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

The QMS® Tacrolimus Calibrator set is intended for use in calibration of the QMS® Tacrolimus Immunoassay.

Device Description

The QMS® Tacrolimus Immunoassay consists of separately packaged reagents (Reagent 1, Reagent 2 and Extraction Reagent) and calibrators (Calibrator A, B, C, D, E, and F).

Reagent 1 (Antibody Reagent): <1.0% Anti-Tacrolimus monoclonal antibody (rabbit) in a buffer as stabilizer and <0.09% sodium azide as preservative. Configuration: 1 x 18 mL.
Reagent 2 (Microparticle Reagent): <0.3% Tacrolimus-coated microparticles in buffer containing <0.09% sodium azide as preservative. Configuration: 1 x 12 mL.
Extraction Reagent: 300 mM Zinc Sulfate and <0.09% sodium azide as preservative. Configuration: 1 x 50 mL.

QMS® Tacrolimus Reagents are provided ready-to-use in liquid form and are to be stored at 2 to 8°C until the expiration date on the label.

Calibrator Level, Target Concentration (ng/mL), Configuration:
Calibrator A, 0.0, 1 x 4 mL
Calibrator B, 2.0, 1 x 2 mL
Calibrator C, 5.0, 1 x 2 mL
Calibrator D, 10.0, 1 x 2 mL
Calibrator E, 20.0, 1 x 2 mL
Calibrator F, 30.0, 1 x 2 mL

The QMS® Tacrolimus Calibrator kit is provided separately and packaged in amber glass bottles in a rectangular cardboard box with a 6-bottle divider. The calibrators are provided in liquid form and are to be stored at -20℃ ± 5℃ until the expiration date on the label. They are ready-to-use upon thawing.

AI/ML Overview

Here's an analysis of the acceptance criteria and study information for the QMS® Tacrolimus Immunoassay, based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (Implied/Contextual)	Reported Device Performance
Functional Sensitivity (LOQ)	Lowest concentration with ≤20% inter-assay CV over extended period	0.9 ng/mL
Precision (Total-Run)	≤7.3% CV	≤7.3% CV (at various levels across the assay range)
Dilution Recovery (Linearity)	Demonstrates linearity throughout the assay range	Linear from 0.8 to 29.9 ng/mL
Spike Recovery	≤10% error	≤10% error (for all samples)
Method Comparison (vs. LC-MS/MS)	High correlation (R value close to 1, slope close to 1, intercept close to 0)	y = 1.111x + 0.53, R = 0.972
Method Comparison (vs. Predicate Device)	High correlation (R value close to 1, slope close to 1, intercept close to 0)	y = 1.126x - 0.03, R = 0.937
Specificity (Major Metabolites)	Acceptable level of cross-reactivity	Partial cross-reactivity
Specificity (Co-administered/OTC Drugs)	Minimal to no cross-reactivity	Minimal to no cross-reactivity
Interfering Substances	≤10% error	≤10% error (at concentrations tested)
Reagent Stability (Accelerated)	Stable for acceptable duration	Up to 13 months at 2-8°C
Reagent On-board Stability	Stable for acceptable duration	Up to 35 days on Beckman AU680® clinical analyzer
Calibrator Stability (Accelerated)	Stable for acceptable duration	Up to 15 months at -20°C
Calibrator Open Vial Stability	Stable for acceptable duration while capped	42 days at 2-8°C

Note: The document implies acceptance criteria based on standard laboratory practices for in vitro diagnostics. Specific numerical thresholds for "high correlation" or "acceptable level" for parameters like comparison studies and specificity are not explicitly stated as acceptance criteria but are inferred from the reported results being presented as evidence of performance.

2. Sample Size Used for the Test Set and Data Provenance

The document does not explicitly state the specific number of samples used for the "test set" for each performance study. It mentions "samples were tested" implying internal validation.

Functional Sensitivity (LOQ): Not specified.
Precision: Not specified.
Dilution Recovery: Not specified.
Spike Recovery: Not specified.
Method Comparison: Not specified. It indicates "samples were tested" and compared to LC-MS/MS and the predicate device.
Specificity: Not specified. Indicated "studies were conducted for available major metabolites... medications routinely co-administered... and other over-the-counter drugs."
Interfering Substances: Not specified. Indicated "endogenous substances... were tested."
Reagent Stability: Not specified.
Calibrator Stability: Not specified.

