The Waters MassTrak Immunosuppressants Kit is indicated for the quantification of the immunosuppressive drug Tacrolimus (FK506; Prograf) in liver and kidney transplant patient whole blood samples for the purposes of monitoring drug levels to direct subsequent patient dosing.

Device Description

The MassTrak Immunosuppressants Kit for Tacrolimus is an in vitro medical device intended to facilitate quantitative determination of Tacrolimus in human whole blood as an aid in the management of kidney and liver transplant patients receiving Tacrolimus drug therapy. The components of the kit are intended for use with an LC/MS/MS system. The kit materials - calibrators, quality control materials, internal standards, and neat solutions, as well as a MassTrakTM 2.1 x 10 mm C18 cartridge column - have been optimized for use with the Waters Quattro micro and Alliance 2795 System, but can be used with any LC/MS/MS configuration optimized for quantification.

AI/ML Overview

The provided text describes the Waters MassTrak™ Immunosuppressants Kit, an in vitro diagnostic device used for quantifying Tacrolimus in human whole blood. The submission outlines performance data and comparison studies to establish substantial equivalence to predicate devices.

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The document describes various performance studies and their acceptance criteria. The table below synthesizes this information for the MassTrak™ Immunosuppressants Kit.

Performance Characteristic	Acceptance Criteria	Reported Device Performance
Precision/Reproducibility	For within-run precision and total precision, a coefficient of variation (%CV) ≤ 10% is deemed acceptable, based on CLSI EP5-A2.	Precision studies were conducted by assaying three levels of spiked whole blood pools. The results of these studies are not explicitly stated in the summary but were "presented in Section 20: Design Testing Summary Report of the 510(k) submission" and presumably met the ≤ 10% CV criterion.
Linearity/Assay Reportable Range	The assay is deemed to be linear if the coefficients for the second-order and third-order terms are not significantly different from zero at the 95% confidence level, based on CLSI EP6-A.	Linearity was assessed using nine test samples prepared from patient specimens. The summary states that these results are "presented in Section 20: Design Testing Summary Report" and implies they met the linearity criteria.
Patient Sample Stability	Conditions that did not cause a statistically significant change from the initial Tacrolimus concentration (t-test, p ≥ 0.05) or caused a change of ≤ 10% from the initial Tacrolimus concentration were acceptable. (Freeze-thaw study: three cycles).	Patient samples were analyzed before and after storage under defined conditions, including a three-cycle freeze-thaw study. The results are referred to Section 20 and inferred to have met the acceptance criteria.
Sample Dilution	Results were considered acceptable if, for each sample, the Tacrolimus concentration measured for the undiluted sample and the Tacrolimus concentration calculated from the 1:1 diluted sample varied by ≤ 10% of the initial concentration.	A minimum of ten patient samples with Tacrolimus concentrations > 15 ng/mL were analyzed before and after 1:1 dilution with drug-free whole blood and with MassTrak Immunosuppressants Kit Calibrator 1. Results are presented in Section 20 and inferred to have met the acceptance criteria.
Spike & Recovery	Recovery is considered acceptable if the overall mean recovery for each concentration is in the range 90% - 110%.	Recovery performance was assessed using patient samples supplemented with Tacrolimus (5, 10, or 20 ng/mL) and drug-free whole blood spiked with Tacrolimus (0.5 - 30 ng/mL). The summary states these results are in Section 20 and implies they met the 90%-110% recovery range.
Interference Studies	Any interference that causes a change in measured Tacrolimus concentration of > 10% is considered to have a significant effect and must be investigated further to determine the maximum concentration at which no interference is observed. (95% confidence, 95% power).	Potential interferences (exogenous/endogenous materials, anticoagulants, hematocrit) were evaluated according to CLSI EP7-A and FDA guidance. The results are referred to Section 20. The implication is that the concentrations evaluated did not cause a change > 10% or were appropriately investigated.
Accuracy	The results for all samples were considered acceptable by the Tacrolimus International Proficiency Testing Scheme (±3 SD of method mean).	Accuracy was established by measuring Tacrolimus concentrations in 44 samples provided by the Tacrolimus International Proficiency Testing Scheme (www.bioanalytics.co.uk). The summary states that "The results for all samples were considered acceptable by the Scheme (±3 SD of method mean)."
Method Comparison	The results of the Test Method for each tissue type are considered acceptable if the predicted bias at both the lower (5 ng/mL) and upper (15 ng/mL) limits of the therapeutic range for Tacrolimus is ≤ 10%, based on Deming Regression analysis (CLSI EP9-A2). (Minimum of 50 samples for each transplant type compared at each site).	Method comparison studies were conducted against the test laboratory's current methodology, comparing a minimum of 50 samples for each transplant type at each site. The predicted bias was calculated using Deming Regression analysis. The summary implies these criteria were met, with results "presented in Section 20: Design Testing Summary Report". Additionally, results from International Proficiency Testing Samples were compared to EMIT 2000 Tacrolimus device data.

