For in vitro diagnostic use in the quantitative determination of the HER-2/neu protein in human serum or using the ADVIA Centaur System. HER-2/neu values obtained may be used in the follow-up and monitoring of patients with metastatic breast cancer whose initial serum HER-2/neu level is greater than 15 ng/mL. HER-2/neu values should be used in conjunction with information available from clinical and other diagnostic procedures in the management of breast cancer. The clinical utility of the measurement of HER-2/neu in serum as a prognostic indicator for early recurrence and in the management of patients on immunotherapy has not been fully established. This test should be used by or under the order of a physician. This assay is not intended for use on any other system.

Device Description

The ADVIA Centaur HER-2/neu assay is a fully automated, two-site sandwich immunoassay using direct, chemiluminescent technology. The Lite Reagent is composed of the monoclonal mouse antibody, TA-1 labeled with acridinium ester. The Fluorescein Conjugate Reagent is composed of the monoclonal mouse antibody, NB-3, labeled with fluorescein. The two monoclonal antibodies are specific for unique epitopes on the extracellular domain of HER-2/neu. The Solid Phase is composed of purified monoclonal mouse capture antibody, which is covalently coupled to paramagnetic particles. The sample is incubated with Fluorescein Conjugate Reagent and Lite Reagent simultaneously for 5.5 minutes. After this incubation, the Solid Phase is added and the mixture is incubated for an additional 2.75 minutes. After this final incubation, the immuno-complex formed is washed. The measured chemiluminescence is directly proportional to the quantity of HER-2/neu antigen in the sample.

AI/ML Overview

The provided text describes the ADVIA Centaur HER-2/neu Immunoassay and its substantial equivalence to a predicate device, the Bayer Immuno-1 HER-2/neu kit. The primary study presented focuses on demonstrating this equivalence rather than establishing new acceptance criteria against a clinical ground truth.

Here's an analysis based on the provided information:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Implicit for Substantial Equivalence)	Reported Device Performance
Correlation Coefficient (r)	0.99
Linear Regression Equation	ADVIA Centaur HER-2/neu = 0.97 (Immuno 1) + 0.56 ng/mL
Assay Range Tested	0.2 - 250 ng/mL
Substantial Equivalence to Predicate Device	Demonstrated as an adjunctive test for management (monitoring) of metastatic breast cancer patients.

Note: The document directly states that the "data demonstrate substantial equivalence." The acceptance criteria here are implicitly the thresholds for correlation and agreement that the FDA and the manufacturer consider sufficient to declare substantial equivalence to the predicate.

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

Sample Size: 196 samples
Data Provenance: Not specified (e.g., country of origin, retrospective/prospective). However, the study involved comparing the new device's results to those of the predicate device on these 196 samples.

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

Not applicable. The study's purpose was to demonstrate substantial equivalence to a predicate device, not to establish a new ground truth based on expert consensus for the 196 samples. The "ground truth" in this context is the results obtained from the predicate device.

4. Adjudication Method for the Test Set

Not applicable. The study involved a direct comparison between two assays: the new ADVIA Centaur HER-2/neu assay and the predicate Bayer Immuno-1 HER-2/neu assay. There was no expert adjudication process for discordant results as the goal was method comparison.

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

No. This was a direct comparison study between two in vitro diagnostic (IVD) assays, not a study evaluating human reader performance with or without AI assistance.

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

Yes. The study assessed the performance of the ADVIA Centaur HER-2/neu assay as a standalone device by comparing its results to those of another standalone IVD, the Bayer Immuno-1 HER-2/neu assay. Human interpretation of the raw chemiluminescence signal is not part of the device's functional mechanism; the device provides a quantitative result directly.

7. The Type of Ground Truth Used

The "ground truth" for this study was the results obtained from the predicate device (Bayer Immuno-1 HER-2/neu assay). The study aimed to show that the new device produced comparable results to an already FDA-cleared device.

8. The Sample Size for the Training Set

Not applicable. This device is an immunoassay kit, not an AI/machine learning algorithm that requires a training set in the conventional sense. The development of such an assay involves reagent optimization and calibration, but not an "AI training set."

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

Not applicable, as there is no "training set" in the context of an immunoassay kit in the same way there would be for an AI algorithm. The development of the assay's reagents and calibration would be based on established biochemical and immunological principles, likely utilizing reference materials and internal validation processes.

Summary

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KO24017
Page 1 of 2

Premarket Notification - 510(k)

JAN 3 0 2003

ADVIA Centaur HER-2/neu Immunoassay

510(k) Summary of Safety and Effectiveness

This summary of safety and effectiveness is being submitted in accordance with the requirements of The Safe Medical Devices Act of 1990 (SMDA 1990) and 21 CFR 807.92.

