The AxSYM® Homocysteine assay is a Fluorescence Polarization Immunoassay (FPIA) for the quantitative measurement of total L-homocysteine in human serum or plasma on the AxSYM System. Homocysteine values can assist in the diagnosis and treatment of patients suspected of having hyperhomocysteinemia and homocystinuria.

Device Description

AxSYM Homocysteine is a Fluorescence Polarization Immunoassay for the quantitative r ate volument of total L-homocysteine in human serum or plasma on the AxSYM System. AxSYM Homocysteine is calibrated with Abbott Homocysteine Calibrators. Abbott Homocysteine Controls are assayed for the verification of the accuracy and precision of the Abbott AxSYM System.

AI/ML Overview

The provided text describes the Abbott AxSYM® Homocysteine assay, which is a Fluorescence Polarization Immunoassay for the quantitative measurement of total L-homocysteine in human serum or plasma. The 510(k) submission seeks to demonstrate substantial equivalence to the previously cleared Abbott IMx® Homocysteine assay.

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The core of the acceptance criteria for this 510(k) submission is demonstrating substantial equivalence to a predicate device, the Abbott IMx® Homocysteine assay. This is primarily evaluated through a comparison of analytical performance, specifically correlation.

Acceptance Criterion (Implicit for Substantial Equivalence)	Reported Device Performance (AxSYM Homocysteine vs. IMx Homocysteine)
High Correlation Coefficient ensuring results from both assays are highly related.	Least Squares Linear Regression: Correlation coefficient of 0.985
Slope close to 1.0 indicating similar quantitative measurement between assays.	Least Squares Linear Regression: Slope of 1.04 (95% CI: 1.02 to 1.06)
Y-intercept close to 0 indicating minimal systematic bias between assays.	Least Squares Linear Regression: Y-axis intercept of -0.56 umol/L (95% CI: -0.87 to -0.25)
High Correlation Coefficient (alternative method)	Passing-Bablok Linear Regression: Correlation coefficient of 0.985
Slope close to 1.0 (alternative method)	Passing-Bablok Linear Regression: Slope of 1.08 (95% CI: 1.05 to 1.10)
Y-intercept close to 0 (alternative method)	Passing-Bablok Linear Regression: Y-axis intercept of -0.80 umol/L (95% CI: -1.16 to -0.47)

Based on these results, the AxSYM Homocysteine assay demonstrated strong agreement with the predicate IMx Homocysteine assay, satisfying the implicit acceptance criteria for substantial equivalence through analytical comparison. The correlation coefficients are very high (0.985), and the slopes are close to 1.0 with y-intercepts close to 0, indicating a high degree of concordance between the two methods.

2. Sample Size and Data Provenance

Sample Size for Test Set: 300 specimens were used for the comparative study between the AxSYM Homocysteine assay and the IMx Homocysteine assay.
Data Provenance: The document does not specify the country of origin of the data or whether the study was retrospective or prospective.

3. Number of Experts and Qualifications for Ground Truth

Number of Experts: This information is not provided in the text.
Qualifications of Experts: This information is not provided in the text.

(It's important to note that for a diagnostic assay like this, "ground truth" often refers to the consensus of a reference method or a previously validated device, rather than the consensus of human experts interpreting images or complex qualitative data.)

4. Adjudication Method for Test Set

Adjudication Method: This information is not provided in the text. Given that the ground truth appears to be comparison against a predicate device's results, a typical human-expert adjudication method (like 2+1 or 3+1) would not be applicable in this context. The "adjudication" is essentially the statistical comparison of the two assay results.

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

MRMC Study: No, an MRMC comparative effectiveness study was not done. This type of study is typically performed for imaging or qualitative diagnostic devices where human interpretation plays a significant role. The Abbott AxSYM® Homocysteine is an automated quantitative immunoassay, where the output is numerical and does not involve human readers in the same way.
Effect Size of Human Readers Improvement: Not applicable, as an MRMC study was not performed.

6. Standalone Performance Study

Standalone Performance: Yes, the essence of the 510(k) submission is to demonstrate the standalone performance of the new AxSYM Homocysteine assay by comparing its output (algorithm only) directly against the predicate IMx Homocysteine assay's output (algorithm only). The statistical analyses (least squares and Passing-Bablok regressions) directly assess the agreement between the two automated systems without human intervention in the result generation. The statement "Substantial equivalence has been demonstrated between the AxSYM Homocysteine assay and the Abbott IMx® Homocysteine assay" directly supports this.

7. Type of Ground Truth Used

Type of Ground Truth: The "ground truth" in this context is the results obtained from the predicate device, the Abbott IMx® Homocysteine assay. The study aims to show that the new device produces results that are substantially equivalent to those of the predicate. This is a common approach for demonstrating substantial equivalence for in vitro diagnostic devices when a well-established and legally marketed predicate device exists.

8. Sample Size for the Training Set

Sample Size for Training Set: This information is not provided in the text. It's common for such submissions to focus on validation (test set) data, assuming the method was developed using appropriate internal training data.

