The AxSYM Cyclosporine assay is a Fluorescence Polarization Immunoassay (FPIA) in vitro reagent system for the quantitative measurement of cyclosporine (cyclosporine A) in human whole blood as an aid in the management of cardiac, liver, and renal transplant patients.

Device Description

The AxSYM Cyclosporine assay requires the use of the AxSYM System, a random and continuous access immunoassay analyzer performs all sample and reagent transfers, incubations, and data processing, and completes the assay with a printed report. Samples (calibrators, controls, and specimens) are pretreated to minimize interference from endogenous protein-bound fluorescent compounds. Sample pretreatment consists of lysing the erythrocytes in the whole blood with Solubilization Reagent and precipitating protein with Precipitation Reagent. Cyclopsorine is dissolved into the liquid phase. The mixture is centrifuged to generate a clarified extract. The AxSYM Cyclopsorine assay is performed on the clarified extract. The AxSYM Cyclosporine Reagents and pretreated sample are pipetted in the following sequence:

Pretreated sample, Cyclosporine Antibody, Cyclosporine Pretreatment and Solution 4 (Line Diluent) required for one test are pipetted by the Sample Probe into one well of a Reaction Vesssel (RV) to form a Sample Solution,
Cyclosporine Fluorescein Tracer is added to a second well of the RV.
The RV is immediately transferred into the Processing Center. Further pipetting is done in the Processing Center by the Processing Probe.
Aliquots of Solution 4 and Sample Solution are dispensed into the RV curvette.
The polarized fluorescent background is measured by the FPIA optical assembly.
Second aliquots of Solution 4 and Sample Solution, and an aliquot of . Cyclosporine Fluorescein Tracer are dispensed into the same RV curvette.
The intensity of polarized fluorescent light is measured by the FPIA optical assembly.

AI/ML Overview

The Abbott AxSYM® Cyclosporine assay is a new device, and its performance was evaluated by comparing it to a predicate device, the Abbott TDx®/TDxFLx® Cyclosporine Monoclonal Whole Blood assay.

1. Table of Acceptance Criteria and Reported Device Performance

The submission does not explicitly state pre-defined acceptance criteria (e.g., minimum correlation coefficient, slope range, intercept range). Instead, it presents the results of a comparison study and concludes that the device is "substantially equivalent" to the predicate. The performance is reported in terms of a linear regression analysis.

Performance Metric	Acceptance Criteria (Implicit - based on substantial equivalence to predicate)	Reported Device Performance (AxSYM vs. TDx/TDxFLx)
Spearman Correlation Coefficient	High correlation indicative of similar measurements	0.974
Slope of Linear Regression	Close to 1.0 (indicating similar magnitude of results)	0.81 (95% CI: 0.80 to 0.82)
Y-axis Intercept of Linear Regression	Close to 0 ng/mL (indicating similar bias at low concentrations)	-4.95 ng/mL (95% CI: -8.11 to -2.12)

2. Sample Size and Data Provenance

Test Set Sample Size: 754 specimens.
- Heart transplant patients: 194
- Kidney transplant patients: 330
- Liver transplant patients: 230
Data Provenance: Not explicitly stated regarding country of origin. The study appears to be retrospective, comparing the new device against the existing predicate device on collected samples.

3. Number of Experts and Qualifications for Ground Truth

This study compares a new quantitative assay (Abbott AxSYM Cyclosporine) against an existing, legally marketed quantitative assay (Abbott TDx/TDxFLx Cyclosporine Monoclonal Whole Blood). In such analytical performance studies for quantitative in vitro diagnostic devices, the "ground truth" is established by the reference method (the predicate device in this case) or a highly accurate laboratory method, rather than through expert human interpretation. Therefore, experts in the traditional sense (e.g., radiologists interpreting images) are not typically involved in establishing ground truth for this type of test.

4. Adjudication Method

Not applicable. As described above, this is an analytical comparison of two quantitative assays. Adjudication methods (like 2+1 or 3+1) are typically used when human interpretation of complex data (e.g., medical images) is involved to establish a consensus ground truth.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

Not applicable. This is an analytical performance study of an in vitro diagnostic device, not a study involving human readers interpreting cases. Therefore, there is no discussion of how human readers improve with or without AI assistance.

6. Standalone Performance

Yes, a standalone performance study was done in the sense that the AxSYM Cyclosporine assay was run independently on the test samples, and its results were then compared to those generated by the predicate device. The performance metrics (correlation, slope, intercept) describe this standalone algorithm's (the AxSYM assay's) agreement with the predicate device.

7. Type of Ground Truth Used

The "ground truth" for comparison was the measurements obtained from the predicate device, the Abbott TDx®/TDxFLx® Cyclosporine Monoclonal Whole Blood assay. This is a common approach for demonstrating substantial equivalence for new in vitro diagnostic devices to existing, legally marketed ones.

8. Sample Size for the Training Set

The document does not provide details about a specific "training set" for the AxSYM Cyclosporine assay. Immunoassays like this are developed using established chemical and immunological principles, and calibration (using calibrators provided with the kit) is a standard part of their operation, not a "training set" in the machine learning sense. The linearity and operating range of the assay would typically be established during the development phase using various concentrations of cyclosporine.

9. How Ground Truth for the Training Set was Established

Not applicable in the machine learning context. For an immunoassay, the "ground truth" for calibrators (which function somewhat analogously to training data by defining the response curve) is established by precise preparations of known concentrations of the analyte (cyclosporine) using highly accurate methods, often traceable to international standards. The document mentions a calibrator range of 0 ng/mL to 800 ng/mL for the AxSYM Cyclosporine.