Data Provenance: The studies appear to be internal validation studies conducted by Thermo Fisher Scientific. The document does not specify country of origin for the data, nor does it explicitly state whether the data was retrospective or prospective, though it's typically prospective for performance validation.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

This information is not applicable to this type of device (immunoassay). The "ground truth" for an immunoassay is established by reference methods or known concentrations, not by expert interpretation of images or other subjective data. For example:

Method Comparison: The "ground truth" is provided by the LC-MS/MS method (a gold standard analytical technique for tacrolimus quantification). The predicate device also serves as a comparison.
Dilution Recovery and Spike Recovery: The "ground truth" is the known concentration of tacrolimus added to the samples.
Specificity: The "ground truth" for cross-reactivity is the known chemical structure and concentration of the potential interfering substances.

4. Adjudication Method for the Test Set

This is not applicable to this type of device. Adjudication methods (like 2+1, 3+1) are typically used in studies where multiple human readers independently assess data (e.g., medical images) and a consensus is needed to establish ground truth or resolve discrepancies. For this immunoassay, results
are quantitative measurements, not subjective interpretations.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. This type of study assesses how human readers' performance changes with an AI aid. The QMS® Tacrolimus Immunoassay is an in vitro diagnostic device that quantifies a substance in whole blood through an automated process, not an AI system that assists human interpretation of complex medical cases.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, the performance studies detailed in the summary (Functional Sensitivity, Precision, Dilution Recovery, Spike Recovery, Method Comparison, Specificity, Interfering Substances, and Stability) represent the standalone performance of the QMS® Tacrolimus Immunoassay. This device operates as an automated system to quantify tacrolimus, without direct human intervention in the interpretative process during testing. The results are generated by the algorithm/device itself.

7. The Type of Ground Truth Used

The ground truth used for validating the QMS® Tacrolimus Immunoassay stems from:

Reference Method: For method comparison, the LC-MS/MS (Liquid Chromatography-Mass Spectrometry/Mass Spectrometry) method served as the primary reference standard. This is considered a highly sensitive and specific analytical technique for drug quantification.
Known Concentrations: For studies like Functional Sensitivity, Dilution Recovery, Spike Recovery, Specificity, and Interfering Substances, the ground truth was based on samples with known, precisely prepared concentrations of tacrolimus, its metabolites, co-administered drugs, or endogenous interfering substances.
Predicate Device Comparison: The previously cleared Abbott ARCHITECT® Tacrolimus Assay served as a comparative reference method for demonstrating substantial equivalence.

8. The Sample Size for the Training Set

The document does not specify a training set sample size. For an immunoassay, the concept of a "training set" in the context of machine learning (where algorithms learn from data) is not directly applicable in the same way. The immunoassays are developed and optimized through iterative processes using various reagents, controls, and calibration materials, rather than "training" an algorithm on a distinct dataset.

9. How the Ground Truth for the Training Set Was Established

As noted above, a traditional "training set" with ground truth in the sense of machine learning is not described or applicable here. The development and optimization of an immunoassay rely on established chemical and biological principles, precise formulation of reagents, and validation against reference methods and known standards to ensure accuracy and reliability. The ground truth for such development is built upon fundamental analytical chemistry and knowledge of the analyte (tacrolimus).

Summary

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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: K123343

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 Fax: (510) 979-5422 karen.lee@thermofisher.com E-mail:

Date Prepared

October 24, 2012

Common / Usual Name	QMS® Tacrolimus Immunoassay
Trade / Proprietary Name	Thermo Scientific QMS® Tacrolimus ImmunoassayThermo Scientific QMS® Tacrolimus Calibrators
Classification Regulation	21 CFR 862.1678, Tacrolimus Test System21 CFR 862. 1150, Calibrator
Device Class	Class II
Device Regulation Panel	Clinical Chemistry
Product Code	MLM, JIT

Regulatory Declarations

Intended Use

QMS® Tacrolimus Immunoassay

QMS® Tacrolimus Calibrators

The QMS® Tacrolimus Calibrator set is intended for use in calibration of the QMS® Tacrolimus Immunoassay.

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Legally Marketed Device to Which Equivalency is Claimed

The Thermo Scientific QMS® Tacrolimus Immunoassay is substantially equivalent to the previously cleared Abbott ARCHITECT® Tacrolimus Assay (K070820).

Device Description

The QMS® Tacrolimus Immunoassay consists of separately packaged reagents (Reagent 1, Reagent 2 and Extraction Reagent) and calibrators (Calibrator A, B, C, D, E, and F).

