THERMO SCIENTIFIC QMS EVEROLIMUS REAGENTS, CALIBRATORS AND CONTROLS

{0}------------------------------------------------ ## 510(k) SUMMARY This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of Safe Medical Devices Act of 1990 and 21 CFR 807,92 The assigned 510(k) number is: K100144 ## COMPANY/CONTACT PERSON Lisa Charter Manager, Requlatory Affairs Microgenics Corporation Thermo Fisher Scientific, Clinical Diagnostics Division 46360 Fremont Blvd. Fremont, CA 94538-6406 (510) 979-5142 Office (510) 979-5422 Fax Lisa. Charter@ThermoFisher.com ## DATE PREPARED January 12, 2011 #### DEVICE NAME | Trade Name: | Thermo Scientific QMS® Everolimus Assay | |------------------------|-----------------------------------------------| | | Thermo Scientific QMS® Everolimus Calibrators | | | Thermo Scientific QMS® Everolimus Controls | | Common Name: | QMS® Everolimus Assay System | | Device Classification: | Sirolimus test system | | Regulation number: | 21 CFR 862.3840 | | Product Code: | NRP | #### INTENDED USE The QMS® Everolimus assay is intended for the quantitative determination of everolimus, the active ingredient of Zortress®, in human whole blood on automated clinical chemistry analyzers. The results obtained are used as an aid in the management of kidney transplant patients receiving Everolimus therapy. This in vitro diagnostic device is intended for clinical laboratory use only. The QMS Everolimus Calibrators set is intended for use in calibration of the QMS Everolimus Assay. The QMS® Everolimus Controls set is intended for use in quality control of the QMS® Everolimus Assay. ## SUBSTANTIALLY EQUIVILANT PREDICATE DEVICE Thermo Scientific QMS® Everolimus Assay is substantially equivalent to the previously cleared CEDIA Sirolimus Assay (K034069). #### PRINCIPLE OF THE ASSAY The QMS® Everolimus Assay system is a homogeneous assay utilizing particle agglutination technology and competitive binding principles. {1}------------------------------------------------ In particle agglutination assays, the degree of agglutination (detected by optical method at 700m) is inversely proportional to the quantity of free drug in the reaction well. Henrio music pressming he on the particle which will cause it to agglutinate and will result in higher absorbance. If increased amount of competing drug is present in the sample, this will result in decreased binding of bound drug by the antibody, resulting in a relative decrease in particle agglutination. This in turn results in lowler absorbance. The precise relationship between particle agglutination of the unlabeled drug in the sample is established by measuring the absorbance values of calibrators with known concentration of the The absorbance of unknown samples can be interpolated from the absorbance values of the drug. calibration curve and the concentration of the drug present in the sample can be calculated. | Comparison | Predicate Device | Thermo Scientific<br>QMS® Everolimus Assay | |----------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | | CEDIA® Sirolimus Assay (K034069) | | | Intended Use | The CEDIA® Sirolimus Assay is an in vitro<br>diagnostic medical device intended for the<br>quantitative determination of sirolimus in human<br>whole blood using automated clinical chemistry<br>analyzers as an aid in the management of<br>sirolimus therapy in renal transplant patients<br>taking sirolimus. | The QMS® Everolimus Assay is intended for<br>the quantitative determination of everolimus,<br>the active ingredient of Certican®, in human<br>whole blood on automated clinical chemistry<br>analyzers. The results obtained are used as<br>an aid in the management of kidney transplant<br>patients receiving Everolimus therapy. | | Test Principle | The CEDIA® Sirolimus Assay uses recombinant<br>DNA technology (US Patent No. 4708929) to<br>produce a unique homogenous enzyme<br>immunoassay system.16 The assay is based<br>on the enzyme β-galactosidase, which has<br>been genetically engineered into two inactive<br>fragments. These fragments spontaneously<br>reassociate to form fully active enzymes that, in<br>assay format, cleave a substrate, generating a<br>color change that can be measured<br>spectrophotometrically.