9. How Ground Truth for Training Set Was Established

How Ground Truth for Training Set Was Established: This information is not provided in the text. Similar to point 8, the text focuses on the validation of the device against a predicate, not on the internal development and training of the assay.

Summary

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¥992858

510(k) Summary Abbott AxSYM® Homocysteine

Summary of Safety and Effectiveness Information Supporting a Substantially Equivalent Determination

The following information as presented in the Premarket Notification [510(k)] for Abbott AxSYM Homocysteine constitutes data supporting a substantially equivalent determination.

Substantial equivalence has been demonstrated between the AxSYM Homocysteine assay and the Abbott IMx® Homocysteine assay. The intended use of both assays is for the quantitative measurement of total L-homocysteine. Both assays are automated, in vitro, competitive immunoassays that use antibodies specific for s-adenosyl-L-homocysteine. A least squares linear regression analysis between these two assays, using 300 specimens, yielded a correlation coefficient of 0.985, slope of 1.04 (95% confidence interval of 1.02 to 1.06), and y-axis intercept of -0.56 umoVL (95% confidence interval of -0.87 to -0.25). A Passing-Bablok linear regression analysis, using 300 specimens, yielded a correlation coefficient of 0.985, slope of 1.08 (95% confidence interval of 1.05 to 1.10), and y-axis intercept of -0.80 umol/L (95% confidence interval of -1.16 to -0.47).

AxSYM Homocysteine 510(k) August 1999 hcy 510k preface to section II lwp

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In conclusion, these data demonstrate that the AxSYM Homocysteine assay is as safe and effective as, and is substantially equivalent to, the IMx Homocysteine assay.

Prepared and Submitted August 24, 1999 by: Margaret Prochniak Regulatory Specialist ADD Regulatory Affairs 1-847-937-4106

Abbott Laboratories Department 9YC, Building AP31 200 Abbott Park Road Abbott Park, IL 60064-6200

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged around the perimeter. Inside the circle is an abstract symbol that resembles an eagle or bird in flight, composed of three curved lines.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

OCT 2 5 1999

Ms. Margaret Prochniak Regulatory Specialist Abbott Laboratories ADD Regulatory Affairs Dept. 9YC, Bldg. AP 31 200 Abbott Park Road Abbott Park, Illinois 60064-6200

K992858 Re: Trade Name: Abbott AxSYM® Homocysteine Regulatory Class: II Product Code: LPS Dated: August 24, 1999 Received: August 25, 1999

Dear Ms. Prochniak:

We have reviewed your Section 510(k) notification of intent to market the device referenced We have reviewed your Section 910(x) notificantially equivalent (for the indications for use above and we nave delemined the ucvice is sedicate devices marketed in interstate commerce
s to devices to legally marketed in the links in the increasedments, or to devices stated in the enclosure) to legally marked processor wondments, or to devices that
prior to May 28, 1976, the enactment date of the Medical Device American Coad, Drug, and prior to May 26, 1970, the chactiven auto of the Federal Food, Drug, and have been reclassified in accordance with the pro the device, subject to the general controls Cosmetic Act (Act). Tou may, merciols, market include requirements for annual provisions of the Act. "The general oonlous provisions provises, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III If your device is classifica (sec above) into sich additional controls. Existing major regulations (Premarket Approval), it may of subject to outer fielderal Regulations, Title 21, Parts 800 to 895. allecting your device can be found in the assumes compliance with the Current Good A substantially equirvalent determination assumts oche system Regulation (QS) for
Manufacturing Practice requirements, as set forth in the Quality System be and in one in the Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS Medical Devices. Gelicial regulation (21 of A P P P P P P P P S will verify such assumptions. F ailure to inspections, the Pood and Drug Nammedation (1 = Laton . In addition, FDA may publish comply with the GMI Tegarator may reading in the Federal Register. Please note: this further alliouncements concorning your submission does not affect any obligation you might It spollse to your promanter as a see for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.

This letter will allow you to begin marketing your device as described in your 510(k) premarket I his letter will and it you to organizatial equivalence of your device to a legally marketed notification. - The I Dr. In and ssification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, (1) = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = entitled, "Misbranding by reference to premarket notification"(21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-frec number (800) 638-2041 or (301) 443-6597, or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours,

Steven Putman

Steven I. Gutman, M.D, M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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510(k) Number (if known): K992858

Device Name: Abbott AxSYM® Homocysteine

Indications For Use:

Cooph

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K992858

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

Concurrence of CDRH, Office of Device Evaluation(ODE)

Prescription Use (Per 21 CFR 801.109)

Over-The-Counter Use__________________________________________________________________________________________________________________________________________________________

(Optional Format 1-2-96)

Regulation Number and Section

§ 862.1377 Urinary homocystine (nonquantitative) test system.

(a)
Identification. A urinary homocystine (nonquantitative) test system is a device intended to identify homocystine (an analogue of the amino acid cystine) in urine. The identification of urinary homocystine is used in the diagnosis and treatment of homocystinuria (homosystine in urine), a heritable metabolic disorder which may cause mental retardation.(b)
Classification. Class II.