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

Sample Size for Test Set:
- Precision/Reproducibility: Not explicitly stated beyond "three levels of spiked whole blood pools," with "Specimens at each level were analyzed in duplicate twice per day for 20 days." This implies a total of (3 levels * 2 duplicates * 2 runs/day * 20 days) = 240 measurements.
- Linearity: "nine test samples."
- Sample Dilution: "A minimum of ten patient samples."
- Accuracy: "series of 44 samples provided by the Tacrolimus International Proficiency Testing Scheme."
- Method Comparison: "A minimum of 50 samples for each transplant type were compared at each site." The types mentioned are kidney and liver, so at least 100 samples across the two types if only one site, or more if multiple sites were used.
Data Provenance:
- The studies were conducted "at the clinical sites using Alliance HT 2795 High Performance Liquid Chromatography Systems coupled to Quattro micro triple quadrupole mass spectrometers." This suggests a clinical laboratory setting.
- Specific country of origin is not directly stated, but the reference to the "Tacrolimus International Proficiency Testing Scheme (www.bioanalytics.co.uk)" implies international data sources for accuracy and potentially method comparison (UK-based scheme).
- The linearity, sample dilution, and method comparison studies used "patient specimens" or "patient samples," indicating the data is from relevant patient populations.
- The nature of "proficiency testing scheme" samples means they represent retrospective, collected samples used for external quality assessment.
- The precision, stability, spike & recovery, and interference studies utilized "spiked whole blood pools" or "drug-free whole blood," which are laboratory-prepared samples.

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

The concept of "ground truth" established by experts, as typically understood in AI/ML contexts for image interpretation or diagnosis, does not directly apply to this device. This device is an analytical instrument for quantitative determination of a drug concentration.
For Accuracy and Method Comparison: The "ground truth" or reference values for accuracy and method comparison are derived from established reference methods or proficiency testing schemes.
- For the Accuracy study, the reference was "the Tacrolimus International Proficiency Testing Scheme (www.bioanalytics.co.uk)." The acceptable range was defined as "±3 SD of method mean," indicating a consensus or calculated mean from multiple laboratories/methods participating in the scheme, rather than a single expert.
- For Method Comparison, the "ground truth" was implied by the "test laboratory's current methodology (the 'Comparative Method')" which the device was compared against. This comparative method would be a previously validated analytical technique for Tacrolimus quantification.
- No information is provided about individual "experts" establishing a single ground truth; rather, it hinges on established analytical reference systems or comparative methods.

4. Adjudication Method for the Test Set

Adjudication methods (like 2+1, 3+1) are typically used in studies where human readers independently assess data and then resolve discrepancies, often in image interpretation.
This is an in vitro diagnostic device for quantitative drug measurement. The "adjudication" (if one can call it that) is inherent in the analytical process:
- Measurements are performed in replicate (e.g., "duplicate twice per day for 20 days" for precision, "replicate determinations" for linearity, "triplicate determinations" for spike & recovery).
- Statistical methods (e.g., %CV, 95% confidence level, Deming Regression, t-test, ±3 SD of method mean) are used to assess the agreement, consistency, and accuracy of these quantitative measurements against predefined criteria or reference values.
- Thus, there is no human adjudication process described in the conventional sense.