<br>In the assay, analyte in the specimen competes<br>with analyte conjugated to one inactive<br>fragment of β-galactosidase for antibody<br>binding site. If analyte is present in the sample,<br>it binds to antibody, leaving the inactive enzyme<br>fragments free to form active enzymes.<br>If analyte is not present in the sample, antibody<br>binds to analyte conjugated to the inactive<br>fragment, inhibiting the reassociation of inactive<br>β-galactosidase fragments, and no active<br>enzyme is formed. The amount of active<br>enzyme formed and resultant absorbance<br>change are directly proportional to the amount<br>of analyte present in the sample. | The QMS® Everolimus Assay system is a<br>homogeneous assay utilizing particle<br>agglutination technology and competitive<br>binding principles.<br>In particle agglutination assays, the degree of<br>agglutination (detected by optical method at<br>700nm) is inversely proportional to the<br>quantity of free drug in the reaction well.<br>Hence, if no drug is present in the sample, the<br>antibodies in the QMS® Everolimus Antibody<br>Reagent (R1) will bind only to the bound drug<br>on the particle which will cause it to<br>agglutinate and will result in higher<br>absorbance. If increased amount of<br>competing drug is present in the sample, this<br>will result in decreased binding of bound drug<br>by the antibody, resulting in a relative<br>decrease in particle agglutination. This in turn<br>results in lower absorbance. The precise<br>relationship between particle agglutination and<br>concentration of the unlabeled drug in the<br>sample is established by measuring the<br>absorbance values of calibrators with known<br>concentration of the drug. The absorbance of<br>unknown samples can be interpolated from<br>the absorbance values of the calibration curve<br>and the concentration of the drug present in<br>the sample can be calculated. | ## COMPARISON OF TECHNOLOGICAL CHARACTERISTICS {2}------------------------------------------------ | Sample Matrix | Human Whole Blood | Human Whole Blood | |------------------------------------------------|----------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------| | gents | Two Lyophilized reagents (R1 and R2)<br>One Liquid Ready-to-Use Reagent<br>(Precipitation reagent) | Three Liquid Ready-to-Use reagents<br>(R1,R2 and Precipitation reagent) | | Reagent storage<br>Condition | 2-8°C | 2-8°C | | Calibrators | Lyophilized<br>(0 and 30 ng/mL) | Liquid ready-to-use<br>(0, 1.5, 3.0, 6.0,12.0 and 20.0 ng/mL) | | Controls | Lyophilized<br>(Low, Medium, High) | Liquid ready-to-use<br>(Low, Medium, High) | | Calibrator and<br>Control Storage<br>Condition | 5°C ±3°C (2-8°C) | -20°C ± 5°C (15-25°C) | | Calibrator<br>Traceability | Traceable to purified sirolimus | Traceable to calibration based on minimization<br>of bias between the QMS assay and an<br>LCMSMS assay for a specified adult renal<br>transplant sample set. | ## PERFORMANCE TESTING SUMMARY ## Functional Sensitivity (LOQ) Functional Sensitivity determines the lowest concentration which results at a C.V. of 20% that has been measured over an extended period. The LOQ claim will be 2.0 ng/mL. ## Precision and Accuracy Everolimus samples tested for precision following a CLSI protocol. In the study, the total run %CV was less than or equal to 15.0%. #### Method Comparison Samples were tested in the Everolimus Assay and compared to LC/MS. The method comparison exhibited correlated well with LC/MS as follows: System 1 = 0.93x + 0.03 R2 = 0.94 System 2 = 1.00x - 0.08 R2 = 0.95 #### Dilution Recovery Samples were tested to demonstrate linearity throughout the assay range. Results showed that the assay performs in a linear fashion. ## On-Board Open Vial reagent Stability Uncapped reagents were stored in an analyzer and all calibrators and controls were tested in the assay. Reagents stored on the analyzer are stable for up to 30 days. ## CONCLUSION As summarized, the Thermo Scientific QMS® Everolimus Assay is substantially equivalent