blood cells (WBC) and Neutrophil percentages (NEUT%) in capillary or K2EDTA venous whole blood. The Athelas One system is for In Vitro Diagnostic use only. The Athelas One is only to be used with Athelas One Test Strips. The Athelas One is indicated for use in clinical laboratories and for point of care settings. The Athelas One is only indicated for use in adult populations (aged 21 and older). 2. Indication(s) for use: Same as intended use 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Athelas One analyzer I. Device Description: The Athelas One is an automated cell counter system which consists of: the Athelas One analyzer and the Athelas One Test Strips. The Athelas One system is intended to analyze capillary whole blood and anticoagulated venous whole blood collected in K2EDTA collection tubes. The Athelas One Tests Strips collects a blood sample (capillary or collected in K2EDTA anticoagulant) to generate a layer of cells for counting and image analysis. The Athelas One Test Strips are comprised of an upper optical panel, lower optical panel and a stain coated region containing methylene blue and cresyl violet stains. The test strip channel is optically clear for the camera module to take pictures of the cells in the blood sample. A smartphone/tablet with the Athelas controlling mobile application is required to initiate a test with the Athelas One System. The smartphone/tablet models compatible to initiate testing are those devices supporting iOS 9, 10, and 11, or Android 7, 8, and 9. In addition, the smartphone/tablet with the Athelas controlling mobile application is required to view test results. J. Substantial Equivalence Information: 1. Predicate device name(s): Sysmex XE-5000 Automated Hematology Analzyer 3 2. Predicate 510(k) number(s): K071967 3. Comparison with predicate: Similarities Item Candidate Athelas One K181288 Predicate Sysmex XE-5000 K071967 Intended Use Athelas One is indicated for use for quantitative determination of white blood cells (WBC) and Neutrophil percentages (NEUT%) in capillary or K2EDTA venous whole blood. The Athelas One system is for In Vitro Diagnostic use only. The Athelas One is only to be used with Athelas One Test Strips. The Athelas One is indicated for use in clinical laboratories and for point of care settings. The Athelas One is only indicated for use in adult populations (aged 21 and older). The Sysmex XE-5000 is an automated hematology analyzer for in-vitro diagnostic use in screening patient populations found in clinical laboratories. The XE-5000 classifies and enumerates the same parameters as the XE-2100 using whole blood as described below, cord blood for HPC and has a body fluid mode for body fluids. The Body Fluid mode analyzes WBC-BF, RBC-BF, MN%/#, PMN%/# and TC-BF in body fluids (cerebrospinal fluids (CSF), serous fluids, and synovial fluids with EDTA as needed). WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMP %/#, MONO %/#, EO%/#, BASO %/#, NRBC, RDW-SD, RDW- CV, MPV, RET %/#, IRF, IG%/#, HPC#, RET-He, IPF, WBC-BF, RBC-BF, MN%/#, PMN%/#, TC-BF#. Intended Use Settings Point of care, clinical laboratory Clinical laboratory Specimen Type Capillary whole blood and K2EDTA venous whole blood Same in addition to body fluids (CSF, serous fluids, and synovial fluids) Parameters WBC, NEUT% WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMP %/#, MONO %/#, EO%/#, BASO %/#, NRBC, RDW-SD, RDW-CV, MPV, 4 Similarities Item Candidate Athelas One K181288 Predicate Sysmex XE-5000 K071967 RET %/#, IRF, IG%/#, HPC#, RET-He, IPF, WBC-BF, RBC- BF, MN%/#, PMN%/#, TC-BF#. Differences Item Candidate Athelas One K181288 Predicate Systex XE-5000 K071967 Test Principle A microfluidic test strip channel creates a stained monolayer of WBCs. Multiple images are taken of the monolayer and the cells are counted and classified by computer vision based image analysis. Performs analyses using the following methods: RF/DC detection method, Sheath Flow DC dectection method, and flow cytometry methods using a semiconductor laser. Controls/Calibrators ATH-CHECK (Three level control) Factory Calibrated e-Check (XE) (Three level control) XE Calibrator (X Cal) Sample Processing Internet connected device for processing results on Cloud server Processing of results occurs locally in device Sample Volume 3.5 µL 130–200 µL depending on operation mode Measurement Range WBC: 1.0–20 x103/µL WBC: 0.0–440 x103/µL Calibration Factory calibrated, no further calibration Automtic and manual calibration using e-Check (XE) control material K. Standard/Guidance Document Referenced (if applicable): CLSI H26-A2: Validation, Verification and Quality Assurance of Automated Hematology Analyzers; Approved Guideline – Second Edition CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline – First Edition CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measreument Procedures – Approved Guideline – Second Edition 5 CLSI EP14-A2: Evluation of Matrix Effects; Approved Guideline – Second Edition CLSI EP25-A: Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline – First Edition CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition CLSI EP05-A3: Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition CLSI EP28-A3c: Defining, Establishing, and Verifying Reference Intervals in Clinical Laboratory; Approved Guideline – Third Edition L. Test Principle: The Athelas One system consists of the Athelas One analyzer and Athelas One test strips. The Athelas One test strips serve as both a sample container and a reaction chamber. A capillary whole blood sample or whole blood specimen anticoagulated in K2EDTA of 3.5 μL is pipetted or directly transferred via fingerstick to the Athelas One test strip which automatically spreads the sample into a monolayer. The pre-coated stain within the strip chamber interacts with the monolayer of blood and stains the WBCs. The Athelas One test strip is inserted into the Athelas One analyzer which utilizes a proximity sensor to lock in place. A servo stabilizes and auto-focuses the blood sample, and then a stage actuator scans the strip across various fields while the optical module takes multiple images of the cells across the monolayer. The images of the blood sample are transmitted to the server where they are analyzed using a locked down image processing algorithm. The algorithm recognizes the nucleation and WBCs to generate a WBC count and NEUT% result based on the concentrations and types of cells present. The WBC count and NEUT% is then returned to the user via the controlling mobile application on an authorized lab or hospital device. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Repeatability: The repeatability study was conducted in accordance with CLSI Purpose for submission:

idK181288_s0_e2000

K181288.txt

measurand

White blood cell count (WBC) and percent neutrophil count (NEUT%)

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM A. 510(k) Number: K181288 B. Purpose for Submission: Clearance of a new device C. Measurand: White blood cell count (WBC) and percent neutrophil count (NEUT%) D. Type of Test: Enumeration of WBCs and NEUT% E. Applicant: Athelas Inc. F. Proprietary and Established Names: Athelas One G. Regulatory Information: 1. Regulation section: 21 CFR 864.5220, Automated differential cell counter 2. Classification: Class II 3. Product code: GKZ, Counter, differential cell 4. Panel: Hematology (81) 2 H. Intended Use: 1. Intended use(s): Athelas One is indicated for use for quantitative determination of white blood cells (WBC) and Neutrophil percentages (NEUT%) in capillary or K2EDTA venous whole blood. The Athelas One system is for In Vitro Diagnostic use only. The Athelas One is only to be used with Athelas One Test Strips. The Athelas One is indicated for use in clinical laboratories and for point of care settings. The Athelas One is only indicated for use in adult populations (aged 21 and older). 2. Indication(s) for use: Same as intended use 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Athelas One analyzer I. Device Description: The Athelas One is an automated cell counter system which consists of: the Athelas One analyzer and the Athelas One Test Strips. The Athelas One system is intended to analyze capillary whole blood and anticoagulated venous whole blood collected in K2EDTA collection tubes. The Athelas One Tests Strips collects a blood sample (capillary or collected in K2EDTA anticoagulant) to generate a layer of cells for counting and image analysis. The Athelas One Test Strips are comprised of an upper optical panel, lower optical panel and a stain coated region containing methylene blue and cresyl violet stains. The test strip channel is optically clear for the camera module to take pictures of the cells in the blood sample. A smartphone/tablet with the Athelas controlling mobile application is required to initiate a test with the Athelas One System. The smartphone/tablet models compatible to initiate testing are those devices supporting iOS 9, 10, and 11, or Android 7, 8, and 9. In addition, the smartphone/tablet with the Athelas controlling mobile application is required to view test results. J. Substantial Equivalence Information: 1. Predicate device name(s): Sysmex XE-5000 Automated Hematology Analzyer 3 2. Predicate 510(k) number(s): K071967 3. Comparison with predicate: Similarities Item Candidate Athelas One K181288 Predicate Sysmex XE-5000 K071967 Intended Use Athelas One is indicated for use for quantitative determination of white blood cells (WBC) and Neutrophil percentages (NEUT%) in capillary or K2EDTA venous whole blood. The Athelas One system is for In Vitro Diagnostic use only. The Athelas One is only to be used with Athelas One Test Strips. The Athelas One is indicated for use in clinical laboratories and for point of care settings. The Athelas One is only indicated for use in adult populations (aged 21 and older). The Sysmex XE-5000 is an automated hematology analyzer for in-vitro diagnostic use in screening patient populations found in clinical laboratories. The XE-5000 classifies and enumerates the same parameters as the XE-2100 using whole blood as described below, cord blood for HPC and has a body fluid mode for body fluids. The Body Fluid mode analyzes WBC-BF, RBC-BF, MN%/#, PMN%/# and TC-BF in body fluids (cerebrospinal fluids (CSF), serous fluids, and synovial fluids with EDTA as needed). WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMP %/#, MONO %/#, EO%/#, BASO %/#, NRBC, RDW-SD, RDW- CV, MPV, RET %/#, IRF, IG%/#, HPC#, RET-He, IPF, WBC-BF, RBC-BF, MN%/#, PMN%/#, TC-BF#. Intended Use Settings Point of care, clinical laboratory Clinical laboratory Specimen Type Capillary whole blood and K2EDTA venous whole blood Same in addition to body fluids (CSF, serous fluids, and synovial fluids) Parameters WBC, NEUT% WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMP %/#, MONO %/#, EO%/#, BASO %/#, NRBC, RDW-SD, RDW-CV, MPV, 4 Similarities Item Candidate Athelas One K181288 Predicate Sysmex XE-5000 K071967 RET %/#, IRF, IG%/#, HPC#, RET-He, IPF, WBC-BF, RBC- BF, MN%/#, PMN%/#, TC-BF#. Differences Item Candidate Athelas One K181288 Predicate Systex XE-5000 K071967 Test Principle A microfluidic test strip channel creates a stained monolayer of WBCs. Multiple images are taken of the monolayer and the cells are counted and classified by computer vision based image analysis. Performs analyses using the following methods: RF/DC detection method, Sheath Flow DC dectection method, and flow cytometry methods using a semiconductor laser. Controls/Calibrators ATH-CHECK (Three level control) Factory Calibrated e-Check (XE) (Three level control) XE Calibrator (X Cal) Sample Processing Internet connected device for processing results on Cloud server Processing of results occurs locally in device Sample Volume 3.5 µL 130–200 µL depending on operation mode Measurement Range WBC: 1.0–20 x103/µL WBC: 0.0–440 x103/µL Calibration Factory calibrated, no further calibration Automtic and manual calibration using e-Check (XE) control material K. Standard/Guidance Document Referenced (if applicable): CLSI H26-A2: Validation, Verification and Quality Assurance of Automated Hematology Analyzers; Approved Guideline – Second Edition CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline – First Edition CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measreument Procedures – Approved Guideline – Second Edition 5 CLSI EP14-A2: Evluation of Matrix Effects; Approved Guideline – Second Edition CLSI EP25-A: Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline – First Edition CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition CLSI EP05-A3: Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition CLSI EP28-A3c: Defining, Establishing, and Verifying Reference Intervals in Clinical Laboratory; Approved Guideline – Third Edition L. Test Principle: The Athelas One system consists of the Athelas One analyzer and Athelas One test strips. The Athelas One test strips serve as both a sample container and a reaction chamber. A capillary whole blood sample or whole blood specimen anticoagulated in K2EDTA of 3.5 μL is pipetted or directly transferred via fingerstick to the Athelas One test strip which automatically spreads the sample into a monolayer. The pre-coated stain within the strip chamber interacts with the monolayer of blood and stains the WBCs. The Athelas One test strip is inserted into the Athelas One analyzer which utilizes a proximity sensor to lock in place. A servo stabilizes and auto-focuses the blood sample, and then a stage actuator scans the strip across various fields while the optical module takes multiple images of the cells across the monolayer. The images of the blood sample are transmitted to the server where they are analyzed using a locked down image processing algorithm. The algorithm recognizes the nucleation and WBCs to generate a WBC count and NEUT% result based on the concentrations and types of cells present. The WBC count and NEUT% is then returned to the user via the controlling mobile application on an authorized lab or hospital device. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Repeatability: The repeatability study was conducted in accordance with CLSI Measurand:

idK181288_s0_e2000

K181288.txt

classification

Class II

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM A. 510(k) Number: K181288 B. Purpose for Submission: Clearance of a new device C. Measurand: White blood cell count (WBC) and percent neutrophil count (NEUT%) D. Type of Test: Enumeration of WBCs and NEUT% E. Applicant: Athelas Inc. F. Proprietary and Established Names: Athelas One G. Regulatory Information: 1. Regulation section: 21 CFR 864.5220, Automated differential cell counter 2. Classification: Class II 3. Product code: GKZ, Counter, differential cell 4. Panel: Hematology (81) 2 H. Intended Use: 1. Intended use(s): Athelas One is indicated for use for quantitative determination of white blood cells (WBC) and Neutrophil percentages (NEUT%) in capillary or K2EDTA venous whole blood. The Athelas One system is for In Vitro Diagnostic use only. The Athelas One is only to be used with Athelas One Test Strips. The Athelas One is indicated for use in clinical laboratories and for point of care settings. The Athelas One is only indicated for use in adult populations (aged 21 and older). 2. Indication(s) for use: Same as intended use 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Athelas One analyzer I. Device Description: The Athelas One is an automated cell counter system which consists of: the Athelas One analyzer and the Athelas One Test Strips. The Athelas One system is intended to analyze capillary whole blood and anticoagulated venous whole blood collected in K2EDTA collection tubes. The Athelas One Tests Strips collects a blood sample (capillary or collected in K2EDTA anticoagulant) to generate a layer of cells for counting and image analysis. The Athelas One Test Strips are comprised of an upper optical panel, lower optical panel and a stain coated region containing methylene blue and cresyl violet stains. The test strip channel is optically clear for the camera module to take pictures of the cells in the blood sample. A smartphone/tablet with the Athelas controlling mobile application is required to initiate a test with the Athelas One System. The smartphone/tablet models compatible to initiate testing are those devices supporting iOS 9, 10, and 11, or Android 7, 8, and 9. In addition, the smartphone/tablet with the Athelas controlling mobile application is required to view test results. J. Substantial Equivalence Information: 1. Predicate device name(s): Sysmex XE-5000 Automated Hematology Analzyer 3 2. Predicate 510(k) number(s): K071967 3. Comparison with predicate: Similarities Item Candidate Athelas One K181288 Predicate Sysmex XE-5000 K071967 Intended Use Athelas One is indicated for use for quantitative determination of white blood cells (WBC) and Neutrophil percentages (NEUT%) in capillary or K2EDTA venous whole blood. The Athelas One system is for In Vitro Diagnostic use only. The Athelas One is only to be used with Athelas One Test Strips. The Athelas One is indicated for use in clinical laboratories and for point of care settings. The Athelas One is only indicated for use in adult populations (aged 21 and older). The Sysmex XE-5000 is an automated hematology analyzer for in-vitro diagnostic use in screening patient populations found in clinical laboratories. The XE-5000 classifies and enumerates the same parameters as the XE-2100 using whole blood as described below, cord blood for HPC and has a body fluid mode for body fluids. The Body Fluid mode analyzes WBC-BF, RBC-BF, MN%/#, PMN%/# and TC-BF in body fluids (cerebrospinal fluids (CSF), serous fluids, and synovial fluids with EDTA as needed). WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMP %/#, MONO %/#, EO%/#, BASO %/#, NRBC, RDW-SD, RDW- CV, MPV, RET %/#, IRF, IG%/#, HPC#, RET-He, IPF, WBC-BF, RBC-BF, MN%/#, PMN%/#, TC-BF#. Intended Use Settings Point of care, clinical laboratory Clinical laboratory Specimen Type Capillary whole blood and K2EDTA venous whole blood Same in addition to body fluids (CSF, serous fluids, and synovial fluids) Parameters WBC, NEUT% WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMP %/#, MONO %/#, EO%/#, BASO %/#, NRBC, RDW-SD, RDW-CV, MPV, 4 Similarities Item Candidate Athelas One K181288 Predicate Sysmex XE-5000 K071967 RET %/#, IRF, IG%/#, HPC#, RET-He, IPF, WBC-BF, RBC- BF, MN%/#, PMN%/#, TC-BF#. Differences Item Candidate Athelas One K181288 Predicate Systex XE-5000 K071967 Test Principle A microfluidic test strip channel creates a stained monolayer of WBCs. Multiple images are taken of the monolayer and the cells are counted and classified by computer vision based image analysis. Performs analyses using the following methods: RF/DC detection method, Sheath Flow DC dectection method, and flow cytometry methods using a semiconductor laser. Controls/Calibrators ATH-CHECK (Three level control) Factory Calibrated e-Check (XE) (Three level control) XE Calibrator (X Cal) Sample Processing Internet connected device for processing results on Cloud server Processing of results occurs locally in device Sample Volume 3.5 µL 130–200 µL depending on operation mode Measurement Range WBC: 1.0–20 x103/µL WBC: 0.0–440 x103/µL Calibration Factory calibrated, no further calibration Automtic and manual calibration using e-Check (XE) control material K. Standard/Guidance Document Referenced (if applicable): CLSI H26-A2: Validation, Verification and Quality Assurance of Automated Hematology Analyzers; Approved Guideline – Second Edition CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline – First Edition CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measreument Procedures – Approved Guideline – Second Edition 5 CLSI EP14-A2: Evluation of Matrix Effects; Approved Guideline – Second Edition CLSI EP25-A: Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline – First Edition CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition CLSI EP05-A3: Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition CLSI EP28-A3c: Defining, Establishing, and Verifying Reference Intervals in Clinical Laboratory; Approved Guideline – Third Edition L. Test Principle: The Athelas One system consists of the Athelas One analyzer and Athelas One test strips. The Athelas One test strips serve as both a sample container and a reaction chamber. A capillary whole blood sample or whole blood specimen anticoagulated in K2EDTA of 3.5 μL is pipetted or directly transferred via fingerstick to the Athelas One test strip which automatically spreads the sample into a monolayer. The pre-coated stain within the strip chamber interacts with the monolayer of blood and stains the WBCs. The Athelas One test strip is inserted into the Athelas One analyzer which utilizes a proximity sensor to lock in place. A servo stabilizes and auto-focuses the blood sample, and then a stage actuator scans the strip across various fields while the optical module takes multiple images of the cells across the monolayer. The images of the blood sample are transmitted to the server where they are analyzed using a locked down image processing algorithm. The algorithm recognizes the nucleation and WBCs to generate a WBC count and NEUT% result based on the concentrations and types of cells present. The WBC count and NEUT% is then returned to the user via the controlling mobile application on an authorized lab or hospital device. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Repeatability: The repeatability study was conducted in accordance with CLSI Classification:

idK181288_s0_e2000

K181288.txt

product code

GKZ, Counter, differential cell

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM A. 510(k) Number: K181288 B. Purpose for Submission: Clearance of a new device C. Measurand: White blood cell count (WBC) and percent neutrophil count (NEUT%) D. Type of Test: Enumeration of WBCs and NEUT% E. Applicant: Athelas Inc. F. Proprietary and Established Names: Athelas One G. Regulatory Information: 1. Regulation section: 21 CFR 864.5220, Automated differential cell counter 2. Classification: Class II 3. Product code: GKZ, Counter, differential cell 4. Panel: Hematology (81) 2 H. Intended Use: 1. Intended use(s): Athelas One is indicated for use for quantitative determination of white blood cells (WBC) and Neutrophil percentages (NEUT%) in capillary or K2EDTA venous whole blood. The Athelas One system is for In Vitro Diagnostic use only. The Athelas One is only to be used with Athelas One Test Strips. The Athelas One is indicated for use in clinical laboratories and for point of care settings. The Athelas One is only indicated for use in adult populations (aged 21 and older). 2. Indication(s) for use: Same as intended use 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Athelas One analyzer I. Device Description: The Athelas One is an automated cell counter system which consists of: the Athelas One analyzer and the Athelas One Test Strips. The Athelas One system is intended to analyze capillary whole blood and anticoagulated venous whole blood collected in K2EDTA collection tubes. The Athelas One Tests Strips collects a blood sample (capillary or collected in K2EDTA anticoagulant) to generate a layer of cells for counting and image analysis. The Athelas One Test Strips are comprised of an upper optical panel, lower optical panel and a stain coated region containing methylene blue and cresyl violet stains. The test strip channel is optically clear for the camera module to take pictures of the cells in the blood sample. A smartphone/tablet with the Athelas controlling mobile application is required to initiate a test with the Athelas One System. The smartphone/tablet models compatible to initiate testing are those devices supporting iOS 9, 10, and 11, or Android 7, 8, and 9. In addition, the smartphone/tablet with the Athelas controlling mobile application is required to view test results. J. Substantial Equivalence Information: 1. Predicate device name(s): Sysmex XE-5000 Automated Hematology Analzyer 3 2. Predicate 510(k) number(s): K071967 3. Comparison with predicate: Similarities Item Candidate Athelas One K181288 Predicate Sysmex XE-5000 K071967 Intended Use Athelas One is indicated for use for quantitative determination of white blood cells (WBC) and Neutrophil percentages (NEUT%) in capillary or K2EDTA venous whole blood. The Athelas One system is for In Vitro Diagnostic use only. The Athelas One is only to be used with Athelas One Test Strips. The Athelas One is indicated for use in clinical laboratories and for point of care settings. The Athelas One is only indicated for use in adult populations (aged 21 and older). The Sysmex XE-5000 is an automated hematology analyzer for in-vitro diagnostic use in screening patient populations found in clinical laboratories. The XE-5000 classifies and enumerates the same parameters as the XE-2100 using whole blood as described below, cord blood for HPC and has a body fluid mode for body fluids. The Body Fluid mode analyzes WBC-BF, RBC-BF, MN%/#, PMN%/# and TC-BF in body fluids (cerebrospinal fluids (CSF), serous fluids, and synovial fluids with EDTA as needed). WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMP %/#, MONO %/#, EO%/#, BASO %/#, NRBC, RDW-SD, RDW- CV, MPV, RET %/#, IRF, IG%/#, HPC#, RET-He, IPF, WBC-BF, RBC-BF, MN%/#, PMN%/#, TC-BF#. Intended Use Settings Point of care, clinical laboratory Clinical laboratory Specimen Type Capillary whole blood and K2EDTA venous whole blood Same in addition to body fluids (CSF, serous fluids, and synovial fluids) Parameters WBC, NEUT% WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMP %/#, MONO %/#, EO%/#, BASO %/#, NRBC, RDW-SD, RDW-CV, MPV, 4 Similarities Item Candidate Athelas One K181288 Predicate Sysmex XE-5000 K071967 RET %/#, IRF, IG%/#, HPC#, RET-He, IPF, WBC-BF, RBC- BF, MN%/#, PMN%/#, TC-BF#. Differences Item Candidate Athelas One K181288 Predicate Systex XE-5000 K071967 Test Principle A microfluidic test strip channel creates a stained monolayer of WBCs. Multiple images are taken of the monolayer and the cells are counted and classified by computer vision based image analysis. Performs analyses using the following methods: RF/DC detection method, Sheath Flow DC dectection method, and flow cytometry methods using a semiconductor laser. Controls/Calibrators ATH-CHECK (Three level control) Factory Calibrated e-Check (XE) (Three level control) XE Calibrator (X Cal) Sample Processing Internet connected device for processing results on Cloud server Processing of results occurs locally in device Sample Volume 3.5 µL 130–200 µL depending on operation mode Measurement Range WBC: 1.0–20 x103/µL WBC: 0.0–440 x103/µL Calibration Factory calibrated, no further calibration Automtic and manual calibration using e-Check (XE) control material K. Standard/Guidance Document Referenced (if applicable): CLSI H26-A2: Validation, Verification and Quality Assurance of Automated Hematology Analyzers; Approved Guideline – Second Edition CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline – First Edition CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measreument Procedures – Approved Guideline – Second Edition 5 CLSI EP14-A2: Evluation of Matrix Effects; Approved Guideline – Second Edition CLSI EP25-A: Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline – First Edition CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition CLSI EP05-A3: Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition CLSI EP28-A3c: Defining, Establishing, and Verifying Reference Intervals in Clinical Laboratory; Approved Guideline – Third Edition L. Test Principle: The Athelas One system consists of the Athelas One analyzer and Athelas One test strips. The Athelas One test strips serve as both a sample container and a reaction chamber. A capillary whole blood sample or whole blood specimen anticoagulated in K2EDTA of 3.5 μL is pipetted or directly transferred via fingerstick to the Athelas One test strip which automatically spreads the sample into a monolayer. The pre-coated stain within the strip chamber interacts with the monolayer of blood and stains the WBCs. The Athelas One test strip is inserted into the Athelas One analyzer which utilizes a proximity sensor to lock in place. A servo stabilizes and auto-focuses the blood sample, and then a stage actuator scans the strip across various fields while the optical module takes multiple images of the cells across the monolayer. The images of the blood sample are transmitted to the server where they are analyzed using a locked down image processing algorithm. The algorithm recognizes the nucleation and WBCs to generate a WBC count and NEUT% result based on the concentrations and types of cells present. The WBC count and NEUT% is then returned to the user via the controlling mobile application on an authorized lab or hospital device. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Repeatability: The repeatability study was conducted in accordance with CLSI Product code:

idK181288_s0_e2000

K181288.txt

panel

Hematology (81)

(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM A. 510(k) Number: K181288 B. Purpose for Submission: Clearance of a new device C. Measurand: White blood cell count (WBC) and percent neutrophil count (NEUT%) D. Type of Test: Enumeration of WBCs and NEUT% E. Applicant: Athelas Inc. F. Proprietary and Established Names: Athelas One G. Regulatory Information: 1. Regulation section: 21 CFR 864.5220, Automated differential cell counter 2. Classification: Class II 3. Product code: GKZ, Counter, differential cell 4. Panel: Hematology (81) 2 H. Intended Use: 1. Intended use(s): Athelas One is indicated for use for quantitative determination of white blood cells (WBC) and Neutrophil percentages (NEUT%) in capillary or K2EDTA venous whole blood. The Athelas One system is for In Vitro Diagnostic use only. The Athelas One is only to be used with Athelas One Test Strips. The Athelas One is indicated for use in clinical laboratories and for point of care settings. The Athelas One is only indicated for use in adult populations (aged 21 and older). 2. Indication(s) for use: Same as intended use 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Athelas One analyzer I. Device Description: The Athelas One is an automated cell counter system which consists of: the Athelas One analyzer and the Athelas One Test Strips. The Athelas One system is intended to analyze capillary whole blood and anticoagulated venous whole blood collected in K2EDTA collection tubes. The Athelas One Tests Strips collects a blood sample (capillary or collected in K2EDTA anticoagulant) to generate a layer of cells for counting and image analysis. The Athelas One Test Strips are comprised of an upper optical panel, lower optical panel and a stain coated region containing methylene blue and cresyl violet stains. The test strip channel is optically clear for the camera module to take pictures of the cells in the blood sample. A smartphone/tablet with the Athelas controlling mobile application is required to initiate a test with the Athelas One System. The smartphone/tablet models compatible to initiate testing are those devices supporting iOS 9, 10, and 11, or Android 7, 8, and 9. In addition, the smartphone/tablet with the Athelas controlling mobile application is required to view test results. J. Substantial Equivalence Information: 1. Predicate device name(s): Sysmex XE-5000 Automated Hematology Analzyer 3 2. Predicate 510(k) number(s): K071967 3. Comparison with predicate: Similarities Item Candidate Athelas One K181288 Predicate Sysmex XE-5000 K071967 Intended Use Athelas One is indicated for use for quantitative determination of white blood cells (WBC) and Neutrophil percentages (NEUT%) in capillary or K2EDTA venous whole blood. The Athelas One system is for In Vitro Diagnostic use only. The Athelas One is only to be used with Athelas One Test Strips. The Athelas One is indicated for use in clinical laboratories and for point of care settings. The Athelas One is only indicated for use in adult populations (aged 21 and older). The Sysmex XE-5000 is an automated hematology analyzer for in-vitro diagnostic use in screening patient populations found in clinical laboratories. The XE-5000 classifies and enumerates the same parameters as the XE-2100 using whole blood as described below, cord blood for HPC and has a body fluid mode for body fluids. The Body Fluid mode analyzes WBC-BF, RBC-BF, MN%/#, PMN%/# and TC-BF in body fluids (cerebrospinal fluids (CSF), serous fluids, and synovial fluids with EDTA as needed). WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMP %/#, MONO %/#, EO%/#, BASO %/#, NRBC, RDW-SD, RDW- CV, MPV, RET %/#, IRF, IG%/#, HPC#, RET-He, IPF, WBC-BF, RBC-BF, MN%/#, PMN%/#, TC-BF#. Intended Use Settings Point of care, clinical laboratory Clinical laboratory Specimen Type Capillary whole blood and K2EDTA venous whole blood Same in addition to body fluids (CSF, serous fluids, and synovial fluids) Parameters WBC, NEUT% WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMP %/#, MONO %/#, EO%/#, BASO %/#, NRBC, RDW-SD, RDW-CV, MPV, 4 Similarities Item Candidate Athelas One K181288 Predicate Sysmex XE-5000 K071967 RET %/#, IRF, IG%/#, HPC#, RET-He, IPF, WBC-BF, RBC- BF, MN%/#, PMN%/#, TC-BF#. Differences Item Candidate Athelas One K181288 Predicate Systex XE-5000 K071967 Test Principle A microfluidic test strip channel creates a stained monolayer of WBCs. Multiple images are taken of the monolayer and the cells are counted and classified by computer vision based image analysis. Performs analyses using the following methods: RF/DC detection method, Sheath Flow DC dectection method, and flow cytometry methods using a semiconductor laser. Controls/Calibrators ATH-CHECK (Three level control) Factory Calibrated e-Check (XE) (Three level control) XE Calibrator (X Cal) Sample Processing Internet connected device for processing results on Cloud server Processing of results occurs locally in device Sample Volume 3.5 µL 130–200 µL depending on operation mode Measurement Range WBC: 1.0–20 x103/µL WBC: 0.0–440 x103/µL Calibration Factory calibrated, no further calibration Automtic and manual calibration using e-Check (XE) control material K. Standard/Guidance Document Referenced (if applicable): CLSI H26-A2: Validation, Verification and Quality Assurance of Automated Hematology Analyzers; Approved Guideline – Second Edition CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline – First Edition CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measreument Procedures – Approved Guideline – Second Edition 5 CLSI EP14-A2: Evluation of Matrix Effects; Approved Guideline – Second Edition CLSI EP25-A: Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline – First Edition CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition CLSI EP05-A3: Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition CLSI EP28-A3c: Defining, Establishing, and Verifying Reference Intervals in Clinical Laboratory; Approved Guideline – Third Edition L. Test Principle: The Athelas One system consists of the Athelas One analyzer and Athelas One test strips. The Athelas One test strips serve as both a sample container and a reaction chamber. A capillary whole blood sample or whole blood specimen anticoagulated in K2EDTA of 3.5 μL is pipetted or directly transferred via fingerstick to the Athelas One test strip which automatically spreads the sample into a monolayer. The pre-coated stain within the strip chamber interacts with the monolayer of blood and stains the WBCs. The Athelas One test strip is inserted into the Athelas One analyzer which utilizes a proximity sensor to lock in place. A servo stabilizes and auto-focuses the blood sample, and then a stage actuator scans the strip across various fields while the optical module takes multiple images of the cells across the monolayer. The images of the blood sample are transmitted to the server where they are analyzed using a locked down image processing algorithm. The algorithm recognizes the nucleation and WBCs to generate a WBC count and NEUT% result based on the concentrations and types of cells present. The WBC count and NEUT% is then returned to the user via the controlling mobile application on an authorized lab or hospital device. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Repeatability: The repeatability study was conducted in accordance with CLSI Panel:

idK181288_s0_e2000

K181288.txt

intended use

Athelas One is indicated for use for quantitative determination of white blood cells (WBC) and Neutrophil percentages (NEUT%) in capillary or K2EDTA venous whole blood. The Athelas One system is for In Vitro Diagnostic use only. The Athelas One is only to be used with Athelas One Test Strips. The Athelas One is indicated for use in clinical laboratories and for point of care settings. The Athelas One is only indicated for use in adult populations (aged 21 and older).

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM A. 510(k) Number: K181288 B. Purpose for Submission: Clearance of a new device C. Measurand: White blood cell count (WBC) and percent neutrophil count (NEUT%) D. Type of Test: Enumeration of WBCs and NEUT% E. Applicant: Athelas Inc. F. Proprietary and Established Names: Athelas One G. Regulatory Information: 1. Regulation section: 21 CFR 864.5220, Automated differential cell counter 2. Classification: Class II 3. Product code: GKZ, Counter, differential cell 4. Panel: Hematology (81) 2 H. Intended Use: 1. Intended use(s): Athelas One is indicated for use for quantitative determination of white blood cells (WBC) and Neutrophil percentages (NEUT%) in capillary or K2EDTA venous whole blood. The Athelas One system is for In Vitro Diagnostic use only. The Athelas One is only to be used with Athelas One Test Strips. The Athelas One is indicated for use in clinical laboratories and for point of care settings. The Athelas One is only indicated for use in adult populations (aged 21 and older). 2. Indication(s) for use: Same as intended use 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Athelas One analyzer I. Device Description: The Athelas One is an automated cell counter system which consists of: the Athelas One analyzer and the Athelas One Test Strips. The Athelas One system is intended to analyze capillary whole blood and anticoagulated venous whole blood collected in K2EDTA collection tubes. The Athelas One Tests Strips collects a blood sample (capillary or collected in K2EDTA anticoagulant) to generate a layer of cells for counting and image analysis. The Athelas One Test Strips are comprised of an upper optical panel, lower optical panel and a stain coated region containing methylene blue and cresyl violet stains. The test strip channel is optically clear for the camera module to take pictures of the cells in the blood sample. A smartphone/tablet with the Athelas controlling mobile application is required to initiate a test with the Athelas One System. The smartphone/tablet models compatible to initiate testing are those devices supporting iOS 9, 10, and 11, or Android 7, 8, and 9. In addition, the smartphone/tablet with the Athelas controlling mobile application is required to view test results. J. Substantial Equivalence Information: 1. Predicate device name(s): Sysmex XE-5000 Automated Hematology Analzyer 3 2. Predicate 510(k) number(s): K071967 3. Comparison with predicate: Similarities Item Candidate Athelas One K181288 Predicate Sysmex XE-5000 K071967 Intended Use Athelas One is indicated for use for quantitative determination of white blood cells (WBC) and Neutrophil percentages (NEUT%) in capillary or K2EDTA venous whole blood. The Athelas One system is for In Vitro Diagnostic use only. The Athelas One is only to be used with Athelas One Test Strips. The Athelas One is indicated for use in clinical laboratories and for point of care settings. The Athelas One is only indicated for use in adult populations (aged 21 and older). The Sysmex XE-5000 is an automated hematology analyzer for in-vitro diagnostic use in screening patient populations found in clinical laboratories. The XE-5000 classifies and enumerates the same parameters as the XE-2100 using whole blood as described below, cord blood for HPC and has a body fluid mode for body fluids. The Body Fluid mode analyzes WBC-BF, RBC-BF, MN%/#, PMN%/# and TC-BF in body fluids (cerebrospinal fluids (CSF), serous fluids, and synovial fluids with EDTA as needed). WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMP %/#, MONO %/#, EO%/#, BASO %/#, NRBC, RDW-SD, RDW- CV, MPV, RET %/#, IRF, IG%/#, HPC#, RET-He, IPF, WBC-BF, RBC-BF, MN%/#, PMN%/#, TC-BF#. Intended Use Settings Point of care, clinical laboratory Clinical laboratory Specimen Type Capillary whole blood and K2EDTA venous whole blood Same in addition to body fluids (CSF, serous fluids, and synovial fluids) Parameters WBC, NEUT% WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMP %/#, MONO %/#, EO%/#, BASO %/#, NRBC, RDW-SD, RDW-CV, MPV, 4 Similarities Item Candidate Athelas One K181288 Predicate Sysmex XE-5000 K071967 RET %/#, IRF, IG%/#, HPC#, RET-He, IPF, WBC-BF, RBC- BF, MN%/#, PMN%/#, TC-BF#. Differences Item Candidate Athelas One K181288 Predicate Systex XE-5000 K071967 Test Principle A microfluidic test strip channel creates a stained monolayer of WBCs. Multiple images are taken of the monolayer and the cells are counted and classified by computer vision based image analysis. Performs analyses using the following methods: RF/DC detection method, Sheath Flow DC dectection method, and flow cytometry methods using a semiconductor laser. Controls/Calibrators ATH-CHECK (Three level control) Factory Calibrated e-Check (XE) (Three level control) XE Calibrator (X Cal) Sample Processing Internet connected device for processing results on Cloud server Processing of results occurs locally in device Sample Volume 3.5 µL 130–200 µL depending on operation mode Measurement Range WBC: 1.0–20 x103/µL WBC: 0.0–440 x103/µL Calibration Factory calibrated, no further calibration Automtic and manual calibration using e-Check (XE) control material K. Standard/Guidance Document Referenced (if applicable): CLSI H26-A2: Validation, Verification and Quality Assurance of Automated Hematology Analyzers; Approved Guideline – Second Edition CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline – First Edition CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measreument Procedures – Approved Guideline – Second Edition 5 CLSI EP14-A2: Evluation of Matrix Effects; Approved Guideline – Second Edition CLSI EP25-A: Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline – First Edition CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition CLSI EP05-A3: Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition CLSI EP28-A3c: Defining, Establishing, and Verifying Reference Intervals in Clinical Laboratory; Approved Guideline – Third Edition L. Test Principle: The Athelas One system consists of the Athelas One analyzer and Athelas One test strips. The Athelas One test strips serve as both a sample container and a reaction chamber. A capillary whole blood sample or whole blood specimen anticoagulated in K2EDTA of 3.5 μL is pipetted or directly transferred via fingerstick to the Athelas One test strip which automatically spreads the sample into a monolayer. The pre-coated stain within the strip chamber interacts with the monolayer of blood and stains the WBCs. The Athelas One test strip is inserted into the Athelas One analyzer which utilizes a proximity sensor to lock in place. A servo stabilizes and auto-focuses the blood sample, and then a stage actuator scans the strip across various fields while the optical module takes multiple images of the cells across the monolayer. The images of the blood sample are transmitted to the server where they are analyzed using a locked down image processing algorithm. The algorithm recognizes the nucleation and WBCs to generate a WBC count and NEUT% result based on the concentrations and types of cells present. The WBC count and NEUT% is then returned to the user via the controlling mobile application on an authorized lab or hospital device. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Repeatability: The repeatability study was conducted in accordance with CLSI Intended use:

idK181288_s0_e2000

K181288.txt

predicate device name

Sysmex XE-5000 Automated Hematology Analzyer

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM A. 510(k) Number: K181288 B. Purpose for Submission: Clearance of a new device C. Measurand: White blood cell count (WBC) and percent neutrophil count (NEUT%) D. Type of Test: Enumeration of WBCs and NEUT% E. Applicant: Athelas Inc. F. Proprietary and Established Names: Athelas One G. Regulatory Information: 1. Regulation section: 21 CFR 864.5220, Automated differential cell counter 2. Classification: Class II 3. Product code: GKZ, Counter, differential cell 4. Panel: Hematology (81) 2 H. Intended Use: 1. Intended use(s): Athelas One is indicated for use for quantitative determination of white blood cells (WBC) and Neutrophil percentages (NEUT%) in capillary or K2EDTA venous whole blood. The Athelas One system is for In Vitro Diagnostic use only. The Athelas One is only to be used with Athelas One Test Strips. The Athelas One is indicated for use in clinical laboratories and for point of care settings. The Athelas One is only indicated for use in adult populations (aged 21 and older). 2. Indication(s) for use: Same as intended use 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Athelas One analyzer I. Device Description: The Athelas One is an automated cell counter system which consists of: the Athelas One analyzer and the Athelas One Test Strips. The Athelas One system is intended to analyze capillary whole blood and anticoagulated venous whole blood collected in K2EDTA collection tubes. The Athelas One Tests Strips collects a blood sample (capillary or collected in K2EDTA anticoagulant) to generate a layer of cells for counting and image analysis. The Athelas One Test Strips are comprised of an upper optical panel, lower optical panel and a stain coated region containing methylene blue and cresyl violet stains. The test strip channel is optically clear for the camera module to take pictures of the cells in the blood sample. A smartphone/tablet with the Athelas controlling mobile application is required to initiate a test with the Athelas One System. The smartphone/tablet models compatible to initiate testing are those devices supporting iOS 9, 10, and 11, or Android 7, 8, and 9. In addition, the smartphone/tablet with the Athelas controlling mobile application is required to view test results. J. Substantial Equivalence Information: 1. Predicate device name(s): Sysmex XE-5000 Automated Hematology Analzyer 3 2. Predicate 510(k) number(s): K071967 3. Comparison with predicate: Similarities Item Candidate Athelas One K181288 Predicate Sysmex XE-5000 K071967 Intended Use Athelas One is indicated for use for quantitative determination of white blood cells (WBC) and Neutrophil percentages (NEUT%) in capillary or K2EDTA venous whole blood. The Athelas One system is for In Vitro Diagnostic use only. The Athelas One is only to be used with Athelas One Test Strips. The Athelas One is indicated for use in clinical laboratories and for point of care settings. The Athelas One is only indicated for use in adult populations (aged 21 and older). The Sysmex XE-5000 is an automated hematology analyzer for in-vitro diagnostic use in screening patient populations found in clinical laboratories. The XE-5000 classifies and enumerates the same parameters as the XE-2100 using whole blood as described below, cord blood for HPC and has a body fluid mode for body fluids. The Body Fluid mode analyzes WBC-BF, RBC-BF, MN%/#, PMN%/# and TC-BF in body fluids (cerebrospinal fluids (CSF), serous fluids, and synovial fluids with EDTA as needed). WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMP %/#, MONO %/#, EO%/#, BASO %/#, NRBC, RDW-SD, RDW- CV, MPV, RET %/#, IRF, IG%/#, HPC#, RET-He, IPF, WBC-BF, RBC-BF, MN%/#, PMN%/#, TC-BF#. Intended Use Settings Point of care, clinical laboratory Clinical laboratory Specimen Type Capillary whole blood and K2EDTA venous whole blood Same in addition to body fluids (CSF, serous fluids, and synovial fluids) Parameters WBC, NEUT% WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMP %/#, MONO %/#, EO%/#, BASO %/#, NRBC, RDW-SD, RDW-CV, MPV, 4 Similarities Item Candidate Athelas One K181288 Predicate Sysmex XE-5000 K071967 RET %/#, IRF, IG%/#, HPC#, RET-He, IPF, WBC-BF, RBC- BF, MN%/#, PMN%/#, TC-BF#. Differences Item Candidate Athelas One K181288 Predicate Systex XE-5000 K071967 Test Principle A microfluidic test strip channel creates a stained monolayer of WBCs. Multiple images are taken of the monolayer and the cells are counted and classified by computer vision based image analysis. Performs analyses using the following methods: RF/DC detection method, Sheath Flow DC dectection method, and flow cytometry methods using a semiconductor laser. Controls/Calibrators ATH-CHECK (Three level control) Factory Calibrated e-Check (XE) (Three level control) XE Calibrator (X Cal) Sample Processing Internet connected device for processing results on Cloud server Processing of results occurs locally in device Sample Volume 3.5 µL 130–200 µL depending on operation mode Measurement Range WBC: 1.0–20 x103/µL WBC: 0.0–440 x103/µL Calibration Factory calibrated, no further calibration Automtic and manual calibration using e-Check (XE) control material K. Standard/Guidance Document Referenced (if applicable): CLSI H26-A2: Validation, Verification and Quality Assurance of Automated Hematology Analyzers; Approved Guideline – Second Edition CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline – First Edition CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measreument Procedures – Approved Guideline – Second Edition 5 CLSI EP14-A2: Evluation of Matrix Effects; Approved Guideline – Second Edition CLSI EP25-A: Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline – First Edition CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition CLSI EP05-A3: Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition CLSI EP28-A3c: Defining, Establishing, and Verifying Reference Intervals in Clinical Laboratory; Approved Guideline – Third Edition L. Test Principle: The Athelas One system consists of the Athelas One analyzer and Athelas One test strips. The Athelas One test strips serve as both a sample container and a reaction chamber. A capillary whole blood sample or whole blood specimen anticoagulated in K2EDTA of 3.5 μL is pipetted or directly transferred via fingerstick to the Athelas One test strip which automatically spreads the sample into a monolayer. The pre-coated stain within the strip chamber interacts with the monolayer of blood and stains the WBCs. The Athelas One test strip is inserted into the Athelas One analyzer which utilizes a proximity sensor to lock in place. A servo stabilizes and auto-focuses the blood sample, and then a stage actuator scans the strip across various fields while the optical module takes multiple images of the cells across the monolayer. The images of the blood sample are transmitted to the server where they are analyzed using a locked down image processing algorithm. The algorithm recognizes the nucleation and WBCs to generate a WBC count and NEUT% result based on the concentrations and types of cells present. The WBC count and NEUT% is then returned to the user via the controlling mobile application on an authorized lab or hospital device. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Repeatability: The repeatability study was conducted in accordance with CLSI Predicate device name:

idK181288_s0_e2000

K181288.txt

applicant

Athelas Inc.

