For the quantitative determination of alpha-fetoprotein (AFP) in the following: human serum, as an aid in managing non-seminomatous testicular cancer when used in conjunction with physical examination, histology/pathology, and other clinical evaluation procedures, using the Bayer Diagnostics ACS:180 Automated Chemiluminescence System or the ADVIA Centaur System.

Device Description

The Bayer Diagnostics ACS:180 & ADVIA Centaur AFP immunoassay is a two-site immunoassay using direct chemiluminometric technology, which uses constant amounts of two antibodies. The first antibody, in the Lite Reagent, is a purified polyclonal rabbit anti-AFP antibody labeled with acridinium ester. The second antibody, in the Solid Phase, is a monoclonal mouse anti-AFP antibody covalently coupled to paramagnetic particles. A direct relationship exists between the amount of AFP present in the patient sample and the amount of relative light units (RLU's) detected by the system.

AI/ML Overview

The provided text describes the performance data for the ACS:180 & ADVIA Centaur AFP Immunoassay. Here's an analysis based on your request:

1. Table of Acceptance Criteria and Reported Device Performance

Feature	Acceptance Criteria (Implied)	Reported Device Performance
Sensitivity	Detect AFP concentration within a specified range/minimum.	ADVIA Centaur: - Measures AFP up to 1000 ng/mL. - Minimum detectable concentration: 1.3 ng/mL. ACS:180: - Measures AFP up to 1000 ng/mL. - Minimum detectable concentration: 0.19 ng/mL.
Accuracy	High correlation with predicate/alternate methods (e.g., r > 0.95).	ADVIA Centaur vs. ACS:180 (N=498): - Equation: ADVIA Centaur AFP = 1.05 (ACS:180 AFP) - 0.3 ng/mL - Correlation coefficient (r) = 0.99 ACS:180 vs. Alternate Methods: - Abbott IMX (N=504): ACS:180 = 0.94(Abbott IMX) + 4.6 - Kallestd AFP/Ob (N=1575): ACS:180 = 0.92(Kallestd AFP/Ob) + 6.2 - Abbott mEIA (N=183): ACS:180 = 0.97(Abbott mEIA) - 1.0 - Kallestd AFP/Ob (N=477): ACS:180 = 1.10(Kallestd AFP/Ob) + 1.0

Note on Acceptance Criteria: The document does not explicitly state specific numerical acceptance criteria for correlation coefficients or minimum detectable limits. Instead, it presents the performance data in comparison to a predicate device (ACS:180 for ADVIA Centaur) and other established methods. The "acceptance criteria" are implied by the excellent correlation values (r=0.99 for ADVIA Centaur vs. ACS:180) which are typically considered a strong indicator of agreement in such assays.

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

ADVIA Centaur Accuracy Test Set: 498 serum samples.
ACS:180 Accuracy Test Set (vs. alternate methods):
- vs. Abbott IMX: 504 samples
- vs. Kallestd AFP/Ob (first test): 1575 samples
- vs. Abbott mEIA: 183 samples
- vs. Kallestd AFP/Ob (second test): 477 samples
Data Provenance: Not explicitly stated. The document describes clinical performance data but does not specify the country of origin of the data or whether it was retrospective or prospective.

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

This information is not provided in the document. The study compares the device's measurements to existing established methods (predicate device and alternate AFP methods), not to a ground truth established by human experts in the traditional sense of image or pathology review.

4. Adjudication Method for the Test Set

Not applicable. The "ground truth" for these tests are the results from the established existing immunoassay methods. There is no mention of human adjudication as would be relevant for subjective assessments.

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

No. This type of study is typically done for diagnostic imaging devices where human interpretation is a key component. The ACS:180 & ADVIA Centaur AFP Immunoassay is an in vitro diagnostic (IVD) immunoassay that provides quantitative results. Therefore, an MRMC study is not relevant for this device.

6. Standalone Performance Study

Yes, standalone performance was assessed. The "Performance Data" section details the sensitivity (minimum detectable concentration) and accuracy (correlation with predicate and other immunoassay methods) of the devices themselves, without direct human intervention in the result generation. The device outputs a quantitative value for AFP concentration based on its internal processes.

7. Type of Ground Truth Used

The "ground truth" in this context is the results obtained from legally marketed and established predicate/alternate AFP immunoassay methods. The study aims to demonstrate that the new devices produce results that are highly correlated and comparable to these existing, accepted methods.

