The QMS® Everolimus Assay is intended for the quantitative determination of Everolimus in human whole blood on automated clinical chemistry analyzers. The results obtained are used as an aid in the management of kidney and liver transplant patients receiving Everolimus therapy. This in vitro diagnostic device is intended for clinical laboratory use only.

Device Description

The QMS® Everolimus Assay consists of separately packaged reagents (R1, R2, and Precipitation Reagent) with the following contents and configurations.
R1 Antibody Reagent: <1.0% Anti-Everolimus polyclonal antibody (rabbit) in a buffer as stabilizer and <0.09% sodium azide as preservative. 1 x 22 mL
R2 Microparticle Reagent: <0.6% Everolimus-coated microparticles in buffer containing <0.05% sodium azide as preservative. 1 x 8 mL
Precipitation Reagent: Precipitating reagent, and <0.09% sodium azide as preservative. 1 x 8 mL
The reagents are supplied ready-to-use in liquid form in plastic HDPE bottles, for storage at 2 to 8°C. The reagent set is sufficient for 100 tests.

AI/ML Overview

Here's an analysis of the acceptance criteria and study findings for the Thermo Scientific QMS® Everolimus Assay, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria / Performance Claim	Reported Device Performance
Analytical Sensitivity (LDD)	≤0.51 ng/mL
Functional Sensitivity (LOQ)	2.0 ng/mL (at 20%CV acceptable inter-assay precision and recovery)
Precision (Total run %CV)	≤10.0%
Linearity (Assay range 2-20 ng/mL)	Performs in a linear fashion
Method Comparison with LC/MS (Correlation Equation)	y = 1.07x + 0.19
Method Comparison with LC/MS (Correlation Coefficient)	R = 0.97

2. Sample size used for the test set and the data provenance

Test Set Sample Size: The document does not explicitly state the total number of samples used for the "Method Comparison" study or for other performance tests like precision and linearity. It mentions "Everolimus samples were tested for precision" and "Samples were tested in the QMS® Everolimus Assay and compared to LC/MS."
Data Provenance: The document does not provide details on the country of origin of the data or whether the data was retrospective or prospective.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This section is not applicable as the device is an in-vitro diagnostic assay for quantitative determination of a drug in human whole blood. The "ground truth" for method comparison and analytical performance is established by comparison to a reference method (LC/MS) or by known concentrations of the analyte in manufactured samples (e.g., calibrators, controls). It does not involve human expert interpretation of images or clinical data.

4. Adjudication method for the test set

This is not applicable for this type of in-vitro diagnostic device. Analytical studies like method comparison and precision do not typically involve adjudication by experts.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

This is not applicable. This device is an automated in-vitro diagnostic (IVD) assay, not an AI-powered diagnostic tool requiring human interpretation or an MRMC study.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

This is essentially how the device operates. The QMS® Everolimus Assay is an automated clinical chemistry assay that provides quantitative results. Its performance (analytical sensitivity, precision, method comparison) is evaluated in a standalone manner, meaning the assay itself generates the readings, which are then used by clinicians for patient management. There isn't a "human-in-the-loop" for the direct measurement process itself, although clinicians interpret the results.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The ground truth for the analytical performance studies appears to be:

LC/MS (Liquid Chromatography/Mass Spectrometry): For the "Method Comparison" study, LC/MS served as the reference method for determining Everolimus concentrations.
Known Concentrations: For studies like Analytical Sensitivity (LDD), Functional Sensitivity (LOQ), Precision, and Dilution Recovery, the ground truth would be based on precisely prepared samples with known concentrations of Everolimus (e.g., calibrators, controls, spiked samples).

8. The sample size for the training set

This information is not provided in the summary. For an IVD assay like this, there isn't a traditional "training set" in the sense of machine learning algorithms. Instead, assay development involves extensive testing and optimization using various formulations and spiked samples to establish performance characteristics, rather than a distinct training/test split of clinical data.

9. How the ground truth for the training set was established

As noted above, a distinct "training set" with ground truth in the machine learning sense is not explicitly described or typically applicable for IVD assay development. The "ground truth" during development and optimization would involve using:

Reference standards: Pure Everolimus used to create calibrators and controls with known concentrations.
LC/MS analysis: As a highly accurate reference method to verify concentrations in samples during development.
Spiked samples: Whole blood samples spiked with known amounts of Everolimus to assess recovery and other analytical parameters.

