For in vitro diagnostic use in the quantitative, serial determination of CA 125 in human serum and to aid in the management of patients with ovarian carcinoma using the ADVIA Centaur® System. The test is intended for use as an aid in monitoring patients previously treated for ovarian cancer. Serial testing for CA 125 in the serum of patients who are clinically free of disease should be used in conjunction with other clinical methods used for the early detection of cancer recurrence. The test is also intended for use as an aid in the management of ovarian cancer patients with metastatic disease by monitoring the progression or regression of disease in response to treatment. It is recommended that the Bayer ADVIA Centaur CA 125 II assay be used under the order of a physician trained and experienced in the management of gynecological cancers. This assay is not intended for screening or diagnosis of ovarian cancer or for use on any other system.

Device Description

The ADVIA Centaur CA 125 II assay is a fully automated, single step sandwich immunoassay using direct, chemiluminescent technology. The Lite Reagent is composed of the monoclonal mouse antibody, OC125, specific for CA 125, labeled with acridinium ester and the monoclonal mouse antibody M11, specific for CA 125, labeled with fluorescein. The Solid Phase is composed of purified monoclonal mouse capture antibody, which is covalently coupled to paramagnetic particles. The sample is incubated with both Lite Reagent and Solid Phase simultaneously for 40 minutes. After incubation, the immuno-complex is washed. The measured chemiluminescence is directly proportional to the quantity of CA 15-3 antigen in the sample.

AI/ML Overview

This document describes the premarket notification (510(k)) for the ADVIA Centaur CA 125 II assay, an in vitro diagnostic device used to quantitatively determine CA 125 levels in human serum to aid in the management and monitoring of ovarian carcinoma patients.

Here's the breakdown of the acceptance criteria and the study results from the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state formal acceptance criteria in a table format with specific thresholds before presenting results. However, it implicitly uses substantial equivalence to a predicate device as the primary acceptance criterion. The key performance metric used to demonstrate this equivalence is correlation and regression analysis between the new device and the predicate device.

Performance Metric	Acceptance Criteria (Implicit)	Reported Device Performance (ADVIA Centaur CA 125 II vs. Immuno 1 CA 125 II)
Correlation Coefficient (r)	High correlation (e.g., close to 1) between new device and predicate	0.992
Regression Equation (Deming Regression)	Close agreement (slope near 1, intercept near 0)	ADVIA Centaur CA 125 II = 1.025 (Immuno 1) + 1.14 U/mL
Clinical Sensitivity (Longitudinal Monitoring)	Not explicitly defined as a threshold, but demonstrated	93.5%
Clinical Specificity (Longitudinal Monitoring)	Not explicitly defined as a threshold, but demonstrated	38.5%

2. Sample Size and Data Provenance for the Test Set

The primary study for substantial equivalence to the predicate device involved:

Sample Size: 227 samples
Data Provenance: Not explicitly stated (e.g., country of origin). The study was likely conducted by the manufacturer, Bayer Corporation. It is a retrospective comparison based on existing samples.
Another study for monitoring: 44 ovarian cancer patients (retrospective clinical study).

3. Number of Experts and their Qualifications for Ground Truth

The document does not mention the use of experts to establish a "ground truth" for the test set in the traditional sense of image analysis or diagnostic decision-making.

For the comparison study, the "ground truth" was essentially the results obtained from the predicate device (Bayer Immuno-1 CA 125 II assay). Therefore, no external experts were used to establish this specific ground truth.

For the retrospective clinical study on monitoring, the changes in clinical status were compared to the Centaur CA 125 II results. The clinical status would have been determined by physicians trained and experienced in the management of gynecological cancers, as indicated in the intended use statement. The exact number of these physicians or their specific qualifications for assessing clinical status in this study are not provided.

4. Adjudication Method for the Test Set

No adjudication method (e.g., 2+1, 3+1) is mentioned or implied for either the primary equivalence study or the clinical monitoring study. The comparison was directly between the new device and the predicate device's measurements, and between the new device's measurements and observed clinical status.

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

No Multi-Reader Multi-Case (MRMC) comparative effectiveness study was mentioned. This type of study is more common for diagnostic imaging devices where human readers interpret results. The ADVIA Centaur CA 125 II assay is an automated immunoassay, and its performance is evaluated against chemical and clinical measures, not human reader interpretation.

6. Standalone (Algorithm Only) Performance Study

Yes, a standalone performance study was done. The entire submission focuses on the performance of the ADVIA Centaur CA 125 II assay itself (the "algorithm only," in this context, refers to the automated immunoassay system) without human interpretation as part of its core function, other than a physician's decision-making based on the quantitative result.

The reported performance metrics (correlation coefficient, regression equation, sensitivity, and specificity) are all based on the device's direct output.