8. Sample Size for the Training Set

This information is not provided in the document. Immunoassays typically involve calibration and validation rather than a "training set" in the machine learning sense. The document describes performance data, likely from validation studies, rather than development or training phases.

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

Not applicable / Information not provided. As mentioned above, the concept of a "training set" and "ground truth" for it, as typically used in machine learning, does not align with the description of this immunoassay. The document focuses on demonstrating performance against established methods.

Summary

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MAR 2 7 2002

Summary of Safety and Effectiveness

As required by 21 CFR 807.92, the following 510(k) Summary is provided:

1. Submitter Information

Contact person: Thomas F. Flynn

Baver Diagnostics Address: 63 North Street Medfield, MA 02052

Phone:	(508) 359-3877
FAX:	(508) 359-3356
e-mail:	thomas.flynn.b@bayer.com

Date Summary March 8, 2002 Prepared:

2. Device Information

Proprietary Name:	ACS:180 & ADVIA Centaur AFP
Common Name:	AFP Immunoassay
Classification Name:	Tumor Associated Antigen Immunological Test System

3. Predicate Device Information

ACS:180 & ADVIA Centaur AFP Immunoassay Name: Manufacturer: Bayer Diagnostics 510(k) Number: ACS:180 - P930036 (reclassified to class II) ADVIA Centaur - K981592

র্ব Device Description

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5. Statement of Intended Use

The intended use of ACS:180 & ADVIA Centaur AFP Immunoassay is for the quantitative determination of alpha-fetoprotein (AFP) in the following:

human serum, as an aid in managing non-seminomatous testicular cancer when used in conjunction with physical examination, histology/pathology, and other clinical evaluation procedures, using the Bayer Diagnostics ACS:180 Automated Chemiluminescence System or the ADVIA Centaur System.

Summary of Technological Characteristics 6.

The Bayer Diagnostics ACS:180 & ADVIA Centaur AFP Immunoassay is a two-site sandwich Chemiluminescence immunoassay.

Performance Data 7.

Sensitivity

The ADVIA Centaur AFP Immunoassay measures AFP concentration up to 1000 ng/mL with a minimum detectable concentration of 1.3 ng/mL.

The ACS:180 Immunoassay measures AFP concentration up to 1000 ng/mL with a minimum detectable concentration of 0.19 ng/mL.

Accuracy

ADVIA Centaur:

For 498 serum samples in the range of 1.3 to 943.6 ng/mL, the correlation between the ADVIA Centaur AFP and the ACS:180 AFP is described by the equation:

ADVIA Centaur AFP = 1.05 (ACS:180 AFP) - 0.3 ng/mL

Correlation coefficient (r) = 0.99

ACS:180:

For serum samples in the range of 0 to >450 ng/mL. the relationship of the ACS:180 AFP assay to four alternate AFP methods are described by the following equations:

(N = 504) ACS:180 = 0.94(Abbott IMX) + 4.6 (N =1575) ACS:180 = 0.92(Kallestd AFP/Ob) + 6.2 (N = 183) ACS:180 = 0.97(Abbott mEIA) - 1.0 (N = 477) ACS:180 = 1.10(Kallestd AFP/Ob) + 1.0

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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 features a stylized caduceus symbol, which is a staff with two snakes entwined around it. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" are arranged in a circular pattern around the caduceus.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

MAR 2 7 2002

Mr. Thomas F. Flynn, RAC Director, Regulatory Affairs Bayer Corporation 63 North Street Medfield, Massachusetts 02052-1688

K020806 Re:

Trade/Device Name: ACS:180 & ADVIA Centaur AFP Immunoassay Regulation Number: 21 CFR § 866.6010 Regulation Name: Carcinoembryonic Antigen CEA Immunological Test System Regulatory Class: II Product Code: LOJ Dated: March 8, 2002 Received: March 12, 2002

Dear Mr. Flynn:

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 Autman

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 of of a

KO20806 -16981592-510(k) Number (if known): _

Device Name: Bayer Diagnostics ACS:180 & ADVIA Centaur AFP Immunoassay

Indications for Use:

For the quantitative determination of alpha-fetoprotein (AFP) in the following:

human serum, as an aid in managing non-seminomatous testicular cancer when used in conjunction with physical examination, histology/pathology, and other dinical evaluation procedures, using the Bayer Diagnostics ACS:180 Automated Chemiluminescence System or the ADVIA Centaur System.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use V

Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________

(Per 21 CFR 801.109)

(Optional Format 1-2-96)

i. Inull H.P.

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.