Summary

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K122766

510(k) Summary

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is:

Company / Contact Person

Karen Lee Regulatory Affairs Specialist Thermo Fisher Scientific, Clinical Diagnostics Division 46360 Fremont Blvd. Fremont, CA 94538 Phone: (510) 979-5000 x31814 (510) 979-5422 Fax: E-mail: karen.lee@thermofisher.com

AUG 2 0 2013

Date Prepared

September 7, 2012

Common / Usual Name	QMS® Everolimus Assay
Trade / Proprietary Name	Thermo Scientific QMS® Everolimus Assay
Classification Regulation	21 CFR 862.3840
Device Class	Class II
Device Regulation Panel	Clinical Chemistry and Clinical Toxicology
Product Code	OUF

Regulatory Declarations

Intended Use

QMS® Everolimus Reagents

Legally Marketed Device to Which Equivalency is Claimed

The Thermo Scientific QMS® Everolimus Assay is substantially equivalent to the previously cleared QMS® Everolimus Assay (K100144).

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Device Description

The QMS® Everolimus Assay consists of separately packaged reagents (R1, R2, and Precipitation Reagent) with the following contents and configurations.

Component	Description	Configuration
R1 AntibodyReagent	<1.0% Anti-Everolimus polyclonal antibody (rabbit) in abuffer as stabilizer and <0.09% sodium azide aspreservative.	1 x 22 mL
R2 MicroparticleReagent	<0.6% Everolimus-coated microparticles in buffercontaining <0.05% sodium azide as preservative.	1 x 8 mL
PrecipitationReagent	Precipitating reagent, and <0.09% sodium azide aspreservative.	1 x 8 mL

The reagents are supplied ready-to-use in liquid form in plastic HDPE bottles, for storage at 2 to 8°C. The reagent set is sufficient for 100 tests.

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Comparison	Proposed Device	Predicate
Proprietary Name	Thermo Scientific QMS® Everolimus Assay	QMS® Everolimus Assay (K100144)
Intended Use	The QMS® Everolimus Assay is intended forthe quantitative determination of Everolimus,in human whole blood on automated clinicalchemistry analyzers. The results obtainedare used as an aid in the management ofkidney and liver transplant patients receivingEverolimus therapy.	The QMS® Everolimus Assay is intended forthe quantitative determination of Everolimusin human whole blood on automated clinicalchemistry analyzers. The results obtainedare used as an aid in the management ofkidney transplant patients receivingEverolimus therapy.
Test Principle	The QMS® Everolimus Assay system is ahomogeneous assay utilizing particleagglutination technology and competitivebinding principles.	The QMS® Everolimus Assay system is ahomogeneous assay utilizing particleagglutination technology and competitivebinding principles.
	In particle agglutination assays, the degreeof agglutination (detected by optical methodat 700 nm) is inversely proportional to thequantity of free drug in the reaction well.Hence, if no drug is present in the sample,the antibodies in the QMS® EverolimusAntibody Reagent (R1) will bind only to thebound drug on the particle which will cause itto agglutinate and will result in higherabsorbance. If increased amount ofcompeting drug is present in the sample, thiswill result in decreased binding of bounddrug by the antibody, resulting in a relativedecrease in particle agglutination. This inturn results in lower absorbance. Theprecise relationship between particleagglutination and concentration of theunlabeled drug in the sample is establishedby measuring the absorbance values ofcalibrators with known concentration of thedrug. The absorbance of unknown samplescan be interpolated from the absorbancevalues of the calibration curve and theconcentration of the drug present in thesample can be calculated.	In particle agglutination assays, the degreeof agglutination (detected by optical methodat 700 nm) is inversely proportional to thequantity of free drug in the reaction well.Hence, if no drug is present in the sample,the antibodies in the QMS® EverolimusAntibody Reagent (R1) will bind only to thebound drug on the particle which will cause itto agglutinate and will result in higherabsorbance. If increased amount ofcompeting drug is present in the sample, thiswill result in decreased binding of bounddrug by the antibody, resulting in a relativedecrease in particle agglutination. This inturn results in lower absorbance. Theprecise relationship between particleagglutination and concentration of theunlabeled drug in the sample is establishedby measuring the absorbance values ofcalibrators with known concentration of thedrug. The absorbance of unknown samplescan be interpolated from the absorbancevalues of the calibration curve and theconcentration of the drug present in thesample can be calculated.
Sample Matrix	Human Whole Blood	Human Whole Blood
Reagents	Three Liquid Ready-to-Use reagents(R1.R2 and Precipitation Reagent)	Three Liquid Ready-to-Use reagents(R1,R2 and Precipitation Reagent)
Reagent StorageCondition	2-8°C	2-8°C
Calibrators	Liquid Ready-To-Use(0, 1.5, 3.0, 6.0,12.0 and 20.0 ng/mL)	Liquid Ready-To-Use(0, 1.5, 3.0, 6.0, 12.0 and 20.0 ng/mL)
Controls	Liquid Ready-To-Use(Low, Medium, High)	Liquid Ready-To-Use(Low, Medium, High)
Calibrators andControls StorageCondition	-20°C ± 5°C	-20°C ± 5°C

