For in vitro diagnostic use in the quantitative determination of total homocysteine (HCY) in serum or EDTA plasma using the ADVIA Centaur® System. This diagnostic test is designed to quantitatively measure HCY in serum or EDTA plasma. Such measurement can aid in the diagnosis and treatment of patients suspected of having homocystinuria or hyperhomocysteinemia.

Device Description

The ADVIA Centaur HCY assay is a competitive immunoassay using direct, The rib vir connecessent technology. It is intended to measure the amino acid Homocysteine (HCY) in serum or EDTA plasma. The homocysteine assay requires four separate reagents, which are added sequentially. A Reducing Reagent releases four separato reagence, willer in a sample or control to free HCY. A Enzyme provem uses the enzyme S-adenosylhomocysteine hydrolase to convert the free HCY to S-adenosylhomocysteine (SAH). SAH from a calibrator, control, or sample to S-adenosyinomes Josent (ethe Solid Phase for binding to a monoclonal anti SAH antibody-acridinium ester conjugate in the Lite Reagent. Following incubation, unbound SAH and anti SAH-acridinium ester conjugate are washed from the Solid Phase. The chemiluminescence of the acridinium ester bound to the Solid Phase is I has . The enemaint of chemiluminescence is inversely proportional to the amount of HCY that was present in the sample.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and study for the ADVIA Centaur HCY Assay:

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state pre-defined acceptance criteria in terms of thresholds for R-value, slope, or intercept. Instead, it presents the results of a method comparison study and infers acceptance based on substantial equivalence to the predicate device. However, based on the provided results, we can infer the achieved performance in comparison to the predicate.

Acceptance Criteria (Implied)	Reported Device Performance (ADVIA Centaur HCY Assay vs. Abbott IMx Homocysteine assay)
Strong Linear Correlation to Predicate (e.g., R-value near 1)	R = 0.981
Slope close to 1 when compared to Predicate	Slope = 0.98
Minimal Intercept (bias) when compared to Predicate	Intercept = 0.42 umol/L

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

Sample Size: 106 samples.
Data Provenance: The document does not specify the country of origin for the samples, nor whether they were retrospective or prospective. It simply states "106 samples were assayed on both systems."

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

This information is not provided in the document. For an immunoassay device, the "ground truth" is typically another established, well-validated method. The study described is a method comparison, where one method (the predicate) serves as the reference, rather than requiring expert adjudication of individual cases.

4. Adjudication Method for the Test Set:

This information is not applicable/provided for this type of immunoassay method comparison study. Adjudication methods (like 2+1 or 3+1) are typically used in imaging or diagnostic studies where human experts interpret ambiguous results to establish a consensus ground truth. In this case, the results from the predicate device (Abbott IMx Homocysteine assay) are implicitly treated as the reference.

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 AI assistance impacts human reader performance, which is not relevant for a standalone immunoassay device like the ADVIA Centaur HCY Assay.

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

Yes, the described study assesses the standalone performance of the ADVIA Centaur HCY Assay. It compares the quantitative results produced solely by the ADVIA Centaur system against those from the predicate Abbott IMx system, without any human interpretation or intervention in the measurement process itself.

7. The Type of Ground Truth Used:

The "ground truth" for this study was established by comparison to a legally marketed predicate device, specifically the Abbott IMx Homocysteine assay. The IMx assay's results served as the reference standard against which the ADVIA Centaur HCY assay's performance was evaluated.

8. The Sample Size for the Training Set:

This information is not provided in the document. Immunoassays are typically developed through a process of reagent formulation, calibration, and optimization rather than "training" in the machine learning sense with a specific training set. The term "training set" is generally not applicable to the development of this type of diagnostic assay.

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

This information is not provided and is generally not applicable in the context of traditional immunoassay development as described in the document. The development involves analytical validation, calibration against known standards, and optimization of reagents and protocols, rather than establishing "ground truth" from a training set of patient samples in the same way machine learning models are trained.

Summary

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DEC 1 82001

K013406

Bayer Diagnostics ADVIA Centaur HCY Assay

Section 2 - Summary of Safety and Effectiveness

1. Submitter Information Kenneth T. Edds, Ph.D. Contact Person: Bayer Diagnostic Corporation Address: 511 Benedict Ave. Tarrytown, N.Y. 10591 Phone: (914) 524 2446 FAX: (914) 524 2500 e-mail: ken.edds.b@bayer.com Date Summary Prepared: 10/10/01 2. Device Information ADVIA Centaur Homocysteine (HCY) Assay Propriety Name: HCY assay Common Name: Classification Name: Urinary Homocysteine Assay Class: II 862.1377 CFR: Product Code: 75 LPS 3. Predicate Device Information IMx Homocysteine Name: Manufacturer: Manufactured by: Axis-Shield ASA Ulvenveien 87 N-0581 Oslo, Norway Manufactured for: Abbott Laboratories Abbott Park Road Abbott Park, Il. 60064 510(k) Number: K 992858

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4. Device Description

1. Statement of Intended Use
  For in vitro diagnostic use in the quantitative determination of total homocysteine (HCY) in serum or EDTA plasma using the ADVIA Centaur® System. This diagnostic test is designed to quantitatively measure HCY in serum or EDTA plasma. Such measurement can aid in the diagnosis and treatment of patients suspected of having homocysteinuria or hyperhomocysteinemia.

Summary of Technological Characteristics

The ADVIA Centaur HCY assay is similar to the Abbott IMx Homocysteine assay in several ways. Both require a chemical and enzymatic step to occur before the actual immunoassay starts. The similarities between the Bayer and Abbott reagents are summarized below:

Step	Bayer ActiveCompound(s)	Abbott ActiveCompound(s)
Chemical reduction of protein bound HCY tofree HCY	Dithiothreitol	Dithiothreitol
Enzymatic conversion of HCY to SAH	S-adenosylhomocysteine hydrolase	S-adenosylhomocysteine hydrolase
Analyte in Calibrator	SAH	SAH
Antibody	Mouse monoclonal anti-SAH	Mouse monoclonal anti-SAH

The systems differ in their detection systems, Abbott assay uses fluorescence polarization while the ADVIA Centaur uses chemiluminescence.

7. Method Comparison

We have compared the ADVIA Centaur HCY assay to the Abbott IMx Homocysteine assay in performance. 106 samples were assayed on both systems and yielded the following linear regression statistics:

IMx = 0.98 (ADVIA Centaur) + 0.42 umol/L, R = 0.981

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Image /page/2/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 stripes representing the department's mission. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the eagle. The logo is black and white.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

DEC 1 82001

Kenneth T. Edds, Ph.D. Manager, Regulatory Affairs Bayer Corporation 511 Benedict Avenue Tarrytown, NY 10591-5097

Re: K013406

Trade/Device Name: Homocysteine Assay for the ADVIA® Centaur™ Regulation Number: 21 CFR 862.1377 Regulation Name: Urinary homocystine (non-quantitative) test system Regulatory Class: Class II; Class II Product Code: LPS; JIS Dated: October 12, 2001 Received: October 15, 2001

Dear Dr. Edds:

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 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); 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 -

This letter will allow you to begin marketing your device as described in your 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 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, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained 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 yours,

Steven Sutman

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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Page 1 of 1

K013406 510(k) Number:

Device Name: HCY Assay for the ADVIA® Centaur™

Indications for Use:

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Thomas C. Ponton, Jr. Jean Cooper
Division Director

(Division Sign-Om
Division of Clinical Laboratory Devices
510(k) Number (K013, 40

Prescription Use (Per 21 CFR 801.109)

Over-The-CounterUse OR

(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.