Component	Description	Configuration
Reagent 1(Antibody Reagent)	<1.0% Anti-Tacrolimus monoclonal antibody (rabbit) in a buffer as stabilizer and <0.09% sodium azide as preservative	1 x 18 mL
Reagent 2(Microparticle Reagent)	<0.3% Tacrolimus-coated microparticles in buffer containing <0.09% sodium azide as preservative	1 x 12 mL
Extraction Reagent	300 mM Zinc Sulfate and <0.09% sodium azide as preservative	1 x 50 mL

Reagent Kit Contents and Configurations 1.

QMS® Tacrolimus Reagents are provided ready-to-use in liquid form and are to be stored at 2 to 8°C until the expiration date on the label.

Calibrator Level	Target Concentration (ng/mL)	Configuration
Calibrator A	0.0	1 x 4 mL
Calibrator B	2.0	1 x 2 mL
Calibrator C	5.0	1 x 2 mL
Calibrator D	10.0	1 x 2 mL
Calibrator E	20.0	1 x 2 mL
Calibrator F	30.0	1 x 2 mL

2. Calibrator Kit Contents and Configurations

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Comparison	Proposed Device	Predicate Device
Proprietary Name	Thermo Scientific QMS® TacrolimusImmunoassay	Abbott ARCHITECT® Tacrolimus Assay(K070820)
Intended Use	The QMS® Tacrolimus Immunoassay isintended for the quantitative determinationof tacrolimus in human whole blood onautomated clinical chemistry analyzers.The results obtained are used as an aid inthe management of kidney, liver, and hearttransplant patients receiving tacrolimustherapy. This in vitro diagnostic device isintended for clinical laboratory use only.	The ARCHITECT Tacrolimus assay is achemiluminescent microparticleimmunoassay (CMIA) for the quantitativedetermination of tacrolimus in human wholeblood on the ARCHITECT i System. TheARCHITECT Tacrolimus assay is to beused as an aid in the management of liverand kidney allograft patients receivingtacrolimus therapy.
Test Principle	The QMS® Tacrolimus Immunoassay is ahomogeneous particle-enhancedturbidimetric inhibition immunoassay. Theassay is based on competition betweendrug in the sample and drug coated onto amicroparticle for antibody binding sites ofthe tacrolimus antibody reagent. Thetacrolimus-coated microparticle reagent israpidly agglutinated in the presence of theanti-tacrolimus antibody reagent and in theabsence of any competing drug in thesample. The rate of absorbance change ismeasured photometrically. When a samplecontaining tacrolimus is added, theagglutination reaction is partially inhibited,slowing down the rate of absorbancechange. A concentration-dependent classicagglutination inhibition curve can beobtained with the maximum rate ofagglutination at the lowest tacrolimusconcentration and the lowest agglutinationrate at the highest tacrolimus concentration.	The ARCHITECT Tacrolimus assay is adelayed one-step immunoassay for thequantitative determination of tacrolimus inhuman whole blood using CMIA technologywith flexible assay protocols, referred to asChemiflex. Prior to the initiation of theautomated ARCHITECT sequence, amanual pretreatment step is performed inwhich the whole blood sample is extractedwith a precipitation reagent and centrifuged.The supernatant is decanted into aTransplant Pretreatment Tube, which isplaced onto the ARCHITECT® System.Sample, assay diluent, and anti-tacrolimuscoated paramagnetic microparticles arecombined to create a reaction mixture.Tacrolimus present in the sample binds tothe anti-tacrolimus coated microparticles.After a delay, tacrolimus acridinium-labeledconjugate is added to the reaction mixture.The tacrolimus on the acridinium-labeledconjugate competes for the availablebinding sites on the microparticles.Following incubation, the microparticles arewashed, and pre-trigger and triggersolutions are added to the reaction mixture.The resulting chemiluminescent reaction ismeasured as relative light units (RLUs). Anindirect relationship exists between theamount of tacrolimus in the sample and theRLUs detected by the ARCHITECT®System optics.
Sample Matrix	Human Whole Blood	Human Whole Blood
SamplePreparation	Manual Pretreatment	Manual Pretreatment
Reagent	Liquid Ready-to-Use (Antibody reagent,Tacrolimus coated microparticle reagent,and Extraction reagent)	Liquid Ready-to-Use (Antibody coatedmicroparticle reagent, Tacrolimus conjugatereagent, and Assay diluent)
Calibrator	Liquid Ready-to-Use, six levels (0.0, 2.0,5.0, 10.0, 20.0, and 30.0 ng/mL)	Liquid Ready-to-Use, six levels (0.0, 3.0,6.0, 12.0, 20.0, and 30.0 ng/mL)
Assay Range	1.0 to 30.0 ng/mL	2.0 to 30.0 ng/mL

Comparison of Technological Characteristics

: :

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Summary of Performance Testing

Functional Sensitivity (LOQ)

The Functional Sensitivity or Limit of Quantitation (LOQ) of the assay is defined as the lowest concentration that will demonstrate a Coefficient of Variance (CV) of inter assay precision at 20% that has been measured over an extended period. The Functional Sensitivity or LOQ is 0.9 ng/mL.