The assigned 510(k) number is:

7.1 General Information

Date of Summary Update:	November 22, 2002
Applicant:	Kenneth T. Edds, Ph.D.Manager, Regulatory AffairsBusiness Group Diagnostics511 Benedict Ave.Tarrytown, NY 10591Phone: 914-524-2446Fax: 914-524-2500Ken.edds.b@bayer.com
Owner:	Bayer CorporationBusiness Group Diagnostics511 Benedict Ave.Tarrytown, NY 10591Establishment Registration No: 2432235
Manufacturer:	Bayer Corporation333 Coney StreetWalpole, MA 02032Establishment Registration No: 1219913
Device Name:	ADVIA Centaur® HER-2/neu assay
Common or Usual Name:	Chemiluminescence immunoassay kit for thedetermination of HER-2/neu antigenusing Bayer Corporation'sADVIA Centaur automated analyzer.
Classification:Name:Class:CFR:Product Code:	Tumor associated antigen immunological systemII866.601082 NCW

This submission was prepared in accordance with "Guidance Document for Submission of Tumor Associated Antigen Premarket Notifications".

Substantial Equivalence To: Bayer Immuno-1 HER-2/neu

K992228 510(k) Number:

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7.2 Intended Use

7.3 Device Description

7.4 Comparison to the Predicate Device

The ADVIA Centaur HER-2/neu immunoassay kit is similar to the Baver Immuno-1 HER-2/neu kit in the indications for use, format, performance characteristics, and results. The ADVIA Centaur tests differ mainly in their signal system as compared to the Immuno-1 principle. In the ADVIA Centaur method, a chemiluminogenic molecule (acridinium ester) is used to replace the Alkaline Phosphatase signal used in the Immuno-1 assay.

7.5 Equivalence to Predicate Device

For 196 samples in the assay range of 0.2-250 ng/mL, the relationship of the ADVIA Centaur HER-2/neu assay to the Bayer Immuno 1™ HER-2/neu assay is described by the following equation (calculated Linear Least Sum Squares Regression):

ADVIA Centaur HER-2/neu = 0.97 (Immuno 1) + 0.56 ng/mL

The correlation coefficient r is 0.99

The data demonstrate substantial equivalence of the ADVIA Centaur HER-2/neu assay to the FDA-cleared Bayer Immuno-1 HER-2/neu assay as an adjunctive test for use in the management (monitoring) of metastatic breast cancer patients during the course of disease and therapy.

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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 consists of a circular border with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the circumference. Inside the circle is a stylized image of an eagle or bird-like figure, represented by a series of curved lines. The design is simple and monochromatic, with the text and image in black against a white background.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JAN 3 0 2003

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

Re: K024017

Trade/Device Name: Bayer ADVIA Centaur HER-2/ neu assay Regulation Number: 21 CFR 866.6010 Regulation Name: Tumor-associated antigen immunological test system Regulatory Class: Class II Product Code: NCW Dated: November 26, 2002 Received: December 4, 2002

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 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 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 yours,

Steven Putman

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Page 1 of 1

510(k) Number:

K024017

Bayer ADVIA Centaur HER-2/ neu assay Device Name:

Indications for Use:

For in vitro diagnostic use in the quantitative determination of the HER-2/neu protein in human serum using the ADVIA Centaur System. HER-2/neu values obtained may be used in the follow-up and monitoring of patients with metastatic breast cancer whose initial serum HER-2/neu level is greater than 15 ng/mL. HER-2/neu values should be used in conjunction with information available from clinical and other diagnostic procedures in the management of breast cancer. The clinical utility of the measurement of HER-2/neu in serum as a prognostic indicator for early recurrence and in the management of patients on immunotherapy has not been fully established. This test should be used by or under the order of a physician. This assay is not intended for use on any other system.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

J. Reeves for J. Bautista

sion of Clinical I

Prescription Use (Per 21 CFR 801.109)

Over-The-CounterUse

(Optional Format 1-2-96)

Regulation Number and Section

§ 866.6010 Tumor-associated antigen immunological test system.

(a)
Identification. A tumor-associated antigen immunological test system is a device that consists of reagents used to qualitatively or quantitatively measure, by immunochemical techniques, tumor-associated antigens in serum, plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease.(b)
Classification. Class II (special controls). Tumor markers must comply with the following special controls: (1) A guidance document entitled “Guidance Document for the Submission of Tumor Associated Antigen Premarket Notifications (510(k)s) to FDA,” and (2) voluntary assay performance standards issued by the National Committee on Clinical Laboratory Standards.