Comparison of Technological Characteristics

Note: The proposed device is the same assay as the predicate device.

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Performance Testing Summary

Analytical Sensitivity (LDD)

Twenty one replicates of Calibrator A were tested in the QMS® Everolimus Assay. The results demonstrate that the LDD is ≤0.51 ng/mL which is in agreement with our currently cleared labeling.

Functional Sensitivity (LOQ)

Functional Sensitivity determines the lowest concentration for which acceptable inter-assay precision and recovery is observed at a 20%CV. The results demonstrate that the LOQ is 2.0 ng/mL, which is in agreement with our currently cleared labeling.

Precision and Accuracy

Everolimus samples were tested for precision following a CLSI protocol. In the study, the total run %CV was less than or equal to 10.0% which is in agreement with our currently cleared labeling.

Method Comparison

Samples were tested in the QMS® Everolimus Assay and compared to LC/MS. The method comparison exhibited correlated well with LC/MS as follows: y = 1.07x + 0.19, R = 0.97.

Dilution Recovery

Samples were tested to demonstrate linearity throughout the assay range of 2-20 ng/mL. Results demonstrate that the assay performs in a linear fashion which is in agreement with our currently cleared labeling.

Conclusion

As summarized, the modification to the indications for use in the Thermo Scientific QMS® Everolimus Assay is substantially equivalent to the originally cleared product (K100144). Substantial equivalence has been demonstrated through performance testing (Section 18) to verify that the device functions as intended and that design specifications have been satisfied.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo consists of a stylized eagle with three lines forming its body and wings. The eagle is facing right. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the eagle.

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MI) 20993-0002

August 20, 2013

Microgenics Corporation C/O Karen Lee ThermoFisher Scientific, Clinical Diagnostics Division 46360 Fremont Blvd FREMONT CA 94538

Re: Ki22766

Trade/Device Name: Thermo Scientific QMS® Everolimus Assay Regulation Number: 21 CFR 862.3840 Regulation Name: Sirolimus test system Regulatory Class: II Product Code: OUF Dated: July 25, 2013 Received: July 29, 2013

Dear Ms. Lee:

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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into cither class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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Page 2-Ms. Lee

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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 toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

Carol C. Benson -S for

Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use Statement

510(k) Number (if known)

K122766

Device Name

Thermo Scientific QMS® Everolimus Assay

Indications For Use

QMS® Everolimus Reagents

Prescription Use _____________________________________________________________________________________________________________________________________________________________

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

(Part 21 CFR 801 Subpart D)

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR) Katherine Serrano -S and the comments of the comments of the comments of the comments of the comments of the comments of the contribution of the contribution of the contribution of the contributi

Division Sign-Off Office of In Vitro Diagnostics and Radiological Health

510(k) K122766

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Regulation Number and Section

§ 862.3840 Sirolimus test system.

(a)
Identification. A sirolimus test system is a device intended to quantitatively determine sirolimus concentrations in whole blood. Measurements are used as an aid in management of transplant patients receiving therapy with sirolimus.(b)
Classification. Class II (special controls). The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Sirolimus Test Systems.” See § 862.1(d) for the availability of this guidance document.