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

No, an MRMC comparative effectiveness study involving human readers and AI assistance was not done.
This device is an in vitro diagnostic (IVD) kit for quantifying drug levels, not an AI-powered diagnostic tool for interpretation by human readers. Its primary function is to provide a quantitative measurement.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, this entire submission describes the standalone performance of the analytical device (MassTrak™ Immunosuppressants Kit) without human-in-the-loop performance in the sense of interpretative AI systems.
The device itself, an LC/MS/MS system with specialized reagents, performs the quantification. While a human operates the instrument and interprets the numerical output, the "performance" described relates to the accuracy, precision, linearity, etc., of the instrument and reagents in generating those numbers.
The acceptance criteria and reported performances directly reflect the standalone analytical capabilities of the kit.

7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)

For this quantitative diagnostic device, the "ground truth" is established by:

Reference Methods/Materials: For accuracy testing, the Tacrolimus International Proficiency Testing Scheme provides reference values (implied consensus/method mean). For method comparison, another established and validated laboratory methodology serves as the comparator.
Calculated or Spiked Concentrations: For studies like linearity, precision, spike & recovery, and interference, the "ground truth" concentrations are known either because they were precisely spiked into a matrix or calculated from known mixtures.
Statistical Definitions: Acceptance criteria often define "ground truth" in terms of statistical acceptability (e.g., %CV ≤ 10%, bias ≤ 10%, p ≥ 0.05).

8. The Sample Size for the Training Set

The concept of "training set" is not directly applicable in the context of this 510(k) submission for a non-AI-based IVD device.
This device is an analytical chemistry kit, not a machine learning algorithm that is "trained" on a dataset.
The manufacturer would have performed internal R&D, method development, and optimization studies, which could be considered analogous to "training," but these activities do not typically involve a formally defined "training set" with established ground truth in the same way an AI model does.

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

As stated above, a formal "training set" as understood in AI/ML is not applicable.
The "ground truth" during method development would have been established through a combination of:
- Reference standards: Using highly pure Tacrolimus standards at known concentrations to calibrate and verify the analytical method.
- Internal validation: Running samples with known "spiked-in" concentrations or comparing with existing, well-established (often more laborious) reference methods to optimize the LC/MS/MS parameters, reagent formulations, and analytical protocols.
- Iterative refinement: Adjusting parameters until desired performance characteristics (e.g., sensitivity, specificity, linearity) are achieved.

Summary

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510(k) SUMMARY

Date of Summary: December 28, 2006

Product Name

Waters MassTrakTM Immunosuppressants Kit

Sponsor

Waters Corporation 34 Maple Street Milford, MA 01757

Manufacturer

Chromsystems Instruments & Chemicals GmbH Heimburgstr. 3 D-81243 München, Germany

Correspondent

Fran White, President MDC Associates, LLC 163 Cabot Street Beverly, MA 01915

telephone:	(978) 927-3808
facsimile:	(978) 927-1308
email:	fran@mdcassoc.com

Substantially Equivalent Devices

The MassTrak Immunosuppressants Kit is substantially equivalent to the Dade Behring Emit® 2000 Tacrolimus Assay and Calibrators and the Microgenics CEDIA® Tacrolimus Assay and Calibrators in its intended use and for the quantitative determination of Tacrolimus concentration in human whole blood as an aid in the management of kidney and liver transplant patients receiving therapy with Tacrolimus.