Precision

The total-run precision of the QMS® Tacrolimus Immunoassay at various levels across the assay range was determined to be less than or equal to 7.3% CV.

Dilution Recovery

Samples were tested to demonstrate linearity throughout the assay range. The assay is linear from 0.8 to 29.9 ng/mL.

Spike Recovery

Samples were tested to verify the recovery of analyte across the dynamic range of the assay. The recovery for all samples were less than or equal to 10% error.

Method Comparison

Samples were tested in the QMS® Tacrolimus Immunoassay and compared to reference method LC-MS/MS and predicate device Abbott ARCHITECT® Tacrolimus assay. The method comparison between the QMS® Tacrolimus Immunoassay and LC-MS/MS is y = 1.111x + 0.53, R = 0.972. The method comparison between the QMS® Tacrolimus Immunoassay and Abbott ARCHITECT® Tacrolimus assay is y = 1.126x - 0.03, R = 0.937.

Specificity

Specificity studies were conducted for available major metabolites of tacrolimus, medications routinely co-administered with tacrolimus, and other over-the-counter drugs. The studies indicate the QMS® Tacrolimus Immunoassay has partial cross reactivity to major metabolites and minimal to no cross reactivity for co-administered and over-the-counter drugs.

Interfering Substances

Endogenous substances that commonly exist in human whole blood were tested to ensure no interference with the quantitation of tacrolimus using the QMS® Tacrolimus Immunoassay. At the concentrations tested, the interfering substances caused less than 10% error with the QMS® Tacrolimus Immunoassay.

Reagent Stability

The reagents for the QMS® Tacrolimus Immunoassay were tested for real time and accelerated time stability. The reagents are stable for up to 13 months at 2-8℃ based on accelerated studies. The on-board reagent stablity is stable for up to 35 days on the Beckman AU680® clinical analyzer.

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Calibrator Stability

The calibrators for the QMS® Tacrolimus Immunoassay were tested for real time and accelerated time stability. The calibrators are stable for up to 15 months at -20°C based on accelerated studies. The calibrator open vial stability is stable for 42 days at 2-8℃ when stored tightly capped.

Conclusion

Substantial equivalence of the QMS® Tacrolimus Immunoassay to the previously cleared Abbott ARCHITECT® Tacrolimus Assay has been demonstrated through performance testing (Section 18) to verify that the device functions as intended and design specifications have been satisfied.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized symbol resembling an abstract caduceus or a bird-like figure with three curved lines representing wings or streams.

Food and Drug Administration 10903 New Hampshire Avenue

Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

Public Health Service

July 11, 2013

Microgenics Corp. C/O Karen Lee 46360 Fremont Blvd. FREMONT CA 94538

Rc: K123343

Trade/Device Name: Thermo Scientific QMS® Tacrolimus Immunoassay Thermo Scientific QMS® Tacrolimus Calibrators Regulation Number: 21 CFR 862.1678 Regulation Name: Tacrolimus test system Regulatory Class: II Product Code: MLM, JIT Dated: June 18, 2013 Received: June 20, 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 either 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 lisuing (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

510(k) Number (if known): K123343

Device Name: Thermo Scientific OMS® Tacrolimus Immunoassay Thermo Scientific QMS® Tacrolimus Calibrators

Indications for Use:

QMS® Tacrolimus Immunoassay

OMS® Tacrolimus Calibrators

The QMS® Tacrolimus Calibrator set is intended for use in calibration of the QMS® Tacrolimus Immunoassay.

X Prescription Use (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

(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)

Denise Johnson-lyles -S 2013.07.10 07:27:22 -04'00'

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

K123343 510(k)

Page 1 of _l _

Regulation Number and Section

§ 862.1678 Tacrolimus test system.

(a)
Identification. A tacrolimus test system is a device intended to quantitatively determine tacrolimus concentrations as an aid in the management of transplant patients receiving therapy with this drug. This generic type of device includes immunoassays and chromatographic assays for tacrolimus.(b)
Classification. Class II (special controls). The special control is “Class II Special Controls Guidance Document: Cyclosporine and Tacrolimus Assays; Guidance for Industry and FDA.” See § 862.1(d) for the availability of this guidance document.