Summary

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K040761

APR 3 0 2004

510(k) Summary of Safety and Effectiveness for Abbott AxSYM® Cyclosporine

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

Submitter's Name:	Abbott LaboratoriesDiagnostic Division100 Abbott Park RoadAbbott Park, IL 60064-3537
Contact:	Grace LeMieuxPhone: (847) 937-0165Fax: (847) 937-9616
Common Name:	Cyclosporine
Trade Name:	AxSYM® Cyclosporine
FDA Classification:	Sec.862.1235Cyclosporine test system.Class II (special control)
Predicate Device:	Abbott TDx®/TDxFLx® Cyclosporine Monoclonal Whole Blood

Device Description:

Pretreated sample, Cyclosporine Antibody, Cyclosporine Pretreatment and Solution 4 (Line Diluent) required for one test are pipetted by the Sample Probe into one well of a Reaction Vesssel (RV) to form a Sample Solution,
Cyclosporine Fluorescein Tracer is added to a second well of the RV. �
. The RV is immediately transferred into the Processing Center. Further pipetting is done in the Processing Center by the Processing Probe.

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Aliquots of Solution 4 and Sample Solution are dispensed into the RV ● curvette.
The polarized fluorescent background is measured by the FPIA optical ● assembly.
Second aliquots of Solution 4 and Sample Solution, and an aliquot of . Cyclosporine Fluorescein Tracer are dispensed into the same RV curvette.
The intensity of polarized fluorescent light is measured by the FPIA optical ● assembly.

Intended Use:

The Abbott AxSYM® Cyclosporine assay is a Fluorescence Polarization Immunoassay (FPIA) in vitro reagent system for the quantitative measurement of cyclosporinc (cyclosporine A) in human whole blood as an aid in the management of cardiac, liver, and renal transplant patients.

Comparison to Predicate Device:

The Abbott AxSYM Cyclosporine assay is substantially equivalent to Abbott TDx/TDxFLx Cyclosporine Monoclonal Whole Blood in that:

1. Both assays utilize Fluorescence Polarization Immunoassay (FPIA) technology.
1. Both are intended for use in quantitative measurement of cyclosporine (cyclosporine A) in human whole blood as an aid in the management of cardiac, liver, and renal transplant patients.
1. Both assays use mouse monoclonal antibody
1. Both assays require pretreatment of samples (calibrators, controls and patient samples) with solubilization reagent and whole blood precipitation reagent before testing.
1. Both assays utilize cyclosporinc monoclonal whole blood fluorescein tracer.

The Abbott AxSYM Cyclosporine and Abbott TDx/TDxFLx Cyclosporine Monoclonal Whole Blood Differ in that:

1. The AxSYM Cyclosporine Calibrators range is 0 ng/mL to 800 ng/mL and TD/TDxFLx Cyclosporine Calibrators range is 0 ng/mL to 1500 ng/mL.
1. The AxSYM Cyclosporine assay is used on the AxSYM instrument platform and the TDx/TDxFLx Cyclosporinc Monocloncal Whole Blood assay is used on the TDx/TDxFLx instrument.

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Summary of Safety and Effectiveness Information Supporting a Substantially Equivalent Determination:

A comparison study was performed between the AxSYM Cyclosporine and TDx/TDxFLx Cyclosporine Monoclonal Whole Blood assay using 754 specimens (Heart = 194, Kidney = 330, Liver = 230: Total 754). A Passing Bablok linear regression analysis yields a Spearman correlation coefficient of 0.974, a slope of 0.81 (95% confidence interval of 0.80 to 0.82) and a y-axis intercept of -4.95 ng/mL (95% confidence interval of -8.11 to -2.12).

Conclusion:

The Abbott AxSYM Cyclosporine assay is substantially equivalent to Abbott TDx/TDxFLx Cyclosporine Monoclonal Whole Blood, approved under the premarket application P890025/S010.

Prepared and submitted by:

Abbott Laboratories Grace LeMieux Section Manager - Devices ADD Regulatory Affairs 100 Abbott Park Road Abbott Park, IL 60064

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle or bird-like symbol with three curved lines representing its wings or feathers. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES (USA)" is arranged in a circular fashion around the symbol.

Public Health Service

APR 3 0 2004

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Grace LeMieux Section Manager ADD Regulatory Affairs Abbott Laboratories Diagnostic Division 100 Abbott Park Road Abbott Park, IL 60064

Re: K040761

Trade/Device Name: Abbott AxSYM® Cyclosporine Regulation Number: 21 CFR 862.1235 Regulation Name: Cyclosporine test system Regulatory Class: Class II Product Code: MK W Dated: March 24, 2004 Received: March 25, 2004

Dear Ms. LeMieux:

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. Yourmust 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 a legally 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 (301) 594-3084. Also, please note 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 toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely vours.

Jean M. Cooper, MS, DVM.

Yean M. Cooper, MS, 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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K040761

Indication For Use Statement

Device Name: Abbott AxSYM® Cyclosporine

Indication for Use:

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

Concurrence of CDRH, Office of Device Evaluation (ODE)
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Prescription Use ✓	OR	Over-The-Counter Use
		(Optional format 1-2-96)

Carol C Benson
Division Sign-Off

Office of In Vitro Diagnostic Device
Evaluation and Safety510(k) K04076

Regulation Number and Section

§ 862.1235 Cyclosporine test system.

(a)
Identification. A cyclosporine test system is a device intended to quantitatively determine cyclosporine 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 cyclosporine.(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.