7. Type of Ground Truth Used

For the substantial equivalence study: The predicate device's results (Bayer Immuno-1 CA 125 II assay) served as the proxy "ground truth" for comparison. This is a common approach for in vitro diagnostics where a new test is compared to a previously cleared, established method.
For the clinical monitoring study: The "ground truth" for evaluating sensitivity and specificity was changes in the clinical status of patients, which would be determined by physicians based on various clinical parameters and outcomes (e.g., disease progression, regression, recurrence). This can be classified as outcomes data or clinical assessment.

8. Sample Size for the Training Set

The document does not explicitly state a separate "training set" size. Given the nature of a 510(k) submission for an immunoassay, the device itself (the assay and analyzer) would have been developed and optimized prior to these validation studies. Therefore, the concept of a "training set" as it applies to machine learning algorithms might not be directly transferrable or explicitly detailed in such a submission. The studies described are more akin to validation or test sets for the finished device.

9. How Ground Truth for the Training Set Was Established

As no explicit "training set" is mentioned in the context of ground truth establishment, this information is not provided. The development and optimization of the assay would involve standard clinical chemistry and immunoassay development practices, where reference materials and known concentrations are used to calibrate and fine-tune the assay's performance characteristics.

Summary

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JL 2 4 2002

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Premarket Notification - 510(k)

ADVIA Centaur 125 Il 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:

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® CA 125 II assay
Common or Usual Name:	Chemiluminescence immunoassay kit for thedetermination of CA 125 antigenusing Bayer Corporation'sADVIA Centaur automated analyzer.
Classification:
Name:	Bayer ADVIA Centaur CA 125 II Assay
Class:	II
CFR:	21 CFR 866.6010
Product Code:	82 LTK

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

Substantial Equivalence To: Bayer Immuno-1 CA 125 II

510(k) Number: K983715

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7.2 Intended Use

7.3 Device Description

7.4 Comparison to the Predicate Device

The ADVIA Centaur CA 125 II immunoassay kit is similar to the Immuno-1 CA 125 II 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 227 samples in the range of 2.3 to 466.6 U/mL, the relationship of the ADV/A Centaur CA 125 II assay to the Immuno 1™ CA 125 II assay is described by the following equation (calculated using Deming Regression):

ADVIA Centaur CA 125 II = 1.025 (Immuno 1) + 1.14 U/mL

The correlation coefficient r is 0.992

The data demonstrate substantial equivalence of the ADVIA Centaur CA 125 II assay to the FDA-cleared Bayer Immuno-1 CA 125 II assay as an adjunctive test for use in the management (monitoring) of metastatic ovarian cancer patients during the course of disease and therapy and for the detection of disease recurrence.

7.6 Monitoring Cancer Patients for Progression or Response

A retrospective clinical study was conducted to evaluate Centaur CA 125 II values in 44 ovarian cancer patients during the course of disease and therapy. Changes in the clinical status of patients were compared to changes in Centaur CA 125 II results. The sensitivity of longitudinal measurements using the method was 93.5% and the specificity was 38.5%.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/Picture/1 description: The image shows the seal of the Department of Health & Human Services USA. The seal features a stylized eagle with three lines representing its body and wings. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" are arranged in a circular pattern around the eagle.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

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

JUL 2 4 2002

Re: K020828

Trade Name: Bayer Advia Centaur CA 125 assay Regulation Number: 21 CFR 866.6010 Regulation Name: Tumor-associated antigen immunological test system Regulatory Class: II Product Code: LTK Dated: March 12, 2002 Received: March 14, 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 indication 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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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/cdrb/dsmaldsmamain.html".

Sincerely yours,

Steven Butman

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): _ KO20828

Device Name: Bayer Diagnostics ADVIA Centaur CA 125 Assay

Indications for Use:

For in vitro diagnostic use in the quantitative, serial determination of CA 125 in human serum and to aid in the management of patients with ovarian carcinoma using the ADVIA Centaur® System. The test is intended for use as an aid in monitoring patients previously treated for ovarian cancer. Serial testing for CA 125 in the serum of patients who are clinically free of disease should be used in conjunction with other clinical methods used for the early detection of cancer recurrence. The test is also intended for use as an aid in the management of ovarian cancer patients with metastatic disease by monitoring the progression or regression of disease in response to treatment. It is recommended that the Baver ADVIA Centaur CA 125 II assay be used under the order of a physician trained and experienced in the management of gynecological cancers. This assay is not intended for screening or diagnosis of ovarian cancer or for use on any other system.

A. Reeves for S. Altaie

Division Sign-Off) (MVision of Clinical Laborato:

510(k) Number K020828

(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

§ 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.