ITEM	DEVICE	PREDICATE I	PREDICATE II
Intended Use	The Waters MassTrakTMImmunosuppressants Kitis indicated for thequantification of theimmunosuppressive drugTacrolimus (FK506;Prograf) in liver andkidney transplant patientwhole blood samples forthe purposes ofmonitoring drug levels todirect subsequent patientdosing.	Intended for in vitroquantitative analysis ofTacrolimus andmetabolite in humanwhole blood as an aid inthe management ofTacrolimus therapy inliver and kidneytransplant patients.The Emit® 2000Tacrolimus Calibrators areintended for use as areference in measuringTacrolimus in humanwhole blood using the	Intended for the quantitativedetermination of Tacrolimusin human whole blood usingautomated clinical chemistryanalyzers as an aid in themanagement of kidney andliver transplant recipientsreceiving Tacrolimustherapy.CEDIA® TacrolimusCalibrators are intended forcalibration of the CEDIA®TacrolimusAssay in whole blood.

K063868

MAY 25 2007

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ITEM	DEVICE	PREDICATE I	PREDICATE II
	Waters MassTrak™Immunosuppressants Kit	Emit® 2000 TacrolimusAssay	CEDIA® Tacrolimus Assay
		Emit® 2000 TacrolimusCalibratorsEmit® 2000 TacrolimusAssay.	CEDIA® TacrolimusCalibrators
Analyte	Tacrolimus	Tacrolimus	Tacrolimus
Matrix	Whole blood	Whole blood	Whole blood
Assay range	3-30 ng/mL	2-30 ng/mL	2-30 ng/mL
Analyticalspecificity	Liquid chromatography /tandem massspectrometry(LC/MS/MS)	EMIT (Enzyme MultipliedImmunoassayTechnology)	Clinical Chemistry Analyzer
Calibrator	Six (6) levels(0 ng/mL 3 ng/mL, 6ng/mL, 12 ng/mL, 20ng/mL, and 30 ng/mL ofTacrolimus)	Six (6) levels(0 ng/mL 2.5 ng/mL, 5ng/mL, 10 ng/mL, 20ng/mL, and 30 ng/mL ofTacrolimus)	Two (2) levels(0 and 30ng/mL)
Storage	Kit is stored at -20°CReconstituted calibratorsand QCs are stored at 2°Cto 8°C	Reagents are stored at 2°Cto 8°C	Reagents are stored at 2°C to8°CCalibrators are stored at-20°C
Stability	Kit stable for up to 2 yearsfrom manufacture datewhen stored as indicatedabove	Reagents stable for up to18 months frommanufacture date whenstored as indicated above	Reagents and Calibratorsstable for up to 24 monthsfrom manufacture datewhen stored as indicatedabove

Product Description

Tacrolimus (FK506) is an immunosuppressive agent approved by FDA that has been successfully implemented following the transplantation of kidney and liver organs. Monitoring and maintenance of appropriate blood levels of Tacrolimus is important to prevent rejection, infection, and other adverse events. Analytical methodology using a high-performance liquid chromatography (HPLC) apparatus equipped with a tandem mass spectrometer detector (LC/MS/MS) is considered to be a candidate reference method for Tacrolimus quantification. Sample preparation is based on simple protein precipitation and centrifugation to isolate the supernatant that is suitable for analysis by LC/MS/MS.

The components of the kit are intended for use with an LC/MS/MS system. The kit

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materials - calibrators, quality control materials, internal standards, and neat solutions, as well as a MassTrakTM 2.1 x 10 mm C18 cartridge column - have been optimized for use with the Waters Quattro micro and Alliance 2795 System, but can be used with any LC/MS/MS configuration optimized for quantification. System calibration is performed using the kit calibrators, and analysis is completed with the aid of the internal standard, ascomycin. The neat solution is used only for tuning the mass spectrometer. The HPLC cartridge columns was selected to isolate Tacrolimus from compounds extracted from the sample that may lead to ion suppression.

Intended Use

Summary of Technology

Sample preparation is based on simple protein precipitation. Whole-blood samples are treated with an organic solvent to precipitate the protein and extract the compound of interest into the organic phase. The supernatant from a protein-precipitated whole-blood sample is injected into an on-line, solid phase, extraction device to perform a preliminary clean-up of the prepared sample. The internal standard and analyte of interest are then eluted into the ionization source of the tandem mass spectrometer.