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM A. 510(k) Number: K181288 B. Purpose for Submission: Clearance of a new device C. Measurand: White blood cell count (WBC) and percent neutrophil count (NEUT%) D. Type of Test: Enumeration of WBCs and NEUT% E. Applicant: Athelas Inc. F. Proprietary and Established Names: Athelas One G. Regulatory Information: 1. Regulation section: 21 CFR 864.5220, Automated differential cell counter 2. Classification: Class II 3. Product code: GKZ, Counter, differential cell 4. Panel: Hematology (81) 2 H. Intended Use: 1. Intended use(s): Athelas One is indicated for use for quantitative determination of white blood cells (WBC) and Neutrophil percentages (NEUT%) in capillary or K2EDTA venous whole blood. The Athelas One system is for In Vitro Diagnostic use only. The Athelas One is only to be used with Athelas One Test Strips. The Athelas One is indicated for use in clinical laboratories and for point of care settings. The Athelas One is only indicated for use in adult populations (aged 21 and older). 2. Indication(s) for use: Same as intended use 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Athelas One analyzer I. Device Description: The Athelas One is an automated cell counter system which consists of: the Athelas One analyzer and the Athelas One Test Strips. The Athelas One system is intended to analyze capillary whole blood and anticoagulated venous whole blood collected in K2EDTA collection tubes. The Athelas One Tests Strips collects a blood sample (capillary or collected in K2EDTA anticoagulant) to generate a layer of cells for counting and image analysis. The Athelas One Test Strips are comprised of an upper optical panel, lower optical panel and a stain coated region containing methylene blue and cresyl violet stains. The test strip channel is optically clear for the camera module to take pictures of the cells in the blood sample. A smartphone/tablet with the Athelas controlling mobile application is required to initiate a test with the Athelas One System. The smartphone/tablet models compatible to initiate testing are those devices supporting iOS 9, 10, and 11, or Android 7, 8, and 9. In addition, the smartphone/tablet with the Athelas controlling mobile application is required to view test results. J. Substantial Equivalence Information: 1. Predicate device name(s): Sysmex XE-5000 Automated Hematology Analzyer 3 2. Predicate 510(k) number(s): K071967 3. Comparison with predicate: Similarities Item Candidate Athelas One K181288 Predicate Sysmex XE-5000 K071967 Intended Use Athelas One is indicated for use for quantitative determination of white blood cells (WBC) and Neutrophil percentages (NEUT%) in capillary or K2EDTA venous whole blood. The Athelas One system is for In Vitro Diagnostic use only. The Athelas One is only to be used with Athelas One Test Strips. The Athelas One is indicated for use in clinical laboratories and for point of care settings. The Athelas One is only indicated for use in adult populations (aged 21 and older). The Sysmex XE-5000 is an automated hematology analyzer for in-vitro diagnostic use in screening patient populations found in clinical laboratories. The XE-5000 classifies and enumerates the same parameters as the XE-2100 using whole blood as described below, cord blood for HPC and has a body fluid mode for body fluids. The Body Fluid mode analyzes WBC-BF, RBC-BF, MN%/#, PMN%/# and TC-BF in body fluids (cerebrospinal fluids (CSF), serous fluids, and synovial fluids with EDTA as needed). WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMP %/#, MONO %/#, EO%/#, BASO %/#, NRBC, RDW-SD, RDW- CV, MPV, RET %/#, IRF, IG%/#, HPC#, RET-He, IPF, WBC-BF, RBC-BF, MN%/#, PMN%/#, TC-BF#. Intended Use Settings Point of care, clinical laboratory Clinical laboratory Specimen Type Capillary whole blood and K2EDTA venous whole blood Same in addition to body fluids (CSF, serous fluids, and synovial fluids) Parameters WBC, NEUT% WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMP %/#, MONO %/#, EO%/#, BASO %/#, NRBC, RDW-SD, RDW-CV, MPV, 4 Similarities Item Candidate Athelas One K181288 Predicate Sysmex XE-5000 K071967 RET %/#, IRF, IG%/#, HPC#, RET-He, IPF, WBC-BF, RBC- BF, MN%/#, PMN%/#, TC-BF#. Differences Item Candidate Athelas One K181288 Predicate Systex XE-5000 K071967 Test Principle A microfluidic test strip channel creates a stained monolayer of WBCs. Multiple images are taken of the monolayer and the cells are counted and classified by computer vision based image analysis. Performs analyses using the following methods: RF/DC detection method, Sheath Flow DC dectection method, and flow cytometry methods using a semiconductor laser. Controls/Calibrators ATH-CHECK (Three level control) Factory Calibrated e-Check (XE) (Three level control) XE Calibrator (X Cal) Sample Processing Internet connected device for processing results on Cloud server Processing of results occurs locally in device Sample Volume 3.5 µL 130–200 µL depending on operation mode Measurement Range WBC: 1.0–20 x103/µL WBC: 0.0–440 x103/µL Calibration Factory calibrated, no further calibration Automtic and manual calibration using e-Check (XE) control material K. Standard/Guidance Document Referenced (if applicable): CLSI H26-A2: Validation, Verification and Quality Assurance of Automated Hematology Analyzers; Approved Guideline – Second Edition CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline – First Edition CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measreument Procedures – Approved Guideline – Second Edition 5 CLSI EP14-A2: Evluation of Matrix Effects; Approved Guideline – Second Edition CLSI EP25-A: Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline – First Edition CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition CLSI EP05-A3: Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition CLSI EP28-A3c: Defining, Establishing, and Verifying Reference Intervals in Clinical Laboratory; Approved Guideline – Third Edition L. Test Principle: The Athelas One system consists of the Athelas One analyzer and Athelas One test strips. The Athelas One test strips serve as both a sample container and a reaction chamber. A capillary whole blood sample or whole blood specimen anticoagulated in K2EDTA of 3.5 μL is pipetted or directly transferred via fingerstick to the Athelas One test strip which automatically spreads the sample into a monolayer. The pre-coated stain within the strip chamber interacts with the monolayer of blood and stains the WBCs. The Athelas One test strip is inserted into the Athelas One analyzer which utilizes a proximity sensor to lock in place. A servo stabilizes and auto-focuses the blood sample, and then a stage actuator scans the strip across various fields while the optical module takes multiple images of the cells across the monolayer. The images of the blood sample are transmitted to the server where they are analyzed using a locked down image processing algorithm. The algorithm recognizes the nucleation and WBCs to generate a WBC count and NEUT% result based on the concentrations and types of cells present. The WBC count and NEUT% is then returned to the user via the controlling mobile application on an authorized lab or hospital device. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Repeatability: The repeatability study was conducted in accordance with CLSI Applicant:

idK181288_s0_e2000

K181288.txt

proprietary and established names

Athelas One

ANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM A. 510(k) Number: K181288 B. Purpose for Submission: Clearance of a new device C. Measurand: White blood cell count (WBC) and percent neutrophil count (NEUT%) D. Type of Test: Enumeration of WBCs and NEUT% E. Applicant: Athelas Inc. F. Proprietary and Established Names: Athelas One G. Regulatory Information: 1. Regulation section: 21 CFR 864.5220, Automated differential cell counter 2. Classification: Class II 3. Product code: GKZ, Counter, differential cell 4. Panel: Hematology (81) 2 H. Intended Use: 1. Intended use(s): Athelas One is indicated for use for quantitative determination of white blood cells (WBC) and Neutrophil percentages (NEUT%) in capillary or K2EDTA venous whole blood. The Athelas One system is for In Vitro Diagnostic use only. The Athelas One is only to be used with Athelas One Test Strips. The Athelas One is indicated for use in clinical laboratories and for point of care settings. The Athelas One is only indicated for use in adult populations (aged 21 and older). 2. Indication(s) for use: Same as intended use 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Athelas One analyzer I. Device Description: The Athelas One is an automated cell counter system which consists of: the Athelas One analyzer and the Athelas One Test Strips. The Athelas One system is intended to analyze capillary whole blood and anticoagulated venous whole blood collected in K2EDTA collection tubes. The Athelas One Tests Strips collects a blood sample (capillary or collected in K2EDTA anticoagulant) to generate a layer of cells for counting and image analysis. The Athelas One Test Strips are comprised of an upper optical panel, lower optical panel and a stain coated region containing methylene blue and cresyl violet stains. The test strip channel is optically clear for the camera module to take pictures of the cells in the blood sample. A smartphone/tablet with the Athelas controlling mobile application is required to initiate a test with the Athelas One System. The smartphone/tablet models compatible to initiate testing are those devices supporting iOS 9, 10, and 11, or Android 7, 8, and 9. In addition, the smartphone/tablet with the Athelas controlling mobile application is required to view test results. J. Substantial Equivalence Information: 1. Predicate device name(s): Sysmex XE-5000 Automated Hematology Analzyer 3 2. Predicate 510(k) number(s): K071967 3. Comparison with predicate: Similarities Item Candidate Athelas One K181288 Predicate Sysmex XE-5000 K071967 Intended Use Athelas One is indicated for use for quantitative determination of white blood cells (WBC) and Neutrophil percentages (NEUT%) in capillary or K2EDTA venous whole blood. The Athelas One system is for In Vitro Diagnostic use only. The Athelas One is only to be used with Athelas One Test Strips. The Athelas One is indicated for use in clinical laboratories and for point of care settings. The Athelas One is only indicated for use in adult populations (aged 21 and older). The Sysmex XE-5000 is an automated hematology analyzer for in-vitro diagnostic use in screening patient populations found in clinical laboratories. The XE-5000 classifies and enumerates the same parameters as the XE-2100 using whole blood as described below, cord blood for HPC and has a body fluid mode for body fluids. The Body Fluid mode analyzes WBC-BF, RBC-BF, MN%/#, PMN%/# and TC-BF in body fluids (cerebrospinal fluids (CSF), serous fluids, and synovial fluids with EDTA as needed). WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMP %/#, MONO %/#, EO%/#, BASO %/#, NRBC, RDW-SD, RDW- CV, MPV, RET %/#, IRF, IG%/#, HPC#, RET-He, IPF, WBC-BF, RBC-BF, MN%/#, PMN%/#, TC-BF#. Intended Use Settings Point of care, clinical laboratory Clinical laboratory Specimen Type Capillary whole blood and K2EDTA venous whole blood Same in addition to body fluids (CSF, serous fluids, and synovial fluids) Parameters WBC, NEUT% WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMP %/#, MONO %/#, EO%/#, BASO %/#, NRBC, RDW-SD, RDW-CV, MPV, 4 Similarities Item Candidate Athelas One K181288 Predicate Sysmex XE-5000 K071967 RET %/#, IRF, IG%/#, HPC#, RET-He, IPF, WBC-BF, RBC- BF, MN%/#, PMN%/#, TC-BF#. Differences Item Candidate Athelas One K181288 Predicate Systex XE-5000 K071967 Test Principle A microfluidic test strip channel creates a stained monolayer of WBCs. Multiple images are taken of the monolayer and the cells are counted and classified by computer vision based image analysis. Performs analyses using the following methods: RF/DC detection method, Sheath Flow DC dectection method, and flow cytometry methods using a semiconductor laser. Controls/Calibrators ATH-CHECK (Three level control) Factory Calibrated e-Check (XE) (Three level control) XE Calibrator (X Cal) Sample Processing Internet connected device for processing results on Cloud server Processing of results occurs locally in device Sample Volume 3.5 µL 130–200 µL depending on operation mode Measurement Range WBC: 1.0–20 x103/µL WBC: 0.0–440 x103/µL Calibration Factory calibrated, no further calibration Automtic and manual calibration using e-Check (XE) control material K. Standard/Guidance Document Referenced (if applicable): CLSI H26-A2: Validation, Verification and Quality Assurance of Automated Hematology Analyzers; Approved Guideline – Second Edition CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline – First Edition CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measreument Procedures – Approved Guideline – Second Edition 5 CLSI EP14-A2: Evluation of Matrix Effects; Approved Guideline – Second Edition CLSI EP25-A: Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline – First Edition CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition CLSI EP05-A3: Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition CLSI EP28-A3c: Defining, Establishing, and Verifying Reference Intervals in Clinical Laboratory; Approved Guideline – Third Edition L. Test Principle: The Athelas One system consists of the Athelas One analyzer and Athelas One test strips. The Athelas One test strips serve as both a sample container and a reaction chamber. A capillary whole blood sample or whole blood specimen anticoagulated in K2EDTA of 3.5 μL is pipetted or directly transferred via fingerstick to the Athelas One test strip which automatically spreads the sample into a monolayer. The pre-coated stain within the strip chamber interacts with the monolayer of blood and stains the WBCs. The Athelas One test strip is inserted into the Athelas One analyzer which utilizes a proximity sensor to lock in place. A servo stabilizes and auto-focuses the blood sample, and then a stage actuator scans the strip across various fields while the optical module takes multiple images of the cells across the monolayer. The images of the blood sample are transmitted to the server where they are analyzed using a locked down image processing algorithm. The algorithm recognizes the nucleation and WBCs to generate a WBC count and NEUT% result based on the concentrations and types of cells present. The WBC count and NEUT% is then returned to the user via the controlling mobile application on an authorized lab or hospital device. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Repeatability: The repeatability study was conducted in accordance with CLSI Proprietary and established names:

idK181288_s0_e2000

K181288.txt

regulation section

21 CFR 864.5220, Automated differential cell counter

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM A. 510(k) Number: K181288 B. Purpose for Submission: Clearance of a new device C. Measurand: White blood cell count (WBC) and percent neutrophil count (NEUT%) D. Type of Test: Enumeration of WBCs and NEUT% E. Applicant: Athelas Inc. F. Proprietary and Established Names: Athelas One G. Regulatory Information: 1. Regulation section: 21 CFR 864.5220, Automated differential cell counter 2. Classification: Class II 3. Product code: GKZ, Counter, differential cell 4. Panel: Hematology (81) 2 H. Intended Use: 1. Intended use(s): Athelas One is indicated for use for quantitative determination of white blood cells (WBC) and Neutrophil percentages (NEUT%) in capillary or K2EDTA venous whole blood. The Athelas One system is for In Vitro Diagnostic use only. The Athelas One is only to be used with Athelas One Test Strips. The Athelas One is indicated for use in clinical laboratories and for point of care settings. The Athelas One is only indicated for use in adult populations (aged 21 and older). 2. Indication(s) for use: Same as intended use 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Athelas One analyzer I. Device Description: The Athelas One is an automated cell counter system which consists of: the Athelas One analyzer and the Athelas One Test Strips. The Athelas One system is intended to analyze capillary whole blood and anticoagulated venous whole blood collected in K2EDTA collection tubes. The Athelas One Tests Strips collects a blood sample (capillary or collected in K2EDTA anticoagulant) to generate a layer of cells for counting and image analysis. The Athelas One Test Strips are comprised of an upper optical panel, lower optical panel and a stain coated region containing methylene blue and cresyl violet stains. The test strip channel is optically clear for the camera module to take pictures of the cells in the blood sample. A smartphone/tablet with the Athelas controlling mobile application is required to initiate a test with the Athelas One System. The smartphone/tablet models compatible to initiate testing are those devices supporting iOS 9, 10, and 11, or Android 7, 8, and 9. In addition, the smartphone/tablet with the Athelas controlling mobile application is required to view test results. J. Substantial Equivalence Information: 1. Predicate device name(s): Sysmex XE-5000 Automated Hematology Analzyer 3 2. Predicate 510(k) number(s): K071967 3. Comparison with predicate: Similarities Item Candidate Athelas One K181288 Predicate Sysmex XE-5000 K071967 Intended Use Athelas One is indicated for use for quantitative determination of white blood cells (WBC) and Neutrophil percentages (NEUT%) in capillary or K2EDTA venous whole blood. The Athelas One system is for In Vitro Diagnostic use only. The Athelas One is only to be used with Athelas One Test Strips. The Athelas One is indicated for use in clinical laboratories and for point of care settings. The Athelas One is only indicated for use in adult populations (aged 21 and older). The Sysmex XE-5000 is an automated hematology analyzer for in-vitro diagnostic use in screening patient populations found in clinical laboratories. The XE-5000 classifies and enumerates the same parameters as the XE-2100 using whole blood as described below, cord blood for HPC and has a body fluid mode for body fluids. The Body Fluid mode analyzes WBC-BF, RBC-BF, MN%/#, PMN%/# and TC-BF in body fluids (cerebrospinal fluids (CSF), serous fluids, and synovial fluids with EDTA as needed). WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMP %/#, MONO %/#, EO%/#, BASO %/#, NRBC, RDW-SD, RDW- CV, MPV, RET %/#, IRF, IG%/#, HPC#, RET-He, IPF, WBC-BF, RBC-BF, MN%/#, PMN%/#, TC-BF#. Intended Use Settings Point of care, clinical laboratory Clinical laboratory Specimen Type Capillary whole blood and K2EDTA venous whole blood Same in addition to body fluids (CSF, serous fluids, and synovial fluids) Parameters WBC, NEUT% WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMP %/#, MONO %/#, EO%/#, BASO %/#, NRBC, RDW-SD, RDW-CV, MPV, 4 Similarities Item Candidate Athelas One K181288 Predicate Sysmex XE-5000 K071967 RET %/#, IRF, IG%/#, HPC#, RET-He, IPF, WBC-BF, RBC- BF, MN%/#, PMN%/#, TC-BF#. Differences Item Candidate Athelas One K181288 Predicate Systex XE-5000 K071967 Test Principle A microfluidic test strip channel creates a stained monolayer of WBCs. Multiple images are taken of the monolayer and the cells are counted and classified by computer vision based image analysis. Performs analyses using the following methods: RF/DC detection method, Sheath Flow DC dectection method, and flow cytometry methods using a semiconductor laser. Controls/Calibrators ATH-CHECK (Three level control) Factory Calibrated e-Check (XE) (Three level control) XE Calibrator (X Cal) Sample Processing Internet connected device for processing results on Cloud server Processing of results occurs locally in device Sample Volume 3.5 µL 130–200 µL depending on operation mode Measurement Range WBC: 1.0–20 x103/µL WBC: 0.0–440 x103/µL Calibration Factory calibrated, no further calibration Automtic and manual calibration using e-Check (XE) control material K. Standard/Guidance Document Referenced (if applicable): CLSI H26-A2: Validation, Verification and Quality Assurance of Automated Hematology Analyzers; Approved Guideline – Second Edition CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline – First Edition CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measreument Procedures – Approved Guideline – Second Edition 5 CLSI EP14-A2: Evluation of Matrix Effects; Approved Guideline – Second Edition CLSI EP25-A: Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline – First Edition CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition CLSI EP05-A3: Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition CLSI EP28-A3c: Defining, Establishing, and Verifying Reference Intervals in Clinical Laboratory; Approved Guideline – Third Edition L. Test Principle: The Athelas One system consists of the Athelas One analyzer and Athelas One test strips. The Athelas One test strips serve as both a sample container and a reaction chamber. A capillary whole blood sample or whole blood specimen anticoagulated in K2EDTA of 3.5 μL is pipetted or directly transferred via fingerstick to the Athelas One test strip which automatically spreads the sample into a monolayer. The pre-coated stain within the strip chamber interacts with the monolayer of blood and stains the WBCs. The Athelas One test strip is inserted into the Athelas One analyzer which utilizes a proximity sensor to lock in place. A servo stabilizes and auto-focuses the blood sample, and then a stage actuator scans the strip across various fields while the optical module takes multiple images of the cells across the monolayer. The images of the blood sample are transmitted to the server where they are analyzed using a locked down image processing algorithm. The algorithm recognizes the nucleation and WBCs to generate a WBC count and NEUT% result based on the concentrations and types of cells present. The WBC count and NEUT% is then returned to the user via the controlling mobile application on an authorized lab or hospital device. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Repeatability: The repeatability study was conducted in accordance with CLSI Regulation section:

idK181288_s6000_e8000

K181288.txt

proposed labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809, as applicable.

No ________ 2. Software: FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: Yes ___X_____ or No ________ 3. Specimen Identification: Before a test can be performed, the Athelas One prompts the end user to input a patient identifier, which is manual entry. This prompt is a mandatory function. 4. Specimen Sampling and Handling: Capillary whole blood or venous whole blood collected in K2EDTA anticoagulant may be used. A drop of blood is collected via fingerstick using a lancet, and held against a Athelas One Test Strip. If pre-collected, K2EDTA samples are used, mix all specimen 12 tubes thoroughly on a mechanical mixer for at least two minutes or invert the tube 10–20 times by hand. The specimen can be stored at room temperature for 2 hours or in a refrigerator for 24 hours. If the specimen has been refrigerated, it should be warmed to room temperature prior to mixing. 5. Calibration: The Athelas One is factory calibrated and is fully functional upon unpackaging. 6. Quality Control: ATH-CHECK QC material is provided at three levels (low, normal and high) which includes preserved human leukocytes (neutrophils, lymphocytes, basophils, eosinophils, monocytes) along with the other components of whole blood (RBCs, platelets) in proportions expected in human whole blood. Value Assignment: Value assignment for the ATH-CHECK QC materials was based on data collected across three Athelas One analyzers conducted at three separate sites, with six operators. Each site ran two runs per day and two replicates per run. Standard deviation from the study was used to determine the range of each parameter of ATH- CHECK QC material through the formula value range = mean ± 3.0*SD. Open-Vial Stability: The open-vial stability study was conducted with two ATH-CHECK QC lots, three QC levels per lot (low, medium, high), two vials per lot and three instruments. Five time points (days 0, 2, 4, 7 and 8) were included in the study and three replicates per measurement point were obtained. Results demonstrated an open-vial stability of 7 days. Closed-Vial Stability: The closed-vial stability study was conducted with two ATH- CHECK QC lots, three QC levels per lot (low, medium, high), two vials per lot and three instruments. Nine time points (days 0, 2, 4, 7, 8, 10, 12, 15, 16) across the closed-vial testing period of 16 days and three replicates per measurement point were obtained. Results demonstrated a closed-vial stability of 15 days. P. Other Supportive Instrument Performance Characteristics Data Not Covered In The “Performance Characteristics” Section above: Flagging Comparison Study: This study was conducted to assess the flagging capabilities (distributional and morphological) of the Athelas One compared to the Sysmex XE-5000 utilizing patient samples covering a range of abnormal conditions. This study was performed with 312 patient samples from either capillary whole blood or venous whole blood collected in K2EDTA anticoagulant. Results met the pre-defined acceptance crtieria. Summarized data is presented below for both distributional flags as well as morphological flags. Distributional Flags The results of the Athelas One WBC distributional flagging (leukocytosis, leukocytopenia) 13 compared to the Sysmex XE-5000 were divided into two categories: 1) No flags, negative judgement and 2) patients with positive distributional abnormalities with flags present, positive judgement. Sysmex XE-5000 Positive (Abnormal) Negative (Normal) Total Athelas One Positive (Abnormal) 34 4 38 Negative (Normal) 5 269 274 Total 39 273 312 %Positive Agreement (Sensitivity) = 87.2%; 95% CI: 72.57, 95.70 %Negative Agreement (Specificity) = 98.5%; 95% CI: 96.29, 99.60 %Overall Agreement = 97.12%; 95% CI: 94.59, 98.67 Morphological Flags The results of the Athelas One WBC morphological flagging (nucleated RBCs, platelet clumps, etc.) compared to the Sysmex XE-5000 were divided into two categories: 1) No flags, negative judgement and 2) patients with positive distributional abnormalities with flags present, positive judgement. Sysmex XE-5000 Positive (Abnormal) Negative (Normal) Total Athelas One Positive (Abnornal) 90 7 97 Negative (Normal) 9 206 215 Total 99 213 312 %Positive Agreement (Sensitivity) = 90.91%; 95% CI: 83.44, 95.76 %Negative Agreement (Specificity) = 96.71%; 95% CI: 93.35, 98.67 %Overall Agreement = 94.87%; 95% CI: 91.81, 97.04 Q. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809, as applicable. R. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK181288_s6000_e8000

K181288.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

_____ or No ________ 2. Software: FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: Yes ___X_____ or No ________ 3. Specimen Identification: Before a test can be performed, the Athelas One prompts the end user to input a patient identifier, which is manual entry. This prompt is a mandatory function. 4. Specimen Sampling and Handling: Capillary whole blood or venous whole blood collected in K2EDTA anticoagulant may be used. A drop of blood is collected via fingerstick using a lancet, and held against a Athelas One Test Strip. If pre-collected, K2EDTA samples are used, mix all specimen 12 tubes thoroughly on a mechanical mixer for at least two minutes or invert the tube 10–20 times by hand. The specimen can be stored at room temperature for 2 hours or in a refrigerator for 24 hours. If the specimen has been refrigerated, it should be warmed to room temperature prior to mixing. 5. Calibration: The Athelas One is factory calibrated and is fully functional upon unpackaging. 6. Quality Control: ATH-CHECK QC material is provided at three levels (low, normal and high) which includes preserved human leukocytes (neutrophils, lymphocytes, basophils, eosinophils, monocytes) along with the other components of whole blood (RBCs, platelets) in proportions expected in human whole blood. Value Assignment: Value assignment for the ATH-CHECK QC materials was based on data collected across three Athelas One analyzers conducted at three separate sites, with six operators. Each site ran two runs per day and two replicates per run. Standard deviation from the study was used to determine the range of each parameter of ATH- CHECK QC material through the formula value range = mean ± 3.0*SD. Open-Vial Stability: The open-vial stability study was conducted with two ATH-CHECK QC lots, three QC levels per lot (low, medium, high), two vials per lot and three instruments. Five time points (days 0, 2, 4, 7 and 8) were included in the study and three replicates per measurement point were obtained. Results demonstrated an open-vial stability of 7 days. Closed-Vial Stability: The closed-vial stability study was conducted with two ATH- CHECK QC lots, three QC levels per lot (low, medium, high), two vials per lot and three instruments. Nine time points (days 0, 2, 4, 7, 8, 10, 12, 15, 16) across the closed-vial testing period of 16 days and three replicates per measurement point were obtained. Results demonstrated a closed-vial stability of 15 days. P. Other Supportive Instrument Performance Characteristics Data Not Covered In The “Performance Characteristics” Section above: Flagging Comparison Study: This study was conducted to assess the flagging capabilities (distributional and morphological) of the Athelas One compared to the Sysmex XE-5000 utilizing patient samples covering a range of abnormal conditions. This study was performed with 312 patient samples from either capillary whole blood or venous whole blood collected in K2EDTA anticoagulant. Results met the pre-defined acceptance crtieria. Summarized data is presented below for both distributional flags as well as morphological flags. Distributional Flags The results of the Athelas One WBC distributional flagging (leukocytosis, leukocytopenia) 13 compared to the Sysmex XE-5000 were divided into two categories: 1) No flags, negative judgement and 2) patients with positive distributional abnormalities with flags present, positive judgement. Sysmex XE-5000 Positive (Abnormal) Negative (Normal) Total Athelas One Positive (Abnormal) 34 4 38 Negative (Normal) 5 269 274 Total 39 273 312 %Positive Agreement (Sensitivity) = 87.2%; 95% CI: 72.57, 95.70 %Negative Agreement (Specificity) = 98.5%; 95% CI: 96.29, 99.60 %Overall Agreement = 97.12%; 95% CI: 94.59, 98.67 Morphological Flags The results of the Athelas One WBC morphological flagging (nucleated RBCs, platelet clumps, etc.) compared to the Sysmex XE-5000 were divided into two categories: 1) No flags, negative judgement and 2) patients with positive distributional abnormalities with flags present, positive judgement. Sysmex XE-5000 Positive (Abnormal) Negative (Normal) Total Athelas One Positive (Abnornal) 90 7 97 Negative (Normal) 9 206 215 Total 99 213 312 %Positive Agreement (Sensitivity) = 90.91%; 95% CI: 83.44, 95.76 %Negative Agreement (Specificity) = 96.71%; 95% CI: 93.35, 98.67 %Overall Agreement = 94.87%; 95% CI: 91.81, 97.04 Q. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809, as applicable. R. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK161831_s0_e2000

K161831.txt

purpose for submission

New device

ANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k161831 B. Purpose for Submission: New device C. Measurand: Total 25-hydroxyvitamin D D. Type of Test: Quantitative chemiluminescent immunoassay E. Applicant: Immunodiagnostic Systems Limited F. Proprietary and Established Names: IDS-iSYS 25VitDS IDS-iSYS 25VitDS Control Set G. Regulatory Information: 1. Regulation section: 1 21 CFR 862.1825, Vitamin D Test System 21 CFR 862.1660, Quality Control Material 2. Classification: Class II Class I, reserved 3. Product code: MRG, Vitamin D Test System JJX, Single (specified) Analyte Controls (Assayed and Unassayed) 4. Panel: 2 Clinical Chemistry (75) H. Intended Use: 1. Intended use(s): See indications for use below. 2. Indication(s) for use: The IDS-iSYS 25 VitDS Assay is intended for the quantitative determination of total 25-hydroxyvitamin D [(25(OH)D] in human serum or plasma on the IDS-iSYS Multi-Discipline Automated System. Results are to be used in conjunction with other clinical and laboratory data to assist the clinician in the assessment of vitamin D sufficiency in an adult population. The IDS-iSYS 25 VitDS Control Set is used for quality control of the IDS-iSYS 25 VitDS assay on the IDS-iSYS Multi- Discipline Automated System. 3. Special conditions for use statement(s): For in vitro diagnostic use only. For prescription use only. 4. Special instrument requirements: For use on the IDS-iSYS Multi- Discipline Automated System. I. Device Description: The IDS-iSYS 25VitDS assay consists of a reagent cartridge (with multiple components) and one set of calibrators. Reagent Cartridge: MPV1 – Magnetic particles coated with streptavidin in phosphate buffer with sodium azide (<0.1%) as preservative (1 bottle, 2.5 mL) NaOH – Sodium hydroxide solution (<0.5 M) (1 bottle, 13.0 mL) 25D ACR – 25D labelled with an acridinium ester derivative, in buffer containing bovine serum albumin with sodium azide (<0.1 %) as preservative (1 bottle, 9.0 mL) Ab-BIOT - Anti-25(OH)D sheep polyclonal antibody labelled with an biotin, in buffer 3 containing bovine, sheep and mouse proteins with sodium azide (<0.1 %) as preservative (1 bottle, 9.0 mL) BUF - Assay buffer containing proprietary displacing compounds, methanol (>10 % but <20%) and sodium azide (<0.1 %) as preservative (1 bottle, 23.0 mL) Calibrators: Kit Calibrators A and B (CAL A & CAL B) (1 bottle of each, 1.5 mL per bottle) contain human serum buffer matrix with two defined concentrations of 25(OH)D and sodium azide (<0.1%) as preservative. Control Set: Controls 1 and 2 (CTL 1 & CTL 2) (3 bottles of each, 2.5 mL per bottle) contain human serum buffer matrix with two defined concentrations of 25(OH)D and sodium azide (<0.1%) as preservative. The target concentrations are 17 ng/mL and 90 ng/mL. Statement in labeling regarding the use of human blood-based materials in calibrators and controls: Human material used in the preparation of this product has been tested by FDA recommended assays for the presence of antibody to Human Immunodeficiency Virus (HIV I and II), Hepatitis B surface antigen, antibody to Hepatitis C, and found negative. J. Substantial Equivalence Information: 1. Predicate device name(s): IDS-iSYS 25-Hydroxy Vitamin DS Assay IDS-iSYS 25-Hydroxy Vitamin DS Control Set 2. Predicate 510(k) number(s): k140554 3. Comparison with predicate: Assay: Similarities Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Intended Use Same For the quantitative determination of 25- hydroxyvitamin D in human blood samples. Analyte Same 25-Hydroxy Vitamin D (25(OH)D) 4 Assay: Similarities Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Reagent Storage Same 2-8 °C Sample preparation (pre- treatment) Same Performed on-board the analyzer Sample volume Same 10μL Method of detection (Test methodology) Same Chemiluminescent immunoassay using magnetic-particle solid phase and acridinium label Automation Same Fully automated assay Calibration procedure Same User-initiated 2 point calibration to adjust the batch related master curve. The system stores the calibration for the interval specified in the kit IFU. Traceability/ Standardization Same Traceable to the isotope dilution-liquid chromatography/tandem mass spectrometry (ID-LC-/MS/MS) 25(OH)D Reference Method Procedure (RMP) which was used in assigning the target value for the VDSP samples. The ID-LC-MS/MS RMP is traceable to the National Institute of Standards and Technology Standard Reference Material (SRM) 2972. On board the analyzer reagent stability Same 21 days 5 Assay: Differences Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Kit Calibrator matrix Human serum buffer matrix with two defined concentrations of 25(OH)D and sodium azide as a preservative. Equine serum buffer matrix with two defined concentrations of 25(OH)D and sodium azide as a preservative. Kit reagent components Reagent cartridge (1 vial each of MPV1, NaOH, 25D-ACR, Ab-BIOT & BUF), two concentration levels of calibrators (A&B) (1 vial of each) & a mini CD Reagent cartridge (1 vial each of MPV1, CONJ, NaOH & BUF), two concentration levels of calibrators (A&B) (1 vial of each) & a mini CD Control Kit components Two concentration levels of controls (3 vials of each) Three concentration levels of controls (3 vials of each) Kit reagent component volumes Reagent cartridge (1 vial each): MPV1 (2.5mL), NaOH (13.0mL), 25D-ACR (9.0mL), Ab-BIOT (9.0mL) & BUF (23.0mL) Reagent cartridge (1 vial each): MPV1 (2.0mL), CONJ (10.1mL), NaOH (13mL) & BUF (26.0mL) Antibodies Same, but with a different source of antibody pool Anti-25 OH D Sheep Polyclonal IgG Calibration interval 7 days 14 days Range of assay 4.00 – 110 ng/mL 7 – 125 ng/mL Sensitivity LoB: 1.31 ng/mL LoD: 1.98 ng/mL LoQ: 3.53 ng/mL LoB: 0.6 ng/mL LoD: 2.6 ng/mL LoQ: 7.0 ng/mL Expected values 10.4 to 59.5 ng/mL 12.7 to 64.2 ng/mL In use (after opening at 2-8°C) reagent stability 42 days 21 days Sample type Serum (standard sampling tubes or tubes containing serum separating gel) or plasma (K2 EDTA, lithium heparin, sodium heparin) Serum 6 Controls: Similarities Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Intended Use Same The quality control of the 25- OH vitamin D assay on the IDS-iSYS. Stability Same After opening at 2 - 8 °C: To the expiry date Reagent storage Same 2-8 °C Controls: Differences Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Control matrix Human serum buffer matrix with two defined concentrations of 25-OH D and sodium azide as a preservative. Equine serum buffer matrix with three defined concentrations of 25-OH D and sodium azide as a preservative. Stability On board the analyzer: 4 hours On board the analyzer: 2.5 hours Control levels Level 1: 17 ng/mL Level 2: 90 ng/mL Level 1: 12.0-18.0 ng/mL Level 2: 26.4-39.6 ng/mL Level 3: 59. Purpose for submission:

idK161831_s0_e2000

K161831.txt

measurand

Total 25-hydroxyvitamin D

ANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k161831 B. Purpose for Submission: New device C. Measurand: Total 25-hydroxyvitamin D D. Type of Test: Quantitative chemiluminescent immunoassay E. Applicant: Immunodiagnostic Systems Limited F. Proprietary and Established Names: IDS-iSYS 25VitDS IDS-iSYS 25VitDS Control Set G. Regulatory Information: 1. Regulation section: 1 21 CFR 862.1825, Vitamin D Test System 21 CFR 862.1660, Quality Control Material 2. Classification: Class II Class I, reserved 3. Product code: MRG, Vitamin D Test System JJX, Single (specified) Analyte Controls (Assayed and Unassayed) 4. Panel: 2 Clinical Chemistry (75) H. Intended Use: 1. Intended use(s): See indications for use below. 2. Indication(s) for use: The IDS-iSYS 25 VitDS Assay is intended for the quantitative determination of total 25-hydroxyvitamin D [(25(OH)D] in human serum or plasma on the IDS-iSYS Multi-Discipline Automated System. Results are to be used in conjunction with other clinical and laboratory data to assist the clinician in the assessment of vitamin D sufficiency in an adult population. The IDS-iSYS 25 VitDS Control Set is used for quality control of the IDS-iSYS 25 VitDS assay on the IDS-iSYS Multi- Discipline Automated System. 3. Special conditions for use statement(s): For in vitro diagnostic use only. For prescription use only. 4. Special instrument requirements: For use on the IDS-iSYS Multi- Discipline Automated System. I. Device Description: The IDS-iSYS 25VitDS assay consists of a reagent cartridge (with multiple components) and one set of calibrators. Reagent Cartridge: MPV1 – Magnetic particles coated with streptavidin in phosphate buffer with sodium azide (<0.1%) as preservative (1 bottle, 2.5 mL) NaOH – Sodium hydroxide solution (<0.5 M) (1 bottle, 13.0 mL) 25D ACR – 25D labelled with an acridinium ester derivative, in buffer containing bovine serum albumin with sodium azide (<0.1 %) as preservative (1 bottle, 9.0 mL) Ab-BIOT - Anti-25(OH)D sheep polyclonal antibody labelled with an biotin, in buffer 3 containing bovine, sheep and mouse proteins with sodium azide (<0.1 %) as preservative (1 bottle, 9.0 mL) BUF - Assay buffer containing proprietary displacing compounds, methanol (>10 % but <20%) and sodium azide (<0.1 %) as preservative (1 bottle, 23.0 mL) Calibrators: Kit Calibrators A and B (CAL A & CAL B) (1 bottle of each, 1.5 mL per bottle) contain human serum buffer matrix with two defined concentrations of 25(OH)D and sodium azide (<0.1%) as preservative. Control Set: Controls 1 and 2 (CTL 1 & CTL 2) (3 bottles of each, 2.5 mL per bottle) contain human serum buffer matrix with two defined concentrations of 25(OH)D and sodium azide (<0.1%) as preservative. The target concentrations are 17 ng/mL and 90 ng/mL. Statement in labeling regarding the use of human blood-based materials in calibrators and controls: Human material used in the preparation of this product has been tested by FDA recommended assays for the presence of antibody to Human Immunodeficiency Virus (HIV I and II), Hepatitis B surface antigen, antibody to Hepatitis C, and found negative. J. Substantial Equivalence Information: 1. Predicate device name(s): IDS-iSYS 25-Hydroxy Vitamin DS Assay IDS-iSYS 25-Hydroxy Vitamin DS Control Set 2. Predicate 510(k) number(s): k140554 3. Comparison with predicate: Assay: Similarities Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Intended Use Same For the quantitative determination of 25- hydroxyvitamin D in human blood samples. Analyte Same 25-Hydroxy Vitamin D (25(OH)D) 4 Assay: Similarities Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Reagent Storage Same 2-8 °C Sample preparation (pre- treatment) Same Performed on-board the analyzer Sample volume Same 10μL Method of detection (Test methodology) Same Chemiluminescent immunoassay using magnetic-particle solid phase and acridinium label Automation Same Fully automated assay Calibration procedure Same User-initiated 2 point calibration to adjust the batch related master curve. The system stores the calibration for the interval specified in the kit IFU. Traceability/ Standardization Same Traceable to the isotope dilution-liquid chromatography/tandem mass spectrometry (ID-LC-/MS/MS) 25(OH)D Reference Method Procedure (RMP) which was used in assigning the target value for the VDSP samples. The ID-LC-MS/MS RMP is traceable to the National Institute of Standards and Technology Standard Reference Material (SRM) 2972. On board the analyzer reagent stability Same 21 days 5 Assay: Differences Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Kit Calibrator matrix Human serum buffer matrix with two defined concentrations of 25(OH)D and sodium azide as a preservative. Equine serum buffer matrix with two defined concentrations of 25(OH)D and sodium azide as a preservative. Kit reagent components Reagent cartridge (1 vial each of MPV1, NaOH, 25D-ACR, Ab-BIOT & BUF), two concentration levels of calibrators (A&B) (1 vial of each) & a mini CD Reagent cartridge (1 vial each of MPV1, CONJ, NaOH & BUF), two concentration levels of calibrators (A&B) (1 vial of each) & a mini CD Control Kit components Two concentration levels of controls (3 vials of each) Three concentration levels of controls (3 vials of each) Kit reagent component volumes Reagent cartridge (1 vial each): MPV1 (2.5mL), NaOH (13.0mL), 25D-ACR (9.0mL), Ab-BIOT (9.0mL) & BUF (23.0mL) Reagent cartridge (1 vial each): MPV1 (2.0mL), CONJ (10.1mL), NaOH (13mL) & BUF (26.0mL) Antibodies Same, but with a different source of antibody pool Anti-25 OH D Sheep Polyclonal IgG Calibration interval 7 days 14 days Range of assay 4.00 – 110 ng/mL 7 – 125 ng/mL Sensitivity LoB: 1.31 ng/mL LoD: 1.98 ng/mL LoQ: 3.53 ng/mL LoB: 0.6 ng/mL LoD: 2.6 ng/mL LoQ: 7.0 ng/mL Expected values 10.4 to 59.5 ng/mL 12.7 to 64.2 ng/mL In use (after opening at 2-8°C) reagent stability 42 days 21 days Sample type Serum (standard sampling tubes or tubes containing serum separating gel) or plasma (K2 EDTA, lithium heparin, sodium heparin) Serum 6 Controls: Similarities Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Intended Use Same The quality control of the 25- OH vitamin D assay on the IDS-iSYS. Stability Same After opening at 2 - 8 °C: To the expiry date Reagent storage Same 2-8 °C Controls: Differences Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Control matrix Human serum buffer matrix with two defined concentrations of 25-OH D and sodium azide as a preservative. Equine serum buffer matrix with three defined concentrations of 25-OH D and sodium azide as a preservative. Stability On board the analyzer: 4 hours On board the analyzer: 2.5 hours Control levels Level 1: 17 ng/mL Level 2: 90 ng/mL Level 1: 12.0-18.0 ng/mL Level 2: 26.4-39.6 ng/mL Level 3: 59. Measurand:

idK161831_s0_e2000

K161831.txt

type of test

Quantitative chemiluminescent immunoassay

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k161831 B. Purpose for Submission: New device C. Measurand: Total 25-hydroxyvitamin D D. Type of Test: Quantitative chemiluminescent immunoassay E. Applicant: Immunodiagnostic Systems Limited F. Proprietary and Established Names: IDS-iSYS 25VitDS IDS-iSYS 25VitDS Control Set G. Regulatory Information: 1. Regulation section: 1 21 CFR 862.1825, Vitamin D Test System 21 CFR 862.1660, Quality Control Material 2. Classification: Class II Class I, reserved 3. Product code: MRG, Vitamin D Test System JJX, Single (specified) Analyte Controls (Assayed and Unassayed) 4. Panel: 2 Clinical Chemistry (75) H. Intended Use: 1. Intended use(s): See indications for use below. 2. Indication(s) for use: The IDS-iSYS 25 VitDS Assay is intended for the quantitative determination of total 25-hydroxyvitamin D [(25(OH)D] in human serum or plasma on the IDS-iSYS Multi-Discipline Automated System. Results are to be used in conjunction with other clinical and laboratory data to assist the clinician in the assessment of vitamin D sufficiency in an adult population. The IDS-iSYS 25 VitDS Control Set is used for quality control of the IDS-iSYS 25 VitDS assay on the IDS-iSYS Multi- Discipline Automated System. 3. Special conditions for use statement(s): For in vitro diagnostic use only. For prescription use only. 4. Special instrument requirements: For use on the IDS-iSYS Multi- Discipline Automated System. I. Device Description: The IDS-iSYS 25VitDS assay consists of a reagent cartridge (with multiple components) and one set of calibrators. Reagent Cartridge: MPV1 – Magnetic particles coated with streptavidin in phosphate buffer with sodium azide (<0.1%) as preservative (1 bottle, 2.5 mL) NaOH – Sodium hydroxide solution (<0.5 M) (1 bottle, 13.0 mL) 25D ACR – 25D labelled with an acridinium ester derivative, in buffer containing bovine serum albumin with sodium azide (<0.1 %) as preservative (1 bottle, 9.0 mL) Ab-BIOT - Anti-25(OH)D sheep polyclonal antibody labelled with an biotin, in buffer 3 containing bovine, sheep and mouse proteins with sodium azide (<0.1 %) as preservative (1 bottle, 9.0 mL) BUF - Assay buffer containing proprietary displacing compounds, methanol (>10 % but <20%) and sodium azide (<0.1 %) as preservative (1 bottle, 23.0 mL) Calibrators: Kit Calibrators A and B (CAL A & CAL B) (1 bottle of each, 1.5 mL per bottle) contain human serum buffer matrix with two defined concentrations of 25(OH)D and sodium azide (<0.1%) as preservative. Control Set: Controls 1 and 2 (CTL 1 & CTL 2) (3 bottles of each, 2.5 mL per bottle) contain human serum buffer matrix with two defined concentrations of 25(OH)D and sodium azide (<0.1%) as preservative. The target concentrations are 17 ng/mL and 90 ng/mL. Statement in labeling regarding the use of human blood-based materials in calibrators and controls: Human material used in the preparation of this product has been tested by FDA recommended assays for the presence of antibody to Human Immunodeficiency Virus (HIV I and II), Hepatitis B surface antigen, antibody to Hepatitis C, and found negative. J. Substantial Equivalence Information: 1. Predicate device name(s): IDS-iSYS 25-Hydroxy Vitamin DS Assay IDS-iSYS 25-Hydroxy Vitamin DS Control Set 2. Predicate 510(k) number(s): k140554 3. Comparison with predicate: Assay: Similarities Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Intended Use Same For the quantitative determination of 25- hydroxyvitamin D in human blood samples. Analyte Same 25-Hydroxy Vitamin D (25(OH)D) 4 Assay: Similarities Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Reagent Storage Same 2-8 °C Sample preparation (pre- treatment) Same Performed on-board the analyzer Sample volume Same 10μL Method of detection (Test methodology) Same Chemiluminescent immunoassay using magnetic-particle solid phase and acridinium label Automation Same Fully automated assay Calibration procedure Same User-initiated 2 point calibration to adjust the batch related master curve. The system stores the calibration for the interval specified in the kit IFU. Traceability/ Standardization Same Traceable to the isotope dilution-liquid chromatography/tandem mass spectrometry (ID-LC-/MS/MS) 25(OH)D Reference Method Procedure (RMP) which was used in assigning the target value for the VDSP samples. The ID-LC-MS/MS RMP is traceable to the National Institute of Standards and Technology Standard Reference Material (SRM) 2972. On board the analyzer reagent stability Same 21 days 5 Assay: Differences Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Kit Calibrator matrix Human serum buffer matrix with two defined concentrations of 25(OH)D and sodium azide as a preservative. Equine serum buffer matrix with two defined concentrations of 25(OH)D and sodium azide as a preservative. Kit reagent components Reagent cartridge (1 vial each of MPV1, NaOH, 25D-ACR, Ab-BIOT & BUF), two concentration levels of calibrators (A&B) (1 vial of each) & a mini CD Reagent cartridge (1 vial each of MPV1, CONJ, NaOH & BUF), two concentration levels of calibrators (A&B) (1 vial of each) & a mini CD Control Kit components Two concentration levels of controls (3 vials of each) Three concentration levels of controls (3 vials of each) Kit reagent component volumes Reagent cartridge (1 vial each): MPV1 (2.5mL), NaOH (13.0mL), 25D-ACR (9.0mL), Ab-BIOT (9.0mL) & BUF (23.0mL) Reagent cartridge (1 vial each): MPV1 (2.0mL), CONJ (10.1mL), NaOH (13mL) & BUF (26.0mL) Antibodies Same, but with a different source of antibody pool Anti-25 OH D Sheep Polyclonal IgG Calibration interval 7 days 14 days Range of assay 4.00 – 110 ng/mL 7 – 125 ng/mL Sensitivity LoB: 1.31 ng/mL LoD: 1.98 ng/mL LoQ: 3.53 ng/mL LoB: 0.6 ng/mL LoD: 2.6 ng/mL LoQ: 7.0 ng/mL Expected values 10.4 to 59.5 ng/mL 12.7 to 64.2 ng/mL In use (after opening at 2-8°C) reagent stability 42 days 21 days Sample type Serum (standard sampling tubes or tubes containing serum separating gel) or plasma (K2 EDTA, lithium heparin, sodium heparin) Serum 6 Controls: Similarities Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Intended Use Same The quality control of the 25- OH vitamin D assay on the IDS-iSYS. Stability Same After opening at 2 - 8 °C: To the expiry date Reagent storage Same 2-8 °C Controls: Differences Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Control matrix Human serum buffer matrix with two defined concentrations of 25-OH D and sodium azide as a preservative. Equine serum buffer matrix with three defined concentrations of 25-OH D and sodium azide as a preservative. Stability On board the analyzer: 4 hours On board the analyzer: 2.5 hours Control levels Level 1: 17 ng/mL Level 2: 90 ng/mL Level 1: 12.0-18.0 ng/mL Level 2: 26.4-39.6 ng/mL Level 3: 59. Type of test:

idK161831_s0_e2000

K161831.txt

panel

Clinical Chemistry (75)

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k161831 B. Purpose for Submission: New device C. Measurand: Total 25-hydroxyvitamin D D. Type of Test: Quantitative chemiluminescent immunoassay E. Applicant: Immunodiagnostic Systems Limited F. Proprietary and Established Names: IDS-iSYS 25VitDS IDS-iSYS 25VitDS Control Set G. Regulatory Information: 1. Regulation section: 1 21 CFR 862.1825, Vitamin D Test System 21 CFR 862.1660, Quality Control Material 2. Classification: Class II Class I, reserved 3. Product code: MRG, Vitamin D Test System JJX, Single (specified) Analyte Controls (Assayed and Unassayed) 4. Panel: 2 Clinical Chemistry (75) H. Intended Use: 1. Intended use(s): See indications for use below. 2. Indication(s) for use: The IDS-iSYS 25 VitDS Assay is intended for the quantitative determination of total 25-hydroxyvitamin D [(25(OH)D] in human serum or plasma on the IDS-iSYS Multi-Discipline Automated System. Results are to be used in conjunction with other clinical and laboratory data to assist the clinician in the assessment of vitamin D sufficiency in an adult population. The IDS-iSYS 25 VitDS Control Set is used for quality control of the IDS-iSYS 25 VitDS assay on the IDS-iSYS Multi- Discipline Automated System. 3. Special conditions for use statement(s): For in vitro diagnostic use only. For prescription use only. 4. Special instrument requirements: For use on the IDS-iSYS Multi- Discipline Automated System. I. Device Description: The IDS-iSYS 25VitDS assay consists of a reagent cartridge (with multiple components) and one set of calibrators. Reagent Cartridge: MPV1 – Magnetic particles coated with streptavidin in phosphate buffer with sodium azide (<0.1%) as preservative (1 bottle, 2.5 mL) NaOH – Sodium hydroxide solution (<0.5 M) (1 bottle, 13.0 mL) 25D ACR – 25D labelled with an acridinium ester derivative, in buffer containing bovine serum albumin with sodium azide (<0.1 %) as preservative (1 bottle, 9.0 mL) Ab-BIOT - Anti-25(OH)D sheep polyclonal antibody labelled with an biotin, in buffer 3 containing bovine, sheep and mouse proteins with sodium azide (<0.1 %) as preservative (1 bottle, 9.0 mL) BUF - Assay buffer containing proprietary displacing compounds, methanol (>10 % but <20%) and sodium azide (<0.1 %) as preservative (1 bottle, 23.0 mL) Calibrators: Kit Calibrators A and B (CAL A & CAL B) (1 bottle of each, 1.5 mL per bottle) contain human serum buffer matrix with two defined concentrations of 25(OH)D and sodium azide (<0.1%) as preservative. Control Set: Controls 1 and 2 (CTL 1 & CTL 2) (3 bottles of each, 2.5 mL per bottle) contain human serum buffer matrix with two defined concentrations of 25(OH)D and sodium azide (<0.1%) as preservative. The target concentrations are 17 ng/mL and 90 ng/mL. Statement in labeling regarding the use of human blood-based materials in calibrators and controls: Human material used in the preparation of this product has been tested by FDA recommended assays for the presence of antibody to Human Immunodeficiency Virus (HIV I and II), Hepatitis B surface antigen, antibody to Hepatitis C, and found negative. J. Substantial Equivalence Information: 1. Predicate device name(s): IDS-iSYS 25-Hydroxy Vitamin DS Assay IDS-iSYS 25-Hydroxy Vitamin DS Control Set 2. Predicate 510(k) number(s): k140554 3. Comparison with predicate: Assay: Similarities Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Intended Use Same For the quantitative determination of 25- hydroxyvitamin D in human blood samples. Analyte Same 25-Hydroxy Vitamin D (25(OH)D) 4 Assay: Similarities Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Reagent Storage Same 2-8 °C Sample preparation (pre- treatment) Same Performed on-board the analyzer Sample volume Same 10μL Method of detection (Test methodology) Same Chemiluminescent immunoassay using magnetic-particle solid phase and acridinium label Automation Same Fully automated assay Calibration procedure Same User-initiated 2 point calibration to adjust the batch related master curve. The system stores the calibration for the interval specified in the kit IFU. Traceability/ Standardization Same Traceable to the isotope dilution-liquid chromatography/tandem mass spectrometry (ID-LC-/MS/MS) 25(OH)D Reference Method Procedure (RMP) which was used in assigning the target value for the VDSP samples. The ID-LC-MS/MS RMP is traceable to the National Institute of Standards and Technology Standard Reference Material (SRM) 2972. On board the analyzer reagent stability Same 21 days 5 Assay: Differences Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Kit Calibrator matrix Human serum buffer matrix with two defined concentrations of 25(OH)D and sodium azide as a preservative. Equine serum buffer matrix with two defined concentrations of 25(OH)D and sodium azide as a preservative. Kit reagent components Reagent cartridge (1 vial each of MPV1, NaOH, 25D-ACR, Ab-BIOT & BUF), two concentration levels of calibrators (A&B) (1 vial of each) & a mini CD Reagent cartridge (1 vial each of MPV1, CONJ, NaOH & BUF), two concentration levels of calibrators (A&B) (1 vial of each) & a mini CD Control Kit components Two concentration levels of controls (3 vials of each) Three concentration levels of controls (3 vials of each) Kit reagent component volumes Reagent cartridge (1 vial each): MPV1 (2.5mL), NaOH (13.0mL), 25D-ACR (9.0mL), Ab-BIOT (9.0mL) & BUF (23.0mL) Reagent cartridge (1 vial each): MPV1 (2.0mL), CONJ (10.1mL), NaOH (13mL) & BUF (26.0mL) Antibodies Same, but with a different source of antibody pool Anti-25 OH D Sheep Polyclonal IgG Calibration interval 7 days 14 days Range of assay 4.00 – 110 ng/mL 7 – 125 ng/mL Sensitivity LoB: 1.31 ng/mL LoD: 1.98 ng/mL LoQ: 3.53 ng/mL LoB: 0.6 ng/mL LoD: 2.6 ng/mL LoQ: 7.0 ng/mL Expected values 10.4 to 59.5 ng/mL 12.7 to 64.2 ng/mL In use (after opening at 2-8°C) reagent stability 42 days 21 days Sample type Serum (standard sampling tubes or tubes containing serum separating gel) or plasma (K2 EDTA, lithium heparin, sodium heparin) Serum 6 Controls: Similarities Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Intended Use Same The quality control of the 25- OH vitamin D assay on the IDS-iSYS. Stability Same After opening at 2 - 8 °C: To the expiry date Reagent storage Same 2-8 °C Controls: Differences Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Control matrix Human serum buffer matrix with two defined concentrations of 25-OH D and sodium azide as a preservative. Equine serum buffer matrix with three defined concentrations of 25-OH D and sodium azide as a preservative. Stability On board the analyzer: 4 hours On board the analyzer: 2.5 hours Control levels Level 1: 17 ng/mL Level 2: 90 ng/mL Level 1: 12.0-18.0 ng/mL Level 2: 26.4-39.6 ng/mL Level 3: 59. Panel:

idK161831_s0_e2000

K161831.txt

intended use

See indications for use below.