to the CEDIA® Sirolimus Assay. Substantial equivalence has been demonstrated through performance testing to verify that the device functions as intended and that design specifications have been satisfied. {3}------------------------------------------------ - Brignol N, McMahon LM, Luo S, et al. High-throughput semi-automated 96-well liguid/liquid 7. extraction and liquid chromatography/mass spectrometric analysis of everolimus (RAD001) and cyclosporine A (CsA) in whole blood. Rapid Commun Mass Spectrom 2002; 15: 1-10. - Streit F, Armstrong VW, Oellerich M, et al. Rapid liquid chromatography-tandem mass spectrometry 8. routine method for simultaneous determination of sirolimus, tacrolimus, and cyclosporine A in whole blood. Clin Chem 2002; 48 (6): 955-958. - 9. Bablok W, Passing H, Bender R, Schneider B. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry. Part III J Clin Chem Clin Biochem 1988; 26 (11): 783-790. - 10. Tholen DW, Kallner A, Kennedy JW, et al. Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline-Second Edition (EP5-A2). Clinical and Laboratory Standards Institute (CLSI), Wayne, PA, 2004. - 11. McEnroe RJ, Burritt MF, Powers DM, et al. Interference Testing in Clinical Chemistry; Approved Guideline-Second Edition (EP7-A2). Clinical and Laboratory Standards Institute (CLSI), Wayne, PA, 2005. ## TRADEMARKS Zortress® is a registered trademark of Novartis®. All other trademarks are the property of Thermo Fisher Scientific Inc. and its subsidiaries. > Microgenics Corporation 46360 Fremont Blvd. Fremont, CA 94538-6406 USA {4}------------------------------------------------ Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle or bird-like symbol on the right. To the left of the symbol, the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion. Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993 Image /page/4/Picture/4 description: The image shows the date February 1, 2011. The month is abbreviated as FEB. The day is the first day of the month. The year is 2011. Microgenics Corporation c/o Ms. Lisa Charter Manager, Regulatory Affairs 46360 Fremont Blvd. Fremont, CA 94538 Re: k100144 > Trade Name: Thermo Scientific QMS® Everolimus Reagents, Thermo Scientific QMS® Calibrators and Thermo Scientific QMS® Controls Regulation Number: 21 CFR 862.3840 Regulation Name: Sirolimus test system. Regulatory Class: Class II Product Codes: OUF, DLJ, LAS Dated: February 3, 2011 Received: February 4, 2011 Dear Ms. Charter: . We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device · reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). {5}------------------------------------------------ Page 2 – If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance. You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its tolli the (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html. Sincerely yours, C.C. Courtney Harper, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health Enclosure {6}------------------------------------------------ # Indication for Use 510(k) Number (if known): K100144 Device Name: Thermo Scientific QMS® Everolimus Reagents Thermo Scientific QMS® Everolimus Calibrators Thermo Scientific QMS® Everolimus Controls Indication For Use: The QMS® Everolimus assay is intended for the quantitative determination of everolimus, the active ingredient of Zortress® in human whole blood on automated clinical chemistry analyzers. The results obtained are used as an aid in the management of kidney transplant patients receiving Everolimus therapy. This in vitro diagnostic device is intended for clinical laboratory use only. The QMS® Everolimus Calibrator set is intended for use in calibration of the QMS® Everolimus Assay. The QMS® Everolimus Control set is intended for use in quality control of the QMS® Everolimus Assay. And/Or Prescription Use × (21 CFR Part 801 Subpart D) Subpart C) Over the Counter Use (21 CFR Part 801 Page 1 of 1 . (PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED) Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD) Carol C. Benson Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety 510(k) k100144