The first stage of mass spectrometry selects precursor ions from the ion source according to their mass-to-charge ratios (m/z). Ions whose m/z ratios correspond to that of the analyte of interest are passed to a collision cell where they collide with a neutral gas, generating structurally specific product ions. The second stage of mass spectrometry passes ions corresponding to one of these product ions (usually the most abundant) to the detector. Therefore, interferences with the signal generated by the analyte of interest will be seen only if the interfering chemical entity generates precursor and product ions of the same m/z values (that is, structural isomers),

The assay method requires the user to tune the instrument in the presence of ammonium acetate. Ammonium adducts are created which are then measured by the mass spectrometer. The most prominent product ion (m/z 768) of the ammonium adduct of Tacrolimus (m/z 821) is detected using tandem mass spectrometry. The measured response of Tacrolimus is compared to the measured response of the internal standard.

The quantification of Tacrolimus in whole blood extracts is made against a linear standard curve prepared using reconstituted freeze-dried whole blood matrix calibrators (6 levels, with targets varying by lot number). The analysis is controlled using three levels of reconstituted freeze-dried whole blood matrix quality control materials (with targets varying by lot number).

Performance Data

All performance data for the MassTrak Immunosuppressants Kit were gathered at the clinical sites using Alliance HT 2795 High Performance Liquid Chromatography Systems

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coupled to Quattro micro triple quadrupole mass spectrometers. Data and results are presented in Section 20: Design Testing Summary Report of the 510(k) submission.

1. Analytical Performance:
- a. Precision/Reproducibility

Precision studies were conducted by assaying three levels of spiked whole blood pools according to CLSI EP5-A2. The pools were prepared from EDTA drug free whole blood with Tacrolimus spiked at three analytical levels: Low, Medium and High. Specimens at each level were analyzed in duplicate twice per day for 20 days. For within-run precision and total precision, a coefficient of variation (%CV) ≤ 10% is deemed acceptable.

b. Linearity/assay reportable range
Linearity was assessed according to CLSI EP6-A using nine test samples. The test samples were prepared by mixing patient specimens with low and high Tacrolimus concentrations in defined proportions such that the final Tacrolimus concentrations were known relative to each other. Replicate determinations of each test sample were made. Second order and third order polynomial curves are fitted to the data and the assay is deemed to be linear if the coefficients for the second order and third order terms are not significantly different from zero at the 95% confidence level.
c. Patient Sample Stability
Patient samples were analyzed in replicate before and after storage under defined conditions to determine the effect of those conditions on the Tacrolimus concentration measured by the device. A freeze-thaw study (three cycles) was also conducted. Conditions that did not cause a statistically significant change from the initial Tacrolimus concentration (ttest, p ≥ 0.05) or caused a change of ≤ 10% from the initial Tacrolimus concentration were acceptable.
d. Sample Dilution
A minimum of ten patient samples with Tacrolimus concentrations > 15ng/mL were analyzed before and after 1:1 dilution with drug-free whole blood and 1:1 dilution with MassTrak Immunosuppressants Kit Calibrator 1. The results were considered acceptable if, for each sample, the Tacrolimus concentration measured for the undiluted sample and the Tacrolimus concentration calculated from the sample diluted 1:1 with drugfree whole blood or MassTrak Immunosuppressants Kit Calibrator 1 varied by ≤ 10% of the initial concentration.
Spike & Recovery e.
The recovery performance of the device was assessed using patient samples supplemented with 5, 10 or 20 ng/mL Tacrolimus and using drug-free whole blood spiked with Tacrolimus from 0.5 - 30 ng/mL to ensure that the analytical range of the assay was covered. Triplicate determinations of each sample were made and recovery is considered acceptable if the overall

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mean recovery for each concentration is in the range 90% - 110%.