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k161831 B. Purpose for Submission: New device C. Measurand: Total 25-hydroxyvitamin D D. Type of Test: Quantitative chemiluminescent immunoassay E. Applicant: Immunodiagnostic Systems Limited F. Proprietary and Established Names: IDS-iSYS 25VitDS IDS-iSYS 25VitDS Control Set G. Regulatory Information: 1. Regulation section: 1 21 CFR 862.1825, Vitamin D Test System 21 CFR 862.1660, Quality Control Material 2. Classification: Class II Class I, reserved 3. Product code: MRG, Vitamin D Test System JJX, Single (specified) Analyte Controls (Assayed and Unassayed) 4. Panel: 2 Clinical Chemistry (75) H. Intended Use: 1. Intended use(s): See indications for use below. 2. Indication(s) for use: The IDS-iSYS 25 VitDS Assay is intended for the quantitative determination of total 25-hydroxyvitamin D [(25(OH)D] in human serum or plasma on the IDS-iSYS Multi-Discipline Automated System. Results are to be used in conjunction with other clinical and laboratory data to assist the clinician in the assessment of vitamin D sufficiency in an adult population. The IDS-iSYS 25 VitDS Control Set is used for quality control of the IDS-iSYS 25 VitDS assay on the IDS-iSYS Multi- Discipline Automated System. 3. Special conditions for use statement(s): For in vitro diagnostic use only. For prescription use only. 4. Special instrument requirements: For use on the IDS-iSYS Multi- Discipline Automated System. I. Device Description: The IDS-iSYS 25VitDS assay consists of a reagent cartridge (with multiple components) and one set of calibrators. Reagent Cartridge: MPV1 – Magnetic particles coated with streptavidin in phosphate buffer with sodium azide (<0.1%) as preservative (1 bottle, 2.5 mL) NaOH – Sodium hydroxide solution (<0.5 M) (1 bottle, 13.0 mL) 25D ACR – 25D labelled with an acridinium ester derivative, in buffer containing bovine serum albumin with sodium azide (<0.1 %) as preservative (1 bottle, 9.0 mL) Ab-BIOT - Anti-25(OH)D sheep polyclonal antibody labelled with an biotin, in buffer 3 containing bovine, sheep and mouse proteins with sodium azide (<0.1 %) as preservative (1 bottle, 9.0 mL) BUF - Assay buffer containing proprietary displacing compounds, methanol (>10 % but <20%) and sodium azide (<0.1 %) as preservative (1 bottle, 23.0 mL) Calibrators: Kit Calibrators A and B (CAL A & CAL B) (1 bottle of each, 1.5 mL per bottle) contain human serum buffer matrix with two defined concentrations of 25(OH)D and sodium azide (<0.1%) as preservative. Control Set: Controls 1 and 2 (CTL 1 & CTL 2) (3 bottles of each, 2.5 mL per bottle) contain human serum buffer matrix with two defined concentrations of 25(OH)D and sodium azide (<0.1%) as preservative. The target concentrations are 17 ng/mL and 90 ng/mL. Statement in labeling regarding the use of human blood-based materials in calibrators and controls: Human material used in the preparation of this product has been tested by FDA recommended assays for the presence of antibody to Human Immunodeficiency Virus (HIV I and II), Hepatitis B surface antigen, antibody to Hepatitis C, and found negative. J. Substantial Equivalence Information: 1. Predicate device name(s): IDS-iSYS 25-Hydroxy Vitamin DS Assay IDS-iSYS 25-Hydroxy Vitamin DS Control Set 2. Predicate 510(k) number(s): k140554 3. Comparison with predicate: Assay: Similarities Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Intended Use Same For the quantitative determination of 25- hydroxyvitamin D in human blood samples. Analyte Same 25-Hydroxy Vitamin D (25(OH)D) 4 Assay: Similarities Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Reagent Storage Same 2-8 °C Sample preparation (pre- treatment) Same Performed on-board the analyzer Sample volume Same 10μL Method of detection (Test methodology) Same Chemiluminescent immunoassay using magnetic-particle solid phase and acridinium label Automation Same Fully automated assay Calibration procedure Same User-initiated 2 point calibration to adjust the batch related master curve. The system stores the calibration for the interval specified in the kit IFU. Traceability/ Standardization Same Traceable to the isotope dilution-liquid chromatography/tandem mass spectrometry (ID-LC-/MS/MS) 25(OH)D Reference Method Procedure (RMP) which was used in assigning the target value for the VDSP samples. The ID-LC-MS/MS RMP is traceable to the National Institute of Standards and Technology Standard Reference Material (SRM) 2972. On board the analyzer reagent stability Same 21 days 5 Assay: Differences Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Kit Calibrator matrix Human serum buffer matrix with two defined concentrations of 25(OH)D and sodium azide as a preservative. Equine serum buffer matrix with two defined concentrations of 25(OH)D and sodium azide as a preservative. Kit reagent components Reagent cartridge (1 vial each of MPV1, NaOH, 25D-ACR, Ab-BIOT & BUF), two concentration levels of calibrators (A&B) (1 vial of each) & a mini CD Reagent cartridge (1 vial each of MPV1, CONJ, NaOH & BUF), two concentration levels of calibrators (A&B) (1 vial of each) & a mini CD Control Kit components Two concentration levels of controls (3 vials of each) Three concentration levels of controls (3 vials of each) Kit reagent component volumes Reagent cartridge (1 vial each): MPV1 (2.5mL), NaOH (13.0mL), 25D-ACR (9.0mL), Ab-BIOT (9.0mL) & BUF (23.0mL) Reagent cartridge (1 vial each): MPV1 (2.0mL), CONJ (10.1mL), NaOH (13mL) & BUF (26.0mL) Antibodies Same, but with a different source of antibody pool Anti-25 OH D Sheep Polyclonal IgG Calibration interval 7 days 14 days Range of assay 4.00 – 110 ng/mL 7 – 125 ng/mL Sensitivity LoB: 1.31 ng/mL LoD: 1.98 ng/mL LoQ: 3.53 ng/mL LoB: 0.6 ng/mL LoD: 2.6 ng/mL LoQ: 7.0 ng/mL Expected values 10.4 to 59.5 ng/mL 12.7 to 64.2 ng/mL In use (after opening at 2-8°C) reagent stability 42 days 21 days Sample type Serum (standard sampling tubes or tubes containing serum separating gel) or plasma (K2 EDTA, lithium heparin, sodium heparin) Serum 6 Controls: Similarities Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Intended Use Same The quality control of the 25- OH vitamin D assay on the IDS-iSYS. Stability Same After opening at 2 - 8 °C: To the expiry date Reagent storage Same 2-8 °C Controls: Differences Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Control matrix Human serum buffer matrix with two defined concentrations of 25-OH D and sodium azide as a preservative. Equine serum buffer matrix with three defined concentrations of 25-OH D and sodium azide as a preservative. Stability On board the analyzer: 4 hours On board the analyzer: 2.5 hours Control levels Level 1: 17 ng/mL Level 2: 90 ng/mL Level 1: 12.0-18.0 ng/mL Level 2: 26.4-39.6 ng/mL Level 3: 59. Intended use:

idK161831_s0_e2000

K161831.txt

applicant

Immunodiagnostic Systems Limited

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k161831 B. Purpose for Submission: New device C. Measurand: Total 25-hydroxyvitamin D D. Type of Test: Quantitative chemiluminescent immunoassay E. Applicant: Immunodiagnostic Systems Limited F. Proprietary and Established Names: IDS-iSYS 25VitDS IDS-iSYS 25VitDS Control Set G. Regulatory Information: 1. Regulation section: 1 21 CFR 862.1825, Vitamin D Test System 21 CFR 862.1660, Quality Control Material 2. Classification: Class II Class I, reserved 3. Product code: MRG, Vitamin D Test System JJX, Single (specified) Analyte Controls (Assayed and Unassayed) 4. Panel: 2 Clinical Chemistry (75) H. Intended Use: 1. Intended use(s): See indications for use below. 2. Indication(s) for use: The IDS-iSYS 25 VitDS Assay is intended for the quantitative determination of total 25-hydroxyvitamin D [(25(OH)D] in human serum or plasma on the IDS-iSYS Multi-Discipline Automated System. Results are to be used in conjunction with other clinical and laboratory data to assist the clinician in the assessment of vitamin D sufficiency in an adult population. The IDS-iSYS 25 VitDS Control Set is used for quality control of the IDS-iSYS 25 VitDS assay on the IDS-iSYS Multi- Discipline Automated System. 3. Special conditions for use statement(s): For in vitro diagnostic use only. For prescription use only. 4. Special instrument requirements: For use on the IDS-iSYS Multi- Discipline Automated System. I. Device Description: The IDS-iSYS 25VitDS assay consists of a reagent cartridge (with multiple components) and one set of calibrators. Reagent Cartridge: MPV1 – Magnetic particles coated with streptavidin in phosphate buffer with sodium azide (<0.1%) as preservative (1 bottle, 2.5 mL) NaOH – Sodium hydroxide solution (<0.5 M) (1 bottle, 13.0 mL) 25D ACR – 25D labelled with an acridinium ester derivative, in buffer containing bovine serum albumin with sodium azide (<0.1 %) as preservative (1 bottle, 9.0 mL) Ab-BIOT - Anti-25(OH)D sheep polyclonal antibody labelled with an biotin, in buffer 3 containing bovine, sheep and mouse proteins with sodium azide (<0.1 %) as preservative (1 bottle, 9.0 mL) BUF - Assay buffer containing proprietary displacing compounds, methanol (>10 % but <20%) and sodium azide (<0.1 %) as preservative (1 bottle, 23.0 mL) Calibrators: Kit Calibrators A and B (CAL A & CAL B) (1 bottle of each, 1.5 mL per bottle) contain human serum buffer matrix with two defined concentrations of 25(OH)D and sodium azide (<0.1%) as preservative. Control Set: Controls 1 and 2 (CTL 1 & CTL 2) (3 bottles of each, 2.5 mL per bottle) contain human serum buffer matrix with two defined concentrations of 25(OH)D and sodium azide (<0.1%) as preservative. The target concentrations are 17 ng/mL and 90 ng/mL. Statement in labeling regarding the use of human blood-based materials in calibrators and controls: Human material used in the preparation of this product has been tested by FDA recommended assays for the presence of antibody to Human Immunodeficiency Virus (HIV I and II), Hepatitis B surface antigen, antibody to Hepatitis C, and found negative. J. Substantial Equivalence Information: 1. Predicate device name(s): IDS-iSYS 25-Hydroxy Vitamin DS Assay IDS-iSYS 25-Hydroxy Vitamin DS Control Set 2. Predicate 510(k) number(s): k140554 3. Comparison with predicate: Assay: Similarities Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Intended Use Same For the quantitative determination of 25- hydroxyvitamin D in human blood samples. Analyte Same 25-Hydroxy Vitamin D (25(OH)D) 4 Assay: Similarities Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Reagent Storage Same 2-8 °C Sample preparation (pre- treatment) Same Performed on-board the analyzer Sample volume Same 10μL Method of detection (Test methodology) Same Chemiluminescent immunoassay using magnetic-particle solid phase and acridinium label Automation Same Fully automated assay Calibration procedure Same User-initiated 2 point calibration to adjust the batch related master curve. The system stores the calibration for the interval specified in the kit IFU. Traceability/ Standardization Same Traceable to the isotope dilution-liquid chromatography/tandem mass spectrometry (ID-LC-/MS/MS) 25(OH)D Reference Method Procedure (RMP) which was used in assigning the target value for the VDSP samples. The ID-LC-MS/MS RMP is traceable to the National Institute of Standards and Technology Standard Reference Material (SRM) 2972. On board the analyzer reagent stability Same 21 days 5 Assay: Differences Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Kit Calibrator matrix Human serum buffer matrix with two defined concentrations of 25(OH)D and sodium azide as a preservative. Equine serum buffer matrix with two defined concentrations of 25(OH)D and sodium azide as a preservative. Kit reagent components Reagent cartridge (1 vial each of MPV1, NaOH, 25D-ACR, Ab-BIOT & BUF), two concentration levels of calibrators (A&B) (1 vial of each) & a mini CD Reagent cartridge (1 vial each of MPV1, CONJ, NaOH & BUF), two concentration levels of calibrators (A&B) (1 vial of each) & a mini CD Control Kit components Two concentration levels of controls (3 vials of each) Three concentration levels of controls (3 vials of each) Kit reagent component volumes Reagent cartridge (1 vial each): MPV1 (2.5mL), NaOH (13.0mL), 25D-ACR (9.0mL), Ab-BIOT (9.0mL) & BUF (23.0mL) Reagent cartridge (1 vial each): MPV1 (2.0mL), CONJ (10.1mL), NaOH (13mL) & BUF (26.0mL) Antibodies Same, but with a different source of antibody pool Anti-25 OH D Sheep Polyclonal IgG Calibration interval 7 days 14 days Range of assay 4.00 – 110 ng/mL 7 – 125 ng/mL Sensitivity LoB: 1.31 ng/mL LoD: 1.98 ng/mL LoQ: 3.53 ng/mL LoB: 0.6 ng/mL LoD: 2.6 ng/mL LoQ: 7.0 ng/mL Expected values 10.4 to 59.5 ng/mL 12.7 to 64.2 ng/mL In use (after opening at 2-8°C) reagent stability 42 days 21 days Sample type Serum (standard sampling tubes or tubes containing serum separating gel) or plasma (K2 EDTA, lithium heparin, sodium heparin) Serum 6 Controls: Similarities Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Intended Use Same The quality control of the 25- OH vitamin D assay on the IDS-iSYS. Stability Same After opening at 2 - 8 °C: To the expiry date Reagent storage Same 2-8 °C Controls: Differences Item Candidate Device IDS-iSYS 25VitDS Predicate IDS-iSYS 25-Hydroxy Vitamin DS (k140554) Control matrix Human serum buffer matrix with two defined concentrations of 25-OH D and sodium azide as a preservative. Equine serum buffer matrix with three defined concentrations of 25-OH D and sodium azide as a preservative. Stability On board the analyzer: 4 hours On board the analyzer: 2.5 hours Control levels Level 1: 17 ng/mL Level 2: 90 ng/mL Level 1: 12.0-18.0 ng/mL Level 2: 26.4-39.6 ng/mL Level 3: 59. Applicant:

idK161831_s6000_e8000

K161831.txt

proposed labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

ok regression analysis was performed on the comparative data: 14 n Slope (ng/mL) [95% CI] Intercept (ng/mL) [95% CI] Correlation Coefficient (r) Sample range tested (ng/mL) 136 0.99 [0.94 to 1.05] -0.51 [-1.93 to 0.75] 0.97 5.6-110 b. Matrix comparison: A matrix comparison study using the IDS-iSYS 25 VitDS assay was performed according to CLSI EP09-A3 to evaluate the difference between serum (serum without additives, SST) and plasma (lithium heparin, sodium heparin, K2 EDTA). Sixty-seven (67) samples, ranging from 4.8 to 108 ng/mL, were tested with ten of these samples spiked in order to cover the measuring range. Passing-Bablok regression analysis was performed on the comparative data relative to serum with no additives: Sample Type Slope (ng/mL) [95% CI] Intercept (ng/mL) [95% CI] R2 Serum – SST 0.98 [0.94 to 1.02] 0.18 [-0.31 to 1.12] 0.99 Plasma – K2 EDTA 0.96 [0.94 to 0.98] 0.05 [-0.31 to 0.59] 1.00 Plasma – Lithium Heparin 0.98 [0.93 to 1.01] 0.22 [-0.52 to 0.86] 1.00 Plasma – Sodium Heparin 0.99 [0.95 to 1.02] 0.05 [-0.66 to 0.71] 0.99 The results of the matrix comparison study support the sponsor’s claim that serum as well as K2 EDTA, Lithium Heparin, and Sodium Heparin are acceptable sample types for this device. 3. Clinical studies: a. Clinical Sensitivity: Not applicable. b. Clinical specificity: Not applicable. c. Other clinical supportive data (when a. and b. are not applicable): Not applicable. 4. Clinical cut-off: 15 Not applicable. 5. Expected values/Reference range: An expected value study was performed according to the non-parametric method in CLSI C28-A3c. Samples were collected from 392 apparently healthy male (51%) and female (49%) adults, aged 21-89 years, during winter and summer seasons and from geographically diverse regions of the United States. This overall diversity in, geographic location, race, and ethnicity represents a broad spectrum of UV light exposure in the intended use population. The samples were tested for 25(OH)D concentrations using the IDS-iSYS 25 VitDS assay. The 2.5th to 97.5th reference interval is shown below: 25-OH vitamin D expected values for adults: 10.4 to 59.5 ng/mL (n = 392) N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK161831_s6000_e8000

K161831.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

Bablok regression analysis was performed on the comparative data: 14 n Slope (ng/mL) [95% CI] Intercept (ng/mL) [95% CI] Correlation Coefficient (r) Sample range tested (ng/mL) 136 0.99 [0.94 to 1.05] -0.51 [-1.93 to 0.75] 0.97 5.6-110 b. Matrix comparison: A matrix comparison study using the IDS-iSYS 25 VitDS assay was performed according to CLSI EP09-A3 to evaluate the difference between serum (serum without additives, SST) and plasma (lithium heparin, sodium heparin, K2 EDTA). Sixty-seven (67) samples, ranging from 4.8 to 108 ng/mL, were tested with ten of these samples spiked in order to cover the measuring range. Passing-Bablok regression analysis was performed on the comparative data relative to serum with no additives: Sample Type Slope (ng/mL) [95% CI] Intercept (ng/mL) [95% CI] R2 Serum – SST 0.98 [0.94 to 1.02] 0.18 [-0.31 to 1.12] 0.99 Plasma – K2 EDTA 0.96 [0.94 to 0.98] 0.05 [-0.31 to 0.59] 1.00 Plasma – Lithium Heparin 0.98 [0.93 to 1.01] 0.22 [-0.52 to 0.86] 1.00 Plasma – Sodium Heparin 0.99 [0.95 to 1.02] 0.05 [-0.66 to 0.71] 0.99 The results of the matrix comparison study support the sponsor’s claim that serum as well as K2 EDTA, Lithium Heparin, and Sodium Heparin are acceptable sample types for this device. 3. Clinical studies: a. Clinical Sensitivity: Not applicable. b. Clinical specificity: Not applicable. c. Other clinical supportive data (when a. and b. are not applicable): Not applicable. 4. Clinical cut-off: 15 Not applicable. 5. Expected values/Reference range: An expected value study was performed according to the non-parametric method in CLSI C28-A3c. Samples were collected from 392 apparently healthy male (51%) and female (49%) adults, aged 21-89 years, during winter and summer seasons and from geographically diverse regions of the United States. This overall diversity in, geographic location, race, and ethnicity represents a broad spectrum of UV light exposure in the intended use population. The samples were tested for 25(OH)D concentrations using the IDS-iSYS 25 VitDS assay. The 2.5th to 97.5th reference interval is shown below: 25-OH vitamin D expected values for adults: 10.4 to 59.5 ng/mL (n = 392) N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK183462_s0_e2000

K183462.txt

purpose for submission

Clearance of the Applied Biosystems Bacillus anthracis Detection Kit on the Applied Biosystems (AB) 7500 Fast Dx instrument and Applied Biosystems Bacillus anthracis Interpretive Software (BaIS).

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K183462 B. Purpose for Submission: Clearance of the Applied Biosystems Bacillus anthracis Detection Kit on the Applied Biosystems (AB) 7500 Fast Dx instrument and Applied Biosystems Bacillus anthracis Interpretive Software (BaIS). C. Measurand: Nucleic acid sequences of Bacillus anthracis pX01 and pX02 plasmids D. Type of Test: Real-time polymerase chain reaction E. Applicant: MRIGlobal F. Proprietary and Established Names: Applied Biosystems Bacillus anthracis Detection Kit Applied Biosystems (AB) 7500 Fast Dx G. Regulatory Information: 1. Regulation section: CFR 866.4000 2. Classification: Class II 3. Product code: QIF, OOI 4. Panel: 83- Microbiology H. Intended Use: 1. Intended use The Applied Biosystems Bacillus anthracis Detection Kit is a real-time polymerase chain reaction (PCR) test kit intended for the qualitative in vitro diagnostic (IVD) detection of target DNA 2 sequences for Bacillus anthracis (B. anthracis, or BA). The Applied Biosystems Bacillus anthracis Detection Kit is intended to test human whole blood (EDTA) specimens and blood culture specimens with growth detected by a continuous monitoring blood culture system. Blood culture specimens must be determined to contain gram-positive bacilli by Gram stain prior to testing. Testing of whole blood specimens must be performed concomitantly with standard of care blood culture. The Applied Biosystems Bacillus anthracis Detection Kit is indicated for use in CLIA-certified high- complexity laboratories in response to a confirmed Bacillus anthracis event only in accordance with the guidelines provided by public health authorities prior to or during a public health emergency. Testing with the Applied Biosystems Bacillus anthracis Detection Kit must only be performed when public health authorities have determined the need for this test. The test must only be used with specimens from individuals with clinical signs and symptoms of B. anthracis infection and who have either been exposed to B. anthracis or may have been exposed to B anthracis. The Applied Biosystems Bacillus anthracis Detection Kit is intended for use as an aid in the diagnosis of anthrax infection and results are for the presumptive identification of Bacillus anthracis. The diagnosis of B. anthracis infection must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidence, in addition to the identification of B. anthracis from cultures or directly from clinical specimens. The definitive identification of B. anthracis requires additional testing and confirmation procedures in consultation with the appropriate public health authorities for whom reports may be required. The Applied Biosystems Bacillus anthracis Detection Kit has not been clinically evaluated with specimens collected from individuals with B. anthracis infection or those presumed to be exposed to B. anthracis. ‘B. anthracis Not detected’ results do not preclude infection with Bacillus anthracis and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. Laboratories implementing this test must have the appropriate biosafety equipment, personal protective equipment (PPE), containment facilities and personnel trained in the safe handling of diagnostic clinical specimens potentially containing B. anthracis. Anthrax is a nationally notifiable disease caused by a biothreat microbial agent and must be reported to public health authorities. The distribution of in vitro diagnostic devices for Bacillus spp. detection is limited to laboratories that follow public health guidelines that address appropriate biosafety conditions, interpretation of test results, and coordination of findings with public health authorities. The Applied Biosystems Bacillus anthracis Detection Kit is intended for use with the ABI 7500 Fast Dx Real-Time PCR Instrument with analysis using the Applied Biosystems Bacillus anthracis Interpretive Software (BaIS). 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): • For Prescription Use Only • Laboratories must maintain records of completed manufacturer required training including training related to use of the assay, instrumentation, biosafety precautions, appropriate PPE and contamination control and waste disposal. • Laboratories must maintain manufacturer required documentation verifying the laboratory is 3 certified as high-complexity, has appropriate biosafety equipment and PPE as required per assay instructions and has procedures for following public health guidelines for working with specimens containing B. anthracis. • Laboratories must maintain manufacturer required documentation verifying the laboratory has procedures for following applicable state, local and federal public health regulations for reporting results and for referring specimens and or isolates to their public health reference laboratory. 4. Special instrument requirements: MagNA Pure LC 2.0 extraction System, Roche Applied Biosystems (AB) 7500 Fast Dx Real-Time PCR Instrument with Sequence Detection System (SDS), Thermo Fisher Scientific (Life Technologies) I. Device Description: The Applied Biosystems Bacillus anthracis Detection Kit is a multiplexed real-time polymerase chain reaction (PCR) test kit intended for the qualitative detection of B. anthracis DNA sequences. PCR reagents are lyophilized in PCR well strips and run in a 96-well plate format. The kit is designed for performing real- time PCR using the Applied Biosystems (AB) 7500 Fast Dx instrument and software, with nucleic acids extracted from clinical specimens using either a Qiagen manual extraction method using Qiagen’s QIAamp DSP DNA Blood Mini Kit (DSP) or Roche’s MagNA Pure LC 2.0 Robot (MagNA Pure, MNP). Roche MagNA Pure is an automated extraction method. An automated interpretative software component (BaIS) is included in the kit, but supplied separately, and operates on a separate computer from the AB 7500 Fast Dx computer. 4 Materials provided Materials Provided in the Applied Biosystem Bacillus anthracis Detection Kit Part Name Quantity and Content Storage Conditions Applied Biosystems Bacillus anthracis Test Kit Lyophilized Assay Plates 10 Plates; Each plate contains a lyophilized Mastermix and primers/probes specific for the Bacillus anthracis 3-plex assay; each plate is individually sealed and foil-wrapped. Ambient or room temperature (20°C – 25°C) Applied Biosystems Bacillus anthracis Test Kit Controls 1 box contains 1 vial of External Positive Control (EPC) and 1 vial of External Negative Control (ENC); Each vial contains enough reagent volume for approximately 10 PCR reactions; no further dilution of the control reagent is necessary. See below for final concentrations of control targets per 20 µl PCR reaction. Frozen (-15°C to -25°C) Applied Biosystems Bacillus anthracis Interpretive Software (BaIS) Version 1.0 1 BaIS Interpretive Software Server Installer; 1 BaIS Interpretive Software Client Installer. Not applicable External Controls and Final Target Concentration External Control Final Target Concentration per Reaction EPC pX01 (100fg), pX02 (200fg) and TERT (750fg) ENC E. coli DNA (4.8ng) Equipment and materials required but not supplied Equipment • Applied Biosystem 7500 Fast Dx Real-Time PCR Instrument with Sequence Detection System (SDS), Thermo Fisher Scientific (Life Technologies) • Separate computer for installation of Applied Biosystems Bacillus anthracis Interpretive Software (BaIS) Version 1.0 (It is not recommended to install and run BaIS on Applied Biosystems 7500 Fast Dx Real-Time PCR instrument computer) • MagNA Pure LC 2.0 Robot, Roche • Automated blood culture monitoring system (for testing blood culture samples only) • Biosafety cabinet (BSC) (Class II, Type A or B) • 2-8°C Refrigerator • < -20°C Freezer • < -70°C Freezer • Plate centrifuge compatible with Applied Biosystems MicroAmp Fast Optical 96-Well Reaction Plate, 0.1 mL, with at least 1000 rpm centrifuging speed 5 • Microcentrifuge, able to hold 2 mL tubes and capable of reaching 20,800 x g • Vortexer • Heat block capable of 56°C with insert for 2 mL tubes • Micropipette 1000 µL, 200 µL, 20 µL • Caplocks for 2 mL microcentrifuge tubes Consumables and Reagents • QIAamp DSP DNA Blood Mini Kit (IVD), Qiagen (DSP) • 100% Ethanol • Nuclease-free water • MagNA Pure LC DNA Isolation Kit – Large Volume, Roche • Blood culture bottles, aerobic and/or anaerobic (for testing blood culture samples only) • Aerosol-resistant filter tips for micropipettes – 1000 µL, 200 µL, 20 µL • Serological pipets – 50 mL, 25 mL, 10 mL, 5 mL • Optical plate film (seals) for 96-well PCR plates, compatible with AB7500 Fast Dx • Clean RNase- and DNase-free 2.0 mL microcentrifuge tubes J. Substantial Equivalence Purpose for submission:

idK183462_s0_e2000

K183462.txt

measurand

Nucleic acid sequences of Bacillus anthracis pX01 and pX02 plasmids

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K183462 B. Purpose for Submission: Clearance of the Applied Biosystems Bacillus anthracis Detection Kit on the Applied Biosystems (AB) 7500 Fast Dx instrument and Applied Biosystems Bacillus anthracis Interpretive Software (BaIS). C. Measurand: Nucleic acid sequences of Bacillus anthracis pX01 and pX02 plasmids D. Type of Test: Real-time polymerase chain reaction E. Applicant: MRIGlobal F. Proprietary and Established Names: Applied Biosystems Bacillus anthracis Detection Kit Applied Biosystems (AB) 7500 Fast Dx G. Regulatory Information: 1. Regulation section: CFR 866.4000 2. Classification: Class II 3. Product code: QIF, OOI 4. Panel: 83- Microbiology H. Intended Use: 1. Intended use The Applied Biosystems Bacillus anthracis Detection Kit is a real-time polymerase chain reaction (PCR) test kit intended for the qualitative in vitro diagnostic (IVD) detection of target DNA 2 sequences for Bacillus anthracis (B. anthracis, or BA). The Applied Biosystems Bacillus anthracis Detection Kit is intended to test human whole blood (EDTA) specimens and blood culture specimens with growth detected by a continuous monitoring blood culture system. Blood culture specimens must be determined to contain gram-positive bacilli by Gram stain prior to testing. Testing of whole blood specimens must be performed concomitantly with standard of care blood culture. The Applied Biosystems Bacillus anthracis Detection Kit is indicated for use in CLIA-certified high- complexity laboratories in response to a confirmed Bacillus anthracis event only in accordance with the guidelines provided by public health authorities prior to or during a public health emergency. Testing with the Applied Biosystems Bacillus anthracis Detection Kit must only be performed when public health authorities have determined the need for this test. The test must only be used with specimens from individuals with clinical signs and symptoms of B. anthracis infection and who have either been exposed to B. anthracis or may have been exposed to B anthracis. The Applied Biosystems Bacillus anthracis Detection Kit is intended for use as an aid in the diagnosis of anthrax infection and results are for the presumptive identification of Bacillus anthracis. The diagnosis of B. anthracis infection must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidence, in addition to the identification of B. anthracis from cultures or directly from clinical specimens. The definitive identification of B. anthracis requires additional testing and confirmation procedures in consultation with the appropriate public health authorities for whom reports may be required. The Applied Biosystems Bacillus anthracis Detection Kit has not been clinically evaluated with specimens collected from individuals with B. anthracis infection or those presumed to be exposed to B. anthracis. ‘B. anthracis Not detected’ results do not preclude infection with Bacillus anthracis and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. Laboratories implementing this test must have the appropriate biosafety equipment, personal protective equipment (PPE), containment facilities and personnel trained in the safe handling of diagnostic clinical specimens potentially containing B. anthracis. Anthrax is a nationally notifiable disease caused by a biothreat microbial agent and must be reported to public health authorities. The distribution of in vitro diagnostic devices for Bacillus spp. detection is limited to laboratories that follow public health guidelines that address appropriate biosafety conditions, interpretation of test results, and coordination of findings with public health authorities. The Applied Biosystems Bacillus anthracis Detection Kit is intended for use with the ABI 7500 Fast Dx Real-Time PCR Instrument with analysis using the Applied Biosystems Bacillus anthracis Interpretive Software (BaIS). 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): • For Prescription Use Only • Laboratories must maintain records of completed manufacturer required training including training related to use of the assay, instrumentation, biosafety precautions, appropriate PPE and contamination control and waste disposal. • Laboratories must maintain manufacturer required documentation verifying the laboratory is 3 certified as high-complexity, has appropriate biosafety equipment and PPE as required per assay instructions and has procedures for following public health guidelines for working with specimens containing B. anthracis. • Laboratories must maintain manufacturer required documentation verifying the laboratory has procedures for following applicable state, local and federal public health regulations for reporting results and for referring specimens and or isolates to their public health reference laboratory. 4. Special instrument requirements: MagNA Pure LC 2.0 extraction System, Roche Applied Biosystems (AB) 7500 Fast Dx Real-Time PCR Instrument with Sequence Detection System (SDS), Thermo Fisher Scientific (Life Technologies) I. Device Description: The Applied Biosystems Bacillus anthracis Detection Kit is a multiplexed real-time polymerase chain reaction (PCR) test kit intended for the qualitative detection of B. anthracis DNA sequences. PCR reagents are lyophilized in PCR well strips and run in a 96-well plate format. The kit is designed for performing real- time PCR using the Applied Biosystems (AB) 7500 Fast Dx instrument and software, with nucleic acids extracted from clinical specimens using either a Qiagen manual extraction method using Qiagen’s QIAamp DSP DNA Blood Mini Kit (DSP) or Roche’s MagNA Pure LC 2.0 Robot (MagNA Pure, MNP). Roche MagNA Pure is an automated extraction method. An automated interpretative software component (BaIS) is included in the kit, but supplied separately, and operates on a separate computer from the AB 7500 Fast Dx computer. 4 Materials provided Materials Provided in the Applied Biosystem Bacillus anthracis Detection Kit Part Name Quantity and Content Storage Conditions Applied Biosystems Bacillus anthracis Test Kit Lyophilized Assay Plates 10 Plates; Each plate contains a lyophilized Mastermix and primers/probes specific for the Bacillus anthracis 3-plex assay; each plate is individually sealed and foil-wrapped. Ambient or room temperature (20°C – 25°C) Applied Biosystems Bacillus anthracis Test Kit Controls 1 box contains 1 vial of External Positive Control (EPC) and 1 vial of External Negative Control (ENC); Each vial contains enough reagent volume for approximately 10 PCR reactions; no further dilution of the control reagent is necessary. See below for final concentrations of control targets per 20 µl PCR reaction. Frozen (-15°C to -25°C) Applied Biosystems Bacillus anthracis Interpretive Software (BaIS) Version 1.0 1 BaIS Interpretive Software Server Installer; 1 BaIS Interpretive Software Client Installer. Not applicable External Controls and Final Target Concentration External Control Final Target Concentration per Reaction EPC pX01 (100fg), pX02 (200fg) and TERT (750fg) ENC E. coli DNA (4.8ng) Equipment and materials required but not supplied Equipment • Applied Biosystem 7500 Fast Dx Real-Time PCR Instrument with Sequence Detection System (SDS), Thermo Fisher Scientific (Life Technologies) • Separate computer for installation of Applied Biosystems Bacillus anthracis Interpretive Software (BaIS) Version 1.0 (It is not recommended to install and run BaIS on Applied Biosystems 7500 Fast Dx Real-Time PCR instrument computer) • MagNA Pure LC 2.0 Robot, Roche • Automated blood culture monitoring system (for testing blood culture samples only) • Biosafety cabinet (BSC) (Class II, Type A or B) • 2-8°C Refrigerator • < -20°C Freezer • < -70°C Freezer • Plate centrifuge compatible with Applied Biosystems MicroAmp Fast Optical 96-Well Reaction Plate, 0.1 mL, with at least 1000 rpm centrifuging speed 5 • Microcentrifuge, able to hold 2 mL tubes and capable of reaching 20,800 x g • Vortexer • Heat block capable of 56°C with insert for 2 mL tubes • Micropipette 1000 µL, 200 µL, 20 µL • Caplocks for 2 mL microcentrifuge tubes Consumables and Reagents • QIAamp DSP DNA Blood Mini Kit (IVD), Qiagen (DSP) • 100% Ethanol • Nuclease-free water • MagNA Pure LC DNA Isolation Kit – Large Volume, Roche • Blood culture bottles, aerobic and/or anaerobic (for testing blood culture samples only) • Aerosol-resistant filter tips for micropipettes – 1000 µL, 200 µL, 20 µL • Serological pipets – 50 mL, 25 mL, 10 mL, 5 mL • Optical plate film (seals) for 96-well PCR plates, compatible with AB7500 Fast Dx • Clean RNase- and DNase-free 2.0 mL microcentrifuge tubes J. Substantial Equivalence Measurand:

idK183462_s0_e2000

K183462.txt

type of test

Real-time polymerase chain reaction

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K183462 B. Purpose for Submission: Clearance of the Applied Biosystems Bacillus anthracis Detection Kit on the Applied Biosystems (AB) 7500 Fast Dx instrument and Applied Biosystems Bacillus anthracis Interpretive Software (BaIS). C. Measurand: Nucleic acid sequences of Bacillus anthracis pX01 and pX02 plasmids D. Type of Test: Real-time polymerase chain reaction E. Applicant: MRIGlobal F. Proprietary and Established Names: Applied Biosystems Bacillus anthracis Detection Kit Applied Biosystems (AB) 7500 Fast Dx G. Regulatory Information: 1. Regulation section: CFR 866.4000 2. Classification: Class II 3. Product code: QIF, OOI 4. Panel: 83- Microbiology H. Intended Use: 1. Intended use The Applied Biosystems Bacillus anthracis Detection Kit is a real-time polymerase chain reaction (PCR) test kit intended for the qualitative in vitro diagnostic (IVD) detection of target DNA 2 sequences for Bacillus anthracis (B. anthracis, or BA). The Applied Biosystems Bacillus anthracis Detection Kit is intended to test human whole blood (EDTA) specimens and blood culture specimens with growth detected by a continuous monitoring blood culture system. Blood culture specimens must be determined to contain gram-positive bacilli by Gram stain prior to testing. Testing of whole blood specimens must be performed concomitantly with standard of care blood culture. The Applied Biosystems Bacillus anthracis Detection Kit is indicated for use in CLIA-certified high- complexity laboratories in response to a confirmed Bacillus anthracis event only in accordance with the guidelines provided by public health authorities prior to or during a public health emergency. Testing with the Applied Biosystems Bacillus anthracis Detection Kit must only be performed when public health authorities have determined the need for this test. The test must only be used with specimens from individuals with clinical signs and symptoms of B. anthracis infection and who have either been exposed to B. anthracis or may have been exposed to B anthracis. The Applied Biosystems Bacillus anthracis Detection Kit is intended for use as an aid in the diagnosis of anthrax infection and results are for the presumptive identification of Bacillus anthracis. The diagnosis of B. anthracis infection must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidence, in addition to the identification of B. anthracis from cultures or directly from clinical specimens. The definitive identification of B. anthracis requires additional testing and confirmation procedures in consultation with the appropriate public health authorities for whom reports may be required. The Applied Biosystems Bacillus anthracis Detection Kit has not been clinically evaluated with specimens collected from individuals with B. anthracis infection or those presumed to be exposed to B. anthracis. ‘B. anthracis Not detected’ results do not preclude infection with Bacillus anthracis and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. Laboratories implementing this test must have the appropriate biosafety equipment, personal protective equipment (PPE), containment facilities and personnel trained in the safe handling of diagnostic clinical specimens potentially containing B. anthracis. Anthrax is a nationally notifiable disease caused by a biothreat microbial agent and must be reported to public health authorities. The distribution of in vitro diagnostic devices for Bacillus spp. detection is limited to laboratories that follow public health guidelines that address appropriate biosafety conditions, interpretation of test results, and coordination of findings with public health authorities. The Applied Biosystems Bacillus anthracis Detection Kit is intended for use with the ABI 7500 Fast Dx Real-Time PCR Instrument with analysis using the Applied Biosystems Bacillus anthracis Interpretive Software (BaIS). 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): • For Prescription Use Only • Laboratories must maintain records of completed manufacturer required training including training related to use of the assay, instrumentation, biosafety precautions, appropriate PPE and contamination control and waste disposal. • Laboratories must maintain manufacturer required documentation verifying the laboratory is 3 certified as high-complexity, has appropriate biosafety equipment and PPE as required per assay instructions and has procedures for following public health guidelines for working with specimens containing B. anthracis. • Laboratories must maintain manufacturer required documentation verifying the laboratory has procedures for following applicable state, local and federal public health regulations for reporting results and for referring specimens and or isolates to their public health reference laboratory. 4. Special instrument requirements: MagNA Pure LC 2.0 extraction System, Roche Applied Biosystems (AB) 7500 Fast Dx Real-Time PCR Instrument with Sequence Detection System (SDS), Thermo Fisher Scientific (Life Technologies) I. Device Description: The Applied Biosystems Bacillus anthracis Detection Kit is a multiplexed real-time polymerase chain reaction (PCR) test kit intended for the qualitative detection of B. anthracis DNA sequences. PCR reagents are lyophilized in PCR well strips and run in a 96-well plate format. The kit is designed for performing real- time PCR using the Applied Biosystems (AB) 7500 Fast Dx instrument and software, with nucleic acids extracted from clinical specimens using either a Qiagen manual extraction method using Qiagen’s QIAamp DSP DNA Blood Mini Kit (DSP) or Roche’s MagNA Pure LC 2.0 Robot (MagNA Pure, MNP). Roche MagNA Pure is an automated extraction method. An automated interpretative software component (BaIS) is included in the kit, but supplied separately, and operates on a separate computer from the AB 7500 Fast Dx computer. 4 Materials provided Materials Provided in the Applied Biosystem Bacillus anthracis Detection Kit Part Name Quantity and Content Storage Conditions Applied Biosystems Bacillus anthracis Test Kit Lyophilized Assay Plates 10 Plates; Each plate contains a lyophilized Mastermix and primers/probes specific for the Bacillus anthracis 3-plex assay; each plate is individually sealed and foil-wrapped. Ambient or room temperature (20°C – 25°C) Applied Biosystems Bacillus anthracis Test Kit Controls 1 box contains 1 vial of External Positive Control (EPC) and 1 vial of External Negative Control (ENC); Each vial contains enough reagent volume for approximately 10 PCR reactions; no further dilution of the control reagent is necessary. See below for final concentrations of control targets per 20 µl PCR reaction. Frozen (-15°C to -25°C) Applied Biosystems Bacillus anthracis Interpretive Software (BaIS) Version 1.0 1 BaIS Interpretive Software Server Installer; 1 BaIS Interpretive Software Client Installer. Not applicable External Controls and Final Target Concentration External Control Final Target Concentration per Reaction EPC pX01 (100fg), pX02 (200fg) and TERT (750fg) ENC E. coli DNA (4.8ng) Equipment and materials required but not supplied Equipment • Applied Biosystem 7500 Fast Dx Real-Time PCR Instrument with Sequence Detection System (SDS), Thermo Fisher Scientific (Life Technologies) • Separate computer for installation of Applied Biosystems Bacillus anthracis Interpretive Software (BaIS) Version 1.0 (It is not recommended to install and run BaIS on Applied Biosystems 7500 Fast Dx Real-Time PCR instrument computer) • MagNA Pure LC 2.0 Robot, Roche • Automated blood culture monitoring system (for testing blood culture samples only) • Biosafety cabinet (BSC) (Class II, Type A or B) • 2-8°C Refrigerator • < -20°C Freezer • < -70°C Freezer • Plate centrifuge compatible with Applied Biosystems MicroAmp Fast Optical 96-Well Reaction Plate, 0.1 mL, with at least 1000 rpm centrifuging speed 5 • Microcentrifuge, able to hold 2 mL tubes and capable of reaching 20,800 x g • Vortexer • Heat block capable of 56°C with insert for 2 mL tubes • Micropipette 1000 µL, 200 µL, 20 µL • Caplocks for 2 mL microcentrifuge tubes Consumables and Reagents • QIAamp DSP DNA Blood Mini Kit (IVD), Qiagen (DSP) • 100% Ethanol • Nuclease-free water • MagNA Pure LC DNA Isolation Kit – Large Volume, Roche • Blood culture bottles, aerobic and/or anaerobic (for testing blood culture samples only) • Aerosol-resistant filter tips for micropipettes – 1000 µL, 200 µL, 20 µL • Serological pipets – 50 mL, 25 mL, 10 mL, 5 mL • Optical plate film (seals) for 96-well PCR plates, compatible with AB7500 Fast Dx • Clean RNase- and DNase-free 2.0 mL microcentrifuge tubes J. Substantial Equivalence Type of test:

idK183462_s0_e2000

K183462.txt

classification

Class II

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K183462 B. Purpose for Submission: Clearance of the Applied Biosystems Bacillus anthracis Detection Kit on the Applied Biosystems (AB) 7500 Fast Dx instrument and Applied Biosystems Bacillus anthracis Interpretive Software (BaIS). C. Measurand: Nucleic acid sequences of Bacillus anthracis pX01 and pX02 plasmids D. Type of Test: Real-time polymerase chain reaction E. Applicant: MRIGlobal F. Proprietary and Established Names: Applied Biosystems Bacillus anthracis Detection Kit Applied Biosystems (AB) 7500 Fast Dx G. Regulatory Information: 1. Regulation section: CFR 866.4000 2. Classification: Class II 3. Product code: QIF, OOI 4. Panel: 83- Microbiology H. Intended Use: 1. Intended use The Applied Biosystems Bacillus anthracis Detection Kit is a real-time polymerase chain reaction (PCR) test kit intended for the qualitative in vitro diagnostic (IVD) detection of target DNA 2 sequences for Bacillus anthracis (B. anthracis, or BA). The Applied Biosystems Bacillus anthracis Detection Kit is intended to test human whole blood (EDTA) specimens and blood culture specimens with growth detected by a continuous monitoring blood culture system. Blood culture specimens must be determined to contain gram-positive bacilli by Gram stain prior to testing. Testing of whole blood specimens must be performed concomitantly with standard of care blood culture. The Applied Biosystems Bacillus anthracis Detection Kit is indicated for use in CLIA-certified high- complexity laboratories in response to a confirmed Bacillus anthracis event only in accordance with the guidelines provided by public health authorities prior to or during a public health emergency. Testing with the Applied Biosystems Bacillus anthracis Detection Kit must only be performed when public health authorities have determined the need for this test. The test must only be used with specimens from individuals with clinical signs and symptoms of B. anthracis infection and who have either been exposed to B. anthracis or may have been exposed to B anthracis. The Applied Biosystems Bacillus anthracis Detection Kit is intended for use as an aid in the diagnosis of anthrax infection and results are for the presumptive identification of Bacillus anthracis. The diagnosis of B. anthracis infection must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidence, in addition to the identification of B. anthracis from cultures or directly from clinical specimens. The definitive identification of B. anthracis requires additional testing and confirmation procedures in consultation with the appropriate public health authorities for whom reports may be required. The Applied Biosystems Bacillus anthracis Detection Kit has not been clinically evaluated with specimens collected from individuals with B. anthracis infection or those presumed to be exposed to B. anthracis. ‘B. anthracis Not detected’ results do not preclude infection with Bacillus anthracis and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. Laboratories implementing this test must have the appropriate biosafety equipment, personal protective equipment (PPE), containment facilities and personnel trained in the safe handling of diagnostic clinical specimens potentially containing B. anthracis. Anthrax is a nationally notifiable disease caused by a biothreat microbial agent and must be reported to public health authorities. The distribution of in vitro diagnostic devices for Bacillus spp. detection is limited to laboratories that follow public health guidelines that address appropriate biosafety conditions, interpretation of test results, and coordination of findings with public health authorities. The Applied Biosystems Bacillus anthracis Detection Kit is intended for use with the ABI 7500 Fast Dx Real-Time PCR Instrument with analysis using the Applied Biosystems Bacillus anthracis Interpretive Software (BaIS). 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): • For Prescription Use Only • Laboratories must maintain records of completed manufacturer required training including training related to use of the assay, instrumentation, biosafety precautions, appropriate PPE and contamination control and waste disposal. • Laboratories must maintain manufacturer required documentation verifying the laboratory is 3 certified as high-complexity, has appropriate biosafety equipment and PPE as required per assay instructions and has procedures for following public health guidelines for working with specimens containing B. anthracis. • Laboratories must maintain manufacturer required documentation verifying the laboratory has procedures for following applicable state, local and federal public health regulations for reporting results and for referring specimens and or isolates to their public health reference laboratory. 4. Special instrument requirements: MagNA Pure LC 2.0 extraction System, Roche Applied Biosystems (AB) 7500 Fast Dx Real-Time PCR Instrument with Sequence Detection System (SDS), Thermo Fisher Scientific (Life Technologies) I. Device Description: The Applied Biosystems Bacillus anthracis Detection Kit is a multiplexed real-time polymerase chain reaction (PCR) test kit intended for the qualitative detection of B. anthracis DNA sequences. PCR reagents are lyophilized in PCR well strips and run in a 96-well plate format. The kit is designed for performing real- time PCR using the Applied Biosystems (AB) 7500 Fast Dx instrument and software, with nucleic acids extracted from clinical specimens using either a Qiagen manual extraction method using Qiagen’s QIAamp DSP DNA Blood Mini Kit (DSP) or Roche’s MagNA Pure LC 2.0 Robot (MagNA Pure, MNP). Roche MagNA Pure is an automated extraction method. An automated interpretative software component (BaIS) is included in the kit, but supplied separately, and operates on a separate computer from the AB 7500 Fast Dx computer. 4 Materials provided Materials Provided in the Applied Biosystem Bacillus anthracis Detection Kit Part Name Quantity and Content Storage Conditions Applied Biosystems Bacillus anthracis Test Kit Lyophilized Assay Plates 10 Plates; Each plate contains a lyophilized Mastermix and primers/probes specific for the Bacillus anthracis 3-plex assay; each plate is individually sealed and foil-wrapped. Ambient or room temperature (20°C – 25°C) Applied Biosystems Bacillus anthracis Test Kit Controls 1 box contains 1 vial of External Positive Control (EPC) and 1 vial of External Negative Control (ENC); Each vial contains enough reagent volume for approximately 10 PCR reactions; no further dilution of the control reagent is necessary. See below for final concentrations of control targets per 20 µl PCR reaction. Frozen (-15°C to -25°C) Applied Biosystems Bacillus anthracis Interpretive Software (BaIS) Version 1.0 1 BaIS Interpretive Software Server Installer; 1 BaIS Interpretive Software Client Installer. Not applicable External Controls and Final Target Concentration External Control Final Target Concentration per Reaction EPC pX01 (100fg), pX02 (200fg) and TERT (750fg) ENC E. coli DNA (4.8ng) Equipment and materials required but not supplied Equipment • Applied Biosystem 7500 Fast Dx Real-Time PCR Instrument with Sequence Detection System (SDS), Thermo Fisher Scientific (Life Technologies) • Separate computer for installation of Applied Biosystems Bacillus anthracis Interpretive Software (BaIS) Version 1.0 (It is not recommended to install and run BaIS on Applied Biosystems 7500 Fast Dx Real-Time PCR instrument computer) • MagNA Pure LC 2.0 Robot, Roche • Automated blood culture monitoring system (for testing blood culture samples only) • Biosafety cabinet (BSC) (Class II, Type A or B) • 2-8°C Refrigerator • < -20°C Freezer • < -70°C Freezer • Plate centrifuge compatible with Applied Biosystems MicroAmp Fast Optical 96-Well Reaction Plate, 0.1 mL, with at least 1000 rpm centrifuging speed 5 • Microcentrifuge, able to hold 2 mL tubes and capable of reaching 20,800 x g • Vortexer • Heat block capable of 56°C with insert for 2 mL tubes • Micropipette 1000 µL, 200 µL, 20 µL • Caplocks for 2 mL microcentrifuge tubes Consumables and Reagents • QIAamp DSP DNA Blood Mini Kit (IVD), Qiagen (DSP) • 100% Ethanol • Nuclease-free water • MagNA Pure LC DNA Isolation Kit – Large Volume, Roche • Blood culture bottles, aerobic and/or anaerobic (for testing blood culture samples only) • Aerosol-resistant filter tips for micropipettes – 1000 µL, 200 µL, 20 µL • Serological pipets – 50 mL, 25 mL, 10 mL, 5 mL • Optical plate film (seals) for 96-well PCR plates, compatible with AB7500 Fast Dx • Clean RNase- and DNase-free 2.0 mL microcentrifuge tubes J. Substantial Equivalence Classification:

idK183462_s0_e2000

K183462.txt

product code

QIF, OOI

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K183462 B. Purpose for Submission: Clearance of the Applied Biosystems Bacillus anthracis Detection Kit on the Applied Biosystems (AB) 7500 Fast Dx instrument and Applied Biosystems Bacillus anthracis Interpretive Software (BaIS). C. Measurand: Nucleic acid sequences of Bacillus anthracis pX01 and pX02 plasmids D. Type of Test: Real-time polymerase chain reaction E. Applicant: MRIGlobal F. Proprietary and Established Names: Applied Biosystems Bacillus anthracis Detection Kit Applied Biosystems (AB) 7500 Fast Dx G. Regulatory Information: 1. Regulation section: CFR 866.4000 2. Classification: Class II 3. Product code: QIF, OOI 4. Panel: 83- Microbiology H. Intended Use: 1. Intended use The Applied Biosystems Bacillus anthracis Detection Kit is a real-time polymerase chain reaction (PCR) test kit intended for the qualitative in vitro diagnostic (IVD) detection of target DNA 2 sequences for Bacillus anthracis (B. anthracis, or BA). The Applied Biosystems Bacillus anthracis Detection Kit is intended to test human whole blood (EDTA) specimens and blood culture specimens with growth detected by a continuous monitoring blood culture system. Blood culture specimens must be determined to contain gram-positive bacilli by Gram stain prior to testing. Testing of whole blood specimens must be performed concomitantly with standard of care blood culture. The Applied Biosystems Bacillus anthracis Detection Kit is indicated for use in CLIA-certified high- complexity laboratories in response to a confirmed Bacillus anthracis event only in accordance with the guidelines provided by public health authorities prior to or during a public health emergency. Testing with the Applied Biosystems Bacillus anthracis Detection Kit must only be performed when public health authorities have determined the need for this test. The test must only be used with specimens from individuals with clinical signs and symptoms of B. anthracis infection and who have either been exposed to B. anthracis or may have been exposed to B anthracis. The Applied Biosystems Bacillus anthracis Detection Kit is intended for use as an aid in the diagnosis of anthrax infection and results are for the presumptive identification of Bacillus anthracis. The diagnosis of B. anthracis infection must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidence, in addition to the identification of B. anthracis from cultures or directly from clinical specimens. The definitive identification of B. anthracis requires additional testing and confirmation procedures in consultation with the appropriate public health authorities for whom reports may be required. The Applied Biosystems Bacillus anthracis Detection Kit has not been clinically evaluated with specimens collected from individuals with B. anthracis infection or those presumed to be exposed to B. anthracis. ‘B. anthracis Not detected’ results do not preclude infection with Bacillus anthracis and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. Laboratories implementing this test must have the appropriate biosafety equipment, personal protective equipment (PPE), containment facilities and personnel trained in the safe handling of diagnostic clinical specimens potentially containing B. anthracis. Anthrax is a nationally notifiable disease caused by a biothreat microbial agent and must be reported to public health authorities. The distribution of in vitro diagnostic devices for Bacillus spp. detection is limited to laboratories that follow public health guidelines that address appropriate biosafety conditions, interpretation of test results, and coordination of findings with public health authorities. The Applied Biosystems Bacillus anthracis Detection Kit is intended for use with the ABI 7500 Fast Dx Real-Time PCR Instrument with analysis using the Applied Biosystems Bacillus anthracis Interpretive Software (BaIS). 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): • For Prescription Use Only • Laboratories must maintain records of completed manufacturer required training including training related to use of the assay, instrumentation, biosafety precautions, appropriate PPE and contamination control and waste disposal. • Laboratories must maintain manufacturer required documentation verifying the laboratory is 3 certified as high-complexity, has appropriate biosafety equipment and PPE as required per assay instructions and has procedures for following public health guidelines for working with specimens containing B. anthracis. • Laboratories must maintain manufacturer required documentation verifying the laboratory has procedures for following applicable state, local and federal public health regulations for reporting results and for referring specimens and or isolates to their public health reference laboratory. 4. Special instrument requirements: MagNA Pure LC 2.0 extraction System, Roche Applied Biosystems (AB) 7500 Fast Dx Real-Time PCR Instrument with Sequence Detection System (SDS), Thermo Fisher Scientific (Life Technologies) I. Device Description: The Applied Biosystems Bacillus anthracis Detection Kit is a multiplexed real-time polymerase chain reaction (PCR) test kit intended for the qualitative detection of B. anthracis DNA sequences. PCR reagents are lyophilized in PCR well strips and run in a 96-well plate format. The kit is designed for performing real- time PCR using the Applied Biosystems (AB) 7500 Fast Dx instrument and software, with nucleic acids extracted from clinical specimens using either a Qiagen manual extraction method using Qiagen’s QIAamp DSP DNA Blood Mini Kit (DSP) or Roche’s MagNA Pure LC 2.0 Robot (MagNA Pure, MNP). Roche MagNA Pure is an automated extraction method. An automated interpretative software component (BaIS) is included in the kit, but supplied separately, and operates on a separate computer from the AB 7500 Fast Dx computer. 4 Materials provided Materials Provided in the Applied Biosystem Bacillus anthracis Detection Kit Part Name Quantity and Content Storage Conditions Applied Biosystems Bacillus anthracis Test Kit Lyophilized Assay Plates 10 Plates; Each plate contains a lyophilized Mastermix and primers/probes specific for the Bacillus anthracis 3-plex assay; each plate is individually sealed and foil-wrapped. Ambient or room temperature (20°C – 25°C) Applied Biosystems Bacillus anthracis Test Kit Controls 1 box contains 1 vial of External Positive Control (EPC) and 1 vial of External Negative Control (ENC); Each vial contains enough reagent volume for approximately 10 PCR reactions; no further dilution of the control reagent is necessary. See below for final concentrations of control targets per 20 µl PCR reaction. Frozen (-15°C to -25°C) Applied Biosystems Bacillus anthracis Interpretive Software (BaIS) Version 1.0 1 BaIS Interpretive Software Server Installer; 1 BaIS Interpretive Software Client Installer. Not applicable External Controls and Final Target Concentration External Control Final Target Concentration per Reaction EPC pX01 (100fg), pX02 (200fg) and TERT (750fg) ENC E. coli DNA (4.8ng) Equipment and materials required but not supplied Equipment • Applied Biosystem 7500 Fast Dx Real-Time PCR Instrument with Sequence Detection System (SDS), Thermo Fisher Scientific (Life Technologies) • Separate computer for installation of Applied Biosystems Bacillus anthracis Interpretive Software (BaIS) Version 1.0 (It is not recommended to install and run BaIS on Applied Biosystems 7500 Fast Dx Real-Time PCR instrument computer) • MagNA Pure LC 2.0 Robot, Roche • Automated blood culture monitoring system (for testing blood culture samples only) • Biosafety cabinet (BSC) (Class II, Type A or B) • 2-8°C Refrigerator • < -20°C Freezer • < -70°C Freezer • Plate centrifuge compatible with Applied Biosystems MicroAmp Fast Optical 96-Well Reaction Plate, 0.1 mL, with at least 1000 rpm centrifuging speed 5 • Microcentrifuge, able to hold 2 mL tubes and capable of reaching 20,800 x g • Vortexer • Heat block capable of 56°C with insert for 2 mL tubes • Micropipette 1000 µL, 200 µL, 20 µL • Caplocks for 2 mL microcentrifuge tubes Consumables and Reagents • QIAamp DSP DNA Blood Mini Kit (IVD), Qiagen (DSP) • 100% Ethanol • Nuclease-free water • MagNA Pure LC DNA Isolation Kit – Large Volume, Roche • Blood culture bottles, aerobic and/or anaerobic (for testing blood culture samples only) • Aerosol-resistant filter tips for micropipettes – 1000 µL, 200 µL, 20 µL • Serological pipets – 50 mL, 25 mL, 10 mL, 5 mL • Optical plate film (seals) for 96-well PCR plates, compatible with AB7500 Fast Dx • Clean RNase- and DNase-free 2.0 mL microcentrifuge tubes J. Substantial Equivalence Product code:

idK183462_s0_e2000

K183462.txt

panel

83- Microbiology

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K183462 B. Purpose for Submission: Clearance of the Applied Biosystems Bacillus anthracis Detection Kit on the Applied Biosystems (AB) 7500 Fast Dx instrument and Applied Biosystems Bacillus anthracis Interpretive Software (BaIS). C. Measurand: Nucleic acid sequences of Bacillus anthracis pX01 and pX02 plasmids D. Type of Test: Real-time polymerase chain reaction E. Applicant: MRIGlobal F. Proprietary and Established Names: Applied Biosystems Bacillus anthracis Detection Kit Applied Biosystems (AB) 7500 Fast Dx G. Regulatory Information: 1. Regulation section: CFR 866.4000 2. Classification: Class II 3. Product code: QIF, OOI 4. Panel: 83- Microbiology H. Intended Use: 1. Intended use The Applied Biosystems Bacillus anthracis Detection Kit is a real-time polymerase chain reaction (PCR) test kit intended for the qualitative in vitro diagnostic (IVD) detection of target DNA 2 sequences for Bacillus anthracis (B. anthracis, or BA). The Applied Biosystems Bacillus anthracis Detection Kit is intended to test human whole blood (EDTA) specimens and blood culture specimens with growth detected by a continuous monitoring blood culture system. Blood culture specimens must be determined to contain gram-positive bacilli by Gram stain prior to testing. Testing of whole blood specimens must be performed concomitantly with standard of care blood culture. The Applied Biosystems Bacillus anthracis Detection Kit is indicated for use in CLIA-certified high- complexity laboratories in response to a confirmed Bacillus anthracis event only in accordance with the guidelines provided by public health authorities prior to or during a public health emergency. Testing with the Applied Biosystems Bacillus anthracis Detection Kit must only be performed when public health authorities have determined the need for this test. The test must only be used with specimens from individuals with clinical signs and symptoms of B. anthracis infection and who have either been exposed to B. anthracis or may have been exposed to B anthracis. The Applied Biosystems Bacillus anthracis Detection Kit is intended for use as an aid in the diagnosis of anthrax infection and results are for the presumptive identification of Bacillus anthracis. The diagnosis of B. anthracis infection must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidence, in addition to the identification of B. anthracis from cultures or directly from clinical specimens. The definitive identification of B. anthracis requires additional testing and confirmation procedures in consultation with the appropriate public health authorities for whom reports may be required. The Applied Biosystems Bacillus anthracis Detection Kit has not been clinically evaluated with specimens collected from individuals with B. anthracis infection or those presumed to be exposed to B. anthracis. ‘B. anthracis Not detected’ results do not preclude infection with Bacillus anthracis and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. Laboratories implementing this test must have the appropriate biosafety equipment, personal protective equipment (PPE), containment facilities and personnel trained in the safe handling of diagnostic clinical specimens potentially containing B. anthracis. Anthrax is a nationally notifiable disease caused by a biothreat microbial agent and must be reported to public health authorities. The distribution of in vitro diagnostic devices for Bacillus spp. detection is limited to laboratories that follow public health guidelines that address appropriate biosafety conditions, interpretation of test results, and coordination of findings with public health authorities. The Applied Biosystems Bacillus anthracis Detection Kit is intended for use with the ABI 7500 Fast Dx Real-Time PCR Instrument with analysis using the Applied Biosystems Bacillus anthracis Interpretive Software (BaIS). 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): • For Prescription Use Only • Laboratories must maintain records of completed manufacturer required training including training related to use of the assay, instrumentation, biosafety precautions, appropriate PPE and contamination control and waste disposal. • Laboratories must maintain manufacturer required documentation verifying the laboratory is 3 certified as high-complexity, has appropriate biosafety equipment and PPE as required per assay instructions and has procedures for following public health guidelines for working with specimens containing B. anthracis. • Laboratories must maintain manufacturer required documentation verifying the laboratory has procedures for following applicable state, local and federal public health regulations for reporting results and for referring specimens and or isolates to their public health reference laboratory. 4. Special instrument requirements: MagNA Pure LC 2.0 extraction System, Roche Applied Biosystems (AB) 7500 Fast Dx Real-Time PCR Instrument with Sequence Detection System (SDS), Thermo Fisher Scientific (Life Technologies) I. Device Description: The Applied Biosystems Bacillus anthracis Detection Kit is a multiplexed real-time polymerase chain reaction (PCR) test kit intended for the qualitative detection of B. anthracis DNA sequences. PCR reagents are lyophilized in PCR well strips and run in a 96-well plate format. The kit is designed for performing real- time PCR using the Applied Biosystems (AB) 7500 Fast Dx instrument and software, with nucleic acids extracted from clinical specimens using either a Qiagen manual extraction method using Qiagen’s QIAamp DSP DNA Blood Mini Kit (DSP) or Roche’s MagNA Pure LC 2.0 Robot (MagNA Pure, MNP). Roche MagNA Pure is an automated extraction method. An automated interpretative software component (BaIS) is included in the kit, but supplied separately, and operates on a separate computer from the AB 7500 Fast Dx computer. 4 Materials provided Materials Provided in the Applied Biosystem Bacillus anthracis Detection Kit Part Name Quantity and Content Storage Conditions Applied Biosystems Bacillus anthracis Test Kit Lyophilized Assay Plates 10 Plates; Each plate contains a lyophilized Mastermix and primers/probes specific for the Bacillus anthracis 3-plex assay; each plate is individually sealed and foil-wrapped. Ambient or room temperature (20°C – 25°C) Applied Biosystems Bacillus anthracis Test Kit Controls 1 box contains 1 vial of External Positive Control (EPC) and 1 vial of External Negative Control (ENC); Each vial contains enough reagent volume for approximately 10 PCR reactions; no further dilution of the control reagent is necessary. See below for final concentrations of control targets per 20 µl PCR reaction. Frozen (-15°C to -25°C) Applied Biosystems Bacillus anthracis Interpretive Software (BaIS) Version 1.0 1 BaIS Interpretive Software Server Installer; 1 BaIS Interpretive Software Client Installer. Not applicable External Controls and Final Target Concentration External Control Final Target Concentration per Reaction EPC pX01 (100fg), pX02 (200fg) and TERT (750fg) ENC E. coli DNA (4.8ng) Equipment and materials required but not supplied Equipment • Applied Biosystem 7500 Fast Dx Real-Time PCR Instrument with Sequence Detection System (SDS), Thermo Fisher Scientific (Life Technologies) • Separate computer for installation of Applied Biosystems Bacillus anthracis Interpretive Software (BaIS) Version 1.0 (It is not recommended to install and run BaIS on Applied Biosystems 7500 Fast Dx Real-Time PCR instrument computer) • MagNA Pure LC 2.0 Robot, Roche • Automated blood culture monitoring system (for testing blood culture samples only) • Biosafety cabinet (BSC) (Class II, Type A or B) • 2-8°C Refrigerator • < -20°C Freezer • < -70°C Freezer • Plate centrifuge compatible with Applied Biosystems MicroAmp Fast Optical 96-Well Reaction Plate, 0.1 mL, with at least 1000 rpm centrifuging speed 5 • Microcentrifuge, able to hold 2 mL tubes and capable of reaching 20,800 x g • Vortexer • Heat block capable of 56°C with insert for 2 mL tubes • Micropipette 1000 µL, 200 µL, 20 µL • Caplocks for 2 mL microcentrifuge tubes Consumables and Reagents • QIAamp DSP DNA Blood Mini Kit (IVD), Qiagen (DSP) • 100% Ethanol • Nuclease-free water • MagNA Pure LC DNA Isolation Kit – Large Volume, Roche • Blood culture bottles, aerobic and/or anaerobic (for testing blood culture samples only) • Aerosol-resistant filter tips for micropipettes – 1000 µL, 200 µL, 20 µL • Serological pipets – 50 mL, 25 mL, 10 mL, 5 mL • Optical plate film (seals) for 96-well PCR plates, compatible with AB7500 Fast Dx • Clean RNase- and DNase-free 2.0 mL microcentrifuge tubes J. Substantial Equivalence Panel:

idK183462_s0_e2000

K183462.txt

applicant

MRIGlobal

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K183462 B. Purpose for Submission: Clearance of the Applied Biosystems Bacillus anthracis Detection Kit on the Applied Biosystems (AB) 7500 Fast Dx instrument and Applied Biosystems Bacillus anthracis Interpretive Software (BaIS). C. Measurand: Nucleic acid sequences of Bacillus anthracis pX01 and pX02 plasmids D. Type of Test: Real-time polymerase chain reaction E. Applicant: MRIGlobal F. Proprietary and Established Names: Applied Biosystems Bacillus anthracis Detection Kit Applied Biosystems (AB) 7500 Fast Dx G. Regulatory Information: 1. Regulation section: CFR 866.4000 2. Classification: Class II 3. Product code: QIF, OOI 4. Panel: 83- Microbiology H. Intended Use: 1. Intended use The Applied Biosystems Bacillus anthracis Detection Kit is a real-time polymerase chain reaction (PCR) test kit intended for the qualitative in vitro diagnostic (IVD) detection of target DNA 2 sequences for Bacillus anthracis (B. anthracis, or BA). The Applied Biosystems Bacillus anthracis Detection Kit is intended to test human whole blood (EDTA) specimens and blood culture specimens with growth detected by a continuous monitoring blood culture system. Blood culture specimens must be determined to contain gram-positive bacilli by Gram stain prior to testing. Testing of whole blood specimens must be performed concomitantly with standard of care blood culture. The Applied Biosystems Bacillus anthracis Detection Kit is indicated for use in CLIA-certified high- complexity laboratories in response to a confirmed Bacillus anthracis event only in accordance with the guidelines provided by public health authorities prior to or during a public health emergency. Testing with the Applied Biosystems Bacillus anthracis Detection Kit must only be performed when public health authorities have determined the need for this test. The test must only be used with specimens from individuals with clinical signs and symptoms of B. anthracis infection and who have either been exposed to B. anthracis or may have been exposed to B anthracis. The Applied Biosystems Bacillus anthracis Detection Kit is intended for use as an aid in the diagnosis of anthrax infection and results are for the presumptive identification of Bacillus anthracis. The diagnosis of B. anthracis infection must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidence, in addition to the identification of B. anthracis from cultures or directly from clinical specimens. The definitive identification of B. anthracis requires additional testing and confirmation procedures in consultation with the appropriate public health authorities for whom reports may be required. The Applied Biosystems Bacillus anthracis Detection Kit has not been clinically evaluated with specimens collected from individuals with B. anthracis infection or those presumed to be exposed to B. anthracis. ‘B. anthracis Not detected’ results do not preclude infection with Bacillus anthracis and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. Laboratories implementing this test must have the appropriate biosafety equipment, personal protective equipment (PPE), containment facilities and personnel trained in the safe handling of diagnostic clinical specimens potentially containing B. anthracis. Anthrax is a nationally notifiable disease caused by a biothreat microbial agent and must be reported to public health authorities. The distribution of in vitro diagnostic devices for Bacillus spp. detection is limited to laboratories that follow public health guidelines that address appropriate biosafety conditions, interpretation of test results, and coordination of findings with public health authorities. The Applied Biosystems Bacillus anthracis Detection Kit is intended for use with the ABI 7500 Fast Dx Real-Time PCR Instrument with analysis using the Applied Biosystems Bacillus anthracis Interpretive Software (BaIS). 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): • For Prescription Use Only • Laboratories must maintain records of completed manufacturer required training including training related to use of the assay, instrumentation, biosafety precautions, appropriate PPE and contamination control and waste disposal. • Laboratories must maintain manufacturer required documentation verifying the laboratory is 3 certified as high-complexity, has appropriate biosafety equipment and PPE as required per assay instructions and has procedures for following public health guidelines for working with specimens containing B. anthracis. • Laboratories must maintain manufacturer required documentation verifying the laboratory has procedures for following applicable state, local and federal public health regulations for reporting results and for referring specimens and or isolates to their public health reference laboratory. 4. Special instrument requirements: MagNA Pure LC 2.0 extraction System, Roche Applied Biosystems (AB) 7500 Fast Dx Real-Time PCR Instrument with Sequence Detection System (SDS), Thermo Fisher Scientific (Life Technologies) I. Device Description: The Applied Biosystems Bacillus anthracis Detection Kit is a multiplexed real-time polymerase chain reaction (PCR) test kit intended for the qualitative detection of B. anthracis DNA sequences. PCR reagents are lyophilized in PCR well strips and run in a 96-well plate format. The kit is designed for performing real- time PCR using the Applied Biosystems (AB) 7500 Fast Dx instrument and software, with nucleic acids extracted from clinical specimens using either a Qiagen manual extraction method using Qiagen’s QIAamp DSP DNA Blood Mini Kit (DSP) or Roche’s MagNA Pure LC 2.0 Robot (MagNA Pure, MNP). Roche MagNA Pure is an automated extraction method. An automated interpretative software component (BaIS) is included in the kit, but supplied separately, and operates on a separate computer from the AB 7500 Fast Dx computer. 4 Materials provided Materials Provided in the Applied Biosystem Bacillus anthracis Detection Kit Part Name Quantity and Content Storage Conditions Applied Biosystems Bacillus anthracis Test Kit Lyophilized Assay Plates 10 Plates; Each plate contains a lyophilized Mastermix and primers/probes specific for the Bacillus anthracis 3-plex assay; each plate is individually sealed and foil-wrapped. Ambient or room temperature (20°C – 25°C) Applied Biosystems Bacillus anthracis Test Kit Controls 1 box contains 1 vial of External Positive Control (EPC) and 1 vial of External Negative Control (ENC); Each vial contains enough reagent volume for approximately 10 PCR reactions; no further dilution of the control reagent is necessary. See below for final concentrations of control targets per 20 µl PCR reaction. Frozen (-15°C to -25°C) Applied Biosystems Bacillus anthracis Interpretive Software (BaIS) Version 1.0 1 BaIS Interpretive Software Server Installer; 1 BaIS Interpretive Software Client Installer. Not applicable External Controls and Final Target Concentration External Control Final Target Concentration per Reaction EPC pX01 (100fg), pX02 (200fg) and TERT (750fg) ENC E. coli DNA (4.8ng) Equipment and materials required but not supplied Equipment • Applied Biosystem 7500 Fast Dx Real-Time PCR Instrument with Sequence Detection System (SDS), Thermo Fisher Scientific (Life Technologies) • Separate computer for installation of Applied Biosystems Bacillus anthracis Interpretive Software (BaIS) Version 1.0 (It is not recommended to install and run BaIS on Applied Biosystems 7500 Fast Dx Real-Time PCR instrument computer) • MagNA Pure LC 2.0 Robot, Roche • Automated blood culture monitoring system (for testing blood culture samples only) • Biosafety cabinet (BSC) (Class II, Type A or B) • 2-8°C Refrigerator • < -20°C Freezer • < -70°C Freezer • Plate centrifuge compatible with Applied Biosystems MicroAmp Fast Optical 96-Well Reaction Plate, 0.1 mL, with at least 1000 rpm centrifuging speed 5 • Microcentrifuge, able to hold 2 mL tubes and capable of reaching 20,800 x g • Vortexer • Heat block capable of 56°C with insert for 2 mL tubes • Micropipette 1000 µL, 200 µL, 20 µL • Caplocks for 2 mL microcentrifuge tubes Consumables and Reagents • QIAamp DSP DNA Blood Mini Kit (IVD), Qiagen (DSP) • 100% Ethanol • Nuclease-free water • MagNA Pure LC DNA Isolation Kit – Large Volume, Roche • Blood culture bottles, aerobic and/or anaerobic (for testing blood culture samples only) • Aerosol-resistant filter tips for micropipettes – 1000 µL, 200 µL, 20 µL • Serological pipets – 50 mL, 25 mL, 10 mL, 5 mL • Optical plate film (seals) for 96-well PCR plates, compatible with AB7500 Fast Dx • Clean RNase- and DNase-free 2.0 mL microcentrifuge tubes J. Substantial Equivalence Applicant:

idK183462_s0_e2000

K183462.txt

regulation section

CFR 866.4000

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K183462 B. Purpose for Submission: Clearance of the Applied Biosystems Bacillus anthracis Detection Kit on the Applied Biosystems (AB) 7500 Fast Dx instrument and Applied Biosystems Bacillus anthracis Interpretive Software (BaIS). C. Measurand: Nucleic acid sequences of Bacillus anthracis pX01 and pX02 plasmids D. Type of Test: Real-time polymerase chain reaction E. Applicant: MRIGlobal F. Proprietary and Established Names: Applied Biosystems Bacillus anthracis Detection Kit Applied Biosystems (AB) 7500 Fast Dx G. Regulatory Information: 1. Regulation section: CFR 866.4000 2. Classification: Class II 3. Product code: QIF, OOI 4. Panel: 83- Microbiology H. Intended Use: 1. Intended use The Applied Biosystems Bacillus anthracis Detection Kit is a real-time polymerase chain reaction (PCR) test kit intended for the qualitative in vitro diagnostic (IVD) detection of target DNA 2 sequences for Bacillus anthracis (B. anthracis, or BA). The Applied Biosystems Bacillus anthracis Detection Kit is intended to test human whole blood (EDTA) specimens and blood culture specimens with growth detected by a continuous monitoring blood culture system. Blood culture specimens must be determined to contain gram-positive bacilli by Gram stain prior to testing. Testing of whole blood specimens must be performed concomitantly with standard of care blood culture. The Applied Biosystems Bacillus anthracis Detection Kit is indicated for use in CLIA-certified high- complexity laboratories in response to a confirmed Bacillus anthracis event only in accordance with the guidelines provided by public health authorities prior to or during a public health emergency. Testing with the Applied Biosystems Bacillus anthracis Detection Kit must only be performed when public health authorities have determined the need for this test. The test must only be used with specimens from individuals with clinical signs and symptoms of B. anthracis infection and who have either been exposed to B. anthracis or may have been exposed to B anthracis. The Applied Biosystems Bacillus anthracis Detection Kit is intended for use as an aid in the diagnosis of anthrax infection and results are for the presumptive identification of Bacillus anthracis. The diagnosis of B. anthracis infection must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidence, in addition to the identification of B. anthracis from cultures or directly from clinical specimens. The definitive identification of B. anthracis requires additional testing and confirmation procedures in consultation with the appropriate public health authorities for whom reports may be required. The Applied Biosystems Bacillus anthracis Detection Kit has not been clinically evaluated with specimens collected from individuals with B. anthracis infection or those presumed to be exposed to B. anthracis. ‘B. anthracis Not detected’ results do not preclude infection with Bacillus anthracis and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. Laboratories implementing this test must have the appropriate biosafety equipment, personal protective equipment (PPE), containment facilities and personnel trained in the safe handling of diagnostic clinical specimens potentially containing B. anthracis. Anthrax is a nationally notifiable disease caused by a biothreat microbial agent and must be reported to public health authorities. The distribution of in vitro diagnostic devices for Bacillus spp. detection is limited to laboratories that follow public health guidelines that address appropriate biosafety conditions, interpretation of test results, and coordination of findings with public health authorities. The Applied Biosystems Bacillus anthracis Detection Kit is intended for use with the ABI 7500 Fast Dx Real-Time PCR Instrument with analysis using the Applied Biosystems Bacillus anthracis Interpretive Software (BaIS). 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): • For Prescription Use Only • Laboratories must maintain records of completed manufacturer required training including training related to use of the assay, instrumentation, biosafety precautions, appropriate PPE and contamination control and waste disposal. • Laboratories must maintain manufacturer required documentation verifying the laboratory is 3 certified as high-complexity, has appropriate biosafety equipment and PPE as required per assay instructions and has procedures for following public health guidelines for working with specimens containing B. anthracis. • Laboratories must maintain manufacturer required documentation verifying the laboratory has procedures for following applicable state, local and federal public health regulations for reporting results and for referring specimens and or isolates to their public health reference laboratory. 4. Special instrument requirements: MagNA Pure LC 2.0 extraction System, Roche Applied Biosystems (AB) 7500 Fast Dx Real-Time PCR Instrument with Sequence Detection System (SDS), Thermo Fisher Scientific (Life Technologies) I. Device Description: The Applied Biosystems Bacillus anthracis Detection Kit is a multiplexed real-time polymerase chain reaction (PCR) test kit intended for the qualitative detection of B. anthracis DNA sequences. PCR reagents are lyophilized in PCR well strips and run in a 96-well plate format. The kit is designed for performing real- time PCR using the Applied Biosystems (AB) 7500 Fast Dx instrument and software, with nucleic acids extracted from clinical specimens using either a Qiagen manual extraction method using Qiagen’s QIAamp DSP DNA Blood Mini Kit (DSP) or Roche’s MagNA Pure LC 2.0 Robot (MagNA Pure, MNP). Roche MagNA Pure is an automated extraction method. An automated interpretative software component (BaIS) is included in the kit, but supplied separately, and operates on a separate computer from the AB 7500 Fast Dx computer. 4 Materials provided Materials Provided in the Applied Biosystem Bacillus anthracis Detection Kit Part Name Quantity and Content Storage Conditions Applied Biosystems Bacillus anthracis Test Kit Lyophilized Assay Plates 10 Plates; Each plate contains a lyophilized Mastermix and primers/probes specific for the Bacillus anthracis 3-plex assay; each plate is individually sealed and foil-wrapped. Ambient or room temperature (20°C – 25°C) Applied Biosystems Bacillus anthracis Test Kit Controls 1 box contains 1 vial of External Positive Control (EPC) and 1 vial of External Negative Control (ENC); Each vial contains enough reagent volume for approximately 10 PCR reactions; no further dilution of the control reagent is necessary. See below for final concentrations of control targets per 20 µl PCR reaction. Frozen (-15°C to -25°C) Applied Biosystems Bacillus anthracis Interpretive Software (BaIS) Version 1.0 1 BaIS Interpretive Software Server Installer; 1 BaIS Interpretive Software Client Installer. Not applicable External Controls and Final Target Concentration External Control Final Target Concentration per Reaction EPC pX01 (100fg), pX02 (200fg) and TERT (750fg) ENC E. coli DNA (4.8ng) Equipment and materials required but not supplied Equipment • Applied Biosystem 7500 Fast Dx Real-Time PCR Instrument with Sequence Detection System (SDS), Thermo Fisher Scientific (Life Technologies) • Separate computer for installation of Applied Biosystems Bacillus anthracis Interpretive Software (BaIS) Version 1.0 (It is not recommended to install and run BaIS on Applied Biosystems 7500 Fast Dx Real-Time PCR instrument computer) • MagNA Pure LC 2.0 Robot, Roche • Automated blood culture monitoring system (for testing blood culture samples only) • Biosafety cabinet (BSC) (Class II, Type A or B) • 2-8°C Refrigerator • < -20°C Freezer • < -70°C Freezer • Plate centrifuge compatible with Applied Biosystems MicroAmp Fast Optical 96-Well Reaction Plate, 0.1 mL, with at least 1000 rpm centrifuging speed 5 • Microcentrifuge, able to hold 2 mL tubes and capable of reaching 20,800 x g • Vortexer • Heat block capable of 56°C with insert for 2 mL tubes • Micropipette 1000 µL, 200 µL, 20 µL • Caplocks for 2 mL microcentrifuge tubes Consumables and Reagents • QIAamp DSP DNA Blood Mini Kit (IVD), Qiagen (DSP) • 100% Ethanol • Nuclease-free water • MagNA Pure LC DNA Isolation Kit – Large Volume, Roche • Blood culture bottles, aerobic and/or anaerobic (for testing blood culture samples only) • Aerosol-resistant filter tips for micropipettes – 1000 µL, 200 µL, 20 µL • Serological pipets – 50 mL, 25 mL, 10 mL, 5 mL • Optical plate film (seals) for 96-well PCR plates, compatible with AB7500 Fast Dx • Clean RNase- and DNase-free 2.0 mL microcentrifuge tubes J. Substantial Equivalence Regulation section:

idK183462_s20000_e22000

K183462.txt

proposed labeling

The labeling supports the finding of substantial equivalence for this device.

result of ‘B. anthracis suspected’ and the sample was considered discordant. • Two simulated positive samples spiked with Bacillus anthracis Carbosap strain at 3x LoD and initially generated “BA suspected” results. Upon repeat testing, one 38 sample generated a negative result and one sample generated a ‘B. anthracis suspected’ result. Both samples were considered discordant. Due to known variation in plasmid copy number among Bacillus anthracis strains, the discordant results were attributed to target concentration levels at or below LoD. Results for the study are shown in Table 31. Table 31: Clinical Study, Contrived Positive Whole Blood Specimens Simulated Positive Whole Blood B. anthracis positive B. anthracis negative Applied Biosystems B. anthracis Detection Kit Test Positive 84 0 Test Negative 0 21 Unresolved 3* 0 Positive Percent Agreement (%) 96% 95% CI (90.4%, 98.8%) Negative percent agreement (%) 100% 95% CI (84.5%, 100%) *Initially reported as ‘B. anthracis suspected’. See above for details on Unresolved/Discordant whole blood specimens. Clinical Study, Summary of Indeterminate Calls: Indeterminate results generated by the BaIS software may occur with specimens that produce a pX01 Ct value without true amplification. An indeterminate result/supervisor review interpretive result for a sample is caused by the combination of a positive pX01 with either a negative or an indeterminate call for pX02. This may be due to the ‘cross-talk’ phenomenon and requires review of the pX01 graph in the 7500 analysis software for resolution. The rate of indeterminate calls that occurred during clinical testing is summarized in the table below. Indeterminate results only occurred in negative or un-spiked whole blood. Indeterminate results did not occur in spiked whole blood specimens or in spiked or un-spiked blood culture specimens. A summary of Indeterminate results is shown in Table 32. 39 Table 32: Clinical Study, Summary of Indeterminate Results by Sample Matrix and Test Site Clinical Study Site Negative WB (w/o B. anthracis) WB (w/ B. anthracis) BC Specificity 1 22/100 22.0% N/A 0/129 0.0% Specificity 2 0/100 0.0% N/A 0/120 0.0% Specificity 3 7/239 2.9% N/A 0/157 0.0% Specificity Total 29/439 6.6% N/A 0/406 0.0% Sensitivity 3 2/21 9.5% 0/87 0.0% N/A All Combined Total 31/460 6.7% 0/87 0.0% 0/406 0.0% N/A: Not applicable; WB: Whole blood; BC: Blood culture Clinical Specificity Testing, Summary of Invalid Results, Failed Runs: There were no invalid results observed for whole blood specimens during the clinical study. A total of 43 blood culture specimens were initially reported as invalid and required repeat testing; 33 of those were invalid due to Sample TERT failure, and 10 were invalid due to QC BLK TERT failure. This yielded an initial error rate of 10.1% [43/425]. Repeat testing was performed on the 43 invalid blood culture samples. A total of 19/43 [44.2%] generated valid results upon repeat testing, while 24/43 remained invalid due to Sample TERT failure. The final invalid rate for blood culture specimens was 24/425 [5.6%] after repeat testing. A total of 32 instrument runs were required to test the 864 samples included in the specificity study. 1/32 [3.1%] runs performed was invalid due to QC failure [BLK TERT Invalid]. The invalid QC was resolved upon repeat testing of the entire run. 40 Tables 33 and 34 include the numbers and percentage of invalid results for initial and repeat testing. Table 35 includes a summary of test runs. Table 33: Initial Invalid Rate During Clinical Specificity Testing Initial Results Samples Tested VALID BC Samples INVALID Site WB BC Total WB BC Total Sample TERT Failure QC BLK Tert Failure Total Invalid 1 100 134 234 100 119 219 5 10 15 2 100 134 234 100 113 213 21 0 21 3 239 157 396 239 150 389 7 0 7 Total 439 425 864 439/439 100% 382/425 89.9% 821/864 95.0% 33/425 7.8% 10/425 5.5% 43/425 10.1% Table 34: Repeat Invalid Rate During Clinical Specificity Testing Repeat Samples Tested Repeat Results VALID INVALID Site Sample TERT Failure QC BLK Tert Failure Total Invalid 1 15 10 5 0 5 2 21 7 14 0 14 3 7 2 5 0 5 Total 43 19/43 44.2% 24/43 55.8% 0/43 0.0% 24/43 55.8% Instrument Runs during Clinical Testing Table 35: Instrument Runs During Clinical Specificity Testing Instrument Runs Performed Instrument Run Results Site Valid Invalid 1 7 6 1 2 11 11 0 3 14 14 0 Total 32 31/32 96.9% [84.3-99.4%] 1/32 3.1% [0.6-15.7%] 5. Clinical cut-off: N/A 6. Expected values/Reference range: 41 N/A N. Instrument Name: Applied Biosystems (AB) 7500 Fast Dx O. System Descriptions: 1. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes _____X___ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No __X______ 2. Software: FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: Yes ____X____ or No ________ 3. Specimen Identification: Users must fill in Batch Information including patient information, number of samples, and sample IDs. Prior to initiating the experiment, the user must prepare a plate layout to assign a location for samples and controls on the plate. For each extracted specimen, a prefix MUST be added to the sample ID to indicate the sample type for recognition by the automated BaIS. In addition to the prefix, for extraction blanks, the task must be changed to NTC in the Well Inspector Screen. 4. Specimen Sampling and Handling: DNA is extracted manually using the Qiagen DSP DNA Mini Kit or the automated MagNA Pure LC 2.0 extraction system. Specimen extracts and controls are then manually pipetted into the Applied Biosystems Bacillus anthracis Test Kit Lyophilized Assay Plate for analysis prior to loading onto the AB 7500 Fast Dx Real-Time PCR Instrument for amplification and detection. 42 5. Calibration: Prior to testing with the Applied Biosystems Bacillus anthracis Detection Kit, the Applied Biosystems 7500 Fast Dx Real-Time PCR Instrument must be calibrated by the manufacturer to read the following dyes: FAM, VIC, ABY, and ROX. It is noted that ABY is outside of the routine calibration dyes and must be specifically requested when scheduling calibration. A background calibration plate should be periodically run as recommended by ThermoFisher or alternatively, the user can perform a background calibration run as per the instructions in the AB 7500 Fast Dx Real Time PCR Instrument Reference Guide. 6. Quality Control: See Section M.1.c. Section above. P. Other Supportive Instrument Performance Characteristics Data Not Covered In The “Performance Characteristics” Section above: None Q. Proposed Labeling: The labeling supports the finding of substantial equivalence for this device. R. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK183462_s20000_e22000

K183462.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

with a result of ‘B. anthracis suspected’ and the sample was considered discordant. • Two simulated positive samples spiked with Bacillus anthracis Carbosap strain at 3x LoD and initially generated “BA suspected” results. Upon repeat testing, one 38 sample generated a negative result and one sample generated a ‘B. anthracis suspected’ result. Both samples were considered discordant. Due to known variation in plasmid copy number among Bacillus anthracis strains, the discordant results were attributed to target concentration levels at or below LoD. Results for the study are shown in Table 31. Table 31: Clinical Study, Contrived Positive Whole Blood Specimens Simulated Positive Whole Blood B. anthracis positive B. anthracis negative Applied Biosystems B. anthracis Detection Kit Test Positive 84 0 Test Negative 0 21 Unresolved 3* 0 Positive Percent Agreement (%) 96% 95% CI (90.4%, 98.8%) Negative percent agreement (%) 100% 95% CI (84.5%, 100%) *Initially reported as ‘B. anthracis suspected’. See above for details on Unresolved/Discordant whole blood specimens. Clinical Study, Summary of Indeterminate Calls: Indeterminate results generated by the BaIS software may occur with specimens that produce a pX01 Ct value without true amplification. An indeterminate result/supervisor review interpretive result for a sample is caused by the combination of a positive pX01 with either a negative or an indeterminate call for pX02. This may be due to the ‘cross-talk’ phenomenon and requires review of the pX01 graph in the 7500 analysis software for resolution. The rate of indeterminate calls that occurred during clinical testing is summarized in the table below. Indeterminate results only occurred in negative or un-spiked whole blood. Indeterminate results did not occur in spiked whole blood specimens or in spiked or un-spiked blood culture specimens. A summary of Indeterminate results is shown in Table 32. 39 Table 32: Clinical Study, Summary of Indeterminate Results by Sample Matrix and Test Site Clinical Study Site Negative WB (w/o B. anthracis) WB (w/ B. anthracis) BC Specificity 1 22/100 22.0% N/A 0/129 0.0% Specificity 2 0/100 0.0% N/A 0/120 0.0% Specificity 3 7/239 2.9% N/A 0/157 0.0% Specificity Total 29/439 6.6% N/A 0/406 0.0% Sensitivity 3 2/21 9.5% 0/87 0.0% N/A All Combined Total 31/460 6.7% 0/87 0.0% 0/406 0.0% N/A: Not applicable; WB: Whole blood; BC: Blood culture Clinical Specificity Testing, Summary of Invalid Results, Failed Runs: There were no invalid results observed for whole blood specimens during the clinical study. A total of 43 blood culture specimens were initially reported as invalid and required repeat testing; 33 of those were invalid due to Sample TERT failure, and 10 were invalid due to QC BLK TERT failure. This yielded an initial error rate of 10.1% [43/425]. Repeat testing was performed on the 43 invalid blood culture samples. A total of 19/43 [44.2%] generated valid results upon repeat testing, while 24/43 remained invalid due to Sample TERT failure. The final invalid rate for blood culture specimens was 24/425 [5.6%] after repeat testing. A total of 32 instrument runs were required to test the 864 samples included in the specificity study. 1/32 [3.1%] runs performed was invalid due to QC failure [BLK TERT Invalid]. The invalid QC was resolved upon repeat testing of the entire run. 40 Tables 33 and 34 include the numbers and percentage of invalid results for initial and repeat testing. Table 35 includes a summary of test runs. Table 33: Initial Invalid Rate During Clinical Specificity Testing Initial Results Samples Tested VALID BC Samples INVALID Site WB BC Total WB BC Total Sample TERT Failure QC BLK Tert Failure Total Invalid 1 100 134 234 100 119 219 5 10 15 2 100 134 234 100 113 213 21 0 21 3 239 157 396 239 150 389 7 0 7 Total 439 425 864 439/439 100% 382/425 89.9% 821/864 95.0% 33/425 7.8% 10/425 5.5% 43/425 10.1% Table 34: Repeat Invalid Rate During Clinical Specificity Testing Repeat Samples Tested Repeat Results VALID INVALID Site Sample TERT Failure QC BLK Tert Failure Total Invalid 1 15 10 5 0 5 2 21 7 14 0 14 3 7 2 5 0 5 Total 43 19/43 44.2% 24/43 55.8% 0/43 0.0% 24/43 55.8% Instrument Runs during Clinical Testing Table 35: Instrument Runs During Clinical Specificity Testing Instrument Runs Performed Instrument Run Results Site Valid Invalid 1 7 6 1 2 11 11 0 3 14 14 0 Total 32 31/32 96.9% [84.3-99.4%] 1/32 3.1% [0.6-15.7%] 5. Clinical cut-off: N/A 6. Expected values/Reference range: 41 N/A N. Instrument Name: Applied Biosystems (AB) 7500 Fast Dx O. System Descriptions: 1. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes _____X___ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No __X______ 2. Software: FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: Yes ____X____ or No ________ 3. Specimen Identification: Users must fill in Batch Information including patient information, number of samples, and sample IDs. Prior to initiating the experiment, the user must prepare a plate layout to assign a location for samples and controls on the plate. For each extracted specimen, a prefix MUST be added to the sample ID to indicate the sample type for recognition by the automated BaIS. In addition to the prefix, for extraction blanks, the task must be changed to NTC in the Well Inspector Screen. 4. Specimen Sampling and Handling: DNA is extracted manually using the Qiagen DSP DNA Mini Kit or the automated MagNA Pure LC 2.0 extraction system. Specimen extracts and controls are then manually pipetted into the Applied Biosystems Bacillus anthracis Test Kit Lyophilized Assay Plate for analysis prior to loading onto the AB 7500 Fast Dx Real-Time PCR Instrument for amplification and detection. 42 5. Calibration: Prior to testing with the Applied Biosystems Bacillus anthracis Detection Kit, the Applied Biosystems 7500 Fast Dx Real-Time PCR Instrument must be calibrated by the manufacturer to read the following dyes: FAM, VIC, ABY, and ROX. It is noted that ABY is outside of the routine calibration dyes and must be specifically requested when scheduling calibration. A background calibration plate should be periodically run as recommended by ThermoFisher or alternatively, the user can perform a background calibration run as per the instructions in the AB 7500 Fast Dx Real Time PCR Instrument Reference Guide. 6. Quality Control: See Section M.1.c. Section above. P. Other Supportive Instrument Performance Characteristics Data Not Covered In The “Performance Characteristics” Section above: None Q. Proposed Labeling: The labeling supports the finding of substantial equivalence for this device. R. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK180936_s0_e2000

K180936.txt

purpose for submission

To obtain a substantial equivalence determination for telavancin at concentrations of 0.002 – 32 µg/mL for susceptibility testing of Gram positive aerobic microorganisms with ETEST.