f. Interference Studies
Potential interferences were evaluated according to CLSI EP7-A and with reference to the list of potential interfering substances in the FDA Class II Special Controls Document and in the FDA Guidance for Industry Bioanalytical Method Validation Document. Known amounts of exogenous or endogenous materials were spiked into separate aliquots of a base pool of drug-free whole blood that had been supplemented with Tacrolimus at a concentration of approximately 20 ng/mL. To test the effect of anticoagulants at up to 5x the normal concentration and to test the effect of hematocrit 15% to 60%, drug-free whole blood was first adjusted to simulate the appropriate condition before spiking with Tacrolimus to a concentration of approximately 20 ng/mL. In all cases, sufficient replicate determinations were made to ensure 95% confidence and 95% power. Any interference that causes a change in measured Tacrolimus concentration of > 10% is considered to have a significant effect and must be investigated further to determine the maximum concentration at which no interference is observed.
g. Accuracy
The accuracy of the measurements performed using the MassTrak Immunosuppressants Kits was established by measuring the Tacrolimus concentrations in a series of 44 samples provided by the Tacrolimus International Proficiency Testing Scheme (www.bioanalytics.co.uk). The results for all samples were considered acceptable by the Scheme (±3 SD of method mean).

2. Comparison Studies

Method Comparison a.
Method comparison studies were conducted according to CLSI EP9-A2 to compare the results obtained with the MassTrak Immunosuppressants Kit (the "Test Method") with those obtained using the test laboratory's current methodology (the "Comparative Method"). According to the FDA Special Controls Document, a minimum of 50 samples for each transplant type were compared at each site. Duplicate analyses of each patient sample were performed in each of two Test Method assays and two Comparative Method assays, with all four assays performed on the same day. A maximum of 10 patient samples were compared in one day. The predicted bias at the lower (5 ng/mL) and upper (15 ng/mL) limits of the therapeutic range for Tacrolimus (Lake Louise Consensus Conference on Tacrolimus monitoring, Oellerich et al, 1998) are calculated using Deming Regression analysis as described in EP9-A2 and the results of the Test Method for each tissue type are considered acceptable if the bias at both concentrations is ≤ 10% .

In addition, the Tacrolimus concentrations for a series of International Proficiency Testing Samples (http://www.bioanalytics.co.uk/html/

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tacrolimus scheme.html) were determined using the MassTrakTM Immunosuppressants Kit and the results compared to those reported to the Scheme for the same samples analyzed using the EMIT 2000 Tacrolimus device.

Statement of Safety and Efficacy

The information provided in this pre-market notification demonstrates that the MassTrak Immunosuppressants Kit is substantially equivalent to the currently-marketed CEDIA® Tacrolimus Assay and Emit® 2000 Tacrolimus Assay.

Waters Corporation has presented laboratory testing in this pre-market notification. Data and results were collected and prepared in accordance with the established guideline, "Class II Special Controls Guidance Document: Cyclosporine and Tacrolimus Assays; Guidance for Industry and FDA" September 16, 2002.

The information presented provides assurance that the MassTrak Immunosuppressants Kit will meet the requirements that are considered acceptable for its intended use.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three lines forming its body and wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

MAY 2 5 2007

Waters Corporation c/o Ms. Fran White MDC Associates, LLC 163 Cabot Street Beverly, MA 01915

Re: K063868

Trade/Device Name: MassTrak™ Immunosuppressants Kit Regulation Number: 21 CFR 862.1678 Regulation Name: Tacrolimus test system Regulatory Class: Class II Product Code: MLM, JIT, JJX Dated: May 18, 2007 Received: May 21, 2007

·Dear Ms. White:

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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to Iogally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0490. Also, please cotte the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its tolloffree mumber (800) 638-2041 or (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Jean M. Cooper, M.S., D.V.M.

Séan M. Cooper, M.S., D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known):

Waters MassTrak™ Immunosuppressants Kit Device Name:

Indications For Use:

Prescription Use XXX (Part 21 CFR 801 Subpart D)

AND/OR

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

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Division Sign-Off

Division Diagnostic Device
Office of In Vitro Diagnostic Device
Office in and Safety Office of and Safety

Page 1 of

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.