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K180936 B. Purpose for Submission: To obtain a substantial equivalence determination for telavancin at concentrations of 0.002 – 32 µg/mL for susceptibility testing of Gram positive aerobic microorganisms with ETEST. C. Measurand: Telavancin 0.002 – 32 µg/mL D. Type of Test: Quantitative AST growth-based detection E. Applicant: bioMérieux, Inc. F. Proprietary and Established Names: ETEST Telavancin (TLA) (0.002 – 32 µg/mL) G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY – Manual Antimicrobial Test Systems 4. Panel: 83 –Microbiology 2 H. Intended Use: 1. Intended use(s): ETEST is a quantitative technique for determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria such as Enterobacteriaceae, Pseudomonas, Staphylococcus, and Enterococcus species and fastidious bacteria, such as anaerobes, N. gonorrhoeae, S. pneumoniae, Streptococcus and Haemophilus species. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC), in µg/mL, of different antimicrobial agents against microorganisms as tested on agar media using overnight incubation. Telavancin has been shown to be active against the Gram positive aerobic microorganisms listed below according to the FDA label for this antimicrobial agent. Active both in vitro and in clinical infections: Staphylococcus aureus (including methicillin-resistant isolates) Enterococcus faecalis (vancomycin-susceptible isolates only) 2. Indication(s) for use: Same as the Intended Use 3. Special conditions for use statement(s): For prescription use only Limitations: · Due to the lack of an intermediate category and the observed trending for Telavancin, testing of S. aureus and E. faecalis have resulted in major discrepancies for isolates that are otherwise within essential agreement with the reference method. If critical to patient care, testing should be repeated using an alternative testing/reference method prior to reporting results for S. aureus when the ETEST TLA MIC is 0.25 µg/mL and 0.5 µg/mL for E. faecalis. 4. Special instrument requirements: N/A I. Device Description: ETEST consists of a thin, inert and non-porous plastic strip 5mm wide and 60 mm long. One side of the strip carries a three letter code designating the identity of the antibiotic and is calibrated with MIC values in terms of µg/mL. On the reverse, a predefined exponential gradient of the dried and stabilized antibiotic covers a continuous concentration range across 3 15 two-fold dilutions of a conventional MIC method. J. Substantial Equivalence Information: 1. Predicate device name(s): ETEST Ceftaroline 2. Predicate 510(k) number(s): K151873 3. Comparison with predicate: 4 Table 1. Comparison with the Predicate Device Similarities Item Device K180936 ETEST Telavancin Predicate K151873 ETEST Ceftaroline Intended Use ETEST is a quantitative technique for determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria such as Enterobacteriaceae, Pseudomonas, Staphylococcus, and Enterococcus species and fastidious bacteria, such as anaerobes, N. gonorrhoeae, S. pneumoniae, Streptococcus and Haemophilus species. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC), in µg/mL, of different antimicrobial agents against microorganism as tested on agar media using overnight incubation. Same Antimicrobial Concentration Range 0.002 – 32 µg/mL Same Test Design A predefined exponential gradient of the dried and stabilized antibiotic covers a continuous concentration range across 15 two- fold dilutions of a conventional MIC method. Same Inoculation Isolated colonies from culture Same Result MIC Same Differences Item Device K180936 ETEST Telavancin Predicate K151873 ETEST Ceftaroline Claimed organisms S. aureus (including MRSA), E. faecalis (vancomycin- susceptible only) S. agalactiae, S. pneumoniae, H. influenza Antimicrobial Agent Telavancin Ceftaroline Incubation 35°± 2° C for 16–20 hours 35°± 2° C for 20–24 hours 5 K. Standard/Guidance Document Referenced (if applicable): Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA CLSI M07-A10, Method for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, January 2015. CLSI M100-S26, Performance Standards for Antimicrobial Susceptibility Testing; Volume 36, No. 1, January 2016. L. Test Principle: The ETEST consists of a thin, inert, nonporous plastic strip that is used to determine the antimicrobial susceptibility of bacteria. One side of the strip carries the minimum inhibitory concentration (MIC) reading scale expressed in µg/mL. The other side of the strip contains a predefined continuous gradient of antibiotic concentrations. When the strip is applied to an inoculated agar surface, the preformed antibiotic gradient immediately transfers into the agar matrix, then forming a stable, continuous and exponential gradient of antibiotic concentrations directly underneath the strip. Bacteria growth becomes visible during incubation, and a symmetrical inhibition ellipse centered along the strip appears. After incubation, the MIC value is read from the scale in terms of µg/mL at complete inhibition of bacterial growth, where the pointed end of the ellipse intersects the strip. Since ETEST generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read must be recorded to the next two-fold dilution. The MIC gradient on ETEST Telavancin ranges from 0.002 to 32 µg/mL. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: A reproducibility study was conducted at three external sites using 10 isolates of Gram positive organisms that were consistent with the intended use. Testing was performed on three separate days and in triplicate for a total of 270 data points among the sites. The isolates tested included five S. aureus and five E. faecalis isolates. The mode MIC was determined and the reproducibility was calculated based on MIC values that fell within ± one doubling dilution from the mode MIC value. All results were on-scale and within ± 1 doubling dilution of the mode MIC value for telavancin. The overall reproducibility was 100.0%. b. Linearity/assay reportable range: 6 Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Inoculum Density Check. Inoculum density checks were performed for all quality control and reproducibility organism suspensions and for 10% of the suspensions prepared for susceptibility testing of the fresh clinical isolates. The mean inoculum density was acceptable at 4.40 X 105 CFU/mL. Purity Check. All clinical, challenge and reproducibility test suspensions were subcultured to assure purity. Growth or Device Failure. There were no growth or device failures during the course of the study. Quality Control Testing. Organisms recommended by both FDA and the CLSI were tested with telavancin at three sites. The QC organisms tested included S. aureus ATCC 29213 and E. faecalis ATCC 29212. These QC strains were tested a minimum of 20 times per site by both the ETEST and the reference method. The results demonstrate that the telavancin ETEST can produce quality control results in the recommended range > 95% of the time. See Table 2 below for a summary of the QC results. Table 2. Quality Control Data for Telavancin QC organism Telavancin expected range (µg/mL) Concentration (µg/mL) Reference ETEST S. aureus ATCC 29213 0.03 – 0.12 0.016 - - 0.03 60 6 0.06 20 71 0.12 1 4 0.25 - - E. faecalis ATCC 29212 0.03 – 0.12 0.016 - - 0.03 - - 0.06 75 41 0.12 6 40 0.25 - - d. Detection limit: Not applicable e. Analytical specificity: Not applicable 7 f. Assay cut-off: Not applicable 2. Comparison studies: a. Method comparison with predicate device: Results obtained with ETEST telavancin were compared to results obtained with the CLSI broth microdilution reference panel. The CLSI panel Purpose for submission:

idK180936_s0_e2000

K180936.txt

measurand

Telavancin 0.002 – 32 µg/mL

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K180936 B. Purpose for Submission: To obtain a substantial equivalence determination for telavancin at concentrations of 0.002 – 32 µg/mL for susceptibility testing of Gram positive aerobic microorganisms with ETEST. C. Measurand: Telavancin 0.002 – 32 µg/mL D. Type of Test: Quantitative AST growth-based detection E. Applicant: bioMérieux, Inc. F. Proprietary and Established Names: ETEST Telavancin (TLA) (0.002 – 32 µg/mL) G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY – Manual Antimicrobial Test Systems 4. Panel: 83 –Microbiology 2 H. Intended Use: 1. Intended use(s): ETEST is a quantitative technique for determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria such as Enterobacteriaceae, Pseudomonas, Staphylococcus, and Enterococcus species and fastidious bacteria, such as anaerobes, N. gonorrhoeae, S. pneumoniae, Streptococcus and Haemophilus species. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC), in µg/mL, of different antimicrobial agents against microorganisms as tested on agar media using overnight incubation. Telavancin has been shown to be active against the Gram positive aerobic microorganisms listed below according to the FDA label for this antimicrobial agent. Active both in vitro and in clinical infections: Staphylococcus aureus (including methicillin-resistant isolates) Enterococcus faecalis (vancomycin-susceptible isolates only) 2. Indication(s) for use: Same as the Intended Use 3. Special conditions for use statement(s): For prescription use only Limitations: · Due to the lack of an intermediate category and the observed trending for Telavancin, testing of S. aureus and E. faecalis have resulted in major discrepancies for isolates that are otherwise within essential agreement with the reference method. If critical to patient care, testing should be repeated using an alternative testing/reference method prior to reporting results for S. aureus when the ETEST TLA MIC is 0.25 µg/mL and 0.5 µg/mL for E. faecalis. 4. Special instrument requirements: N/A I. Device Description: ETEST consists of a thin, inert and non-porous plastic strip 5mm wide and 60 mm long. One side of the strip carries a three letter code designating the identity of the antibiotic and is calibrated with MIC values in terms of µg/mL. On the reverse, a predefined exponential gradient of the dried and stabilized antibiotic covers a continuous concentration range across 3 15 two-fold dilutions of a conventional MIC method. J. Substantial Equivalence Information: 1. Predicate device name(s): ETEST Ceftaroline 2. Predicate 510(k) number(s): K151873 3. Comparison with predicate: 4 Table 1. Comparison with the Predicate Device Similarities Item Device K180936 ETEST Telavancin Predicate K151873 ETEST Ceftaroline Intended Use ETEST is a quantitative technique for determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria such as Enterobacteriaceae, Pseudomonas, Staphylococcus, and Enterococcus species and fastidious bacteria, such as anaerobes, N. gonorrhoeae, S. pneumoniae, Streptococcus and Haemophilus species. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC), in µg/mL, of different antimicrobial agents against microorganism as tested on agar media using overnight incubation. Same Antimicrobial Concentration Range 0.002 – 32 µg/mL Same Test Design A predefined exponential gradient of the dried and stabilized antibiotic covers a continuous concentration range across 15 two- fold dilutions of a conventional MIC method. Same Inoculation Isolated colonies from culture Same Result MIC Same Differences Item Device K180936 ETEST Telavancin Predicate K151873 ETEST Ceftaroline Claimed organisms S. aureus (including MRSA), E. faecalis (vancomycin- susceptible only) S. agalactiae, S. pneumoniae, H. influenza Antimicrobial Agent Telavancin Ceftaroline Incubation 35°± 2° C for 16–20 hours 35°± 2° C for 20–24 hours 5 K. Standard/Guidance Document Referenced (if applicable): Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA CLSI M07-A10, Method for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, January 2015. CLSI M100-S26, Performance Standards for Antimicrobial Susceptibility Testing; Volume 36, No. 1, January 2016. L. Test Principle: The ETEST consists of a thin, inert, nonporous plastic strip that is used to determine the antimicrobial susceptibility of bacteria. One side of the strip carries the minimum inhibitory concentration (MIC) reading scale expressed in µg/mL. The other side of the strip contains a predefined continuous gradient of antibiotic concentrations. When the strip is applied to an inoculated agar surface, the preformed antibiotic gradient immediately transfers into the agar matrix, then forming a stable, continuous and exponential gradient of antibiotic concentrations directly underneath the strip. Bacteria growth becomes visible during incubation, and a symmetrical inhibition ellipse centered along the strip appears. After incubation, the MIC value is read from the scale in terms of µg/mL at complete inhibition of bacterial growth, where the pointed end of the ellipse intersects the strip. Since ETEST generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read must be recorded to the next two-fold dilution. The MIC gradient on ETEST Telavancin ranges from 0.002 to 32 µg/mL. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: A reproducibility study was conducted at three external sites using 10 isolates of Gram positive organisms that were consistent with the intended use. Testing was performed on three separate days and in triplicate for a total of 270 data points among the sites. The isolates tested included five S. aureus and five E. faecalis isolates. The mode MIC was determined and the reproducibility was calculated based on MIC values that fell within ± one doubling dilution from the mode MIC value. All results were on-scale and within ± 1 doubling dilution of the mode MIC value for telavancin. The overall reproducibility was 100.0%. b. Linearity/assay reportable range: 6 Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Inoculum Density Check. Inoculum density checks were performed for all quality control and reproducibility organism suspensions and for 10% of the suspensions prepared for susceptibility testing of the fresh clinical isolates. The mean inoculum density was acceptable at 4.40 X 105 CFU/mL. Purity Check. All clinical, challenge and reproducibility test suspensions were subcultured to assure purity. Growth or Device Failure. There were no growth or device failures during the course of the study. Quality Control Testing. Organisms recommended by both FDA and the CLSI were tested with telavancin at three sites. The QC organisms tested included S. aureus ATCC 29213 and E. faecalis ATCC 29212. These QC strains were tested a minimum of 20 times per site by both the ETEST and the reference method. The results demonstrate that the telavancin ETEST can produce quality control results in the recommended range > 95% of the time. See Table 2 below for a summary of the QC results. Table 2. Quality Control Data for Telavancin QC organism Telavancin expected range (µg/mL) Concentration (µg/mL) Reference ETEST S. aureus ATCC 29213 0.03 – 0.12 0.016 - - 0.03 60 6 0.06 20 71 0.12 1 4 0.25 - - E. faecalis ATCC 29212 0.03 – 0.12 0.016 - - 0.03 - - 0.06 75 41 0.12 6 40 0.25 - - d. Detection limit: Not applicable e. Analytical specificity: Not applicable 7 f. Assay cut-off: Not applicable 2. Comparison studies: a. Method comparison with predicate device: Results obtained with ETEST telavancin were compared to results obtained with the CLSI broth microdilution reference panel. The CLSI panel Measurand:

idK180936_s0_e2000

K180936.txt

type of test

Quantitative AST growth-based detection

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K180936 B. Purpose for Submission: To obtain a substantial equivalence determination for telavancin at concentrations of 0.002 – 32 µg/mL for susceptibility testing of Gram positive aerobic microorganisms with ETEST. C. Measurand: Telavancin 0.002 – 32 µg/mL D. Type of Test: Quantitative AST growth-based detection E. Applicant: bioMérieux, Inc. F. Proprietary and Established Names: ETEST Telavancin (TLA) (0.002 – 32 µg/mL) G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY – Manual Antimicrobial Test Systems 4. Panel: 83 –Microbiology 2 H. Intended Use: 1. Intended use(s): ETEST is a quantitative technique for determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria such as Enterobacteriaceae, Pseudomonas, Staphylococcus, and Enterococcus species and fastidious bacteria, such as anaerobes, N. gonorrhoeae, S. pneumoniae, Streptococcus and Haemophilus species. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC), in µg/mL, of different antimicrobial agents against microorganisms as tested on agar media using overnight incubation. Telavancin has been shown to be active against the Gram positive aerobic microorganisms listed below according to the FDA label for this antimicrobial agent. Active both in vitro and in clinical infections: Staphylococcus aureus (including methicillin-resistant isolates) Enterococcus faecalis (vancomycin-susceptible isolates only) 2. Indication(s) for use: Same as the Intended Use 3. Special conditions for use statement(s): For prescription use only Limitations: · Due to the lack of an intermediate category and the observed trending for Telavancin, testing of S. aureus and E. faecalis have resulted in major discrepancies for isolates that are otherwise within essential agreement with the reference method. If critical to patient care, testing should be repeated using an alternative testing/reference method prior to reporting results for S. aureus when the ETEST TLA MIC is 0.25 µg/mL and 0.5 µg/mL for E. faecalis. 4. Special instrument requirements: N/A I. Device Description: ETEST consists of a thin, inert and non-porous plastic strip 5mm wide and 60 mm long. One side of the strip carries a three letter code designating the identity of the antibiotic and is calibrated with MIC values in terms of µg/mL. On the reverse, a predefined exponential gradient of the dried and stabilized antibiotic covers a continuous concentration range across 3 15 two-fold dilutions of a conventional MIC method. J. Substantial Equivalence Information: 1. Predicate device name(s): ETEST Ceftaroline 2. Predicate 510(k) number(s): K151873 3. Comparison with predicate: 4 Table 1. Comparison with the Predicate Device Similarities Item Device K180936 ETEST Telavancin Predicate K151873 ETEST Ceftaroline Intended Use ETEST is a quantitative technique for determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria such as Enterobacteriaceae, Pseudomonas, Staphylococcus, and Enterococcus species and fastidious bacteria, such as anaerobes, N. gonorrhoeae, S. pneumoniae, Streptococcus and Haemophilus species. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC), in µg/mL, of different antimicrobial agents against microorganism as tested on agar media using overnight incubation. Same Antimicrobial Concentration Range 0.002 – 32 µg/mL Same Test Design A predefined exponential gradient of the dried and stabilized antibiotic covers a continuous concentration range across 15 two- fold dilutions of a conventional MIC method. Same Inoculation Isolated colonies from culture Same Result MIC Same Differences Item Device K180936 ETEST Telavancin Predicate K151873 ETEST Ceftaroline Claimed organisms S. aureus (including MRSA), E. faecalis (vancomycin- susceptible only) S. agalactiae, S. pneumoniae, H. influenza Antimicrobial Agent Telavancin Ceftaroline Incubation 35°± 2° C for 16–20 hours 35°± 2° C for 20–24 hours 5 K. Standard/Guidance Document Referenced (if applicable): Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA CLSI M07-A10, Method for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, January 2015. CLSI M100-S26, Performance Standards for Antimicrobial Susceptibility Testing; Volume 36, No. 1, January 2016. L. Test Principle: The ETEST consists of a thin, inert, nonporous plastic strip that is used to determine the antimicrobial susceptibility of bacteria. One side of the strip carries the minimum inhibitory concentration (MIC) reading scale expressed in µg/mL. The other side of the strip contains a predefined continuous gradient of antibiotic concentrations. When the strip is applied to an inoculated agar surface, the preformed antibiotic gradient immediately transfers into the agar matrix, then forming a stable, continuous and exponential gradient of antibiotic concentrations directly underneath the strip. Bacteria growth becomes visible during incubation, and a symmetrical inhibition ellipse centered along the strip appears. After incubation, the MIC value is read from the scale in terms of µg/mL at complete inhibition of bacterial growth, where the pointed end of the ellipse intersects the strip. Since ETEST generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read must be recorded to the next two-fold dilution. The MIC gradient on ETEST Telavancin ranges from 0.002 to 32 µg/mL. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: A reproducibility study was conducted at three external sites using 10 isolates of Gram positive organisms that were consistent with the intended use. Testing was performed on three separate days and in triplicate for a total of 270 data points among the sites. The isolates tested included five S. aureus and five E. faecalis isolates. The mode MIC was determined and the reproducibility was calculated based on MIC values that fell within ± one doubling dilution from the mode MIC value. All results were on-scale and within ± 1 doubling dilution of the mode MIC value for telavancin. The overall reproducibility was 100.0%. b. Linearity/assay reportable range: 6 Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Inoculum Density Check. Inoculum density checks were performed for all quality control and reproducibility organism suspensions and for 10% of the suspensions prepared for susceptibility testing of the fresh clinical isolates. The mean inoculum density was acceptable at 4.40 X 105 CFU/mL. Purity Check. All clinical, challenge and reproducibility test suspensions were subcultured to assure purity. Growth or Device Failure. There were no growth or device failures during the course of the study. Quality Control Testing. Organisms recommended by both FDA and the CLSI were tested with telavancin at three sites. The QC organisms tested included S. aureus ATCC 29213 and E. faecalis ATCC 29212. These QC strains were tested a minimum of 20 times per site by both the ETEST and the reference method. The results demonstrate that the telavancin ETEST can produce quality control results in the recommended range > 95% of the time. See Table 2 below for a summary of the QC results. Table 2. Quality Control Data for Telavancin QC organism Telavancin expected range (µg/mL) Concentration (µg/mL) Reference ETEST S. aureus ATCC 29213 0.03 – 0.12 0.016 - - 0.03 60 6 0.06 20 71 0.12 1 4 0.25 - - E. faecalis ATCC 29212 0.03 – 0.12 0.016 - - 0.03 - - 0.06 75 41 0.12 6 40 0.25 - - d. Detection limit: Not applicable e. Analytical specificity: Not applicable 7 f. Assay cut-off: Not applicable 2. Comparison studies: a. Method comparison with predicate device: Results obtained with ETEST telavancin were compared to results obtained with the CLSI broth microdilution reference panel. The CLSI panel Type of test:

idK180936_s0_e2000

K180936.txt

classification

Class II

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K180936 B. Purpose for Submission: To obtain a substantial equivalence determination for telavancin at concentrations of 0.002 – 32 µg/mL for susceptibility testing of Gram positive aerobic microorganisms with ETEST. C. Measurand: Telavancin 0.002 – 32 µg/mL D. Type of Test: Quantitative AST growth-based detection E. Applicant: bioMérieux, Inc. F. Proprietary and Established Names: ETEST Telavancin (TLA) (0.002 – 32 µg/mL) G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY – Manual Antimicrobial Test Systems 4. Panel: 83 –Microbiology 2 H. Intended Use: 1. Intended use(s): ETEST is a quantitative technique for determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria such as Enterobacteriaceae, Pseudomonas, Staphylococcus, and Enterococcus species and fastidious bacteria, such as anaerobes, N. gonorrhoeae, S. pneumoniae, Streptococcus and Haemophilus species. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC), in µg/mL, of different antimicrobial agents against microorganisms as tested on agar media using overnight incubation. Telavancin has been shown to be active against the Gram positive aerobic microorganisms listed below according to the FDA label for this antimicrobial agent. Active both in vitro and in clinical infections: Staphylococcus aureus (including methicillin-resistant isolates) Enterococcus faecalis (vancomycin-susceptible isolates only) 2. Indication(s) for use: Same as the Intended Use 3. Special conditions for use statement(s): For prescription use only Limitations: · Due to the lack of an intermediate category and the observed trending for Telavancin, testing of S. aureus and E. faecalis have resulted in major discrepancies for isolates that are otherwise within essential agreement with the reference method. If critical to patient care, testing should be repeated using an alternative testing/reference method prior to reporting results for S. aureus when the ETEST TLA MIC is 0.25 µg/mL and 0.5 µg/mL for E. faecalis. 4. Special instrument requirements: N/A I. Device Description: ETEST consists of a thin, inert and non-porous plastic strip 5mm wide and 60 mm long. One side of the strip carries a three letter code designating the identity of the antibiotic and is calibrated with MIC values in terms of µg/mL. On the reverse, a predefined exponential gradient of the dried and stabilized antibiotic covers a continuous concentration range across 3 15 two-fold dilutions of a conventional MIC method. J. Substantial Equivalence Information: 1. Predicate device name(s): ETEST Ceftaroline 2. Predicate 510(k) number(s): K151873 3. Comparison with predicate: 4 Table 1. Comparison with the Predicate Device Similarities Item Device K180936 ETEST Telavancin Predicate K151873 ETEST Ceftaroline Intended Use ETEST is a quantitative technique for determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria such as Enterobacteriaceae, Pseudomonas, Staphylococcus, and Enterococcus species and fastidious bacteria, such as anaerobes, N. gonorrhoeae, S. pneumoniae, Streptococcus and Haemophilus species. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC), in µg/mL, of different antimicrobial agents against microorganism as tested on agar media using overnight incubation. Same Antimicrobial Concentration Range 0.002 – 32 µg/mL Same Test Design A predefined exponential gradient of the dried and stabilized antibiotic covers a continuous concentration range across 15 two- fold dilutions of a conventional MIC method. Same Inoculation Isolated colonies from culture Same Result MIC Same Differences Item Device K180936 ETEST Telavancin Predicate K151873 ETEST Ceftaroline Claimed organisms S. aureus (including MRSA), E. faecalis (vancomycin- susceptible only) S. agalactiae, S. pneumoniae, H. influenza Antimicrobial Agent Telavancin Ceftaroline Incubation 35°± 2° C for 16–20 hours 35°± 2° C for 20–24 hours 5 K. Standard/Guidance Document Referenced (if applicable): Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA CLSI M07-A10, Method for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, January 2015. CLSI M100-S26, Performance Standards for Antimicrobial Susceptibility Testing; Volume 36, No. 1, January 2016. L. Test Principle: The ETEST consists of a thin, inert, nonporous plastic strip that is used to determine the antimicrobial susceptibility of bacteria. One side of the strip carries the minimum inhibitory concentration (MIC) reading scale expressed in µg/mL. The other side of the strip contains a predefined continuous gradient of antibiotic concentrations. When the strip is applied to an inoculated agar surface, the preformed antibiotic gradient immediately transfers into the agar matrix, then forming a stable, continuous and exponential gradient of antibiotic concentrations directly underneath the strip. Bacteria growth becomes visible during incubation, and a symmetrical inhibition ellipse centered along the strip appears. After incubation, the MIC value is read from the scale in terms of µg/mL at complete inhibition of bacterial growth, where the pointed end of the ellipse intersects the strip. Since ETEST generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read must be recorded to the next two-fold dilution. The MIC gradient on ETEST Telavancin ranges from 0.002 to 32 µg/mL. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: A reproducibility study was conducted at three external sites using 10 isolates of Gram positive organisms that were consistent with the intended use. Testing was performed on three separate days and in triplicate for a total of 270 data points among the sites. The isolates tested included five S. aureus and five E. faecalis isolates. The mode MIC was determined and the reproducibility was calculated based on MIC values that fell within ± one doubling dilution from the mode MIC value. All results were on-scale and within ± 1 doubling dilution of the mode MIC value for telavancin. The overall reproducibility was 100.0%. b. Linearity/assay reportable range: 6 Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Inoculum Density Check. Inoculum density checks were performed for all quality control and reproducibility organism suspensions and for 10% of the suspensions prepared for susceptibility testing of the fresh clinical isolates. The mean inoculum density was acceptable at 4.40 X 105 CFU/mL. Purity Check. All clinical, challenge and reproducibility test suspensions were subcultured to assure purity. Growth or Device Failure. There were no growth or device failures during the course of the study. Quality Control Testing. Organisms recommended by both FDA and the CLSI were tested with telavancin at three sites. The QC organisms tested included S. aureus ATCC 29213 and E. faecalis ATCC 29212. These QC strains were tested a minimum of 20 times per site by both the ETEST and the reference method. The results demonstrate that the telavancin ETEST can produce quality control results in the recommended range > 95% of the time. See Table 2 below for a summary of the QC results. Table 2. Quality Control Data for Telavancin QC organism Telavancin expected range (µg/mL) Concentration (µg/mL) Reference ETEST S. aureus ATCC 29213 0.03 – 0.12 0.016 - - 0.03 60 6 0.06 20 71 0.12 1 4 0.25 - - E. faecalis ATCC 29212 0.03 – 0.12 0.016 - - 0.03 - - 0.06 75 41 0.12 6 40 0.25 - - d. Detection limit: Not applicable e. Analytical specificity: Not applicable 7 f. Assay cut-off: Not applicable 2. Comparison studies: a. Method comparison with predicate device: Results obtained with ETEST telavancin were compared to results obtained with the CLSI broth microdilution reference panel. The CLSI panel Classification:

idK180936_s0_e2000

K180936.txt

product code

JWY – Manual Antimicrobial Test Systems

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K180936 B. Purpose for Submission: To obtain a substantial equivalence determination for telavancin at concentrations of 0.002 – 32 µg/mL for susceptibility testing of Gram positive aerobic microorganisms with ETEST. C. Measurand: Telavancin 0.002 – 32 µg/mL D. Type of Test: Quantitative AST growth-based detection E. Applicant: bioMérieux, Inc. F. Proprietary and Established Names: ETEST Telavancin (TLA) (0.002 – 32 µg/mL) G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY – Manual Antimicrobial Test Systems 4. Panel: 83 –Microbiology 2 H. Intended Use: 1. Intended use(s): ETEST is a quantitative technique for determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria such as Enterobacteriaceae, Pseudomonas, Staphylococcus, and Enterococcus species and fastidious bacteria, such as anaerobes, N. gonorrhoeae, S. pneumoniae, Streptococcus and Haemophilus species. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC), in µg/mL, of different antimicrobial agents against microorganisms as tested on agar media using overnight incubation. Telavancin has been shown to be active against the Gram positive aerobic microorganisms listed below according to the FDA label for this antimicrobial agent. Active both in vitro and in clinical infections: Staphylococcus aureus (including methicillin-resistant isolates) Enterococcus faecalis (vancomycin-susceptible isolates only) 2. Indication(s) for use: Same as the Intended Use 3. Special conditions for use statement(s): For prescription use only Limitations: · Due to the lack of an intermediate category and the observed trending for Telavancin, testing of S. aureus and E. faecalis have resulted in major discrepancies for isolates that are otherwise within essential agreement with the reference method. If critical to patient care, testing should be repeated using an alternative testing/reference method prior to reporting results for S. aureus when the ETEST TLA MIC is 0.25 µg/mL and 0.5 µg/mL for E. faecalis. 4. Special instrument requirements: N/A I. Device Description: ETEST consists of a thin, inert and non-porous plastic strip 5mm wide and 60 mm long. One side of the strip carries a three letter code designating the identity of the antibiotic and is calibrated with MIC values in terms of µg/mL. On the reverse, a predefined exponential gradient of the dried and stabilized antibiotic covers a continuous concentration range across 3 15 two-fold dilutions of a conventional MIC method. J. Substantial Equivalence Information: 1. Predicate device name(s): ETEST Ceftaroline 2. Predicate 510(k) number(s): K151873 3. Comparison with predicate: 4 Table 1. Comparison with the Predicate Device Similarities Item Device K180936 ETEST Telavancin Predicate K151873 ETEST Ceftaroline Intended Use ETEST is a quantitative technique for determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria such as Enterobacteriaceae, Pseudomonas, Staphylococcus, and Enterococcus species and fastidious bacteria, such as anaerobes, N. gonorrhoeae, S. pneumoniae, Streptococcus and Haemophilus species. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC), in µg/mL, of different antimicrobial agents against microorganism as tested on agar media using overnight incubation. Same Antimicrobial Concentration Range 0.002 – 32 µg/mL Same Test Design A predefined exponential gradient of the dried and stabilized antibiotic covers a continuous concentration range across 15 two- fold dilutions of a conventional MIC method. Same Inoculation Isolated colonies from culture Same Result MIC Same Differences Item Device K180936 ETEST Telavancin Predicate K151873 ETEST Ceftaroline Claimed organisms S. aureus (including MRSA), E. faecalis (vancomycin- susceptible only) S. agalactiae, S. pneumoniae, H. influenza Antimicrobial Agent Telavancin Ceftaroline Incubation 35°± 2° C for 16–20 hours 35°± 2° C for 20–24 hours 5 K. Standard/Guidance Document Referenced (if applicable): Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA CLSI M07-A10, Method for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, January 2015. CLSI M100-S26, Performance Standards for Antimicrobial Susceptibility Testing; Volume 36, No. 1, January 2016. L. Test Principle: The ETEST consists of a thin, inert, nonporous plastic strip that is used to determine the antimicrobial susceptibility of bacteria. One side of the strip carries the minimum inhibitory concentration (MIC) reading scale expressed in µg/mL. The other side of the strip contains a predefined continuous gradient of antibiotic concentrations. When the strip is applied to an inoculated agar surface, the preformed antibiotic gradient immediately transfers into the agar matrix, then forming a stable, continuous and exponential gradient of antibiotic concentrations directly underneath the strip. Bacteria growth becomes visible during incubation, and a symmetrical inhibition ellipse centered along the strip appears. After incubation, the MIC value is read from the scale in terms of µg/mL at complete inhibition of bacterial growth, where the pointed end of the ellipse intersects the strip. Since ETEST generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read must be recorded to the next two-fold dilution. The MIC gradient on ETEST Telavancin ranges from 0.002 to 32 µg/mL. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: A reproducibility study was conducted at three external sites using 10 isolates of Gram positive organisms that were consistent with the intended use. Testing was performed on three separate days and in triplicate for a total of 270 data points among the sites. The isolates tested included five S. aureus and five E. faecalis isolates. The mode MIC was determined and the reproducibility was calculated based on MIC values that fell within ± one doubling dilution from the mode MIC value. All results were on-scale and within ± 1 doubling dilution of the mode MIC value for telavancin. The overall reproducibility was 100.0%. b. Linearity/assay reportable range: 6 Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Inoculum Density Check. Inoculum density checks were performed for all quality control and reproducibility organism suspensions and for 10% of the suspensions prepared for susceptibility testing of the fresh clinical isolates. The mean inoculum density was acceptable at 4.40 X 105 CFU/mL. Purity Check. All clinical, challenge and reproducibility test suspensions were subcultured to assure purity. Growth or Device Failure. There were no growth or device failures during the course of the study. Quality Control Testing. Organisms recommended by both FDA and the CLSI were tested with telavancin at three sites. The QC organisms tested included S. aureus ATCC 29213 and E. faecalis ATCC 29212. These QC strains were tested a minimum of 20 times per site by both the ETEST and the reference method. The results demonstrate that the telavancin ETEST can produce quality control results in the recommended range > 95% of the time. See Table 2 below for a summary of the QC results. Table 2. Quality Control Data for Telavancin QC organism Telavancin expected range (µg/mL) Concentration (µg/mL) Reference ETEST S. aureus ATCC 29213 0.03 – 0.12 0.016 - - 0.03 60 6 0.06 20 71 0.12 1 4 0.25 - - E. faecalis ATCC 29212 0.03 – 0.12 0.016 - - 0.03 - - 0.06 75 41 0.12 6 40 0.25 - - d. Detection limit: Not applicable e. Analytical specificity: Not applicable 7 f. Assay cut-off: Not applicable 2. Comparison studies: a. Method comparison with predicate device: Results obtained with ETEST telavancin were compared to results obtained with the CLSI broth microdilution reference panel. The CLSI panel Product code:

idK180936_s0_e2000

K180936.txt

panel

83 –Microbiology

(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K180936 B. Purpose for Submission: To obtain a substantial equivalence determination for telavancin at concentrations of 0.002 – 32 µg/mL for susceptibility testing of Gram positive aerobic microorganisms with ETEST. C. Measurand: Telavancin 0.002 – 32 µg/mL D. Type of Test: Quantitative AST growth-based detection E. Applicant: bioMérieux, Inc. F. Proprietary and Established Names: ETEST Telavancin (TLA) (0.002 – 32 µg/mL) G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY – Manual Antimicrobial Test Systems 4. Panel: 83 –Microbiology 2 H. Intended Use: 1. Intended use(s): ETEST is a quantitative technique for determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria such as Enterobacteriaceae, Pseudomonas, Staphylococcus, and Enterococcus species and fastidious bacteria, such as anaerobes, N. gonorrhoeae, S. pneumoniae, Streptococcus and Haemophilus species. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC), in µg/mL, of different antimicrobial agents against microorganisms as tested on agar media using overnight incubation. Telavancin has been shown to be active against the Gram positive aerobic microorganisms listed below according to the FDA label for this antimicrobial agent. Active both in vitro and in clinical infections: Staphylococcus aureus (including methicillin-resistant isolates) Enterococcus faecalis (vancomycin-susceptible isolates only) 2. Indication(s) for use: Same as the Intended Use 3. Special conditions for use statement(s): For prescription use only Limitations: · Due to the lack of an intermediate category and the observed trending for Telavancin, testing of S. aureus and E. faecalis have resulted in major discrepancies for isolates that are otherwise within essential agreement with the reference method. If critical to patient care, testing should be repeated using an alternative testing/reference method prior to reporting results for S. aureus when the ETEST TLA MIC is 0.25 µg/mL and 0.5 µg/mL for E. faecalis. 4. Special instrument requirements: N/A I. Device Description: ETEST consists of a thin, inert and non-porous plastic strip 5mm wide and 60 mm long. One side of the strip carries a three letter code designating the identity of the antibiotic and is calibrated with MIC values in terms of µg/mL. On the reverse, a predefined exponential gradient of the dried and stabilized antibiotic covers a continuous concentration range across 3 15 two-fold dilutions of a conventional MIC method. J. Substantial Equivalence Information: 1. Predicate device name(s): ETEST Ceftaroline 2. Predicate 510(k) number(s): K151873 3. Comparison with predicate: 4 Table 1. Comparison with the Predicate Device Similarities Item Device K180936 ETEST Telavancin Predicate K151873 ETEST Ceftaroline Intended Use ETEST is a quantitative technique for determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria such as Enterobacteriaceae, Pseudomonas, Staphylococcus, and Enterococcus species and fastidious bacteria, such as anaerobes, N. gonorrhoeae, S. pneumoniae, Streptococcus and Haemophilus species. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC), in µg/mL, of different antimicrobial agents against microorganism as tested on agar media using overnight incubation. Same Antimicrobial Concentration Range 0.002 – 32 µg/mL Same Test Design A predefined exponential gradient of the dried and stabilized antibiotic covers a continuous concentration range across 15 two- fold dilutions of a conventional MIC method. Same Inoculation Isolated colonies from culture Same Result MIC Same Differences Item Device K180936 ETEST Telavancin Predicate K151873 ETEST Ceftaroline Claimed organisms S. aureus (including MRSA), E. faecalis (vancomycin- susceptible only) S. agalactiae, S. pneumoniae, H. influenza Antimicrobial Agent Telavancin Ceftaroline Incubation 35°± 2° C for 16–20 hours 35°± 2° C for 20–24 hours 5 K. Standard/Guidance Document Referenced (if applicable): Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA CLSI M07-A10, Method for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, January 2015. CLSI M100-S26, Performance Standards for Antimicrobial Susceptibility Testing; Volume 36, No. 1, January 2016. L. Test Principle: The ETEST consists of a thin, inert, nonporous plastic strip that is used to determine the antimicrobial susceptibility of bacteria. One side of the strip carries the minimum inhibitory concentration (MIC) reading scale expressed in µg/mL. The other side of the strip contains a predefined continuous gradient of antibiotic concentrations. When the strip is applied to an inoculated agar surface, the preformed antibiotic gradient immediately transfers into the agar matrix, then forming a stable, continuous and exponential gradient of antibiotic concentrations directly underneath the strip. Bacteria growth becomes visible during incubation, and a symmetrical inhibition ellipse centered along the strip appears. After incubation, the MIC value is read from the scale in terms of µg/mL at complete inhibition of bacterial growth, where the pointed end of the ellipse intersects the strip. Since ETEST generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read must be recorded to the next two-fold dilution. The MIC gradient on ETEST Telavancin ranges from 0.002 to 32 µg/mL. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: A reproducibility study was conducted at three external sites using 10 isolates of Gram positive organisms that were consistent with the intended use. Testing was performed on three separate days and in triplicate for a total of 270 data points among the sites. The isolates tested included five S. aureus and five E. faecalis isolates. The mode MIC was determined and the reproducibility was calculated based on MIC values that fell within ± one doubling dilution from the mode MIC value. All results were on-scale and within ± 1 doubling dilution of the mode MIC value for telavancin. The overall reproducibility was 100.0%. b. Linearity/assay reportable range: 6 Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Inoculum Density Check. Inoculum density checks were performed for all quality control and reproducibility organism suspensions and for 10% of the suspensions prepared for susceptibility testing of the fresh clinical isolates. The mean inoculum density was acceptable at 4.40 X 105 CFU/mL. Purity Check. All clinical, challenge and reproducibility test suspensions were subcultured to assure purity. Growth or Device Failure. There were no growth or device failures during the course of the study. Quality Control Testing. Organisms recommended by both FDA and the CLSI were tested with telavancin at three sites. The QC organisms tested included S. aureus ATCC 29213 and E. faecalis ATCC 29212. These QC strains were tested a minimum of 20 times per site by both the ETEST and the reference method. The results demonstrate that the telavancin ETEST can produce quality control results in the recommended range > 95% of the time. See Table 2 below for a summary of the QC results. Table 2. Quality Control Data for Telavancin QC organism Telavancin expected range (µg/mL) Concentration (µg/mL) Reference ETEST S. aureus ATCC 29213 0.03 – 0.12 0.016 - - 0.03 60 6 0.06 20 71 0.12 1 4 0.25 - - E. faecalis ATCC 29212 0.03 – 0.12 0.016 - - 0.03 - - 0.06 75 41 0.12 6 40 0.25 - - d. Detection limit: Not applicable e. Analytical specificity: Not applicable 7 f. Assay cut-off: Not applicable 2. Comparison studies: a. Method comparison with predicate device: Results obtained with ETEST telavancin were compared to results obtained with the CLSI broth microdilution reference panel. The CLSI panel Panel:

idK180936_s0_e2000

K180936.txt

predicate device name

ETEST Ceftaroline

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K180936 B. Purpose for Submission: To obtain a substantial equivalence determination for telavancin at concentrations of 0.002 – 32 µg/mL for susceptibility testing of Gram positive aerobic microorganisms with ETEST. C. Measurand: Telavancin 0.002 – 32 µg/mL D. Type of Test: Quantitative AST growth-based detection E. Applicant: bioMérieux, Inc. F. Proprietary and Established Names: ETEST Telavancin (TLA) (0.002 – 32 µg/mL) G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY – Manual Antimicrobial Test Systems 4. Panel: 83 –Microbiology 2 H. Intended Use: 1. Intended use(s): ETEST is a quantitative technique for determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria such as Enterobacteriaceae, Pseudomonas, Staphylococcus, and Enterococcus species and fastidious bacteria, such as anaerobes, N. gonorrhoeae, S. pneumoniae, Streptococcus and Haemophilus species. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC), in µg/mL, of different antimicrobial agents against microorganisms as tested on agar media using overnight incubation. Telavancin has been shown to be active against the Gram positive aerobic microorganisms listed below according to the FDA label for this antimicrobial agent. Active both in vitro and in clinical infections: Staphylococcus aureus (including methicillin-resistant isolates) Enterococcus faecalis (vancomycin-susceptible isolates only) 2. Indication(s) for use: Same as the Intended Use 3. Special conditions for use statement(s): For prescription use only Limitations: · Due to the lack of an intermediate category and the observed trending for Telavancin, testing of S. aureus and E. faecalis have resulted in major discrepancies for isolates that are otherwise within essential agreement with the reference method. If critical to patient care, testing should be repeated using an alternative testing/reference method prior to reporting results for S. aureus when the ETEST TLA MIC is 0.25 µg/mL and 0.5 µg/mL for E. faecalis. 4. Special instrument requirements: N/A I. Device Description: ETEST consists of a thin, inert and non-porous plastic strip 5mm wide and 60 mm long. One side of the strip carries a three letter code designating the identity of the antibiotic and is calibrated with MIC values in terms of µg/mL. On the reverse, a predefined exponential gradient of the dried and stabilized antibiotic covers a continuous concentration range across 3 15 two-fold dilutions of a conventional MIC method. J. Substantial Equivalence Information: 1. Predicate device name(s): ETEST Ceftaroline 2. Predicate 510(k) number(s): K151873 3. Comparison with predicate: 4 Table 1. Comparison with the Predicate Device Similarities Item Device K180936 ETEST Telavancin Predicate K151873 ETEST Ceftaroline Intended Use ETEST is a quantitative technique for determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria such as Enterobacteriaceae, Pseudomonas, Staphylococcus, and Enterococcus species and fastidious bacteria, such as anaerobes, N. gonorrhoeae, S. pneumoniae, Streptococcus and Haemophilus species. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC), in µg/mL, of different antimicrobial agents against microorganism as tested on agar media using overnight incubation. Same Antimicrobial Concentration Range 0.002 – 32 µg/mL Same Test Design A predefined exponential gradient of the dried and stabilized antibiotic covers a continuous concentration range across 15 two- fold dilutions of a conventional MIC method. Same Inoculation Isolated colonies from culture Same Result MIC Same Differences Item Device K180936 ETEST Telavancin Predicate K151873 ETEST Ceftaroline Claimed organisms S. aureus (including MRSA), E. faecalis (vancomycin- susceptible only) S. agalactiae, S. pneumoniae, H. influenza Antimicrobial Agent Telavancin Ceftaroline Incubation 35°± 2° C for 16–20 hours 35°± 2° C for 20–24 hours 5 K. Standard/Guidance Document Referenced (if applicable): Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA CLSI M07-A10, Method for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, January 2015. CLSI M100-S26, Performance Standards for Antimicrobial Susceptibility Testing; Volume 36, No. 1, January 2016. L. Test Principle: The ETEST consists of a thin, inert, nonporous plastic strip that is used to determine the antimicrobial susceptibility of bacteria. One side of the strip carries the minimum inhibitory concentration (MIC) reading scale expressed in µg/mL. The other side of the strip contains a predefined continuous gradient of antibiotic concentrations. When the strip is applied to an inoculated agar surface, the preformed antibiotic gradient immediately transfers into the agar matrix, then forming a stable, continuous and exponential gradient of antibiotic concentrations directly underneath the strip. Bacteria growth becomes visible during incubation, and a symmetrical inhibition ellipse centered along the strip appears. After incubation, the MIC value is read from the scale in terms of µg/mL at complete inhibition of bacterial growth, where the pointed end of the ellipse intersects the strip. Since ETEST generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read must be recorded to the next two-fold dilution. The MIC gradient on ETEST Telavancin ranges from 0.002 to 32 µg/mL. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: A reproducibility study was conducted at three external sites using 10 isolates of Gram positive organisms that were consistent with the intended use. Testing was performed on three separate days and in triplicate for a total of 270 data points among the sites. The isolates tested included five S. aureus and five E. faecalis isolates. The mode MIC was determined and the reproducibility was calculated based on MIC values that fell within ± one doubling dilution from the mode MIC value. All results were on-scale and within ± 1 doubling dilution of the mode MIC value for telavancin. The overall reproducibility was 100.0%. b. Linearity/assay reportable range: 6 Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Inoculum Density Check. Inoculum density checks were performed for all quality control and reproducibility organism suspensions and for 10% of the suspensions prepared for susceptibility testing of the fresh clinical isolates. The mean inoculum density was acceptable at 4.40 X 105 CFU/mL. Purity Check. All clinical, challenge and reproducibility test suspensions were subcultured to assure purity. Growth or Device Failure. There were no growth or device failures during the course of the study. Quality Control Testing. Organisms recommended by both FDA and the CLSI were tested with telavancin at three sites. The QC organisms tested included S. aureus ATCC 29213 and E. faecalis ATCC 29212. These QC strains were tested a minimum of 20 times per site by both the ETEST and the reference method. The results demonstrate that the telavancin ETEST can produce quality control results in the recommended range > 95% of the time. See Table 2 below for a summary of the QC results. Table 2. Quality Control Data for Telavancin QC organism Telavancin expected range (µg/mL) Concentration (µg/mL) Reference ETEST S. aureus ATCC 29213 0.03 – 0.12 0.016 - - 0.03 60 6 0.06 20 71 0.12 1 4 0.25 - - E. faecalis ATCC 29212 0.03 – 0.12 0.016 - - 0.03 - - 0.06 75 41 0.12 6 40 0.25 - - d. Detection limit: Not applicable e. Analytical specificity: Not applicable 7 f. Assay cut-off: Not applicable 2. Comparison studies: a. Method comparison with predicate device: Results obtained with ETEST telavancin were compared to results obtained with the CLSI broth microdilution reference panel. The CLSI panel Predicate device name:

idK180936_s0_e2000

K180936.txt

applicant

bioMérieux, Inc.

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K180936 B. Purpose for Submission: To obtain a substantial equivalence determination for telavancin at concentrations of 0.002 – 32 µg/mL for susceptibility testing of Gram positive aerobic microorganisms with ETEST. C. Measurand: Telavancin 0.002 – 32 µg/mL D. Type of Test: Quantitative AST growth-based detection E. Applicant: bioMérieux, Inc. F. Proprietary and Established Names: ETEST Telavancin (TLA) (0.002 – 32 µg/mL) G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY – Manual Antimicrobial Test Systems 4. Panel: 83 –Microbiology 2 H. Intended Use: 1. Intended use(s): ETEST is a quantitative technique for determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria such as Enterobacteriaceae, Pseudomonas, Staphylococcus, and Enterococcus species and fastidious bacteria, such as anaerobes, N. gonorrhoeae, S. pneumoniae, Streptococcus and Haemophilus species. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC), in µg/mL, of different antimicrobial agents against microorganisms as tested on agar media using overnight incubation. Telavancin has been shown to be active against the Gram positive aerobic microorganisms listed below according to the FDA label for this antimicrobial agent. Active both in vitro and in clinical infections: Staphylococcus aureus (including methicillin-resistant isolates) Enterococcus faecalis (vancomycin-susceptible isolates only) 2. Indication(s) for use: Same as the Intended Use 3. Special conditions for use statement(s): For prescription use only Limitations: · Due to the lack of an intermediate category and the observed trending for Telavancin, testing of S. aureus and E. faecalis have resulted in major discrepancies for isolates that are otherwise within essential agreement with the reference method. If critical to patient care, testing should be repeated using an alternative testing/reference method prior to reporting results for S. aureus when the ETEST TLA MIC is 0.25 µg/mL and 0.5 µg/mL for E. faecalis. 4. Special instrument requirements: N/A I. Device Description: ETEST consists of a thin, inert and non-porous plastic strip 5mm wide and 60 mm long. One side of the strip carries a three letter code designating the identity of the antibiotic and is calibrated with MIC values in terms of µg/mL. On the reverse, a predefined exponential gradient of the dried and stabilized antibiotic covers a continuous concentration range across 3 15 two-fold dilutions of a conventional MIC method. J. Substantial Equivalence Information: 1. Predicate device name(s): ETEST Ceftaroline 2. Predicate 510(k) number(s): K151873 3. Comparison with predicate: 4 Table 1. Comparison with the Predicate Device Similarities Item Device K180936 ETEST Telavancin Predicate K151873 ETEST Ceftaroline Intended Use ETEST is a quantitative technique for determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria such as Enterobacteriaceae, Pseudomonas, Staphylococcus, and Enterococcus species and fastidious bacteria, such as anaerobes, N. gonorrhoeae, S. pneumoniae, Streptococcus and Haemophilus species. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC), in µg/mL, of different antimicrobial agents against microorganism as tested on agar media using overnight incubation. Same Antimicrobial Concentration Range 0.002 – 32 µg/mL Same Test Design A predefined exponential gradient of the dried and stabilized antibiotic covers a continuous concentration range across 15 two- fold dilutions of a conventional MIC method. Same Inoculation Isolated colonies from culture Same Result MIC Same Differences Item Device K180936 ETEST Telavancin Predicate K151873 ETEST Ceftaroline Claimed organisms S. aureus (including MRSA), E. faecalis (vancomycin- susceptible only) S. agalactiae, S. pneumoniae, H. influenza Antimicrobial Agent Telavancin Ceftaroline Incubation 35°± 2° C for 16–20 hours 35°± 2° C for 20–24 hours 5 K. Standard/Guidance Document Referenced (if applicable): Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA CLSI M07-A10, Method for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, January 2015. CLSI M100-S26, Performance Standards for Antimicrobial Susceptibility Testing; Volume 36, No. 1, January 2016. L. Test Principle: The ETEST consists of a thin, inert, nonporous plastic strip that is used to determine the antimicrobial susceptibility of bacteria. One side of the strip carries the minimum inhibitory concentration (MIC) reading scale expressed in µg/mL. The other side of the strip contains a predefined continuous gradient of antibiotic concentrations. When the strip is applied to an inoculated agar surface, the preformed antibiotic gradient immediately transfers into the agar matrix, then forming a stable, continuous and exponential gradient of antibiotic concentrations directly underneath the strip. Bacteria growth becomes visible during incubation, and a symmetrical inhibition ellipse centered along the strip appears. After incubation, the MIC value is read from the scale in terms of µg/mL at complete inhibition of bacterial growth, where the pointed end of the ellipse intersects the strip. Since ETEST generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read must be recorded to the next two-fold dilution. The MIC gradient on ETEST Telavancin ranges from 0.002 to 32 µg/mL. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: A reproducibility study was conducted at three external sites using 10 isolates of Gram positive organisms that were consistent with the intended use. Testing was performed on three separate days and in triplicate for a total of 270 data points among the sites. The isolates tested included five S. aureus and five E. faecalis isolates. The mode MIC was determined and the reproducibility was calculated based on MIC values that fell within ± one doubling dilution from the mode MIC value. All results were on-scale and within ± 1 doubling dilution of the mode MIC value for telavancin. The overall reproducibility was 100.0%. b. Linearity/assay reportable range: 6 Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Inoculum Density Check. Inoculum density checks were performed for all quality control and reproducibility organism suspensions and for 10% of the suspensions prepared for susceptibility testing of the fresh clinical isolates. The mean inoculum density was acceptable at 4.40 X 105 CFU/mL. Purity Check. All clinical, challenge and reproducibility test suspensions were subcultured to assure purity. Growth or Device Failure. There were no growth or device failures during the course of the study. Quality Control Testing. Organisms recommended by both FDA and the CLSI were tested with telavancin at three sites. The QC organisms tested included S. aureus ATCC 29213 and E. faecalis ATCC 29212. These QC strains were tested a minimum of 20 times per site by both the ETEST and the reference method. The results demonstrate that the telavancin ETEST can produce quality control results in the recommended range > 95% of the time. See Table 2 below for a summary of the QC results. Table 2. Quality Control Data for Telavancin QC organism Telavancin expected range (µg/mL) Concentration (µg/mL) Reference ETEST S. aureus ATCC 29213 0.03 – 0.12 0.016 - - 0.03 60 6 0.06 20 71 0.12 1 4 0.25 - - E. faecalis ATCC 29212 0.03 – 0.12 0.016 - - 0.03 - - 0.06 75 41 0.12 6 40 0.25 - - d. Detection limit: Not applicable e. Analytical specificity: Not applicable 7 f. Assay cut-off: Not applicable 2. Comparison studies: a. Method comparison with predicate device: Results obtained with ETEST telavancin were compared to results obtained with the CLSI broth microdilution reference panel. The CLSI panel Applicant:

idK180936_s0_e2000

K180936.txt

proprietary and established names

ETEST Telavancin (TLA) (0.002 – 32 µg/mL)

ANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K180936 B. Purpose for Submission: To obtain a substantial equivalence determination for telavancin at concentrations of 0.002 – 32 µg/mL for susceptibility testing of Gram positive aerobic microorganisms with ETEST. C. Measurand: Telavancin 0.002 – 32 µg/mL D. Type of Test: Quantitative AST growth-based detection E. Applicant: bioMérieux, Inc. F. Proprietary and Established Names: ETEST Telavancin (TLA) (0.002 – 32 µg/mL) G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY – Manual Antimicrobial Test Systems 4. Panel: 83 –Microbiology 2 H. Intended Use: 1. Intended use(s): ETEST is a quantitative technique for determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria such as Enterobacteriaceae, Pseudomonas, Staphylococcus, and Enterococcus species and fastidious bacteria, such as anaerobes, N. gonorrhoeae, S. pneumoniae, Streptococcus and Haemophilus species. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC), in µg/mL, of different antimicrobial agents against microorganisms as tested on agar media using overnight incubation. Telavancin has been shown to be active against the Gram positive aerobic microorganisms listed below according to the FDA label for this antimicrobial agent. Active both in vitro and in clinical infections: Staphylococcus aureus (including methicillin-resistant isolates) Enterococcus faecalis (vancomycin-susceptible isolates only) 2. Indication(s) for use: Same as the Intended Use 3. Special conditions for use statement(s): For prescription use only Limitations: · Due to the lack of an intermediate category and the observed trending for Telavancin, testing of S. aureus and E. faecalis have resulted in major discrepancies for isolates that are otherwise within essential agreement with the reference method. If critical to patient care, testing should be repeated using an alternative testing/reference method prior to reporting results for S. aureus when the ETEST TLA MIC is 0.25 µg/mL and 0.5 µg/mL for E. faecalis. 4. Special instrument requirements: N/A I. Device Description: ETEST consists of a thin, inert and non-porous plastic strip 5mm wide and 60 mm long. One side of the strip carries a three letter code designating the identity of the antibiotic and is calibrated with MIC values in terms of µg/mL. On the reverse, a predefined exponential gradient of the dried and stabilized antibiotic covers a continuous concentration range across 3 15 two-fold dilutions of a conventional MIC method. J. Substantial Equivalence Information: 1. Predicate device name(s): ETEST Ceftaroline 2. Predicate 510(k) number(s): K151873 3. Comparison with predicate: 4 Table 1. Comparison with the Predicate Device Similarities Item Device K180936 ETEST Telavancin Predicate K151873 ETEST Ceftaroline Intended Use ETEST is a quantitative technique for determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria such as Enterobacteriaceae, Pseudomonas, Staphylococcus, and Enterococcus species and fastidious bacteria, such as anaerobes, N. gonorrhoeae, S. pneumoniae, Streptococcus and Haemophilus species. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC), in µg/mL, of different antimicrobial agents against microorganism as tested on agar media using overnight incubation. Same Antimicrobial Concentration Range 0.002 – 32 µg/mL Same Test Design A predefined exponential gradient of the dried and stabilized antibiotic covers a continuous concentration range across 15 two- fold dilutions of a conventional MIC method. Same Inoculation Isolated colonies from culture Same Result MIC Same Differences Item Device K180936 ETEST Telavancin Predicate K151873 ETEST Ceftaroline Claimed organisms S. aureus (including MRSA), E. faecalis (vancomycin- susceptible only) S. agalactiae, S. pneumoniae, H. influenza Antimicrobial Agent Telavancin Ceftaroline Incubation 35°± 2° C for 16–20 hours 35°± 2° C for 20–24 hours 5 K. Standard/Guidance Document Referenced (if applicable): Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA CLSI M07-A10, Method for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, January 2015. CLSI M100-S26, Performance Standards for Antimicrobial Susceptibility Testing; Volume 36, No. 1, January 2016. L. Test Principle: The ETEST consists of a thin, inert, nonporous plastic strip that is used to determine the antimicrobial susceptibility of bacteria. One side of the strip carries the minimum inhibitory concentration (MIC) reading scale expressed in µg/mL. The other side of the strip contains a predefined continuous gradient of antibiotic concentrations. When the strip is applied to an inoculated agar surface, the preformed antibiotic gradient immediately transfers into the agar matrix, then forming a stable, continuous and exponential gradient of antibiotic concentrations directly underneath the strip. Bacteria growth becomes visible during incubation, and a symmetrical inhibition ellipse centered along the strip appears. After incubation, the MIC value is read from the scale in terms of µg/mL at complete inhibition of bacterial growth, where the pointed end of the ellipse intersects the strip. Since ETEST generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read must be recorded to the next two-fold dilution. The MIC gradient on ETEST Telavancin ranges from 0.002 to 32 µg/mL. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: A reproducibility study was conducted at three external sites using 10 isolates of Gram positive organisms that were consistent with the intended use. Testing was performed on three separate days and in triplicate for a total of 270 data points among the sites. The isolates tested included five S. aureus and five E. faecalis isolates. The mode MIC was determined and the reproducibility was calculated based on MIC values that fell within ± one doubling dilution from the mode MIC value. All results were on-scale and within ± 1 doubling dilution of the mode MIC value for telavancin. The overall reproducibility was 100.0%. b. Linearity/assay reportable range: 6 Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Inoculum Density Check. Inoculum density checks were performed for all quality control and reproducibility organism suspensions and for 10% of the suspensions prepared for susceptibility testing of the fresh clinical isolates. The mean inoculum density was acceptable at 4.40 X 105 CFU/mL. Purity Check. All clinical, challenge and reproducibility test suspensions were subcultured to assure purity. Growth or Device Failure. There were no growth or device failures during the course of the study. Quality Control Testing. Organisms recommended by both FDA and the CLSI were tested with telavancin at three sites. The QC organisms tested included S. aureus ATCC 29213 and E. faecalis ATCC 29212. These QC strains were tested a minimum of 20 times per site by both the ETEST and the reference method. The results demonstrate that the telavancin ETEST can produce quality control results in the recommended range > 95% of the time. See Table 2 below for a summary of the QC results. Table 2. Quality Control Data for Telavancin QC organism Telavancin expected range (µg/mL) Concentration (µg/mL) Reference ETEST S. aureus ATCC 29213 0.03 – 0.12 0.016 - - 0.03 60 6 0.06 20 71 0.12 1 4 0.25 - - E. faecalis ATCC 29212 0.03 – 0.12 0.016 - - 0.03 - - 0.06 75 41 0.12 6 40 0.25 - - d. Detection limit: Not applicable e. Analytical specificity: Not applicable 7 f. Assay cut-off: Not applicable 2. Comparison studies: a. Method comparison with predicate device: Results obtained with ETEST telavancin were compared to results obtained with the CLSI broth microdilution reference panel. The CLSI panel Proprietary and established names:

idK180936_s0_e2000

K180936.txt

regulation section

866.1640 Antimicrobial Susceptibility Test Powder

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K180936 B. Purpose for Submission: To obtain a substantial equivalence determination for telavancin at concentrations of 0.002 – 32 µg/mL for susceptibility testing of Gram positive aerobic microorganisms with ETEST. C. Measurand: Telavancin 0.002 – 32 µg/mL D. Type of Test: Quantitative AST growth-based detection E. Applicant: bioMérieux, Inc. F. Proprietary and Established Names: ETEST Telavancin (TLA) (0.002 – 32 µg/mL) G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY – Manual Antimicrobial Test Systems 4. Panel: 83 –Microbiology 2 H. Intended Use: 1. Intended use(s): ETEST is a quantitative technique for determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria such as Enterobacteriaceae, Pseudomonas, Staphylococcus, and Enterococcus species and fastidious bacteria, such as anaerobes, N. gonorrhoeae, S. pneumoniae, Streptococcus and Haemophilus species. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC), in µg/mL, of different antimicrobial agents against microorganisms as tested on agar media using overnight incubation. Telavancin has been shown to be active against the Gram positive aerobic microorganisms listed below according to the FDA label for this antimicrobial agent. Active both in vitro and in clinical infections: Staphylococcus aureus (including methicillin-resistant isolates) Enterococcus faecalis (vancomycin-susceptible isolates only) 2. Indication(s) for use: Same as the Intended Use 3. Special conditions for use statement(s): For prescription use only Limitations: · Due to the lack of an intermediate category and the observed trending for Telavancin, testing of S. aureus and E. faecalis have resulted in major discrepancies for isolates that are otherwise within essential agreement with the reference method. If critical to patient care, testing should be repeated using an alternative testing/reference method prior to reporting results for S. aureus when the ETEST TLA MIC is 0.25 µg/mL and 0.5 µg/mL for E. faecalis. 4. Special instrument requirements: N/A I. Device Description: ETEST consists of a thin, inert and non-porous plastic strip 5mm wide and 60 mm long. One side of the strip carries a three letter code designating the identity of the antibiotic and is calibrated with MIC values in terms of µg/mL. On the reverse, a predefined exponential gradient of the dried and stabilized antibiotic covers a continuous concentration range across 3 15 two-fold dilutions of a conventional MIC method. J. Substantial Equivalence Information: 1. Predicate device name(s): ETEST Ceftaroline 2. Predicate 510(k) number(s): K151873 3. Comparison with predicate: 4 Table 1. Comparison with the Predicate Device Similarities Item Device K180936 ETEST Telavancin Predicate K151873 ETEST Ceftaroline Intended Use ETEST is a quantitative technique for determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria such as Enterobacteriaceae, Pseudomonas, Staphylococcus, and Enterococcus species and fastidious bacteria, such as anaerobes, N. gonorrhoeae, S. pneumoniae, Streptococcus and Haemophilus species. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC), in µg/mL, of different antimicrobial agents against microorganism as tested on agar media using overnight incubation. Same Antimicrobial Concentration Range 0.002 – 32 µg/mL Same Test Design A predefined exponential gradient of the dried and stabilized antibiotic covers a continuous concentration range across 15 two- fold dilutions of a conventional MIC method. Same Inoculation Isolated colonies from culture Same Result MIC Same Differences Item Device K180936 ETEST Telavancin Predicate K151873 ETEST Ceftaroline Claimed organisms S. aureus (including MRSA), E. faecalis (vancomycin- susceptible only) S. agalactiae, S. pneumoniae, H. influenza Antimicrobial Agent Telavancin Ceftaroline Incubation 35°± 2° C for 16–20 hours 35°± 2° C for 20–24 hours 5 K. Standard/Guidance Document Referenced (if applicable): Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA CLSI M07-A10, Method for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, January 2015. CLSI M100-S26, Performance Standards for Antimicrobial Susceptibility Testing; Volume 36, No. 1, January 2016. L. Test Principle: The ETEST consists of a thin, inert, nonporous plastic strip that is used to determine the antimicrobial susceptibility of bacteria. One side of the strip carries the minimum inhibitory concentration (MIC) reading scale expressed in µg/mL. The other side of the strip contains a predefined continuous gradient of antibiotic concentrations. When the strip is applied to an inoculated agar surface, the preformed antibiotic gradient immediately transfers into the agar matrix, then forming a stable, continuous and exponential gradient of antibiotic concentrations directly underneath the strip. Bacteria growth becomes visible during incubation, and a symmetrical inhibition ellipse centered along the strip appears. After incubation, the MIC value is read from the scale in terms of µg/mL at complete inhibition of bacterial growth, where the pointed end of the ellipse intersects the strip. Since ETEST generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read must be recorded to the next two-fold dilution. The MIC gradient on ETEST Telavancin ranges from 0.002 to 32 µg/mL. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: A reproducibility study was conducted at three external sites using 10 isolates of Gram positive organisms that were consistent with the intended use. Testing was performed on three separate days and in triplicate for a total of 270 data points among the sites. The isolates tested included five S. aureus and five E. faecalis isolates. The mode MIC was determined and the reproducibility was calculated based on MIC values that fell within ± one doubling dilution from the mode MIC value. All results were on-scale and within ± 1 doubling dilution of the mode MIC value for telavancin. The overall reproducibility was 100.0%. b. Linearity/assay reportable range: 6 Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Inoculum Density Check. Inoculum density checks were performed for all quality control and reproducibility organism suspensions and for 10% of the suspensions prepared for susceptibility testing of the fresh clinical isolates. The mean inoculum density was acceptable at 4.40 X 105 CFU/mL. Purity Check. All clinical, challenge and reproducibility test suspensions were subcultured to assure purity. Growth or Device Failure. There were no growth or device failures during the course of the study. Quality Control Testing. Organisms recommended by both FDA and the CLSI were tested with telavancin at three sites. The QC organisms tested included S. aureus ATCC 29213 and E. faecalis ATCC 29212. These QC strains were tested a minimum of 20 times per site by both the ETEST and the reference method. The results demonstrate that the telavancin ETEST can produce quality control results in the recommended range > 95% of the time. See Table 2 below for a summary of the QC results. Table 2. Quality Control Data for Telavancin QC organism Telavancin expected range (µg/mL) Concentration (µg/mL) Reference ETEST S. aureus ATCC 29213 0.03 – 0.12 0.016 - - 0.03 60 6 0.06 20 71 0.12 1 4 0.25 - - E. faecalis ATCC 29212 0.03 – 0.12 0.016 - - 0.03 - - 0.06 75 41 0.12 6 40 0.25 - - d. Detection limit: Not applicable e. Analytical specificity: Not applicable 7 f. Assay cut-off: Not applicable 2. Comparison studies: a. Method comparison with predicate device: Results obtained with ETEST telavancin were compared to results obtained with the CLSI broth microdilution reference panel. The CLSI panel Regulation section:

idK180936_s4000_e6000

K180936.txt

proposed labeling

The labeling supports the finding of substantial equivalence for this device.

when a. and b. are not applicable): No applicable 4. Clinical cut-off: Not applicable 5. Expected values/Reference range: Table 5. Interpretive Criteria (Breakpoints) for Telavancin Organism Interpretive Criteria for Telavancin (MIC, µg/mL) S I R S. aureus (including MRSA) ≤ 0.12 NA NA E. faecalis (vancomycin-susceptible only) ≤ 0.25 NA NA N. Proposed Labeling: The labeling supports the finding of substantial equivalence for this device. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK180936_s4000_e6000

K180936.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

data (when a. and b. are not applicable): No applicable 4. Clinical cut-off: Not applicable 5. Expected values/Reference range: Table 5. Interpretive Criteria (Breakpoints) for Telavancin Organism Interpretive Criteria for Telavancin (MIC, µg/mL) S I R S. aureus (including MRSA) ≤ 0.12 NA NA E. faecalis (vancomycin-susceptible only) ≤ 0.25 NA NA N. Proposed Labeling: The labeling supports the finding of substantial equivalence for this device. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK141114_s0_e2000

K141114.txt

purpose for submission

New Device

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k141114 B. Purpose for Submission: New Device C. Measurand: 25-hydroxyvitamin D [25(OH) Vitamin D] D. Type of Test: Quantitative multiplexed flow immunoassay E. Applicant: Bio-Rad Laboratories F. Proprietary and Established Names: BioPlex® 2200 25-OH Vitamin D Kit BioPlex® 2200 25-OH Vitamin D Calibrator Set BioPlex® 2200 25-OH Vitamin D Control Set G. Regulatory Information: Product Code Classification Regulation Section Panel MRG II 862.1825 Vitamin D Test System Chemistry (75) JIT II 862.1150 Calibrator Chemistry (75) JJX I, Reserved 862.1660 Quality Control Material (Assayed and Unassayed) Chemistry (75) 2 H. Intended Use: 1. Intended use(s): See indication for use below. 2. Indication(s) for use: The BioPlex 2200 25-OH Vitamin D kit is a flow competitive immunoassay intended for the quantitative determination of 25-hydroxyvitamin D in human serum. The BioPlex 2200 25- OH vitamin D assay is to be used to aid in the assessment of vitamin D sufficiency. The BioPlex 2200 25-OH Vitamin D kit is intended for use with the BioPlex 2200 System. The BioPlex 2200 25-OH Vitamin D Calibrator Set is intended for the calibration of the BioPlex 2200 25-OH Vitamin D reagent Pack. The BioPlex 2200 25-OH Vitamin D Control Set is intended for use as an assayed quality control to monitor the overall performance of the BioPlex 2200 system and corresponding BioPlex® 25-OH Vitamin D reagent pack in the clinical laboratory. The performance of the BioPlex 2200 25-OH Vitamin D Control Set has not been established with any other 25- hydroxyvitamin D assays. 3. Special conditions for use statement(s): For in vitro diagnostics For prescription use only 4. Special instrument requirements: BioPlex 2200 system I. Device Description: The BioPlex 2200 25-OH Vitamin D Kit consists of the following: 1. One 10mL vial of Bead Set containing dyed beads coated with anti-25-OH D antibody (sheep), an Internal Standard bead (ISB), and a Serum Verification bead (SVB) in buffer with protein stabilizers (bovine). ProClin 950 (<1.0%) and sodium azide (<0.1%) as preservatives. 2. One 10mL vial of Release Buffer containing 25-OH Vitamin D releasing reagents in citrate and trisodium citrate acid buffer at pH 4.1 and ProClin 950 (<1.0%) as preservative. 3. One 5mL vial of Conjugate 1 containing biotinylated 25-OH Vitamin D conjugate and biotinylated anti-human FXIII antibody conjugate (murine) in buffer with protein stabilizer (bovine). ProClin 950 (<1.0%) and 5-bromo-5-nitro-1, 3-dioxane (<0.1%) as preservatives 3 and chemical blockers. 4. One 5mL vial of Conjugate 2 containing phycoerythrin conjugated streptavidin (SA-PE) in buffer comprising protein stabilizers (bovine). ProClin 950 (<1.0%) and sodium azide (<0.1%) as preservatives, chemical blockers and detergent (Tween 20). BioPlex 2200 25-OH Vitamin D Calibrator set (sold separately) contains six 0.5 mL 25-OH Vitamin D vials. Calibrator level 1 contains 25% horse serum without 25-OH Vitamin D. The calibrator levels 2 to 6 are provided in a Vitamin D depleted human serum matrix supplemented with known concentration of 25-hydroxyvitamin D3. All calibrators contain ProClin 950 (<0.3%), sodium benzoate (<0.1%) and 5-bromo-5-nitro-1, 3-dioxane (<0.1%) as preservatives. Calibrator Set Target (ng/mL) Level 1 0.0 Level 2 10.0 Level 3 30.0 Level 4 75.0 Level 5 110.0 Level 6 165.0 BioPlex 2200 25-OH control set (sold separately) contains two 1.5 mL of Level 1 and two 1.5 mL of Level 2 control vials. Each vial contains 25-OH Vitamin D in human serum matrix. All controls contain ProClin 950 (<0.3%), sodium benzoate (<0.1%) and 5-bromo-5-nitro-1, 3- dioxane (<0.1%) as preservatives. Control Set Target (ng/mL) Range (ng/mL) Level 1 19.0 14.5 – 23.5 Level 2 55.0 45.0 – 65.0 Calibrator and Control contain human source material. Each donor unit of serum in the preparation of these materials were tested and found negative for the Human Immunodeficiency Virus Antibody (HIV I/II Ab), Hepatitis B Surface Antigen (HBsAg), and Hepatitis C Virus Antibody (HCV). J. Substantial Equivalence Information: 1. Predicate device name(s): EUROIMMUN 25-OH Vitamin D ELISA 2. Predicate 510(k) number(s): k123660 4 3. Comparison with predicate: Assay: Similarities / Differences Item BioPlex® 2200 25-OH Vitamin D Kit Candidate Device EUROIMMUN 25-OH Vitamin D ELISA Predicate Device (k123660) Intended Use For the quantitative determination of 25- hydroxyvitamin D in human serum. Same Assay Type Quantitative Same Test Principle Competitive immunoassay Same Antibody Monoclonal Sheep antibody against 25 OH Vitamin D Same Signal Detection Fluorescence Same Unit of Measure ng/mL Same Assay Technology Automated multiplex flow competitive immunoassay Manually competitive immunoassay Conjugate Biotinylated 25- hydroxyvitamin D and phycoerythrin streptavidin Biotinylated 25- hydroxyvitamin D and Peroxidase-labeled streptavidin and substrate TMB Solid Phase Antibody-coated paramagnetic microbeads Antibody coated 96 microwell ELISA plate Measuring Range 6.5 ng/mL – 125.0 ng/mL 4.0 ng/mL – 120 ng/mL Sample Matrix Serum Serum or EDTA or Lithium heparin plasma Sample Size 10µL 20µL Open Pack Stability 60 days Not Applicable Reagent Storage On-board or in refrigerator at 2-8°C Not Applicable Sample Handling Automated Manually Instrumentation Bio-Rad BioPlex® 2200 System ELISA plate reader Measuring Wavelength 550-610 nm 450/620 nm 5 Calibrator: Similarities / Differences Item BioPlex® 2200 25-OH Vitamin D Calibrator Candidate Device EUROIMMUN 25-OH Vitamin D ELISA Calibrator Predicate Device Intended Use For the calibration of the Vitamin D reagent pack. Same Calibrator(s) and Calibration 6 calibrator levels (sold separately); 4-PL (parameter logistic) curve fit algorithm Same Calibrator Matrix 25% horse serum and depleted human serum with ProClin 950, sodium benzoate and BND Liquid in horse serum with preservatives Calibrator Open Storage at 2-8°C 30 days 3 months Calibration Frequency Every 30 days Every 96 well plate Controls: Similarities / Differences Item BioPlex® 2200 25-OH Vitamin D Control Candidate Device EUROIMMUN 25-OH Vitamin D ELISA Controls Predicate Device Intended Use Use as an assayed quality control to monitor the overall performance of the Vitamin D reagent. Same Storage Sore at 2-8°C until ready to use Same Matrix Human serum with ProClin 950, Sodium benzoate and BND Liquid in horse serum with preservatives K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A2: Evaluation of Precision Performance of Quantitative Measurement Methods CLSI EP6-A: Evaluation of Linearity of Quantitative Measurement Procedures CLSI EP07-A2: Interference Testing in Clinical Chemistry CLSI EP09-A2IR: Method comparison and Bias Estimation CLSI EP15-A2: User Verification of Performance for Precision and Trueness CLSI EP17-A2: Evaluation of Detection Capability for Clinical laboratory measurements 6 Procedure CLSI EP25-A: Evaluation of Stability of In-vitro diagnostic Reagents CLSI C28-A3c: Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory L. Test Principle: The BioPlex 2200 25-OH Vitamin D assay is a multiplex flow competitive immunoassay for the quantitative determination of 25-hydroxyvitamin D in human serum. The BioPlex 2200 System combines an aliquot of patient sample with the Vitamin D Purpose for submission:

idK141114_s0_e2000

K141114.txt

measurand

25-hydroxyvitamin D [25(OH) Vitamin D]

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k141114 B. Purpose for Submission: New Device C. Measurand: 25-hydroxyvitamin D [25(OH) Vitamin D] D. Type of Test: Quantitative multiplexed flow immunoassay E. Applicant: Bio-Rad Laboratories F. Proprietary and Established Names: BioPlex® 2200 25-OH Vitamin D Kit BioPlex® 2200 25-OH Vitamin D Calibrator Set BioPlex® 2200 25-OH Vitamin D Control Set G. Regulatory Information: Product Code Classification Regulation Section Panel MRG II 862.1825 Vitamin D Test System Chemistry (75) JIT II 862.1150 Calibrator Chemistry (75) JJX I, Reserved 862.1660 Quality Control Material (Assayed and Unassayed) Chemistry (75) 2 H. Intended Use: 1. Intended use(s): See indication for use below. 2. Indication(s) for use: The BioPlex 2200 25-OH Vitamin D kit is a flow competitive immunoassay intended for the quantitative determination of 25-hydroxyvitamin D in human serum. The BioPlex 2200 25- OH vitamin D assay is to be used to aid in the assessment of vitamin D sufficiency. The BioPlex 2200 25-OH Vitamin D kit is intended for use with the BioPlex 2200 System. The BioPlex 2200 25-OH Vitamin D Calibrator Set is intended for the calibration of the BioPlex 2200 25-OH Vitamin D reagent Pack. The BioPlex 2200 25-OH Vitamin D Control Set is intended for use as an assayed quality control to monitor the overall performance of the BioPlex 2200 system and corresponding BioPlex® 25-OH Vitamin D reagent pack in the clinical laboratory. The performance of the BioPlex 2200 25-OH Vitamin D Control Set has not been established with any other 25- hydroxyvitamin D assays. 3. Special conditions for use statement(s): For in vitro diagnostics For prescription use only 4. Special instrument requirements: BioPlex 2200 system I. Device Description: The BioPlex 2200 25-OH Vitamin D Kit consists of the following: 1. One 10mL vial of Bead Set containing dyed beads coated with anti-25-OH D antibody (sheep), an Internal Standard bead (ISB), and a Serum Verification bead (SVB) in buffer with protein stabilizers (bovine). ProClin 950 (<1.0%) and sodium azide (<0.1%) as preservatives. 2. One 10mL vial of Release Buffer containing 25-OH Vitamin D releasing reagents in citrate and trisodium citrate acid buffer at pH 4.1 and ProClin 950 (<1.0%) as preservative. 3. One 5mL vial of Conjugate 1 containing biotinylated 25-OH Vitamin D conjugate and biotinylated anti-human FXIII antibody conjugate (murine) in buffer with protein stabilizer (bovine). ProClin 950 (<1.0%) and 5-bromo-5-nitro-1, 3-dioxane (<0.1%) as preservatives 3 and chemical blockers. 4. One 5mL vial of Conjugate 2 containing phycoerythrin conjugated streptavidin (SA-PE) in buffer comprising protein stabilizers (bovine). ProClin 950 (<1.0%) and sodium azide (<0.1%) as preservatives, chemical blockers and detergent (Tween 20). BioPlex 2200 25-OH Vitamin D Calibrator set (sold separately) contains six 0.5 mL 25-OH Vitamin D vials. Calibrator level 1 contains 25% horse serum without 25-OH Vitamin D. The calibrator levels 2 to 6 are provided in a Vitamin D depleted human serum matrix supplemented with known concentration of 25-hydroxyvitamin D3. All calibrators contain ProClin 950 (<0.3%), sodium benzoate (<0.1%) and 5-bromo-5-nitro-1, 3-dioxane (<0.1%) as preservatives. Calibrator Set Target (ng/mL) Level 1 0.0 Level 2 10.0 Level 3 30.0 Level 4 75.0 Level 5 110.0 Level 6 165.0 BioPlex 2200 25-OH control set (sold separately) contains two 1.5 mL of Level 1 and two 1.5 mL of Level 2 control vials. Each vial contains 25-OH Vitamin D in human serum matrix. All controls contain ProClin 950 (<0.3%), sodium benzoate (<0.1%) and 5-bromo-5-nitro-1, 3- dioxane (<0.1%) as preservatives. Control Set Target (ng/mL) Range (ng/mL) Level 1 19.0 14.5 – 23.5 Level 2 55.0 45.0 – 65.0 Calibrator and Control contain human source material. Each donor unit of serum in the preparation of these materials were tested and found negative for the Human Immunodeficiency Virus Antibody (HIV I/II Ab), Hepatitis B Surface Antigen (HBsAg), and Hepatitis C Virus Antibody (HCV). J. Substantial Equivalence Information: 1. Predicate device name(s): EUROIMMUN 25-OH Vitamin D ELISA 2. Predicate 510(k) number(s): k123660 4 3. Comparison with predicate: Assay: Similarities / Differences Item BioPlex® 2200 25-OH Vitamin D Kit Candidate Device EUROIMMUN 25-OH Vitamin D ELISA Predicate Device (k123660) Intended Use For the quantitative determination of 25- hydroxyvitamin D in human serum. Same Assay Type Quantitative Same Test Principle Competitive immunoassay Same Antibody Monoclonal Sheep antibody against 25 OH Vitamin D Same Signal Detection Fluorescence Same Unit of Measure ng/mL Same Assay Technology Automated multiplex flow competitive immunoassay Manually competitive immunoassay Conjugate Biotinylated 25- hydroxyvitamin D and phycoerythrin streptavidin Biotinylated 25- hydroxyvitamin D and Peroxidase-labeled streptavidin and substrate TMB Solid Phase Antibody-coated paramagnetic microbeads Antibody coated 96 microwell ELISA plate Measuring Range 6.5 ng/mL – 125.0 ng/mL 4.0 ng/mL – 120 ng/mL Sample Matrix Serum Serum or EDTA or Lithium heparin plasma Sample Size 10µL 20µL Open Pack Stability 60 days Not Applicable Reagent Storage On-board or in refrigerator at 2-8°C Not Applicable Sample Handling Automated Manually Instrumentation Bio-Rad BioPlex® 2200 System ELISA plate reader Measuring Wavelength 550-610 nm 450/620 nm 5 Calibrator: Similarities / Differences Item BioPlex® 2200 25-OH Vitamin D Calibrator Candidate Device EUROIMMUN 25-OH Vitamin D ELISA Calibrator Predicate Device Intended Use For the calibration of the Vitamin D reagent pack. Same Calibrator(s) and Calibration 6 calibrator levels (sold separately); 4-PL (parameter logistic) curve fit algorithm Same Calibrator Matrix 25% horse serum and depleted human serum with ProClin 950, sodium benzoate and BND Liquid in horse serum with preservatives Calibrator Open Storage at 2-8°C 30 days 3 months Calibration Frequency Every 30 days Every 96 well plate Controls: Similarities / Differences Item BioPlex® 2200 25-OH Vitamin D Control Candidate Device EUROIMMUN 25-OH Vitamin D ELISA Controls Predicate Device Intended Use Use as an assayed quality control to monitor the overall performance of the Vitamin D reagent. Same Storage Sore at 2-8°C until ready to use Same Matrix Human serum with ProClin 950, Sodium benzoate and BND Liquid in horse serum with preservatives K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A2: Evaluation of Precision Performance of Quantitative Measurement Methods CLSI EP6-A: Evaluation of Linearity of Quantitative Measurement Procedures CLSI EP07-A2: Interference Testing in Clinical Chemistry CLSI EP09-A2IR: Method comparison and Bias Estimation CLSI EP15-A2: User Verification of Performance for Precision and Trueness CLSI EP17-A2: Evaluation of Detection Capability for Clinical laboratory measurements 6 Procedure CLSI EP25-A: Evaluation of Stability of In-vitro diagnostic Reagents CLSI C28-A3c: Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory L. Test Principle: The BioPlex 2200 25-OH Vitamin D assay is a multiplex flow competitive immunoassay for the quantitative determination of 25-hydroxyvitamin D in human serum. The BioPlex 2200 System combines an aliquot of patient sample with the Vitamin D Measurand:

idK141114_s0_e2000

K141114.txt

type of test

Quantitative multiplexed flow immunoassay

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k141114 B. Purpose for Submission: New Device C. Measurand: 25-hydroxyvitamin D [25(OH) Vitamin D] D. Type of Test: Quantitative multiplexed flow immunoassay E. Applicant: Bio-Rad Laboratories F. Proprietary and Established Names: BioPlex® 2200 25-OH Vitamin D Kit BioPlex® 2200 25-OH Vitamin D Calibrator Set BioPlex® 2200 25-OH Vitamin D Control Set G. Regulatory Information: Product Code Classification Regulation Section Panel MRG II 862.1825 Vitamin D Test System Chemistry (75) JIT II 862.1150 Calibrator Chemistry (75) JJX I, Reserved 862.1660 Quality Control Material (Assayed and Unassayed) Chemistry (75) 2 H. Intended Use: 1. Intended use(s): See indication for use below. 2. Indication(s) for use: The BioPlex 2200 25-OH Vitamin D kit is a flow competitive immunoassay intended for the quantitative determination of 25-hydroxyvitamin D in human serum. The BioPlex 2200 25- OH vitamin D assay is to be used to aid in the assessment of vitamin D sufficiency. The BioPlex 2200 25-OH Vitamin D kit is intended for use with the BioPlex 2200 System. The BioPlex 2200 25-OH Vitamin D Calibrator Set is intended for the calibration of the BioPlex 2200 25-OH Vitamin D reagent Pack. The BioPlex 2200 25-OH Vitamin D Control Set is intended for use as an assayed quality control to monitor the overall performance of the BioPlex 2200 system and corresponding BioPlex® 25-OH Vitamin D reagent pack in the clinical laboratory. The performance of the BioPlex 2200 25-OH Vitamin D Control Set has not been established with any other 25- hydroxyvitamin D assays. 3. Special conditions for use statement(s): For in vitro diagnostics For prescription use only 4. Special instrument requirements: BioPlex 2200 system I. Device Description: The BioPlex 2200 25-OH Vitamin D Kit consists of the following: 1. One 10mL vial of Bead Set containing dyed beads coated with anti-25-OH D antibody (sheep), an Internal Standard bead (ISB), and a Serum Verification bead (SVB) in buffer with protein stabilizers (bovine). ProClin 950 (<1.0%) and sodium azide (<0.1%) as preservatives. 2. One 10mL vial of Release Buffer containing 25-OH Vitamin D releasing reagents in citrate and trisodium citrate acid buffer at pH 4.1 and ProClin 950 (<1.0%) as preservative. 3. One 5mL vial of Conjugate 1 containing biotinylated 25-OH Vitamin D conjugate and biotinylated anti-human FXIII antibody conjugate (murine) in buffer with protein stabilizer (bovine). ProClin 950 (<1.0%) and 5-bromo-5-nitro-1, 3-dioxane (<0.1%) as preservatives 3 and chemical blockers. 4. One 5mL vial of Conjugate 2 containing phycoerythrin conjugated streptavidin (SA-PE) in buffer comprising protein stabilizers (bovine). ProClin 950 (<1.0%) and sodium azide (<0.1%) as preservatives, chemical blockers and detergent (Tween 20). BioPlex 2200 25-OH Vitamin D Calibrator set (sold separately) contains six 0.5 mL 25-OH Vitamin D vials. Calibrator level 1 contains 25% horse serum without 25-OH Vitamin D. The calibrator levels 2 to 6 are provided in a Vitamin D depleted human serum matrix supplemented with known concentration of 25-hydroxyvitamin D3. All calibrators contain ProClin 950 (<0.3%), sodium benzoate (<0.1%) and 5-bromo-5-nitro-1, 3-dioxane (<0.1%) as preservatives. Calibrator Set Target (ng/mL) Level 1 0.0 Level 2 10.0 Level 3 30.0 Level 4 75.0 Level 5 110.0 Level 6 165.0 BioPlex 2200 25-OH control set (sold separately) contains two 1.5 mL of Level 1 and two 1.5 mL of Level 2 control vials. Each vial contains 25-OH Vitamin D in human serum matrix. All controls contain ProClin 950 (<0.3%), sodium benzoate (<0.1%) and 5-bromo-5-nitro-1, 3- dioxane (<0.1%) as preservatives. Control Set Target (ng/mL) Range (ng/mL) Level 1 19.0 14.5 – 23.5 Level 2 55.0 45.0 – 65.0 Calibrator and Control contain human source material. Each donor unit of serum in the preparation of these materials were tested and found negative for the Human Immunodeficiency Virus Antibody (HIV I/II Ab), Hepatitis B Surface Antigen (HBsAg), and Hepatitis C Virus Antibody (HCV). J. Substantial Equivalence Information: 1. Predicate device name(s): EUROIMMUN 25-OH Vitamin D ELISA 2. Predicate 510(k) number(s): k123660 4 3. Comparison with predicate: Assay: Similarities / Differences Item BioPlex® 2200 25-OH Vitamin D Kit Candidate Device EUROIMMUN 25-OH Vitamin D ELISA Predicate Device (k123660) Intended Use For the quantitative determination of 25- hydroxyvitamin D in human serum. Same Assay Type Quantitative Same Test Principle Competitive immunoassay Same Antibody Monoclonal Sheep antibody against 25 OH Vitamin D Same Signal Detection Fluorescence Same Unit of Measure ng/mL Same Assay Technology Automated multiplex flow competitive immunoassay Manually competitive immunoassay Conjugate Biotinylated 25- hydroxyvitamin D and phycoerythrin streptavidin Biotinylated 25- hydroxyvitamin D and Peroxidase-labeled streptavidin and substrate TMB Solid Phase Antibody-coated paramagnetic microbeads Antibody coated 96 microwell ELISA plate Measuring Range 6.5 ng/mL – 125.0 ng/mL 4.0 ng/mL – 120 ng/mL Sample Matrix Serum Serum or EDTA or Lithium heparin plasma Sample Size 10µL 20µL Open Pack Stability 60 days Not Applicable Reagent Storage On-board or in refrigerator at 2-8°C Not Applicable Sample Handling Automated Manually Instrumentation Bio-Rad BioPlex® 2200 System ELISA plate reader Measuring Wavelength 550-610 nm 450/620 nm 5 Calibrator: Similarities / Differences Item BioPlex® 2200 25-OH Vitamin D Calibrator Candidate Device EUROIMMUN 25-OH Vitamin D ELISA Calibrator Predicate Device Intended Use For the calibration of the Vitamin D reagent pack. Same Calibrator(s) and Calibration 6 calibrator levels (sold separately); 4-PL (parameter logistic) curve fit algorithm Same Calibrator Matrix 25% horse serum and depleted human serum with ProClin 950, sodium benzoate and BND Liquid in horse serum with preservatives Calibrator Open Storage at 2-8°C 30 days 3 months Calibration Frequency Every 30 days Every 96 well plate Controls: Similarities / Differences Item BioPlex® 2200 25-OH Vitamin D Control Candidate Device EUROIMMUN 25-OH Vitamin D ELISA Controls Predicate Device Intended Use Use as an assayed quality control to monitor the overall performance of the Vitamin D reagent. Same Storage Sore at 2-8°C until ready to use Same Matrix Human serum with ProClin 950, Sodium benzoate and BND Liquid in horse serum with preservatives K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A2: Evaluation of Precision Performance of Quantitative Measurement Methods CLSI EP6-A: Evaluation of Linearity of Quantitative Measurement Procedures CLSI EP07-A2: Interference Testing in Clinical Chemistry CLSI EP09-A2IR: Method comparison and Bias Estimation CLSI EP15-A2: User Verification of Performance for Precision and Trueness CLSI EP17-A2: Evaluation of Detection Capability for Clinical laboratory measurements 6 Procedure CLSI EP25-A: Evaluation of Stability of In-vitro diagnostic Reagents CLSI C28-A3c: Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory L. Test Principle: The BioPlex 2200 25-OH Vitamin D assay is a multiplex flow competitive immunoassay for the quantitative determination of 25-hydroxyvitamin D in human serum. The BioPlex 2200 System combines an aliquot of patient sample with the Vitamin D Type of test:

idK141114_s0_e2000

K141114.txt

intended use

See indication for use below.

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k141114 B. Purpose for Submission: New Device C. Measurand: 25-hydroxyvitamin D [25(OH) Vitamin D] D. Type of Test: Quantitative multiplexed flow immunoassay E. Applicant: Bio-Rad Laboratories F. Proprietary and Established Names: BioPlex® 2200 25-OH Vitamin D Kit BioPlex® 2200 25-OH Vitamin D Calibrator Set BioPlex® 2200 25-OH Vitamin D Control Set G. Regulatory Information: Product Code Classification Regulation Section Panel MRG II 862.1825 Vitamin D Test System Chemistry (75) JIT II 862.1150 Calibrator Chemistry (75) JJX I, Reserved 862.1660 Quality Control Material (Assayed and Unassayed) Chemistry (75) 2 H. Intended Use: 1. Intended use(s): See indication for use below. 2. Indication(s) for use: The BioPlex 2200 25-OH Vitamin D kit is a flow competitive immunoassay intended for the quantitative determination of 25-hydroxyvitamin D in human serum. The BioPlex 2200 25- OH vitamin D assay is to be used to aid in the assessment of vitamin D sufficiency. The BioPlex 2200 25-OH Vitamin D kit is intended for use with the BioPlex 2200 System. The BioPlex 2200 25-OH Vitamin D Calibrator Set is intended for the calibration of the BioPlex 2200 25-OH Vitamin D reagent Pack. The BioPlex 2200 25-OH Vitamin D Control Set is intended for use as an assayed quality control to monitor the overall performance of the BioPlex 2200 system and corresponding BioPlex® 25-OH Vitamin D reagent pack in the clinical laboratory. The performance of the BioPlex 2200 25-OH Vitamin D Control Set has not been established with any other 25- hydroxyvitamin D assays. 3. Special conditions for use statement(s): For in vitro diagnostics For prescription use only 4. Special instrument requirements: BioPlex 2200 system I. Device Description: The BioPlex 2200 25-OH Vitamin D Kit consists of the following: 1. One 10mL vial of Bead Set containing dyed beads coated with anti-25-OH D antibody (sheep), an Internal Standard bead (ISB), and a Serum Verification bead (SVB) in buffer with protein stabilizers (bovine). ProClin 950 (<1.0%) and sodium azide (<0.1%) as preservatives. 2. One 10mL vial of Release Buffer containing 25-OH Vitamin D releasing reagents in citrate and trisodium citrate acid buffer at pH 4.1 and ProClin 950 (<1.0%) as preservative. 3. One 5mL vial of Conjugate 1 containing biotinylated 25-OH Vitamin D conjugate and biotinylated anti-human FXIII antibody conjugate (murine) in buffer with protein stabilizer (bovine). ProClin 950 (<1.0%) and 5-bromo-5-nitro-1, 3-dioxane (<0.1%) as preservatives 3 and chemical blockers. 4. One 5mL vial of Conjugate 2 containing phycoerythrin conjugated streptavidin (SA-PE) in buffer comprising protein stabilizers (bovine). ProClin 950 (<1.0%) and sodium azide (<0.1%) as preservatives, chemical blockers and detergent (Tween 20). BioPlex 2200 25-OH Vitamin D Calibrator set (sold separately) contains six 0.5 mL 25-OH Vitamin D vials. Calibrator level 1 contains 25% horse serum without 25-OH Vitamin D. The calibrator levels 2 to 6 are provided in a Vitamin D depleted human serum matrix supplemented with known concentration of 25-hydroxyvitamin D3. All calibrators contain ProClin 950 (<0.3%), sodium benzoate (<0.1%) and 5-bromo-5-nitro-1, 3-dioxane (<0.1%) as preservatives. Calibrator Set Target (ng/mL) Level 1 0.0 Level 2 10.0 Level 3 30.0 Level 4 75.0 Level 5 110.0 Level 6 165.0 BioPlex 2200 25-OH control set (sold separately) contains two 1.5 mL of Level 1 and two 1.5 mL of Level 2 control vials. Each vial contains 25-OH Vitamin D in human serum matrix. All controls contain ProClin 950 (<0.3%), sodium benzoate (<0.1%) and 5-bromo-5-nitro-1, 3- dioxane (<0.1%) as preservatives. Control Set Target (ng/mL) Range (ng/mL) Level 1 19.0 14.5 – 23.5 Level 2 55.0 45.0 – 65.0 Calibrator and Control contain human source material. Each donor unit of serum in the preparation of these materials were tested and found negative for the Human Immunodeficiency Virus Antibody (HIV I/II Ab), Hepatitis B Surface Antigen (HBsAg), and Hepatitis C Virus Antibody (HCV). J. Substantial Equivalence Information: 1. Predicate device name(s): EUROIMMUN 25-OH Vitamin D ELISA 2. Predicate 510(k) number(s): k123660 4 3. Comparison with predicate: Assay: Similarities / Differences Item BioPlex® 2200 25-OH Vitamin D Kit Candidate Device EUROIMMUN 25-OH Vitamin D ELISA Predicate Device (k123660) Intended Use For the quantitative determination of 25- hydroxyvitamin D in human serum. Same Assay Type Quantitative Same Test Principle Competitive immunoassay Same Antibody Monoclonal Sheep antibody against 25 OH Vitamin D Same Signal Detection Fluorescence Same Unit of Measure ng/mL Same Assay Technology Automated multiplex flow competitive immunoassay Manually competitive immunoassay Conjugate Biotinylated 25- hydroxyvitamin D and phycoerythrin streptavidin Biotinylated 25- hydroxyvitamin D and Peroxidase-labeled streptavidin and substrate TMB Solid Phase Antibody-coated paramagnetic microbeads Antibody coated 96 microwell ELISA plate Measuring Range 6.5 ng/mL – 125.0 ng/mL 4.0 ng/mL – 120 ng/mL Sample Matrix Serum Serum or EDTA or Lithium heparin plasma Sample Size 10µL 20µL Open Pack Stability 60 days Not Applicable Reagent Storage On-board or in refrigerator at 2-8°C Not Applicable Sample Handling Automated Manually Instrumentation Bio-Rad BioPlex® 2200 System ELISA plate reader Measuring Wavelength 550-610 nm 450/620 nm 5 Calibrator: Similarities / Differences Item BioPlex® 2200 25-OH Vitamin D Calibrator Candidate Device EUROIMMUN 25-OH Vitamin D ELISA Calibrator Predicate Device Intended Use For the calibration of the Vitamin D reagent pack. Same Calibrator(s) and Calibration 6 calibrator levels (sold separately); 4-PL (parameter logistic) curve fit algorithm Same Calibrator Matrix 25% horse serum and depleted human serum with ProClin 950, sodium benzoate and BND Liquid in horse serum with preservatives Calibrator Open Storage at 2-8°C 30 days 3 months Calibration Frequency Every 30 days Every 96 well plate Controls: Similarities / Differences Item BioPlex® 2200 25-OH Vitamin D Control Candidate Device EUROIMMUN 25-OH Vitamin D ELISA Controls Predicate Device Intended Use Use as an assayed quality control to monitor the overall performance of the Vitamin D reagent. Same Storage Sore at 2-8°C until ready to use Same Matrix Human serum with ProClin 950, Sodium benzoate and BND Liquid in horse serum with preservatives K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A2: Evaluation of Precision Performance of Quantitative Measurement Methods CLSI EP6-A: Evaluation of Linearity of Quantitative Measurement Procedures CLSI EP07-A2: Interference Testing in Clinical Chemistry CLSI EP09-A2IR: Method comparison and Bias Estimation CLSI EP15-A2: User Verification of Performance for Precision and Trueness CLSI EP17-A2: Evaluation of Detection Capability for Clinical laboratory measurements 6 Procedure CLSI EP25-A: Evaluation of Stability of In-vitro diagnostic Reagents CLSI C28-A3c: Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory L. Test Principle: The BioPlex 2200 25-OH Vitamin D assay is a multiplex flow competitive immunoassay for the quantitative determination of 25-hydroxyvitamin D in human serum. The BioPlex 2200 System combines an aliquot of patient sample with the Vitamin D Intended use:

idK141114_s0_e2000

K141114.txt

predicate device name

EUROIMMUN 25-OH Vitamin D ELISA

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k141114 B. Purpose for Submission: New Device C. Measurand: 25-hydroxyvitamin D [25(OH) Vitamin D] D. Type of Test: Quantitative multiplexed flow immunoassay E. Applicant: Bio-Rad Laboratories F. Proprietary and Established Names: BioPlex® 2200 25-OH Vitamin D Kit BioPlex® 2200 25-OH Vitamin D Calibrator Set BioPlex® 2200 25-OH Vitamin D Control Set G. Regulatory Information: Product Code Classification Regulation Section Panel MRG II 862.1825 Vitamin D Test System Chemistry (75) JIT II 862.1150 Calibrator Chemistry (75) JJX I, Reserved 862.1660 Quality Control Material (Assayed and Unassayed) Chemistry (75) 2 H. Intended Use: 1. Intended use(s): See indication for use below. 2. Indication(s) for use: The BioPlex 2200 25-OH Vitamin D kit is a flow competitive immunoassay intended for the quantitative determination of 25-hydroxyvitamin D in human serum. The BioPlex 2200 25- OH vitamin D assay is to be used to aid in the assessment of vitamin D sufficiency. The BioPlex 2200 25-OH Vitamin D kit is intended for use with the BioPlex 2200 System. The BioPlex 2200 25-OH Vitamin D Calibrator Set is intended for the calibration of the BioPlex 2200 25-OH Vitamin D reagent Pack. The BioPlex 2200 25-OH Vitamin D Control Set is intended for use as an assayed quality control to monitor the overall performance of the BioPlex 2200 system and corresponding BioPlex® 25-OH Vitamin D reagent pack in the clinical laboratory. The performance of the BioPlex 2200 25-OH Vitamin D Control Set has not been established with any other 25- hydroxyvitamin D assays. 3. Special conditions for use statement(s): For in vitro diagnostics For prescription use only 4. Special instrument requirements: BioPlex 2200 system I. Device Description: The BioPlex 2200 25-OH Vitamin D Kit consists of the following: 1. One 10mL vial of Bead Set containing dyed beads coated with anti-25-OH D antibody (sheep), an Internal Standard bead (ISB), and a Serum Verification bead (SVB) in buffer with protein stabilizers (bovine). ProClin 950 (<1.0%) and sodium azide (<0.1%) as preservatives. 2. One 10mL vial of Release Buffer containing 25-OH Vitamin D releasing reagents in citrate and trisodium citrate acid buffer at pH 4.1 and ProClin 950 (<1.0%) as preservative. 3. One 5mL vial of Conjugate 1 containing biotinylated 25-OH Vitamin D conjugate and biotinylated anti-human FXIII antibody conjugate (murine) in buffer with protein stabilizer (bovine). ProClin 950 (<1.0%) and 5-bromo-5-nitro-1, 3-dioxane (<0.1%) as preservatives 3 and chemical blockers. 4. One 5mL vial of Conjugate 2 containing phycoerythrin conjugated streptavidin (SA-PE) in buffer comprising protein stabilizers (bovine). ProClin 950 (<1.0%) and sodium azide (<0.1%) as preservatives, chemical blockers and detergent (Tween 20). BioPlex 2200 25-OH Vitamin D Calibrator set (sold separately) contains six 0.5 mL 25-OH Vitamin D vials. Calibrator level 1 contains 25% horse serum without 25-OH Vitamin D. The calibrator levels 2 to 6 are provided in a Vitamin D depleted human serum matrix supplemented with known concentration of 25-hydroxyvitamin D3. All calibrators contain ProClin 950 (<0.3%), sodium benzoate (<0.1%) and 5-bromo-5-nitro-1, 3-dioxane (<0.1%) as preservatives. Calibrator Set Target (ng/mL) Level 1 0.0 Level 2 10.0 Level 3 30.0 Level 4 75.0 Level 5 110.0 Level 6 165.0 BioPlex 2200 25-OH control set (sold separately) contains two 1.5 mL of Level 1 and two 1.5 mL of Level 2 control vials. Each vial contains 25-OH Vitamin D in human serum matrix. All controls contain ProClin 950 (<0.3%), sodium benzoate (<0.1%) and 5-bromo-5-nitro-1, 3- dioxane (<0.1%) as preservatives. Control Set Target (ng/mL) Range (ng/mL) Level 1 19.0 14.5 – 23.5 Level 2 55.0 45.0 – 65.0 Calibrator and Control contain human source material. Each donor unit of serum in the preparation of these materials were tested and found negative for the Human Immunodeficiency Virus Antibody (HIV I/II Ab), Hepatitis B Surface Antigen (HBsAg), and Hepatitis C Virus Antibody (HCV). J. Substantial Equivalence Information: 1. Predicate device name(s): EUROIMMUN 25-OH Vitamin D ELISA 2. Predicate 510(k) number(s): k123660 4 3. Comparison with predicate: Assay: Similarities / Differences Item BioPlex® 2200 25-OH Vitamin D Kit Candidate Device EUROIMMUN 25-OH Vitamin D ELISA Predicate Device (k123660) Intended Use For the quantitative determination of 25- hydroxyvitamin D in human serum. Same Assay Type Quantitative Same Test Principle Competitive immunoassay Same Antibody Monoclonal Sheep antibody against 25 OH Vitamin D Same Signal Detection Fluorescence Same Unit of Measure ng/mL Same Assay Technology Automated multiplex flow competitive immunoassay Manually competitive immunoassay Conjugate Biotinylated 25- hydroxyvitamin D and phycoerythrin streptavidin Biotinylated 25- hydroxyvitamin D and Peroxidase-labeled streptavidin and substrate TMB Solid Phase Antibody-coated paramagnetic microbeads Antibody coated 96 microwell ELISA plate Measuring Range 6.5 ng/mL – 125.0 ng/mL 4.0 ng/mL – 120 ng/mL Sample Matrix Serum Serum or EDTA or Lithium heparin plasma Sample Size 10µL 20µL Open Pack Stability 60 days Not Applicable Reagent Storage On-board or in refrigerator at 2-8°C Not Applicable Sample Handling Automated Manually Instrumentation Bio-Rad BioPlex® 2200 System ELISA plate reader Measuring Wavelength 550-610 nm 450/620 nm 5 Calibrator: Similarities / Differences Item BioPlex® 2200 25-OH Vitamin D Calibrator Candidate Device EUROIMMUN 25-OH Vitamin D ELISA Calibrator Predicate Device Intended Use For the calibration of the Vitamin D reagent pack. Same Calibrator(s) and Calibration 6 calibrator levels (sold separately); 4-PL (parameter logistic) curve fit algorithm Same Calibrator Matrix 25% horse serum and depleted human serum with ProClin 950, sodium benzoate and BND Liquid in horse serum with preservatives Calibrator Open Storage at 2-8°C 30 days 3 months Calibration Frequency Every 30 days Every 96 well plate Controls: Similarities / Differences Item BioPlex® 2200 25-OH Vitamin D Control Candidate Device EUROIMMUN 25-OH Vitamin D ELISA Controls Predicate Device Intended Use Use as an assayed quality control to monitor the overall performance of the Vitamin D reagent. Same Storage Sore at 2-8°C until ready to use Same Matrix Human serum with ProClin 950, Sodium benzoate and BND Liquid in horse serum with preservatives K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A2: Evaluation of Precision Performance of Quantitative Measurement Methods CLSI EP6-A: Evaluation of Linearity of Quantitative Measurement Procedures CLSI EP07-A2: Interference Testing in Clinical Chemistry CLSI EP09-A2IR: Method comparison and Bias Estimation CLSI EP15-A2: User Verification of Performance for Precision and Trueness CLSI EP17-A2: Evaluation of Detection Capability for Clinical laboratory measurements 6 Procedure CLSI EP25-A: Evaluation of Stability of In-vitro diagnostic Reagents CLSI C28-A3c: Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory L. Test Principle: The BioPlex 2200 25-OH Vitamin D assay is a multiplex flow competitive immunoassay for the quantitative determination of 25-hydroxyvitamin D in human serum. The BioPlex 2200 System combines an aliquot of patient sample with the Vitamin D Predicate device name:

idK141114_s0_e2000

K141114.txt

applicant

Bio-Rad Laboratories

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k141114 B. Purpose for Submission: New Device C. Measurand: 25-hydroxyvitamin D [25(OH) Vitamin D] D. Type of Test: Quantitative multiplexed flow immunoassay E. Applicant: Bio-Rad Laboratories F. Proprietary and Established Names: BioPlex® 2200 25-OH Vitamin D Kit BioPlex® 2200 25-OH Vitamin D Calibrator Set BioPlex® 2200 25-OH Vitamin D Control Set G. Regulatory Information: Product Code Classification Regulation Section Panel MRG II 862.1825 Vitamin D Test System Chemistry (75) JIT II 862.1150 Calibrator Chemistry (75) JJX I, Reserved 862.1660 Quality Control Material (Assayed and Unassayed) Chemistry (75) 2 H. Intended Use: 1. Intended use(s): See indication for use below. 2. Indication(s) for use: The BioPlex 2200 25-OH Vitamin D kit is a flow competitive immunoassay intended for the quantitative determination of 25-hydroxyvitamin D in human serum. The BioPlex 2200 25- OH vitamin D assay is to be used to aid in the assessment of vitamin D sufficiency. The BioPlex 2200 25-OH Vitamin D kit is intended for use with the BioPlex 2200 System. The BioPlex 2200 25-OH Vitamin D Calibrator Set is intended for the calibration of the BioPlex 2200 25-OH Vitamin D reagent Pack. The BioPlex 2200 25-OH Vitamin D Control Set is intended for use as an assayed quality control to monitor the overall performance of the BioPlex 2200 system and corresponding BioPlex® 25-OH Vitamin D reagent pack in the clinical laboratory. The performance of the BioPlex 2200 25-OH Vitamin D Control Set has not been established with any other 25- hydroxyvitamin D assays. 3. Special conditions for use statement(s): For in vitro diagnostics For prescription use only 4. Special instrument requirements: BioPlex 2200 system I. Device Description: The BioPlex 2200 25-OH Vitamin D Kit consists of the following: 1. One 10mL vial of Bead Set containing dyed beads coated with anti-25-OH D antibody (sheep), an Internal Standard bead (ISB), and a Serum Verification bead (SVB) in buffer with protein stabilizers (bovine). ProClin 950 (<1.0%) and sodium azide (<0.1%) as preservatives. 2. One 10mL vial of Release Buffer containing 25-OH Vitamin D releasing reagents in citrate and trisodium citrate acid buffer at pH 4.1 and ProClin 950 (<1.0%) as preservative. 3. One 5mL vial of Conjugate 1 containing biotinylated 25-OH Vitamin D conjugate and biotinylated anti-human FXIII antibody conjugate (murine) in buffer with protein stabilizer (bovine). ProClin 950 (<1.0%) and 5-bromo-5-nitro-1, 3-dioxane (<0.1%) as preservatives 3 and chemical blockers. 4. One 5mL vial of Conjugate 2 containing phycoerythrin conjugated streptavidin (SA-PE) in buffer comprising protein stabilizers (bovine). ProClin 950 (<1.0%) and sodium azide (<0.1%) as preservatives, chemical blockers and detergent (Tween 20). BioPlex 2200 25-OH Vitamin D Calibrator set (sold separately) contains six 0.5 mL 25-OH Vitamin D vials. Calibrator level 1 contains 25% horse serum without 25-OH Vitamin D. The calibrator levels 2 to 6 are provided in a Vitamin D depleted human serum matrix supplemented with known concentration of 25-hydroxyvitamin D3. All calibrators contain ProClin 950 (<0.3%), sodium benzoate (<0.1%) and 5-bromo-5-nitro-1, 3-dioxane (<0.1%) as preservatives. Calibrator Set Target (ng/mL) Level 1 0.0 Level 2 10.0 Level 3 30.0 Level 4 75.0 Level 5 110.0 Level 6 165.0 BioPlex 2200 25-OH control set (sold separately) contains two 1.5 mL of Level 1 and two 1.5 mL of Level 2 control vials. Each vial contains 25-OH Vitamin D in human serum matrix. All controls contain ProClin 950 (<0.3%), sodium benzoate (<0.1%) and 5-bromo-5-nitro-1, 3- dioxane (<0.1%) as preservatives. Control Set Target (ng/mL) Range (ng/mL) Level 1 19.0 14.5 – 23.5 Level 2 55.0 45.0 – 65.0 Calibrator and Control contain human source material. Each donor unit of serum in the preparation of these materials were tested and found negative for the Human Immunodeficiency Virus Antibody (HIV I/II Ab), Hepatitis B Surface Antigen (HBsAg), and Hepatitis C Virus Antibody (HCV). J. Substantial Equivalence Information: 1. Predicate device name(s): EUROIMMUN 25-OH Vitamin D ELISA 2. Predicate 510(k) number(s): k123660 4 3. Comparison with predicate: Assay: Similarities / Differences Item BioPlex® 2200 25-OH Vitamin D Kit Candidate Device EUROIMMUN 25-OH Vitamin D ELISA Predicate Device (k123660) Intended Use For the quantitative determination of 25- hydroxyvitamin D in human serum. Same Assay Type Quantitative Same Test Principle Competitive immunoassay Same Antibody Monoclonal Sheep antibody against 25 OH Vitamin D Same Signal Detection Fluorescence Same Unit of Measure ng/mL Same Assay Technology Automated multiplex flow competitive immunoassay Manually competitive immunoassay Conjugate Biotinylated 25- hydroxyvitamin D and phycoerythrin streptavidin Biotinylated 25- hydroxyvitamin D and Peroxidase-labeled streptavidin and substrate TMB Solid Phase Antibody-coated paramagnetic microbeads Antibody coated 96 microwell ELISA plate Measuring Range 6.5 ng/mL – 125.0 ng/mL 4.0 ng/mL – 120 ng/mL Sample Matrix Serum Serum or EDTA or Lithium heparin plasma Sample Size 10µL 20µL Open Pack Stability 60 days Not Applicable Reagent Storage On-board or in refrigerator at 2-8°C Not Applicable Sample Handling Automated Manually Instrumentation Bio-Rad BioPlex® 2200 System ELISA plate reader Measuring Wavelength 550-610 nm 450/620 nm 5 Calibrator: Similarities / Differences Item BioPlex® 2200 25-OH Vitamin D Calibrator Candidate Device EUROIMMUN 25-OH Vitamin D ELISA Calibrator Predicate Device Intended Use For the calibration of the Vitamin D reagent pack. Same Calibrator(s) and Calibration 6 calibrator levels (sold separately); 4-PL (parameter logistic) curve fit algorithm Same Calibrator Matrix 25% horse serum and depleted human serum with ProClin 950, sodium benzoate and BND Liquid in horse serum with preservatives Calibrator Open Storage at 2-8°C 30 days 3 months Calibration Frequency Every 30 days Every 96 well plate Controls: Similarities / Differences Item BioPlex® 2200 25-OH Vitamin D Control Candidate Device EUROIMMUN 25-OH Vitamin D ELISA Controls Predicate Device Intended Use Use as an assayed quality control to monitor the overall performance of the Vitamin D reagent. Same Storage Sore at 2-8°C until ready to use Same Matrix Human serum with ProClin 950, Sodium benzoate and BND Liquid in horse serum with preservatives K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A2: Evaluation of Precision Performance of Quantitative Measurement Methods CLSI EP6-A: Evaluation of Linearity of Quantitative Measurement Procedures CLSI EP07-A2: Interference Testing in Clinical Chemistry CLSI EP09-A2IR: Method comparison and Bias Estimation CLSI EP15-A2: User Verification of Performance for Precision and Trueness CLSI EP17-A2: Evaluation of Detection Capability for Clinical laboratory measurements 6 Procedure CLSI EP25-A: Evaluation of Stability of In-vitro diagnostic Reagents CLSI C28-A3c: Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory L. Test Principle: The BioPlex 2200 25-OH Vitamin D assay is a multiplex flow competitive immunoassay for the quantitative determination of 25-hydroxyvitamin D in human serum. The BioPlex 2200 System combines an aliquot of patient sample with the Vitamin D Applicant:

idK141114_s4000_e6000

K141114.txt

proposed labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

maximum levels tested are shown in the table below: 10 Substances Highest Concentration of substance tested which demonstrated no significant interference. Hemoglobin 150 mg/dL Bilirubin (conjugated) 20 mg/dL Bilirubin (unconjugated) 30 mg/dL Triglycerides 400 mg/dL Total Protein 12 g/dL Cholesterol 500 mg/dL Uric Acid 20 mg/dL HAMA 100 ng/mL Rheumatoid Factor 350 IU/mL Ascorbic Acid 3 mg/dL The sponsor has the following limitations in their labeling: “Hemoglobin > 150 mg/dL may interfere and cause increased Vitamin D results. Do not use visibly hemolyzed samples.” Cross-Reactivity: The study was conducted using 2 serum pools at 25-hydroxyvitamin D concentrations of 20 ng/mL and 35 ng/mL. Nine cross reactants at levels listed below were spiked into the serum pools. The spiked and non-spiked samples were then evaluated in replicates of five to calculate the cross reactivity as shown below: % cross reactivity = [(mean recovery of test samples in ng/mL) – (mean recovery of control sample in ng/mL) / (concentration of cross reactant in ng/mL)] * 100 Cross Reactant Spiked Concentration (ng/mL) % Cross Reactivity 25-hydroxyvitamin D2 30 103% 25-hydroxyvitamin D3 30 97% Vitamin D2 1000 0.2% Vitamin D3 1000 0.0% 1,25-dihydroxyvitamin D2 30 >100% 1,25-dihydroxyvitamin D3 30 79% 3-epi 25-hydroxyvitamin D3 30 59% 24,25-dihydroxyvitamin D3 20 9% Paricalcitol (Zemplar) 24 >100% The sponsor has the following limitations in their labeling: “Paricalcitol (Zemplar) has been found to cross-react and interfere with the BioPlex® 2200 25- OH Vitamin D assay.” 11 f. Assay cut-off: Not Applicable 2. Comparison studies: a. Method comparison with predicate device: A method comparison study using 204 human serum samples was performed to compare the candidate device BioPlex 2200 25-OH Vitamin D to the predicate device EUROIMMUN 25-OH Vitamin D ELISA. 185 samples were unaltered and 19 samples were spiked with 25-hydroxyvitamin D3. A total of 196 human serum samples with 25- OH Vitamin D values ranging from 6.6 ng/mL to 124.9 ng/mL were analyzed. There were eight samples with values lower or higher than the measuring range of the predicate method that were excluded in the data analysis. The samples were assayed in singlicate using one reagent lot of the candidate and predicate device. Deming regression was used for the regression analysis and the results are summarized below: N Slope (95% CI) Intercept (95% CI) Correlation Coefficient (r) (95% CI) Sample Range Tested (ng/mL) 196 1.0039 (0.9365 to 1.0712) -0.2256 (-2.4121 to 1.9608) 0.9553 (0.9412 to 0.9661) BioPlex: 6.6 – 124.9 b. Matrix comparison: Not Applicable, only serum is recommended 3. Clinical studies: a. Clinical Sensitivity: Not Applicable b. Clinical specificity: Not Applicable c. Other clinical supportive data (when a. and b. are not applicable): Not Applicable 4. Clinical cut-off: Not Applicable 12 5. Expected values/Reference range: The study was performed in accordance with CLSI C28-A3c guideline. Two hundred and eighty-seven samples from apparently healthy donors including 160 males and 127 female were collected from three regions (North, Central, and South) in the US and in three seasons (spring, summer and winter), including Caucasians and African American subjects. The 287 samples from apparently healthy donors met the following inclusion / exclusion criteria as follows and tested with the BioPlex 25-OH Vitamin D kit in singlicate. *One sample <6.5 ng/ml was excluded from the data analysis. · Age from 21 to 90 · 50% female and 50% male · 20% from Northern, 20% from Central, and 60% from Southern region · 40% collected in Summer and 60% in Winter · At least 30% dark and 30% light skin · 90% not taking Vitamin D supplements and <30% of those taking Vitamin D supplements at or more than 1000 IU, but less than 2000 IU · Normal TSH, PTH, and Total Calcium · No family history of parathyroid or calcium regulatory disease. In addition, no personal history of kidney disease, GI disease, and no bariatric surgery The observed median, mean, and ranges between 2.5th to 97.5th percentile are summarized below: N Mean Median 2.5th to 97.5th Percentile 286 29.7 ng/mL 27.7 ng/mL 12.7 – 65.7 ng/mL Each laboratory should establish its own reference range pertinent to their specific populations. N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK141114_s4000_e6000

K141114.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

and the maximum levels tested are shown in the table below: 10 Substances Highest Concentration of substance tested which demonstrated no significant interference. Hemoglobin 150 mg/dL Bilirubin (conjugated) 20 mg/dL Bilirubin (unconjugated) 30 mg/dL Triglycerides 400 mg/dL Total Protein 12 g/dL Cholesterol 500 mg/dL Uric Acid 20 mg/dL HAMA 100 ng/mL Rheumatoid Factor 350 IU/mL Ascorbic Acid 3 mg/dL The sponsor has the following limitations in their labeling: “Hemoglobin > 150 mg/dL may interfere and cause increased Vitamin D results. Do not use visibly hemolyzed samples.” Cross-Reactivity: The study was conducted using 2 serum pools at 25-hydroxyvitamin D concentrations of 20 ng/mL and 35 ng/mL. Nine cross reactants at levels listed below were spiked into the serum pools. The spiked and non-spiked samples were then evaluated in replicates of five to calculate the cross reactivity as shown below: % cross reactivity = [(mean recovery of test samples in ng/mL) – (mean recovery of control sample in ng/mL) / (concentration of cross reactant in ng/mL)] * 100 Cross Reactant Spiked Concentration (ng/mL) % Cross Reactivity 25-hydroxyvitamin D2 30 103% 25-hydroxyvitamin D3 30 97% Vitamin D2 1000 0.2% Vitamin D3 1000 0.0% 1,25-dihydroxyvitamin D2 30 >100% 1,25-dihydroxyvitamin D3 30 79% 3-epi 25-hydroxyvitamin D3 30 59% 24,25-dihydroxyvitamin D3 20 9% Paricalcitol (Zemplar) 24 >100% The sponsor has the following limitations in their labeling: “Paricalcitol (Zemplar) has been found to cross-react and interfere with the BioPlex® 2200 25- OH Vitamin D assay.” 11 f. Assay cut-off: Not Applicable 2. Comparison studies: a. Method comparison with predicate device: A method comparison study using 204 human serum samples was performed to compare the candidate device BioPlex 2200 25-OH Vitamin D to the predicate device EUROIMMUN 25-OH Vitamin D ELISA. 185 samples were unaltered and 19 samples were spiked with 25-hydroxyvitamin D3. A total of 196 human serum samples with 25- OH Vitamin D values ranging from 6.6 ng/mL to 124.9 ng/mL were analyzed. There were eight samples with values lower or higher than the measuring range of the predicate method that were excluded in the data analysis. The samples were assayed in singlicate using one reagent lot of the candidate and predicate device. Deming regression was used for the regression analysis and the results are summarized below: N Slope (95% CI) Intercept (95% CI) Correlation Coefficient (r) (95% CI) Sample Range Tested (ng/mL) 196 1.0039 (0.9365 to 1.0712) -0.2256 (-2.4121 to 1.9608) 0.9553 (0.9412 to 0.9661) BioPlex: 6.6 – 124.9 b. Matrix comparison: Not Applicable, only serum is recommended 3. Clinical studies: a. Clinical Sensitivity: Not Applicable b. Clinical specificity: Not Applicable c. Other clinical supportive data (when a. and b. are not applicable): Not Applicable 4. Clinical cut-off: Not Applicable 12 5. Expected values/Reference range: The study was performed in accordance with CLSI C28-A3c guideline. Two hundred and eighty-seven samples from apparently healthy donors including 160 males and 127 female were collected from three regions (North, Central, and South) in the US and in three seasons (spring, summer and winter), including Caucasians and African American subjects. The 287 samples from apparently healthy donors met the following inclusion / exclusion criteria as follows and tested with the BioPlex 25-OH Vitamin D kit in singlicate. *One sample <6.5 ng/ml was excluded from the data analysis. · Age from 21 to 90 · 50% female and 50% male · 20% from Northern, 20% from Central, and 60% from Southern region · 40% collected in Summer and 60% in Winter · At least 30% dark and 30% light skin · 90% not taking Vitamin D supplements and <30% of those taking Vitamin D supplements at or more than 1000 IU, but less than 2000 IU · Normal TSH, PTH, and Total Calcium · No family history of parathyroid or calcium regulatory disease. In addition, no personal history of kidney disease, GI disease, and no bariatric surgery The observed median, mean, and ranges between 2.5th to 97.5th percentile are summarized below: N Mean Median 2.5th to 97.5th Percentile 286 29.7 ng/mL 27.7 ng/mL 12.7 – 65.7 ng/mL Each laboratory should establish its own reference range pertinent to their specific populations. N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK172287_s0_e2000

K172287.txt

purpose for submission

Expansion of the Indications for Use.

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172287 B. Purpose for Submission: Expansion of the Indications for Use. C. Measurand: Janus Tyrosine Kinase 2 (JAK2) gene mutation G1849T (V617F) D. Type of Test: Allele-specific, quantitative, polymerase chain reaction (PCR) using an amplification refractory mutation system (ARMS) E. Applicant: QIAGEN F. Proprietary and Established Names: Trade Name: QIAGEN ipsogen® JAK2 RGQ PCR Kit G. Regulatory Information: 1. Regulation section: 21 CFR 866.6070 2. Classification: Class II 3. Product code: PSU 4. Panel: 88 – Pathology 2 H. Intended Use: 1. Intended use(s): The ipsogen JAK2 RGQ PCR Kit is a qualitative in vitro diagnostic test for the detection of the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood. The ipsogen JAK2 RGQ PCR Kit is a real time PCR test performed on the QIAGEN Rotor-Gene Q MDx instrument. The test is intended for use as an adjunct to evaluation of suspected myeloproliferative neoplasms, in conjunction with other clinicopathological factors. This test does not detect less common JAK2 mutations associated with Myeloproliferative Neoplasms including mutations in exon 12 and is not intended for stand-alone diagnosis of Myeloproliferative Neoplasm. 2. Indication(s) for use: Same as Intended use 3. Special conditions for use statement(s): For prescription use only. For in vitro diagnostic use only. 4. Special instrument requirements: QIAGEN Rotor-Gene Q MDx platform using Rotor-Gene AssayManager software version 2.1. I. Device Description: The ipsogen JAK2 RGQ PCR Kit employs allele-specific, quantitative, polymerase chain reaction (PCR) using an amplification refractory mutation system (ARMS). DNA is extracted from K2-EDTA anti-coagulated whole blood using the QIAsymphony instrument (QSSP) and QIAsymphony® DSP DNA Mini Kit. Purified DNA must be diluted to 10 ng/μl using the TE buffer provided in the JAK2 Kit. Each PCR reaction of the Rotor-Gene Q MDx is optimized for 50 ng of purified gDNA diluted in a final volume of 5 μl. A total of 100 ng per tested sample (50 ng for each reaction) is needed. The Kit contains sufficient reagents to test 24 reactions. Table 1 describes the components of the ipsogen JAK2 RGQ PCR Kit. Table 1. Components of the ipsogen JAK2 RGQ Assay Item Description Use JAK2 Mutant Control 100% V617F allele Assay Positive Control JAK2 WT Control 100% WT allele Assay Negative Control 3 JAK2 MT Quant Standard 1 5x101 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 2 5x102 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 3 5x103 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 4 5x104 V617F copies in 5 µL Mutation Standard Curve JAK2 WT Quant Standard 1 5x101 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 2 5x102 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 3 5x103 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 4 5x104 wild-type copies in 5 µL Wild-type Standard Curve JAK2 MT Reaction Mix Primers, probes, and necessary components for the mutation- specific and internal control PCR reaction Mutation Specific PCR Reaction JAK2 WT Reaction Mix Primers, probes, and necessary components for the wild-type and internal control PCR reaction Wild-type Specific PCR Reaction Taq DNA Polymerase PCR reaction enzyme Mutation and Wild-type PCR TE buffer Tris-EDTA Sample Dilution Nuclease-Free Water Water No Template Control Rotor-Gene AssayManager JAK2 plug-in JAK2 Assay-specific software Results Acquisition and Analysis JAK2 Assay Profile JAK2 Assay-specific software parameters Results Acquisition and Analysis Additional materials required but not provided with the JAK2 RGQ PCR Kit:  QIAsymphony® DSP DNA Mini Kit  QIAsymphony Sample Preparation instrument and accessories  QIAsymphony software version 4.0 that operates the QIAsymphony instrument  QIAGEN Rotor-Gene Q MDx Platform  Rotor-Gene AssayManager® software version 2.1 that operates the Rotor Gene Q MDx J. Substantial Equivalence Information: 4 1. Predicate device name(s): ipsogen® JAK2 RGQ PCR Kit 2. Predicate 510(k) number(s): DEN160028 3. Comparison with predicate: Characteristic Device Predicate Similarities Intended Use The ipsogen JAK2 RGQ PCR Kit is a qualitative in vitro diagnostic test for the detection of the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood. The ipsogen JAK2 RGQ PCR Kit is a real-time PCR test performed on the QIAGEN Rotor-Gene Q MDx instrument. Same Specimen Type Genomic DNA extracted from EDTA whole blood Same Assay Targets JAK2 V617F/G1849T allele Same Genomic DNA Extraction DNA should be extracted using the QIAsymphony SP instrument in combination with the QIAsymphony DSP DNA Mini Kit Same Amplification and Detection Technology Real-time PCR DNA amplification Same Amplification and Detection Instrument System Assay uses the Rotor-Gene Q MDx Same Assay Controls Positive Control, Negative Control and Internal Control included in the kit Same Characteristic Device Predicate Differences Indications for Use The test is intended for use as an adjunct to evaluation of suspected Myeloproliferative The test is intended for use as an adjunct to evaluation of suspected Polycythemia Vera, 5 Neoplasms, in conjunction with other clinicopathological factors. This test does not detect less common JAK2 mutations associated with Myeloproliferative Neoplasms including mutations in exon 12 and is not intended for stand- alone diagnosis of Myeloproliferative Neoplasms. in conjunction with other clinicopathological factors. This test does not detect less common mutations associated with Polycythemia Vera including mutations in exon 12 and is not intended for stand- alone diagnosis of Polycythemia Vera. Amplification and Detection Instrument System Software Rotor-Gene AssayManager® software version 2.1 Rotor-Gene AssayManager® software version 1.04 K. Standard/Guidance Document Referenced (if applicable): CLSI EP25-A: Evaluation of stability of in vitro diagnostic reagents L. Test Principle: Refer to DEN160028. M. Performance Characteristics (if/when applicable): 1. Analytical performance: Overall analytical performance of the QIAGEN ipsogen® JAK2 RGQ PCR Kit was previously demonstrated using specimens from patients with suspected polycythemia vera (PV). Refer to decision summary for DEN160028 available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/denovo.cfm?ID=DEN160028 for a description of the following analytical performance studies:  Repeatability/Reproducibility/Lot-to-Lot  Linearity/assay reportable range and DNA input  Traceability/Calibration  Detection limit (Limit of Blank and Limit o Detection)  Analytical specificity (including Interfering Substances)  Reagent Stability  Extracted DNA stability Analytical performance studies provided to support expansion of the indications for use claim to include additional JAK2 positive myeloproliferative neoplasms included accuracy study using specimens from essential thrombocytopenia (ET) and primary 6 myelofibrosis (PMF) patients, and specimen stability study. The studies are described below. a. Accuracy study – Comparison to a Reference Method A study was conducted to demonstrate the accuracy for detecting JAK2 V617F/G1849T allele in clinical specimens from patients representing the target population. Because the original study included suspected MPNs, specimens in this study were selected based on diagnosis which included both JAK2 positive and negative specimens. A total of 197 specimens (98 ET and 99 PMF) was tested with the ipsogen JAK2 RGQ PCR Kit and compared with validated bi-directional Sanger Sequencing (BDS). All specimens were concordant except for 9 ET and 5 PMF samples, all of which were JAK2 V617F positive with the ipsogen JAK2 RGQ PCR Kit and negative with BDS. Concordance between the two methods is shown Purpose for submission:

idK172287_s0_e2000

K172287.txt

measurand

Janus Tyrosine Kinase 2 (JAK2) gene mutation G1849T (V617F)

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172287 B. Purpose for Submission: Expansion of the Indications for Use. C. Measurand: Janus Tyrosine Kinase 2 (JAK2) gene mutation G1849T (V617F) D. Type of Test: Allele-specific, quantitative, polymerase chain reaction (PCR) using an amplification refractory mutation system (ARMS) E. Applicant: QIAGEN F. Proprietary and Established Names: Trade Name: QIAGEN ipsogen® JAK2 RGQ PCR Kit G. Regulatory Information: 1. Regulation section: 21 CFR 866.6070 2. Classification: Class II 3. Product code: PSU 4. Panel: 88 – Pathology 2 H. Intended Use: 1. Intended use(s): The ipsogen JAK2 RGQ PCR Kit is a qualitative in vitro diagnostic test for the detection of the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood. The ipsogen JAK2 RGQ PCR Kit is a real time PCR test performed on the QIAGEN Rotor-Gene Q MDx instrument. The test is intended for use as an adjunct to evaluation of suspected myeloproliferative neoplasms, in conjunction with other clinicopathological factors. This test does not detect less common JAK2 mutations associated with Myeloproliferative Neoplasms including mutations in exon 12 and is not intended for stand-alone diagnosis of Myeloproliferative Neoplasm. 2. Indication(s) for use: Same as Intended use 3. Special conditions for use statement(s): For prescription use only. For in vitro diagnostic use only. 4. Special instrument requirements: QIAGEN Rotor-Gene Q MDx platform using Rotor-Gene AssayManager software version 2.1. I. Device Description: The ipsogen JAK2 RGQ PCR Kit employs allele-specific, quantitative, polymerase chain reaction (PCR) using an amplification refractory mutation system (ARMS). DNA is extracted from K2-EDTA anti-coagulated whole blood using the QIAsymphony instrument (QSSP) and QIAsymphony® DSP DNA Mini Kit. Purified DNA must be diluted to 10 ng/μl using the TE buffer provided in the JAK2 Kit. Each PCR reaction of the Rotor-Gene Q MDx is optimized for 50 ng of purified gDNA diluted in a final volume of 5 μl. A total of 100 ng per tested sample (50 ng for each reaction) is needed. The Kit contains sufficient reagents to test 24 reactions. Table 1 describes the components of the ipsogen JAK2 RGQ PCR Kit. Table 1. Components of the ipsogen JAK2 RGQ Assay Item Description Use JAK2 Mutant Control 100% V617F allele Assay Positive Control JAK2 WT Control 100% WT allele Assay Negative Control 3 JAK2 MT Quant Standard 1 5x101 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 2 5x102 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 3 5x103 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 4 5x104 V617F copies in 5 µL Mutation Standard Curve JAK2 WT Quant Standard 1 5x101 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 2 5x102 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 3 5x103 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 4 5x104 wild-type copies in 5 µL Wild-type Standard Curve JAK2 MT Reaction Mix Primers, probes, and necessary components for the mutation- specific and internal control PCR reaction Mutation Specific PCR Reaction JAK2 WT Reaction Mix Primers, probes, and necessary components for the wild-type and internal control PCR reaction Wild-type Specific PCR Reaction Taq DNA Polymerase PCR reaction enzyme Mutation and Wild-type PCR TE buffer Tris-EDTA Sample Dilution Nuclease-Free Water Water No Template Control Rotor-Gene AssayManager JAK2 plug-in JAK2 Assay-specific software Results Acquisition and Analysis JAK2 Assay Profile JAK2 Assay-specific software parameters Results Acquisition and Analysis Additional materials required but not provided with the JAK2 RGQ PCR Kit:  QIAsymphony® DSP DNA Mini Kit  QIAsymphony Sample Preparation instrument and accessories  QIAsymphony software version 4.0 that operates the QIAsymphony instrument  QIAGEN Rotor-Gene Q MDx Platform  Rotor-Gene AssayManager® software version 2.1 that operates the Rotor Gene Q MDx J. Substantial Equivalence Information: 4 1. Predicate device name(s): ipsogen® JAK2 RGQ PCR Kit 2. Predicate 510(k) number(s): DEN160028 3. Comparison with predicate: Characteristic Device Predicate Similarities Intended Use The ipsogen JAK2 RGQ PCR Kit is a qualitative in vitro diagnostic test for the detection of the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood. The ipsogen JAK2 RGQ PCR Kit is a real-time PCR test performed on the QIAGEN Rotor-Gene Q MDx instrument. Same Specimen Type Genomic DNA extracted from EDTA whole blood Same Assay Targets JAK2 V617F/G1849T allele Same Genomic DNA Extraction DNA should be extracted using the QIAsymphony SP instrument in combination with the QIAsymphony DSP DNA Mini Kit Same Amplification and Detection Technology Real-time PCR DNA amplification Same Amplification and Detection Instrument System Assay uses the Rotor-Gene Q MDx Same Assay Controls Positive Control, Negative Control and Internal Control included in the kit Same Characteristic Device Predicate Differences Indications for Use The test is intended for use as an adjunct to evaluation of suspected Myeloproliferative The test is intended for use as an adjunct to evaluation of suspected Polycythemia Vera, 5 Neoplasms, in conjunction with other clinicopathological factors. This test does not detect less common JAK2 mutations associated with Myeloproliferative Neoplasms including mutations in exon 12 and is not intended for stand- alone diagnosis of Myeloproliferative Neoplasms. in conjunction with other clinicopathological factors. This test does not detect less common mutations associated with Polycythemia Vera including mutations in exon 12 and is not intended for stand- alone diagnosis of Polycythemia Vera. Amplification and Detection Instrument System Software Rotor-Gene AssayManager® software version 2.1 Rotor-Gene AssayManager® software version 1.04 K. Standard/Guidance Document Referenced (if applicable): CLSI EP25-A: Evaluation of stability of in vitro diagnostic reagents L. Test Principle: Refer to DEN160028. M. Performance Characteristics (if/when applicable): 1. Analytical performance: Overall analytical performance of the QIAGEN ipsogen® JAK2 RGQ PCR Kit was previously demonstrated using specimens from patients with suspected polycythemia vera (PV). Refer to decision summary for DEN160028 available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/denovo.cfm?ID=DEN160028 for a description of the following analytical performance studies:  Repeatability/Reproducibility/Lot-to-Lot  Linearity/assay reportable range and DNA input  Traceability/Calibration  Detection limit (Limit of Blank and Limit o Detection)  Analytical specificity (including Interfering Substances)  Reagent Stability  Extracted DNA stability Analytical performance studies provided to support expansion of the indications for use claim to include additional JAK2 positive myeloproliferative neoplasms included accuracy study using specimens from essential thrombocytopenia (ET) and primary 6 myelofibrosis (PMF) patients, and specimen stability study. The studies are described below. a. Accuracy study – Comparison to a Reference Method A study was conducted to demonstrate the accuracy for detecting JAK2 V617F/G1849T allele in clinical specimens from patients representing the target population. Because the original study included suspected MPNs, specimens in this study were selected based on diagnosis which included both JAK2 positive and negative specimens. A total of 197 specimens (98 ET and 99 PMF) was tested with the ipsogen JAK2 RGQ PCR Kit and compared with validated bi-directional Sanger Sequencing (BDS). All specimens were concordant except for 9 ET and 5 PMF samples, all of which were JAK2 V617F positive with the ipsogen JAK2 RGQ PCR Kit and negative with BDS. Concordance between the two methods is shown Measurand:

idK172287_s0_e2000

K172287.txt

type of test

Allele-specific, quantitative, polymerase chain reaction (PCR) using an amplification refractory mutation system (ARMS)

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172287 B. Purpose for Submission: Expansion of the Indications for Use. C. Measurand: Janus Tyrosine Kinase 2 (JAK2) gene mutation G1849T (V617F) D. Type of Test: Allele-specific, quantitative, polymerase chain reaction (PCR) using an amplification refractory mutation system (ARMS) E. Applicant: QIAGEN F. Proprietary and Established Names: Trade Name: QIAGEN ipsogen® JAK2 RGQ PCR Kit G. Regulatory Information: 1. Regulation section: 21 CFR 866.6070 2. Classification: Class II 3. Product code: PSU 4. Panel: 88 – Pathology 2 H. Intended Use: 1. Intended use(s): The ipsogen JAK2 RGQ PCR Kit is a qualitative in vitro diagnostic test for the detection of the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood. The ipsogen JAK2 RGQ PCR Kit is a real time PCR test performed on the QIAGEN Rotor-Gene Q MDx instrument. The test is intended for use as an adjunct to evaluation of suspected myeloproliferative neoplasms, in conjunction with other clinicopathological factors. This test does not detect less common JAK2 mutations associated with Myeloproliferative Neoplasms including mutations in exon 12 and is not intended for stand-alone diagnosis of Myeloproliferative Neoplasm. 2. Indication(s) for use: Same as Intended use 3. Special conditions for use statement(s): For prescription use only. For in vitro diagnostic use only. 4. Special instrument requirements: QIAGEN Rotor-Gene Q MDx platform using Rotor-Gene AssayManager software version 2.1. I. Device Description: The ipsogen JAK2 RGQ PCR Kit employs allele-specific, quantitative, polymerase chain reaction (PCR) using an amplification refractory mutation system (ARMS). DNA is extracted from K2-EDTA anti-coagulated whole blood using the QIAsymphony instrument (QSSP) and QIAsymphony® DSP DNA Mini Kit. Purified DNA must be diluted to 10 ng/μl using the TE buffer provided in the JAK2 Kit. Each PCR reaction of the Rotor-Gene Q MDx is optimized for 50 ng of purified gDNA diluted in a final volume of 5 μl. A total of 100 ng per tested sample (50 ng for each reaction) is needed. The Kit contains sufficient reagents to test 24 reactions. Table 1 describes the components of the ipsogen JAK2 RGQ PCR Kit. Table 1. Components of the ipsogen JAK2 RGQ Assay Item Description Use JAK2 Mutant Control 100% V617F allele Assay Positive Control JAK2 WT Control 100% WT allele Assay Negative Control 3 JAK2 MT Quant Standard 1 5x101 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 2 5x102 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 3 5x103 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 4 5x104 V617F copies in 5 µL Mutation Standard Curve JAK2 WT Quant Standard 1 5x101 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 2 5x102 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 3 5x103 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 4 5x104 wild-type copies in 5 µL Wild-type Standard Curve JAK2 MT Reaction Mix Primers, probes, and necessary components for the mutation- specific and internal control PCR reaction Mutation Specific PCR Reaction JAK2 WT Reaction Mix Primers, probes, and necessary components for the wild-type and internal control PCR reaction Wild-type Specific PCR Reaction Taq DNA Polymerase PCR reaction enzyme Mutation and Wild-type PCR TE buffer Tris-EDTA Sample Dilution Nuclease-Free Water Water No Template Control Rotor-Gene AssayManager JAK2 plug-in JAK2 Assay-specific software Results Acquisition and Analysis JAK2 Assay Profile JAK2 Assay-specific software parameters Results Acquisition and Analysis Additional materials required but not provided with the JAK2 RGQ PCR Kit:  QIAsymphony® DSP DNA Mini Kit  QIAsymphony Sample Preparation instrument and accessories  QIAsymphony software version 4.0 that operates the QIAsymphony instrument  QIAGEN Rotor-Gene Q MDx Platform  Rotor-Gene AssayManager® software version 2.1 that operates the Rotor Gene Q MDx J. Substantial Equivalence Information: 4 1. Predicate device name(s): ipsogen® JAK2 RGQ PCR Kit 2. Predicate 510(k) number(s): DEN160028 3. Comparison with predicate: Characteristic Device Predicate Similarities Intended Use The ipsogen JAK2 RGQ PCR Kit is a qualitative in vitro diagnostic test for the detection of the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood. The ipsogen JAK2 RGQ PCR Kit is a real-time PCR test performed on the QIAGEN Rotor-Gene Q MDx instrument. Same Specimen Type Genomic DNA extracted from EDTA whole blood Same Assay Targets JAK2 V617F/G1849T allele Same Genomic DNA Extraction DNA should be extracted using the QIAsymphony SP instrument in combination with the QIAsymphony DSP DNA Mini Kit Same Amplification and Detection Technology Real-time PCR DNA amplification Same Amplification and Detection Instrument System Assay uses the Rotor-Gene Q MDx Same Assay Controls Positive Control, Negative Control and Internal Control included in the kit Same Characteristic Device Predicate Differences Indications for Use The test is intended for use as an adjunct to evaluation of suspected Myeloproliferative The test is intended for use as an adjunct to evaluation of suspected Polycythemia Vera, 5 Neoplasms, in conjunction with other clinicopathological factors. This test does not detect less common JAK2 mutations associated with Myeloproliferative Neoplasms including mutations in exon 12 and is not intended for stand- alone diagnosis of Myeloproliferative Neoplasms. in conjunction with other clinicopathological factors. This test does not detect less common mutations associated with Polycythemia Vera including mutations in exon 12 and is not intended for stand- alone diagnosis of Polycythemia Vera. Amplification and Detection Instrument System Software Rotor-Gene AssayManager® software version 2.1 Rotor-Gene AssayManager® software version 1.04 K. Standard/Guidance Document Referenced (if applicable): CLSI EP25-A: Evaluation of stability of in vitro diagnostic reagents L. Test Principle: Refer to DEN160028. M. Performance Characteristics (if/when applicable): 1. Analytical performance: Overall analytical performance of the QIAGEN ipsogen® JAK2 RGQ PCR Kit was previously demonstrated using specimens from patients with suspected polycythemia vera (PV). Refer to decision summary for DEN160028 available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/denovo.cfm?ID=DEN160028 for a description of the following analytical performance studies:  Repeatability/Reproducibility/Lot-to-Lot  Linearity/assay reportable range and DNA input  Traceability/Calibration  Detection limit (Limit of Blank and Limit o Detection)  Analytical specificity (including Interfering Substances)  Reagent Stability  Extracted DNA stability Analytical performance studies provided to support expansion of the indications for use claim to include additional JAK2 positive myeloproliferative neoplasms included accuracy study using specimens from essential thrombocytopenia (ET) and primary 6 myelofibrosis (PMF) patients, and specimen stability study. The studies are described below. a. Accuracy study – Comparison to a Reference Method A study was conducted to demonstrate the accuracy for detecting JAK2 V617F/G1849T allele in clinical specimens from patients representing the target population. Because the original study included suspected MPNs, specimens in this study were selected based on diagnosis which included both JAK2 positive and negative specimens. A total of 197 specimens (98 ET and 99 PMF) was tested with the ipsogen JAK2 RGQ PCR Kit and compared with validated bi-directional Sanger Sequencing (BDS). All specimens were concordant except for 9 ET and 5 PMF samples, all of which were JAK2 V617F positive with the ipsogen JAK2 RGQ PCR Kit and negative with BDS. Concordance between the two methods is shown Type of test:

idK172287_s0_e2000

K172287.txt

classification

Class II

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172287 B. Purpose for Submission: Expansion of the Indications for Use. C. Measurand: Janus Tyrosine Kinase 2 (JAK2) gene mutation G1849T (V617F) D. Type of Test: Allele-specific, quantitative, polymerase chain reaction (PCR) using an amplification refractory mutation system (ARMS) E. Applicant: QIAGEN F. Proprietary and Established Names: Trade Name: QIAGEN ipsogen® JAK2 RGQ PCR Kit G. Regulatory Information: 1. Regulation section: 21 CFR 866.6070 2. Classification: Class II 3. Product code: PSU 4. Panel: 88 – Pathology 2 H. Intended Use: 1. Intended use(s): The ipsogen JAK2 RGQ PCR Kit is a qualitative in vitro diagnostic test for the detection of the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood. The ipsogen JAK2 RGQ PCR Kit is a real time PCR test performed on the QIAGEN Rotor-Gene Q MDx instrument. The test is intended for use as an adjunct to evaluation of suspected myeloproliferative neoplasms, in conjunction with other clinicopathological factors. This test does not detect less common JAK2 mutations associated with Myeloproliferative Neoplasms including mutations in exon 12 and is not intended for stand-alone diagnosis of Myeloproliferative Neoplasm. 2. Indication(s) for use: Same as Intended use 3. Special conditions for use statement(s): For prescription use only. For in vitro diagnostic use only. 4. Special instrument requirements: QIAGEN Rotor-Gene Q MDx platform using Rotor-Gene AssayManager software version 2.1. I. Device Description: The ipsogen JAK2 RGQ PCR Kit employs allele-specific, quantitative, polymerase chain reaction (PCR) using an amplification refractory mutation system (ARMS). DNA is extracted from K2-EDTA anti-coagulated whole blood using the QIAsymphony instrument (QSSP) and QIAsymphony® DSP DNA Mini Kit. Purified DNA must be diluted to 10 ng/μl using the TE buffer provided in the JAK2 Kit. Each PCR reaction of the Rotor-Gene Q MDx is optimized for 50 ng of purified gDNA diluted in a final volume of 5 μl. A total of 100 ng per tested sample (50 ng for each reaction) is needed. The Kit contains sufficient reagents to test 24 reactions. Table 1 describes the components of the ipsogen JAK2 RGQ PCR Kit. Table 1. Components of the ipsogen JAK2 RGQ Assay Item Description Use JAK2 Mutant Control 100% V617F allele Assay Positive Control JAK2 WT Control 100% WT allele Assay Negative Control 3 JAK2 MT Quant Standard 1 5x101 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 2 5x102 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 3 5x103 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 4 5x104 V617F copies in 5 µL Mutation Standard Curve JAK2 WT Quant Standard 1 5x101 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 2 5x102 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 3 5x103 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 4 5x104 wild-type copies in 5 µL Wild-type Standard Curve JAK2 MT Reaction Mix Primers, probes, and necessary components for the mutation- specific and internal control PCR reaction Mutation Specific PCR Reaction JAK2 WT Reaction Mix Primers, probes, and necessary components for the wild-type and internal control PCR reaction Wild-type Specific PCR Reaction Taq DNA Polymerase PCR reaction enzyme Mutation and Wild-type PCR TE buffer Tris-EDTA Sample Dilution Nuclease-Free Water Water No Template Control Rotor-Gene AssayManager JAK2 plug-in JAK2 Assay-specific software Results Acquisition and Analysis JAK2 Assay Profile JAK2 Assay-specific software parameters Results Acquisition and Analysis Additional materials required but not provided with the JAK2 RGQ PCR Kit:  QIAsymphony® DSP DNA Mini Kit  QIAsymphony Sample Preparation instrument and accessories  QIAsymphony software version 4.0 that operates the QIAsymphony instrument  QIAGEN Rotor-Gene Q MDx Platform  Rotor-Gene AssayManager® software version 2.1 that operates the Rotor Gene Q MDx J. Substantial Equivalence Information: 4 1. Predicate device name(s): ipsogen® JAK2 RGQ PCR Kit 2. Predicate 510(k) number(s): DEN160028 3. Comparison with predicate: Characteristic Device Predicate Similarities Intended Use The ipsogen JAK2 RGQ PCR Kit is a qualitative in vitro diagnostic test for the detection of the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood. The ipsogen JAK2 RGQ PCR Kit is a real-time PCR test performed on the QIAGEN Rotor-Gene Q MDx instrument. Same Specimen Type Genomic DNA extracted from EDTA whole blood Same Assay Targets JAK2 V617F/G1849T allele Same Genomic DNA Extraction DNA should be extracted using the QIAsymphony SP instrument in combination with the QIAsymphony DSP DNA Mini Kit Same Amplification and Detection Technology Real-time PCR DNA amplification Same Amplification and Detection Instrument System Assay uses the Rotor-Gene Q MDx Same Assay Controls Positive Control, Negative Control and Internal Control included in the kit Same Characteristic Device Predicate Differences Indications for Use The test is intended for use as an adjunct to evaluation of suspected Myeloproliferative The test is intended for use as an adjunct to evaluation of suspected Polycythemia Vera, 5 Neoplasms, in conjunction with other clinicopathological factors. This test does not detect less common JAK2 mutations associated with Myeloproliferative Neoplasms including mutations in exon 12 and is not intended for stand- alone diagnosis of Myeloproliferative Neoplasms. in conjunction with other clinicopathological factors. This test does not detect less common mutations associated with Polycythemia Vera including mutations in exon 12 and is not intended for stand- alone diagnosis of Polycythemia Vera. Amplification and Detection Instrument System Software Rotor-Gene AssayManager® software version 2.1 Rotor-Gene AssayManager® software version 1.04 K. Standard/Guidance Document Referenced (if applicable): CLSI EP25-A: Evaluation of stability of in vitro diagnostic reagents L. Test Principle: Refer to DEN160028. M. Performance Characteristics (if/when applicable): 1. Analytical performance: Overall analytical performance of the QIAGEN ipsogen® JAK2 RGQ PCR Kit was previously demonstrated using specimens from patients with suspected polycythemia vera (PV). Refer to decision summary for DEN160028 available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/denovo.cfm?ID=DEN160028 for a description of the following analytical performance studies:  Repeatability/Reproducibility/Lot-to-Lot  Linearity/assay reportable range and DNA input  Traceability/Calibration  Detection limit (Limit of Blank and Limit o Detection)  Analytical specificity (including Interfering Substances)  Reagent Stability  Extracted DNA stability Analytical performance studies provided to support expansion of the indications for use claim to include additional JAK2 positive myeloproliferative neoplasms included accuracy study using specimens from essential thrombocytopenia (ET) and primary 6 myelofibrosis (PMF) patients, and specimen stability study. The studies are described below. a. Accuracy study – Comparison to a Reference Method A study was conducted to demonstrate the accuracy for detecting JAK2 V617F/G1849T allele in clinical specimens from patients representing the target population. Because the original study included suspected MPNs, specimens in this study were selected based on diagnosis which included both JAK2 positive and negative specimens. A total of 197 specimens (98 ET and 99 PMF) was tested with the ipsogen JAK2 RGQ PCR Kit and compared with validated bi-directional Sanger Sequencing (BDS). All specimens were concordant except for 9 ET and 5 PMF samples, all of which were JAK2 V617F positive with the ipsogen JAK2 RGQ PCR Kit and negative with BDS. Concordance between the two methods is shown Classification:

idK172287_s0_e2000

K172287.txt

product code

PSU

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172287 B. Purpose for Submission: Expansion of the Indications for Use. C. Measurand: Janus Tyrosine Kinase 2 (JAK2) gene mutation G1849T (V617F) D. Type of Test: Allele-specific, quantitative, polymerase chain reaction (PCR) using an amplification refractory mutation system (ARMS) E. Applicant: QIAGEN F. Proprietary and Established Names: Trade Name: QIAGEN ipsogen® JAK2 RGQ PCR Kit G. Regulatory Information: 1. Regulation section: 21 CFR 866.6070 2. Classification: Class II 3. Product code: PSU 4. Panel: 88 – Pathology 2 H. Intended Use: 1. Intended use(s): The ipsogen JAK2 RGQ PCR Kit is a qualitative in vitro diagnostic test for the detection of the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood. The ipsogen JAK2 RGQ PCR Kit is a real time PCR test performed on the QIAGEN Rotor-Gene Q MDx instrument. The test is intended for use as an adjunct to evaluation of suspected myeloproliferative neoplasms, in conjunction with other clinicopathological factors. This test does not detect less common JAK2 mutations associated with Myeloproliferative Neoplasms including mutations in exon 12 and is not intended for stand-alone diagnosis of Myeloproliferative Neoplasm. 2. Indication(s) for use: Same as Intended use 3. Special conditions for use statement(s): For prescription use only. For in vitro diagnostic use only. 4. Special instrument requirements: QIAGEN Rotor-Gene Q MDx platform using Rotor-Gene AssayManager software version 2.1. I. Device Description: The ipsogen JAK2 RGQ PCR Kit employs allele-specific, quantitative, polymerase chain reaction (PCR) using an amplification refractory mutation system (ARMS). DNA is extracted from K2-EDTA anti-coagulated whole blood using the QIAsymphony instrument (QSSP) and QIAsymphony® DSP DNA Mini Kit. Purified DNA must be diluted to 10 ng/μl using the TE buffer provided in the JAK2 Kit. Each PCR reaction of the Rotor-Gene Q MDx is optimized for 50 ng of purified gDNA diluted in a final volume of 5 μl. A total of 100 ng per tested sample (50 ng for each reaction) is needed. The Kit contains sufficient reagents to test 24 reactions. Table 1 describes the components of the ipsogen JAK2 RGQ PCR Kit. Table 1. Components of the ipsogen JAK2 RGQ Assay Item Description Use JAK2 Mutant Control 100% V617F allele Assay Positive Control JAK2 WT Control 100% WT allele Assay Negative Control 3 JAK2 MT Quant Standard 1 5x101 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 2 5x102 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 3 5x103 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 4 5x104 V617F copies in 5 µL Mutation Standard Curve JAK2 WT Quant Standard 1 5x101 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 2 5x102 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 3 5x103 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 4 5x104 wild-type copies in 5 µL Wild-type Standard Curve JAK2 MT Reaction Mix Primers, probes, and necessary components for the mutation- specific and internal control PCR reaction Mutation Specific PCR Reaction JAK2 WT Reaction Mix Primers, probes, and necessary components for the wild-type and internal control PCR reaction Wild-type Specific PCR Reaction Taq DNA Polymerase PCR reaction enzyme Mutation and Wild-type PCR TE buffer Tris-EDTA Sample Dilution Nuclease-Free Water Water No Template Control Rotor-Gene AssayManager JAK2 plug-in JAK2 Assay-specific software Results Acquisition and Analysis JAK2 Assay Profile JAK2 Assay-specific software parameters Results Acquisition and Analysis Additional materials required but not provided with the JAK2 RGQ PCR Kit:  QIAsymphony® DSP DNA Mini Kit  QIAsymphony Sample Preparation instrument and accessories  QIAsymphony software version 4.0 that operates the QIAsymphony instrument  QIAGEN Rotor-Gene Q MDx Platform  Rotor-Gene AssayManager® software version 2.1 that operates the Rotor Gene Q MDx J. Substantial Equivalence Information: 4 1. Predicate device name(s): ipsogen® JAK2 RGQ PCR Kit 2. Predicate 510(k) number(s): DEN160028 3. Comparison with predicate: Characteristic Device Predicate Similarities Intended Use The ipsogen JAK2 RGQ PCR Kit is a qualitative in vitro diagnostic test for the detection of the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood. The ipsogen JAK2 RGQ PCR Kit is a real-time PCR test performed on the QIAGEN Rotor-Gene Q MDx instrument. Same Specimen Type Genomic DNA extracted from EDTA whole blood Same Assay Targets JAK2 V617F/G1849T allele Same Genomic DNA Extraction DNA should be extracted using the QIAsymphony SP instrument in combination with the QIAsymphony DSP DNA Mini Kit Same Amplification and Detection Technology Real-time PCR DNA amplification Same Amplification and Detection Instrument System Assay uses the Rotor-Gene Q MDx Same Assay Controls Positive Control, Negative Control and Internal Control included in the kit Same Characteristic Device Predicate Differences Indications for Use The test is intended for use as an adjunct to evaluation of suspected Myeloproliferative The test is intended for use as an adjunct to evaluation of suspected Polycythemia Vera, 5 Neoplasms, in conjunction with other clinicopathological factors. This test does not detect less common JAK2 mutations associated with Myeloproliferative Neoplasms including mutations in exon 12 and is not intended for stand- alone diagnosis of Myeloproliferative Neoplasms. in conjunction with other clinicopathological factors. This test does not detect less common mutations associated with Polycythemia Vera including mutations in exon 12 and is not intended for stand- alone diagnosis of Polycythemia Vera. Amplification and Detection Instrument System Software Rotor-Gene AssayManager® software version 2.1 Rotor-Gene AssayManager® software version 1.04 K. Standard/Guidance Document Referenced (if applicable): CLSI EP25-A: Evaluation of stability of in vitro diagnostic reagents L. Test Principle: Refer to DEN160028. M. Performance Characteristics (if/when applicable): 1. Analytical performance: Overall analytical performance of the QIAGEN ipsogen® JAK2 RGQ PCR Kit was previously demonstrated using specimens from patients with suspected polycythemia vera (PV). Refer to decision summary for DEN160028 available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/denovo.cfm?ID=DEN160028 for a description of the following analytical performance studies:  Repeatability/Reproducibility/Lot-to-Lot  Linearity/assay reportable range and DNA input  Traceability/Calibration  Detection limit (Limit of Blank and Limit o Detection)  Analytical specificity (including Interfering Substances)  Reagent Stability  Extracted DNA stability Analytical performance studies provided to support expansion of the indications for use claim to include additional JAK2 positive myeloproliferative neoplasms included accuracy study using specimens from essential thrombocytopenia (ET) and primary 6 myelofibrosis (PMF) patients, and specimen stability study. The studies are described below. a. Accuracy study – Comparison to a Reference Method A study was conducted to demonstrate the accuracy for detecting JAK2 V617F/G1849T allele in clinical specimens from patients representing the target population. Because the original study included suspected MPNs, specimens in this study were selected based on diagnosis which included both JAK2 positive and negative specimens. A total of 197 specimens (98 ET and 99 PMF) was tested with the ipsogen JAK2 RGQ PCR Kit and compared with validated bi-directional Sanger Sequencing (BDS). All specimens were concordant except for 9 ET and 5 PMF samples, all of which were JAK2 V617F positive with the ipsogen JAK2 RGQ PCR Kit and negative with BDS. Concordance between the two methods is shown Product code:

idK172287_s0_e2000

K172287.txt

panel

88 – Pathology

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172287 B. Purpose for Submission: Expansion of the Indications for Use. C. Measurand: Janus Tyrosine Kinase 2 (JAK2) gene mutation G1849T (V617F) D. Type of Test: Allele-specific, quantitative, polymerase chain reaction (PCR) using an amplification refractory mutation system (ARMS) E. Applicant: QIAGEN F. Proprietary and Established Names: Trade Name: QIAGEN ipsogen® JAK2 RGQ PCR Kit G. Regulatory Information: 1. Regulation section: 21 CFR 866.6070 2. Classification: Class II 3. Product code: PSU 4. Panel: 88 – Pathology 2 H. Intended Use: 1. Intended use(s): The ipsogen JAK2 RGQ PCR Kit is a qualitative in vitro diagnostic test for the detection of the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood. The ipsogen JAK2 RGQ PCR Kit is a real time PCR test performed on the QIAGEN Rotor-Gene Q MDx instrument. The test is intended for use as an adjunct to evaluation of suspected myeloproliferative neoplasms, in conjunction with other clinicopathological factors. This test does not detect less common JAK2 mutations associated with Myeloproliferative Neoplasms including mutations in exon 12 and is not intended for stand-alone diagnosis of Myeloproliferative Neoplasm. 2. Indication(s) for use: Same as Intended use 3. Special conditions for use statement(s): For prescription use only. For in vitro diagnostic use only. 4. Special instrument requirements: QIAGEN Rotor-Gene Q MDx platform using Rotor-Gene AssayManager software version 2.1. I. Device Description: The ipsogen JAK2 RGQ PCR Kit employs allele-specific, quantitative, polymerase chain reaction (PCR) using an amplification refractory mutation system (ARMS). DNA is extracted from K2-EDTA anti-coagulated whole blood using the QIAsymphony instrument (QSSP) and QIAsymphony® DSP DNA Mini Kit. Purified DNA must be diluted to 10 ng/μl using the TE buffer provided in the JAK2 Kit. Each PCR reaction of the Rotor-Gene Q MDx is optimized for 50 ng of purified gDNA diluted in a final volume of 5 μl. A total of 100 ng per tested sample (50 ng for each reaction) is needed. The Kit contains sufficient reagents to test 24 reactions. Table 1 describes the components of the ipsogen JAK2 RGQ PCR Kit. Table 1. Components of the ipsogen JAK2 RGQ Assay Item Description Use JAK2 Mutant Control 100% V617F allele Assay Positive Control JAK2 WT Control 100% WT allele Assay Negative Control 3 JAK2 MT Quant Standard 1 5x101 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 2 5x102 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 3 5x103 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 4 5x104 V617F copies in 5 µL Mutation Standard Curve JAK2 WT Quant Standard 1 5x101 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 2 5x102 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 3 5x103 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 4 5x104 wild-type copies in 5 µL Wild-type Standard Curve JAK2 MT Reaction Mix Primers, probes, and necessary components for the mutation- specific and internal control PCR reaction Mutation Specific PCR Reaction JAK2 WT Reaction Mix Primers, probes, and necessary components for the wild-type and internal control PCR reaction Wild-type Specific PCR Reaction Taq DNA Polymerase PCR reaction enzyme Mutation and Wild-type PCR TE buffer Tris-EDTA Sample Dilution Nuclease-Free Water Water No Template Control Rotor-Gene AssayManager JAK2 plug-in JAK2 Assay-specific software Results Acquisition and Analysis JAK2 Assay Profile JAK2 Assay-specific software parameters Results Acquisition and Analysis Additional materials required but not provided with the JAK2 RGQ PCR Kit:  QIAsymphony® DSP DNA Mini Kit  QIAsymphony Sample Preparation instrument and accessories  QIAsymphony software version 4.0 that operates the QIAsymphony instrument  QIAGEN Rotor-Gene Q MDx Platform  Rotor-Gene AssayManager® software version 2.1 that operates the Rotor Gene Q MDx J. Substantial Equivalence Information: 4 1. Predicate device name(s): ipsogen® JAK2 RGQ PCR Kit 2. Predicate 510(k) number(s): DEN160028 3. Comparison with predicate: Characteristic Device Predicate Similarities Intended Use The ipsogen JAK2 RGQ PCR Kit is a qualitative in vitro diagnostic test for the detection of the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood. The ipsogen JAK2 RGQ PCR Kit is a real-time PCR test performed on the QIAGEN Rotor-Gene Q MDx instrument. Same Specimen Type Genomic DNA extracted from EDTA whole blood Same Assay Targets JAK2 V617F/G1849T allele Same Genomic DNA Extraction DNA should be extracted using the QIAsymphony SP instrument in combination with the QIAsymphony DSP DNA Mini Kit Same Amplification and Detection Technology Real-time PCR DNA amplification Same Amplification and Detection Instrument System Assay uses the Rotor-Gene Q MDx Same Assay Controls Positive Control, Negative Control and Internal Control included in the kit Same Characteristic Device Predicate Differences Indications for Use The test is intended for use as an adjunct to evaluation of suspected Myeloproliferative The test is intended for use as an adjunct to evaluation of suspected Polycythemia Vera, 5 Neoplasms, in conjunction with other clinicopathological factors. This test does not detect less common JAK2 mutations associated with Myeloproliferative Neoplasms including mutations in exon 12 and is not intended for stand- alone diagnosis of Myeloproliferative Neoplasms. in conjunction with other clinicopathological factors. This test does not detect less common mutations associated with Polycythemia Vera including mutations in exon 12 and is not intended for stand- alone diagnosis of Polycythemia Vera. Amplification and Detection Instrument System Software Rotor-Gene AssayManager® software version 2.1 Rotor-Gene AssayManager® software version 1.04 K. Standard/Guidance Document Referenced (if applicable): CLSI EP25-A: Evaluation of stability of in vitro diagnostic reagents L. Test Principle: Refer to DEN160028. M. Performance Characteristics (if/when applicable): 1. Analytical performance: Overall analytical performance of the QIAGEN ipsogen® JAK2 RGQ PCR Kit was previously demonstrated using specimens from patients with suspected polycythemia vera (PV). Refer to decision summary for DEN160028 available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/denovo.cfm?ID=DEN160028 for a description of the following analytical performance studies:  Repeatability/Reproducibility/Lot-to-Lot  Linearity/assay reportable range and DNA input  Traceability/Calibration  Detection limit (Limit of Blank and Limit o Detection)  Analytical specificity (including Interfering Substances)  Reagent Stability  Extracted DNA stability Analytical performance studies provided to support expansion of the indications for use claim to include additional JAK2 positive myeloproliferative neoplasms included accuracy study using specimens from essential thrombocytopenia (ET) and primary 6 myelofibrosis (PMF) patients, and specimen stability study. The studies are described below. a. Accuracy study – Comparison to a Reference Method A study was conducted to demonstrate the accuracy for detecting JAK2 V617F/G1849T allele in clinical specimens from patients representing the target population. Because the original study included suspected MPNs, specimens in this study were selected based on diagnosis which included both JAK2 positive and negative specimens. A total of 197 specimens (98 ET and 99 PMF) was tested with the ipsogen JAK2 RGQ PCR Kit and compared with validated bi-directional Sanger Sequencing (BDS). All specimens were concordant except for 9 ET and 5 PMF samples, all of which were JAK2 V617F positive with the ipsogen JAK2 RGQ PCR Kit and negative with BDS. Concordance between the two methods is shown Panel:

idK172287_s0_e2000

K172287.txt

indications for use

Same as Intended use

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172287 B. Purpose for Submission: Expansion of the Indications for Use. C. Measurand: Janus Tyrosine Kinase 2 (JAK2) gene mutation G1849T (V617F) D. Type of Test: Allele-specific, quantitative, polymerase chain reaction (PCR) using an amplification refractory mutation system (ARMS) E. Applicant: QIAGEN F. Proprietary and Established Names: Trade Name: QIAGEN ipsogen® JAK2 RGQ PCR Kit G. Regulatory Information: 1. Regulation section: 21 CFR 866.6070 2. Classification: Class II 3. Product code: PSU 4. Panel: 88 – Pathology 2 H. Intended Use: 1. Intended use(s): The ipsogen JAK2 RGQ PCR Kit is a qualitative in vitro diagnostic test for the detection of the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood. The ipsogen JAK2 RGQ PCR Kit is a real time PCR test performed on the QIAGEN Rotor-Gene Q MDx instrument. The test is intended for use as an adjunct to evaluation of suspected myeloproliferative neoplasms, in conjunction with other clinicopathological factors. This test does not detect less common JAK2 mutations associated with Myeloproliferative Neoplasms including mutations in exon 12 and is not intended for stand-alone diagnosis of Myeloproliferative Neoplasm. 2. Indication(s) for use: Same as Intended use 3. Special conditions for use statement(s): For prescription use only. For in vitro diagnostic use only. 4. Special instrument requirements: QIAGEN Rotor-Gene Q MDx platform using Rotor-Gene AssayManager software version 2.1. I. Device Description: The ipsogen JAK2 RGQ PCR Kit employs allele-specific, quantitative, polymerase chain reaction (PCR) using an amplification refractory mutation system (ARMS). DNA is extracted from K2-EDTA anti-coagulated whole blood using the QIAsymphony instrument (QSSP) and QIAsymphony® DSP DNA Mini Kit. Purified DNA must be diluted to 10 ng/μl using the TE buffer provided in the JAK2 Kit. Each PCR reaction of the Rotor-Gene Q MDx is optimized for 50 ng of purified gDNA diluted in a final volume of 5 μl. A total of 100 ng per tested sample (50 ng for each reaction) is needed. The Kit contains sufficient reagents to test 24 reactions. Table 1 describes the components of the ipsogen JAK2 RGQ PCR Kit. Table 1. Components of the ipsogen JAK2 RGQ Assay Item Description Use JAK2 Mutant Control 100% V617F allele Assay Positive Control JAK2 WT Control 100% WT allele Assay Negative Control 3 JAK2 MT Quant Standard 1 5x101 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 2 5x102 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 3 5x103 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 4 5x104 V617F copies in 5 µL Mutation Standard Curve JAK2 WT Quant Standard 1 5x101 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 2 5x102 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 3 5x103 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 4 5x104 wild-type copies in 5 µL Wild-type Standard Curve JAK2 MT Reaction Mix Primers, probes, and necessary components for the mutation- specific and internal control PCR reaction Mutation Specific PCR Reaction JAK2 WT Reaction Mix Primers, probes, and necessary components for the wild-type and internal control PCR reaction Wild-type Specific PCR Reaction Taq DNA Polymerase PCR reaction enzyme Mutation and Wild-type PCR TE buffer Tris-EDTA Sample Dilution Nuclease-Free Water Water No Template Control Rotor-Gene AssayManager JAK2 plug-in JAK2 Assay-specific software Results Acquisition and Analysis JAK2 Assay Profile JAK2 Assay-specific software parameters Results Acquisition and Analysis Additional materials required but not provided with the JAK2 RGQ PCR Kit:  QIAsymphony® DSP DNA Mini Kit  QIAsymphony Sample Preparation instrument and accessories  QIAsymphony software version 4.0 that operates the QIAsymphony instrument  QIAGEN Rotor-Gene Q MDx Platform  Rotor-Gene AssayManager® software version 2.1 that operates the Rotor Gene Q MDx J. Substantial Equivalence Information: 4 1. Predicate device name(s): ipsogen® JAK2 RGQ PCR Kit 2. Predicate 510(k) number(s): DEN160028 3. Comparison with predicate: Characteristic Device Predicate Similarities Intended Use The ipsogen JAK2 RGQ PCR Kit is a qualitative in vitro diagnostic test for the detection of the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood. The ipsogen JAK2 RGQ PCR Kit is a real-time PCR test performed on the QIAGEN Rotor-Gene Q MDx instrument. Same Specimen Type Genomic DNA extracted from EDTA whole blood Same Assay Targets JAK2 V617F/G1849T allele Same Genomic DNA Extraction DNA should be extracted using the QIAsymphony SP instrument in combination with the QIAsymphony DSP DNA Mini Kit Same Amplification and Detection Technology Real-time PCR DNA amplification Same Amplification and Detection Instrument System Assay uses the Rotor-Gene Q MDx Same Assay Controls Positive Control, Negative Control and Internal Control included in the kit Same Characteristic Device Predicate Differences Indications for Use The test is intended for use as an adjunct to evaluation of suspected Myeloproliferative The test is intended for use as an adjunct to evaluation of suspected Polycythemia Vera, 5 Neoplasms, in conjunction with other clinicopathological factors. This test does not detect less common JAK2 mutations associated with Myeloproliferative Neoplasms including mutations in exon 12 and is not intended for stand- alone diagnosis of Myeloproliferative Neoplasms. in conjunction with other clinicopathological factors. This test does not detect less common mutations associated with Polycythemia Vera including mutations in exon 12 and is not intended for stand- alone diagnosis of Polycythemia Vera. Amplification and Detection Instrument System Software Rotor-Gene AssayManager® software version 2.1 Rotor-Gene AssayManager® software version 1.04 K. Standard/Guidance Document Referenced (if applicable): CLSI EP25-A: Evaluation of stability of in vitro diagnostic reagents L. Test Principle: Refer to DEN160028. M. Performance Characteristics (if/when applicable): 1. Analytical performance: Overall analytical performance of the QIAGEN ipsogen® JAK2 RGQ PCR Kit was previously demonstrated using specimens from patients with suspected polycythemia vera (PV). Refer to decision summary for DEN160028 available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/denovo.cfm?ID=DEN160028 for a description of the following analytical performance studies:  Repeatability/Reproducibility/Lot-to-Lot  Linearity/assay reportable range and DNA input  Traceability/Calibration  Detection limit (Limit of Blank and Limit o Detection)  Analytical specificity (including Interfering Substances)  Reagent Stability  Extracted DNA stability Analytical performance studies provided to support expansion of the indications for use claim to include additional JAK2 positive myeloproliferative neoplasms included accuracy study using specimens from essential thrombocytopenia (ET) and primary 6 myelofibrosis (PMF) patients, and specimen stability study. The studies are described below. a. Accuracy study – Comparison to a Reference Method A study was conducted to demonstrate the accuracy for detecting JAK2 V617F/G1849T allele in clinical specimens from patients representing the target population. Because the original study included suspected MPNs, specimens in this study were selected based on diagnosis which included both JAK2 positive and negative specimens. A total of 197 specimens (98 ET and 99 PMF) was tested with the ipsogen JAK2 RGQ PCR Kit and compared with validated bi-directional Sanger Sequencing (BDS). All specimens were concordant except for 9 ET and 5 PMF samples, all of which were JAK2 V617F positive with the ipsogen JAK2 RGQ PCR Kit and negative with BDS. Concordance between the two methods is shown Indications for use:

idK172287_s0_e2000

K172287.txt

predicate device name

ipsogen® JAK2 RGQ PCR Kit

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172287 B. Purpose for Submission: Expansion of the Indications for Use. C. Measurand: Janus Tyrosine Kinase 2 (JAK2) gene mutation G1849T (V617F) D. Type of Test: Allele-specific, quantitative, polymerase chain reaction (PCR) using an amplification refractory mutation system (ARMS) E. Applicant: QIAGEN F. Proprietary and Established Names: Trade Name: QIAGEN ipsogen® JAK2 RGQ PCR Kit G. Regulatory Information: 1. Regulation section: 21 CFR 866.6070 2. Classification: Class II 3. Product code: PSU 4. Panel: 88 – Pathology 2 H. Intended Use: 1. Intended use(s): The ipsogen JAK2 RGQ PCR Kit is a qualitative in vitro diagnostic test for the detection of the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood. The ipsogen JAK2 RGQ PCR Kit is a real time PCR test performed on the QIAGEN Rotor-Gene Q MDx instrument. The test is intended for use as an adjunct to evaluation of suspected myeloproliferative neoplasms, in conjunction with other clinicopathological factors. This test does not detect less common JAK2 mutations associated with Myeloproliferative Neoplasms including mutations in exon 12 and is not intended for stand-alone diagnosis of Myeloproliferative Neoplasm. 2. Indication(s) for use: Same as Intended use 3. Special conditions for use statement(s): For prescription use only. For in vitro diagnostic use only. 4. Special instrument requirements: QIAGEN Rotor-Gene Q MDx platform using Rotor-Gene AssayManager software version 2.1. I. Device Description: The ipsogen JAK2 RGQ PCR Kit employs allele-specific, quantitative, polymerase chain reaction (PCR) using an amplification refractory mutation system (ARMS). DNA is extracted from K2-EDTA anti-coagulated whole blood using the QIAsymphony instrument (QSSP) and QIAsymphony® DSP DNA Mini Kit. Purified DNA must be diluted to 10 ng/μl using the TE buffer provided in the JAK2 Kit. Each PCR reaction of the Rotor-Gene Q MDx is optimized for 50 ng of purified gDNA diluted in a final volume of 5 μl. A total of 100 ng per tested sample (50 ng for each reaction) is needed. The Kit contains sufficient reagents to test 24 reactions. Table 1 describes the components of the ipsogen JAK2 RGQ PCR Kit. Table 1. Components of the ipsogen JAK2 RGQ Assay Item Description Use JAK2 Mutant Control 100% V617F allele Assay Positive Control JAK2 WT Control 100% WT allele Assay Negative Control 3 JAK2 MT Quant Standard 1 5x101 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 2 5x102 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 3 5x103 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 4 5x104 V617F copies in 5 µL Mutation Standard Curve JAK2 WT Quant Standard 1 5x101 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 2 5x102 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 3 5x103 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 4 5x104 wild-type copies in 5 µL Wild-type Standard Curve JAK2 MT Reaction Mix Primers, probes, and necessary components for the mutation- specific and internal control PCR reaction Mutation Specific PCR Reaction JAK2 WT Reaction Mix Primers, probes, and necessary components for the wild-type and internal control PCR reaction Wild-type Specific PCR Reaction Taq DNA Polymerase PCR reaction enzyme Mutation and Wild-type PCR TE buffer Tris-EDTA Sample Dilution Nuclease-Free Water Water No Template Control Rotor-Gene AssayManager JAK2 plug-in JAK2 Assay-specific software Results Acquisition and Analysis JAK2 Assay Profile JAK2 Assay-specific software parameters Results Acquisition and Analysis Additional materials required but not provided with the JAK2 RGQ PCR Kit:  QIAsymphony® DSP DNA Mini Kit  QIAsymphony Sample Preparation instrument and accessories  QIAsymphony software version 4.0 that operates the QIAsymphony instrument  QIAGEN Rotor-Gene Q MDx Platform  Rotor-Gene AssayManager® software version 2.1 that operates the Rotor Gene Q MDx J. Substantial Equivalence Information: 4 1. Predicate device name(s): ipsogen® JAK2 RGQ PCR Kit 2. Predicate 510(k) number(s): DEN160028 3. Comparison with predicate: Characteristic Device Predicate Similarities Intended Use The ipsogen JAK2 RGQ PCR Kit is a qualitative in vitro diagnostic test for the detection of the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood. The ipsogen JAK2 RGQ PCR Kit is a real-time PCR test performed on the QIAGEN Rotor-Gene Q MDx instrument. Same Specimen Type Genomic DNA extracted from EDTA whole blood Same Assay Targets JAK2 V617F/G1849T allele Same Genomic DNA Extraction DNA should be extracted using the QIAsymphony SP instrument in combination with the QIAsymphony DSP DNA Mini Kit Same Amplification and Detection Technology Real-time PCR DNA amplification Same Amplification and Detection Instrument System Assay uses the Rotor-Gene Q MDx Same Assay Controls Positive Control, Negative Control and Internal Control included in the kit Same Characteristic Device Predicate Differences Indications for Use The test is intended for use as an adjunct to evaluation of suspected Myeloproliferative The test is intended for use as an adjunct to evaluation of suspected Polycythemia Vera, 5 Neoplasms, in conjunction with other clinicopathological factors. This test does not detect less common JAK2 mutations associated with Myeloproliferative Neoplasms including mutations in exon 12 and is not intended for stand- alone diagnosis of Myeloproliferative Neoplasms. in conjunction with other clinicopathological factors. This test does not detect less common mutations associated with Polycythemia Vera including mutations in exon 12 and is not intended for stand- alone diagnosis of Polycythemia Vera. Amplification and Detection Instrument System Software Rotor-Gene AssayManager® software version 2.1 Rotor-Gene AssayManager® software version 1.04 K. Standard/Guidance Document Referenced (if applicable): CLSI EP25-A: Evaluation of stability of in vitro diagnostic reagents L. Test Principle: Refer to DEN160028. M. Performance Characteristics (if/when applicable): 1. Analytical performance: Overall analytical performance of the QIAGEN ipsogen® JAK2 RGQ PCR Kit was previously demonstrated using specimens from patients with suspected polycythemia vera (PV). Refer to decision summary for DEN160028 available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/denovo.cfm?ID=DEN160028 for a description of the following analytical performance studies:  Repeatability/Reproducibility/Lot-to-Lot  Linearity/assay reportable range and DNA input  Traceability/Calibration  Detection limit (Limit of Blank and Limit o Detection)  Analytical specificity (including Interfering Substances)  Reagent Stability  Extracted DNA stability Analytical performance studies provided to support expansion of the indications for use claim to include additional JAK2 positive myeloproliferative neoplasms included accuracy study using specimens from essential thrombocytopenia (ET) and primary 6 myelofibrosis (PMF) patients, and specimen stability study. The studies are described below. a. Accuracy study – Comparison to a Reference Method A study was conducted to demonstrate the accuracy for detecting JAK2 V617F/G1849T allele in clinical specimens from patients representing the target population. Because the original study included suspected MPNs, specimens in this study were selected based on diagnosis which included both JAK2 positive and negative specimens. A total of 197 specimens (98 ET and 99 PMF) was tested with the ipsogen JAK2 RGQ PCR Kit and compared with validated bi-directional Sanger Sequencing (BDS). All specimens were concordant except for 9 ET and 5 PMF samples, all of which were JAK2 V617F positive with the ipsogen JAK2 RGQ PCR Kit and negative with BDS. Concordance between the two methods is shown Predicate device name:

idK172287_s0_e2000

K172287.txt

applicant

QIAGEN

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172287 B. Purpose for Submission: Expansion of the Indications for Use. C. Measurand: Janus Tyrosine Kinase 2 (JAK2) gene mutation G1849T (V617F) D. Type of Test: Allele-specific, quantitative, polymerase chain reaction (PCR) using an amplification refractory mutation system (ARMS) E. Applicant: QIAGEN F. Proprietary and Established Names: Trade Name: QIAGEN ipsogen® JAK2 RGQ PCR Kit G. Regulatory Information: 1. Regulation section: 21 CFR 866.6070 2. Classification: Class II 3. Product code: PSU 4. Panel: 88 – Pathology 2 H. Intended Use: 1. Intended use(s): The ipsogen JAK2 RGQ PCR Kit is a qualitative in vitro diagnostic test for the detection of the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood. The ipsogen JAK2 RGQ PCR Kit is a real time PCR test performed on the QIAGEN Rotor-Gene Q MDx instrument. The test is intended for use as an adjunct to evaluation of suspected myeloproliferative neoplasms, in conjunction with other clinicopathological factors. This test does not detect less common JAK2 mutations associated with Myeloproliferative Neoplasms including mutations in exon 12 and is not intended for stand-alone diagnosis of Myeloproliferative Neoplasm. 2. Indication(s) for use: Same as Intended use 3. Special conditions for use statement(s): For prescription use only. For in vitro diagnostic use only. 4. Special instrument requirements: QIAGEN Rotor-Gene Q MDx platform using Rotor-Gene AssayManager software version 2.1. I. Device Description: The ipsogen JAK2 RGQ PCR Kit employs allele-specific, quantitative, polymerase chain reaction (PCR) using an amplification refractory mutation system (ARMS). DNA is extracted from K2-EDTA anti-coagulated whole blood using the QIAsymphony instrument (QSSP) and QIAsymphony® DSP DNA Mini Kit. Purified DNA must be diluted to 10 ng/μl using the TE buffer provided in the JAK2 Kit. Each PCR reaction of the Rotor-Gene Q MDx is optimized for 50 ng of purified gDNA diluted in a final volume of 5 μl. A total of 100 ng per tested sample (50 ng for each reaction) is needed. The Kit contains sufficient reagents to test 24 reactions. Table 1 describes the components of the ipsogen JAK2 RGQ PCR Kit. Table 1. Components of the ipsogen JAK2 RGQ Assay Item Description Use JAK2 Mutant Control 100% V617F allele Assay Positive Control JAK2 WT Control 100% WT allele Assay Negative Control 3 JAK2 MT Quant Standard 1 5x101 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 2 5x102 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 3 5x103 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 4 5x104 V617F copies in 5 µL Mutation Standard Curve JAK2 WT Quant Standard 1 5x101 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 2 5x102 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 3 5x103 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 4 5x104 wild-type copies in 5 µL Wild-type Standard Curve JAK2 MT Reaction Mix Primers, probes, and necessary components for the mutation- specific and internal control PCR reaction Mutation Specific PCR Reaction JAK2 WT Reaction Mix Primers, probes, and necessary components for the wild-type and internal control PCR reaction Wild-type Specific PCR Reaction Taq DNA Polymerase PCR reaction enzyme Mutation and Wild-type PCR TE buffer Tris-EDTA Sample Dilution Nuclease-Free Water Water No Template Control Rotor-Gene AssayManager JAK2 plug-in JAK2 Assay-specific software Results Acquisition and Analysis JAK2 Assay Profile JAK2 Assay-specific software parameters Results Acquisition and Analysis Additional materials required but not provided with the JAK2 RGQ PCR Kit:  QIAsymphony® DSP DNA Mini Kit  QIAsymphony Sample Preparation instrument and accessories  QIAsymphony software version 4.0 that operates the QIAsymphony instrument  QIAGEN Rotor-Gene Q MDx Platform  Rotor-Gene AssayManager® software version 2.1 that operates the Rotor Gene Q MDx J. Substantial Equivalence Information: 4 1. Predicate device name(s): ipsogen® JAK2 RGQ PCR Kit 2. Predicate 510(k) number(s): DEN160028 3. Comparison with predicate: Characteristic Device Predicate Similarities Intended Use The ipsogen JAK2 RGQ PCR Kit is a qualitative in vitro diagnostic test for the detection of the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood. The ipsogen JAK2 RGQ PCR Kit is a real-time PCR test performed on the QIAGEN Rotor-Gene Q MDx instrument. Same Specimen Type Genomic DNA extracted from EDTA whole blood Same Assay Targets JAK2 V617F/G1849T allele Same Genomic DNA Extraction DNA should be extracted using the QIAsymphony SP instrument in combination with the QIAsymphony DSP DNA Mini Kit Same Amplification and Detection Technology Real-time PCR DNA amplification Same Amplification and Detection Instrument System Assay uses the Rotor-Gene Q MDx Same Assay Controls Positive Control, Negative Control and Internal Control included in the kit Same Characteristic Device Predicate Differences Indications for Use The test is intended for use as an adjunct to evaluation of suspected Myeloproliferative The test is intended for use as an adjunct to evaluation of suspected Polycythemia Vera, 5 Neoplasms, in conjunction with other clinicopathological factors. This test does not detect less common JAK2 mutations associated with Myeloproliferative Neoplasms including mutations in exon 12 and is not intended for stand- alone diagnosis of Myeloproliferative Neoplasms. in conjunction with other clinicopathological factors. This test does not detect less common mutations associated with Polycythemia Vera including mutations in exon 12 and is not intended for stand- alone diagnosis of Polycythemia Vera. Amplification and Detection Instrument System Software Rotor-Gene AssayManager® software version 2.1 Rotor-Gene AssayManager® software version 1.04 K. Standard/Guidance Document Referenced (if applicable): CLSI EP25-A: Evaluation of stability of in vitro diagnostic reagents L. Test Principle: Refer to DEN160028. M. Performance Characteristics (if/when applicable): 1. Analytical performance: Overall analytical performance of the QIAGEN ipsogen® JAK2 RGQ PCR Kit was previously demonstrated using specimens from patients with suspected polycythemia vera (PV). Refer to decision summary for DEN160028 available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/denovo.cfm?ID=DEN160028 for a description of the following analytical performance studies:  Repeatability/Reproducibility/Lot-to-Lot  Linearity/assay reportable range and DNA input  Traceability/Calibration  Detection limit (Limit of Blank and Limit o Detection)  Analytical specificity (including Interfering Substances)  Reagent Stability  Extracted DNA stability Analytical performance studies provided to support expansion of the indications for use claim to include additional JAK2 positive myeloproliferative neoplasms included accuracy study using specimens from essential thrombocytopenia (ET) and primary 6 myelofibrosis (PMF) patients, and specimen stability study. The studies are described below. a. Accuracy study – Comparison to a Reference Method A study was conducted to demonstrate the accuracy for detecting JAK2 V617F/G1849T allele in clinical specimens from patients representing the target population. Because the original study included suspected MPNs, specimens in this study were selected based on diagnosis which included both JAK2 positive and negative specimens. A total of 197 specimens (98 ET and 99 PMF) was tested with the ipsogen JAK2 RGQ PCR Kit and compared with validated bi-directional Sanger Sequencing (BDS). All specimens were concordant except for 9 ET and 5 PMF samples, all of which were JAK2 V617F positive with the ipsogen JAK2 RGQ PCR Kit and negative with BDS. Concordance between the two methods is shown Applicant:

idK172287_s0_e2000

K172287.txt

proprietary and established names

Trade Name: QIAGEN ipsogen® JAK2 RGQ PCR Kit

IAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172287 B. Purpose for Submission: Expansion of the Indications for Use. C. Measurand: Janus Tyrosine Kinase 2 (JAK2) gene mutation G1849T (V617F) D. Type of Test: Allele-specific, quantitative, polymerase chain reaction (PCR) using an amplification refractory mutation system (ARMS) E. Applicant: QIAGEN F. Proprietary and Established Names: Trade Name: QIAGEN ipsogen® JAK2 RGQ PCR Kit G. Regulatory Information: 1. Regulation section: 21 CFR 866.6070 2. Classification: Class II 3. Product code: PSU 4. Panel: 88 – Pathology 2 H. Intended Use: 1. Intended use(s): The ipsogen JAK2 RGQ PCR Kit is a qualitative in vitro diagnostic test for the detection of the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood. The ipsogen JAK2 RGQ PCR Kit is a real time PCR test performed on the QIAGEN Rotor-Gene Q MDx instrument. The test is intended for use as an adjunct to evaluation of suspected myeloproliferative neoplasms, in conjunction with other clinicopathological factors. This test does not detect less common JAK2 mutations associated with Myeloproliferative Neoplasms including mutations in exon 12 and is not intended for stand-alone diagnosis of Myeloproliferative Neoplasm. 2. Indication(s) for use: Same as Intended use 3. Special conditions for use statement(s): For prescription use only. For in vitro diagnostic use only. 4. Special instrument requirements: QIAGEN Rotor-Gene Q MDx platform using Rotor-Gene AssayManager software version 2.1. I. Device Description: The ipsogen JAK2 RGQ PCR Kit employs allele-specific, quantitative, polymerase chain reaction (PCR) using an amplification refractory mutation system (ARMS). DNA is extracted from K2-EDTA anti-coagulated whole blood using the QIAsymphony instrument (QSSP) and QIAsymphony® DSP DNA Mini Kit. Purified DNA must be diluted to 10 ng/μl using the TE buffer provided in the JAK2 Kit. Each PCR reaction of the Rotor-Gene Q MDx is optimized for 50 ng of purified gDNA diluted in a final volume of 5 μl. A total of 100 ng per tested sample (50 ng for each reaction) is needed. The Kit contains sufficient reagents to test 24 reactions. Table 1 describes the components of the ipsogen JAK2 RGQ PCR Kit. Table 1. Components of the ipsogen JAK2 RGQ Assay Item Description Use JAK2 Mutant Control 100% V617F allele Assay Positive Control JAK2 WT Control 100% WT allele Assay Negative Control 3 JAK2 MT Quant Standard 1 5x101 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 2 5x102 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 3 5x103 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 4 5x104 V617F copies in 5 µL Mutation Standard Curve JAK2 WT Quant Standard 1 5x101 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 2 5x102 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 3 5x103 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 4 5x104 wild-type copies in 5 µL Wild-type Standard Curve JAK2 MT Reaction Mix Primers, probes, and necessary components for the mutation- specific and internal control PCR reaction Mutation Specific PCR Reaction JAK2 WT Reaction Mix Primers, probes, and necessary components for the wild-type and internal control PCR reaction Wild-type Specific PCR Reaction Taq DNA Polymerase PCR reaction enzyme Mutation and Wild-type PCR TE buffer Tris-EDTA Sample Dilution Nuclease-Free Water Water No Template Control Rotor-Gene AssayManager JAK2 plug-in JAK2 Assay-specific software Results Acquisition and Analysis JAK2 Assay Profile JAK2 Assay-specific software parameters Results Acquisition and Analysis Additional materials required but not provided with the JAK2 RGQ PCR Kit:  QIAsymphony® DSP DNA Mini Kit  QIAsymphony Sample Preparation instrument and accessories  QIAsymphony software version 4.0 that operates the QIAsymphony instrument  QIAGEN Rotor-Gene Q MDx Platform  Rotor-Gene AssayManager® software version 2.1 that operates the Rotor Gene Q MDx J. Substantial Equivalence Information: 4 1. Predicate device name(s): ipsogen® JAK2 RGQ PCR Kit 2. Predicate 510(k) number(s): DEN160028 3. Comparison with predicate: Characteristic Device Predicate Similarities Intended Use The ipsogen JAK2 RGQ PCR Kit is a qualitative in vitro diagnostic test for the detection of the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood. The ipsogen JAK2 RGQ PCR Kit is a real-time PCR test performed on the QIAGEN Rotor-Gene Q MDx instrument. Same Specimen Type Genomic DNA extracted from EDTA whole blood Same Assay Targets JAK2 V617F/G1849T allele Same Genomic DNA Extraction DNA should be extracted using the QIAsymphony SP instrument in combination with the QIAsymphony DSP DNA Mini Kit Same Amplification and Detection Technology Real-time PCR DNA amplification Same Amplification and Detection Instrument System Assay uses the Rotor-Gene Q MDx Same Assay Controls Positive Control, Negative Control and Internal Control included in the kit Same Characteristic Device Predicate Differences Indications for Use The test is intended for use as an adjunct to evaluation of suspected Myeloproliferative The test is intended for use as an adjunct to evaluation of suspected Polycythemia Vera, 5 Neoplasms, in conjunction with other clinicopathological factors. This test does not detect less common JAK2 mutations associated with Myeloproliferative Neoplasms including mutations in exon 12 and is not intended for stand- alone diagnosis of Myeloproliferative Neoplasms. in conjunction with other clinicopathological factors. This test does not detect less common mutations associated with Polycythemia Vera including mutations in exon 12 and is not intended for stand- alone diagnosis of Polycythemia Vera. Amplification and Detection Instrument System Software Rotor-Gene AssayManager® software version 2.1 Rotor-Gene AssayManager® software version 1.04 K. Standard/Guidance Document Referenced (if applicable): CLSI EP25-A: Evaluation of stability of in vitro diagnostic reagents L. Test Principle: Refer to DEN160028. M. Performance Characteristics (if/when applicable): 1. Analytical performance: Overall analytical performance of the QIAGEN ipsogen® JAK2 RGQ PCR Kit was previously demonstrated using specimens from patients with suspected polycythemia vera (PV). Refer to decision summary for DEN160028 available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/denovo.cfm?ID=DEN160028 for a description of the following analytical performance studies:  Repeatability/Reproducibility/Lot-to-Lot  Linearity/assay reportable range and DNA input  Traceability/Calibration  Detection limit (Limit of Blank and Limit o Detection)  Analytical specificity (including Interfering Substances)  Reagent Stability  Extracted DNA stability Analytical performance studies provided to support expansion of the indications for use claim to include additional JAK2 positive myeloproliferative neoplasms included accuracy study using specimens from essential thrombocytopenia (ET) and primary 6 myelofibrosis (PMF) patients, and specimen stability study. The studies are described below. a. Accuracy study – Comparison to a Reference Method A study was conducted to demonstrate the accuracy for detecting JAK2 V617F/G1849T allele in clinical specimens from patients representing the target population. Because the original study included suspected MPNs, specimens in this study were selected based on diagnosis which included both JAK2 positive and negative specimens. A total of 197 specimens (98 ET and 99 PMF) was tested with the ipsogen JAK2 RGQ PCR Kit and compared with validated bi-directional Sanger Sequencing (BDS). All specimens were concordant except for 9 ET and 5 PMF samples, all of which were JAK2 V617F positive with the ipsogen JAK2 RGQ PCR Kit and negative with BDS. Concordance between the two methods is shown Proprietary and established names:

idK172287_s0_e2000

K172287.txt

regulation section

21 CFR 866.6070

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172287 B. Purpose for Submission: Expansion of the Indications for Use. C. Measurand: Janus Tyrosine Kinase 2 (JAK2) gene mutation G1849T (V617F) D. Type of Test: Allele-specific, quantitative, polymerase chain reaction (PCR) using an amplification refractory mutation system (ARMS) E. Applicant: QIAGEN F. Proprietary and Established Names: Trade Name: QIAGEN ipsogen® JAK2 RGQ PCR Kit G. Regulatory Information: 1. Regulation section: 21 CFR 866.6070 2. Classification: Class II 3. Product code: PSU 4. Panel: 88 – Pathology 2 H. Intended Use: 1. Intended use(s): The ipsogen JAK2 RGQ PCR Kit is a qualitative in vitro diagnostic test for the detection of the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood. The ipsogen JAK2 RGQ PCR Kit is a real time PCR test performed on the QIAGEN Rotor-Gene Q MDx instrument. The test is intended for use as an adjunct to evaluation of suspected myeloproliferative neoplasms, in conjunction with other clinicopathological factors. This test does not detect less common JAK2 mutations associated with Myeloproliferative Neoplasms including mutations in exon 12 and is not intended for stand-alone diagnosis of Myeloproliferative Neoplasm. 2. Indication(s) for use: Same as Intended use 3. Special conditions for use statement(s): For prescription use only. For in vitro diagnostic use only. 4. Special instrument requirements: QIAGEN Rotor-Gene Q MDx platform using Rotor-Gene AssayManager software version 2.1. I. Device Description: The ipsogen JAK2 RGQ PCR Kit employs allele-specific, quantitative, polymerase chain reaction (PCR) using an amplification refractory mutation system (ARMS). DNA is extracted from K2-EDTA anti-coagulated whole blood using the QIAsymphony instrument (QSSP) and QIAsymphony® DSP DNA Mini Kit. Purified DNA must be diluted to 10 ng/μl using the TE buffer provided in the JAK2 Kit. Each PCR reaction of the Rotor-Gene Q MDx is optimized for 50 ng of purified gDNA diluted in a final volume of 5 μl. A total of 100 ng per tested sample (50 ng for each reaction) is needed. The Kit contains sufficient reagents to test 24 reactions. Table 1 describes the components of the ipsogen JAK2 RGQ PCR Kit. Table 1. Components of the ipsogen JAK2 RGQ Assay Item Description Use JAK2 Mutant Control 100% V617F allele Assay Positive Control JAK2 WT Control 100% WT allele Assay Negative Control 3 JAK2 MT Quant Standard 1 5x101 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 2 5x102 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 3 5x103 V617F copies in 5 µL Mutation Standard Curve JAK2 MT Quant Standard 4 5x104 V617F copies in 5 µL Mutation Standard Curve JAK2 WT Quant Standard 1 5x101 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 2 5x102 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 3 5x103 wild-type copies in 5 µL Wild-type Standard Curve JAK2 WT Quant Standard 4 5x104 wild-type copies in 5 µL Wild-type Standard Curve JAK2 MT Reaction Mix Primers, probes, and necessary components for the mutation- specific and internal control PCR reaction Mutation Specific PCR Reaction JAK2 WT Reaction Mix Primers, probes, and necessary components for the wild-type and internal control PCR reaction Wild-type Specific PCR Reaction Taq DNA Polymerase PCR reaction enzyme Mutation and Wild-type PCR TE buffer Tris-EDTA Sample Dilution Nuclease-Free Water Water No Template Control Rotor-Gene AssayManager JAK2 plug-in JAK2 Assay-specific software Results Acquisition and Analysis JAK2 Assay Profile JAK2 Assay-specific software parameters Results Acquisition and Analysis Additional materials required but not provided with the JAK2 RGQ PCR Kit:  QIAsymphony® DSP DNA Mini Kit  QIAsymphony Sample Preparation instrument and accessories  QIAsymphony software version 4.0 that operates the QIAsymphony instrument  QIAGEN Rotor-Gene Q MDx Platform  Rotor-Gene AssayManager® software version 2.1 that operates the Rotor Gene Q MDx J. Substantial Equivalence Information: 4 1. Predicate device name(s): ipsogen® JAK2 RGQ PCR Kit 2. Predicate 510(k) number(s): DEN160028 3. Comparison with predicate: Characteristic Device Predicate Similarities Intended Use The ipsogen JAK2 RGQ PCR Kit is a qualitative in vitro diagnostic test for the detection of the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood. The ipsogen JAK2 RGQ PCR Kit is a real-time PCR test performed on the QIAGEN Rotor-Gene Q MDx instrument. Same Specimen Type Genomic DNA extracted from EDTA whole blood Same Assay Targets JAK2 V617F/G1849T allele Same Genomic DNA Extraction DNA should be extracted using the QIAsymphony SP instrument in combination with the QIAsymphony DSP DNA Mini Kit Same Amplification and Detection Technology Real-time PCR DNA amplification Same Amplification and Detection Instrument System Assay uses the Rotor-Gene Q MDx Same Assay Controls Positive Control, Negative Control and Internal Control included in the kit Same Characteristic Device Predicate Differences Indications for Use The test is intended for use as an adjunct to evaluation of suspected Myeloproliferative The test is intended for use as an adjunct to evaluation of suspected Polycythemia Vera, 5 Neoplasms, in conjunction with other clinicopathological factors. This test does not detect less common JAK2 mutations associated with Myeloproliferative Neoplasms including mutations in exon 12 and is not intended for stand- alone diagnosis of Myeloproliferative Neoplasms. in conjunction with other clinicopathological factors. This test does not detect less common mutations associated with Polycythemia Vera including mutations in exon 12 and is not intended for stand- alone diagnosis of Polycythemia Vera. Amplification and Detection Instrument System Software Rotor-Gene AssayManager® software version 2.1 Rotor-Gene AssayManager® software version 1.04 K. Standard/Guidance Document Referenced (if applicable): CLSI EP25-A: Evaluation of stability of in vitro diagnostic reagents L. Test Principle: Refer to DEN160028. M. Performance Characteristics (if/when applicable): 1. Analytical performance: Overall analytical performance of the QIAGEN ipsogen® JAK2 RGQ PCR Kit was previously demonstrated using specimens from patients with suspected polycythemia vera (PV). Refer to decision summary for DEN160028 available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/denovo.cfm?ID=DEN160028 for a description of the following analytical performance studies:  Repeatability/Reproducibility/Lot-to-Lot  Linearity/assay reportable range and DNA input  Traceability/Calibration  Detection limit (Limit of Blank and Limit o Detection)  Analytical specificity (including Interfering Substances)  Reagent Stability  Extracted DNA stability Analytical performance studies provided to support expansion of the indications for use claim to include additional JAK2 positive myeloproliferative neoplasms included accuracy study using specimens from essential thrombocytopenia (ET) and primary 6 myelofibrosis (PMF) patients, and specimen stability study. The studies are described below. a. Accuracy study – Comparison to a Reference Method A study was conducted to demonstrate the accuracy for detecting JAK2 V617F/G1849T allele in clinical specimens from patients representing the target population. Because the original study included suspected MPNs, specimens in this study were selected based on diagnosis which included both JAK2 positive and negative specimens. A total of 197 specimens (98 ET and 99 PMF) was tested with the ipsogen JAK2 RGQ PCR Kit and compared with validated bi-directional Sanger Sequencing (BDS). All specimens were concordant except for 9 ET and 5 PMF samples, all of which were JAK2 V617F positive with the ipsogen JAK2 RGQ PCR Kit and negative with BDS. Concordance between the two methods is shown Regulation section:

idK172287_s2000_e4000

K172287.txt

proposed labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809 and the special controls for this device type.

specimens and Table 3 for PMF specimens. Table 2. Concordance table between ipsogen JAK2 RGQ PCR Kit and Sanger Bidirectional Sequencing in ET population Sanger bi-directional sequencing JAK2 V617F positive JAK2 V617F negative Total ipsogen JAK2 RGQ PCR Kit JAK2 V617F positive 43 9 52 JAK2 V617F negative 0 46 46 Total 43 55 98 The overall agreement is 90.8% (89/98 subjects; 95% CI: [83.3% – 95.7%]), the positive agreement is 100% (43/43 subjects; 95% CI: [91.8% – 100%]), and the negative agreement is 83.6% (46/55 subjects; 95% CI: [71.2% – 92.2%]). 7 Table 3. Concordance table between ipsogen JAK2 RGQ PCR Kit and Sanger Bidirectional Sequencing in PMF population Sanger Bi-directional sequencing JAK2 V617F positive JAK2 V617F negative Total ipsogen JAK2 RGQ PCR Kit JAK2 V617F positive 51 5 56 JAK2 V617F negative 0 43 43 Total 51 48 99 The overall agreement is 94.9% (94/99 subjects; 95% CI: [88.6% – 98.3%]), the positive agreement is 100% (51/51 subjects; 95% CI: [93.0% – 100%]), and the negative agreement is 89.6% (43/48 subjects; 95% CI: [77.3% – 96.5%]). Previously in DEN160028, a clinical study was conducted in which 276 PV samples were evaluated with the ipsogen JAK2 RGQ PCR Kit and the results were compared to results obtained with BDS. One PV sample was found JAK2 V617F positive with the ipsogen JAK2 RGQ PCR Kit and negative with BDS. Concordance between the two methods is shown in Table 4 for PV specimens. The overall agreement is 99.6% (275/276 subjects; 95% CI: [98.0% – 100%]), the positive agreement is 100% (71/71 subjects; 95% CI: [94.9% – 100%]), and the negative agreement is 99.5% (204/205 subjects; 95% CI: [97.3% – 100%]). Table 4. Concordance table between ipsogen JAK2 RGQ PCR Kit and Sanger Bidirectional Sequencing in PV population Sanger Bi-directional sequencing JAK2 V617F positive JAK2 V617F negative Total ipsogen JAK2 RGQ PCR Kit JAK2 V617F positive 71 1 72 JAK2 V617F negative 0 204 204 Total 71 205 276 Accuracy with all MPN specimens evaluated combined The overall accuracy of the test in MPN specimens was assessed by combining the 8 data obtained from each specimen cohort. A total of 473 MPN specimens were evaluated and a total of 15 samples were discordant. The overall agreement is 96.8% (458/473 subjects; 95% CI: [94.8%; 98.2%]). The positive agreement was 100% (165/165 subjects; 95%CI: [97.8%; 100%] and the negative agreement was 95.1 % (293/308 subjects; 95% CI: [92.1%; 97.2 %]). The results are shown in Table 5. Table 5. Concordance table between ipsogen JAK2 RGQ PCR Kit and Sanger Bidirectional Sequencing in MPN population (combined ET, PMF and PV populations) Sanger bi-directional sequencing JAK2 V617F positive JAK2 V617F negative Total ipsogen JAK2 RGQ PCR Kit JAK2 V617F positive 165 15 180 JAK2 V617F negative 0 293 293 Total 165 308 473 The specimens yielding discordant results appeared to have mutation levels below the BDS detection capability (around 10%). Because Sanger sequencing is not as sensitive as the JAK2 assay, and the JAK2 assay sensitivity is 1%, a separate study was conducted using a validated next generation sequencing (NGS) method to detect JAK2 V617F allele in the 15 discordant samples (9 ET, 5 PMF, and 1 PV), as well as a randomly selected set of 22 JAK2 V617F concordant specimens (11 positive and 11 negative specimens). All 15 discordants tested positive by NGS, agreeing with the ipsogen JAK2 RGQ PCR Kit. All concordant samples tested the same with NGS. b. Whole blood stability A specimen stability was conducted with 6 PV specimens (3 JAK2 V617F positive and 3 JAK2 V617F negative samples in K2-EDTA tubes) collected and stored at 4°C or room temperature (RT) before proceeding to gDNA extraction. Specimen stability was tested by assessing the agreement between qualitative results, and separately, for trends in changes in the percent mutation measured with the JAK2 Kit at each time point (i.e., baseline, day 2, 3, 4 and day 4 + 2h) and storage condition (RT or 2-8°C). At each extraction, 3 aliquots per sample were extracted using QIAsymphony. The results passed acceptance criteria and support the claim that whole blood can be stored at RT and 2-8°C for 96 hours before being processed for gDNA extraction to assess the JAK2 V617F status with the JAK2 Kit. 9 2. Comparison studies: a. Method comparison with predicate device: Not applicable. b. Matrix comparison: Not applicable. 3. Clinical studies: Not applicable. 4. Clinical cut-off: Specimens < 1% are considered negative and no value is generated. Specimens ≥1% are considered positive. The assay reports the JAK2 percentage because the additional information on potential mutant allele burden enhances diagnostic evaluation, however the assay is not intended for quantitative use. There is currently no consensus on the clinical value of extremely low JAK2 V617F loads, however a 1% mutation load is considered by experts and literature (Tefferi, 2011 and Martinaud, 2010) as a meaningful cut-off for reporting JAK2 V617F positivity. 5. Expected values/Reference range: The assay is not intended for quantitative use. Low JAK2 allele has been detected in subjects without MPNs. . N. Instrument Name: QIAGEN Rotor-Gene Q MDx platform using Rotor-Gene AssayManager software version 2.1. The instrument was cleared by FDA under K113319 on February 06, 2012. O. System Descriptions: 1. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes ____X____ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No ___X_____ 10 2. Software: FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: Yes ___X____ or No ________ 3. Specimen Identification: Whole blood. 4. Specimen Sampling and Handling: 4C or RT for 96 hours. 5. Calibration and Quality Control: Installation and calibration are performed by the manufacturer. The assay uses standards for generation of a curve by which the % mutation is assessed. The Instrument and assay employ both in-process QC checks and array QC metrics to assist in identifying problems in the assay and instances in which the assay has failed. P. Other Supportive Instrument Performance Characteristics Data Not Covered In The “Performance Characteristics” Section above: None. Q. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809 and the special controls for this device type. R. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling: