The Chiron Diagnostics ACS:Centaur BR assay is an in vitro diagnostic test for the quantitative serial determination of cancer antigen CA 27.29 in human serum using the Chiron Diagnostics ACS:Centaur" Automated Chemiluminescence System. The test is intended for use as an aid in monitoring patients previously treated for Stage Il or Stage III breast cancer. Serial testing for CA 27,25 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 breast cancer patients with metastatic disease by monitoring the progression or regression of disease in response to treatment.

Device Description

The Chiron Diagnostics ACS:Centaur BR assay is a fully automated, competitive immunoassay using direct, chemiluminescent technology. The Lite Reagent is composed of a monoclonal mouse antibody specific for CA 27.29, labeled with acridinium ester. The antibody used in the assay, MAb B27,29, binds to a peptide epitope in the tandem repeat region of the MUC-1 gene product. The Solid Phase is composed of purified CA 27.29, which is covalently coupled to paramagnetic particles. After onboard pretreatment, the sample is incubated with both Lite Reagent and Solid Phase simultaneously for 7.5 minutes.

AI/ML Overview

Here's an analysis of the provided text, focusing on acceptance criteria and the study proving device performance:

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (Implied)	Reported Device Performance
Analytical Sensitivity	Minimum detectable concentration for CA 27.29	3.5 U/mL
Accuracy (Correlation to Predicate)	Strong correlation to the predicate device (ACS:180 BR)	Correlation coefficient (r) = 0.99
Measuring Range	Range for CA 27.29 concentrations	Up to 450 U/mL
Linearity/Relationship	Close to 1:1 relationship with predicate device	ACS:Centaur BR = 1.00 (ACS:180 BR) - 0.94 U/mL

Note on Implied Acceptance Criteria: The document primarily provides performance data without explicitly stating pre-defined acceptance criteria. However, when evaluating substantial equivalence, the performance of the new device is compared to a legally marketed predicate device. Therefore, the "acceptance criteria" are implicitly that the new device's performance should be comparable to or better than the predicate's, and meet general expectations for a diagnostic assay. A correlation coefficient of 0.99 is generally considered excellent for method comparisons.

2. Sample Size and Data Provenance for the Test Set

Sample Size for Test Set: 225 samples were used for the accuracy study comparing the ACS:Centaur BR to the predicate device.
Data Provenance: Not explicitly stated. The document doesn't mention the country of origin of the data or whether it was retrospective or prospective.

3. Number of Experts and Qualifications for Ground Truth

This information is not provided in the given text. The study described is a method comparison (accuracy) study against a predicate device, not a study where a ground truth needed to be established by experts for classification or diagnosis.

4. Adjudication Method for the Test Set

None. Adjudication is typically used when multiple observers assess a case and their interpretations need to be reconciled to establish a single ground truth. In this method comparison study, the "ground truth" for the new device's accuracy is its agreement with the predicate device's measurements. There are no human readers or diagnostic interpretations described that would require adjudication.

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

No, an MRMC study was not done. The study described is an analytical performance study comparing a new immunoassay to a predicate immunoassay. It does not involve human readers interpreting results or assessing the impact of AI assistance.

6. Standalone (Algorithm Only) Performance Study

Yes, this is an analogous standalone performance study. The ACS:Centaur BR Immunoassay is an in-vitro diagnostic device that provides a quantitative measurement. The "algorithm" here is the entire immunoassay system (reagents, analyzer, and analytical process). The "standalone" performance is measured by its analytical sensitivity, measuring range, and accuracy when compared to a reference method (the predicate device). It's operating without human intervention for the measurement itself, only for collecting and interpreting the results.

7. Type of Ground Truth Used

The "ground truth" for the accuracy study was the measurements obtained from the predicate device, the ACS:180 BR Immunoassay. This is a form of reference method comparison, where a new method's results are compared against an already established and validated method.

8. Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of machine learning or algorithm development. For an immunoassay, the "training" equivalent would be the development and optimization of the assay itself through various experiments. The reported data relates to the final, validated product's performance.

9. How Ground Truth for the Training Set Was Established

As a training set is not explicitly mentioned in the context of this immunoassay's validation, this information is not applicable/provided. The development of an immunoassay involves optimizing reagents and reaction conditions, which is an iterative process, but not typically referred to as "establishing ground truth for a training set" in the same way it would be for a machine learning model.

Summary

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OCT 1 5 1998

Summary of Safety and Effectiveness

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

1. Submitter Information

number

Contact person:	William J. Pignato
Address:63 North StreetMedfield, MA 02052	Chiron Diagnostics Corporation
Phone:FAX:e-mail:	(508) 359-3825(508) 359-3885william.pignato@chirondiag.com
Date Summary Prepared:	July 28, 1998
Device Information
Proprietary Name:Common Name:Classification Name:	ACS:Centaur BR ImmunoassayCA 27.29 antigen ImmunoassayReclassified to Class II classification

3. Predicate Device Information

Name:	ACS:180 BR Immunoassay
Manufacturer:	Chiron Diagnostics
510(k) Number:	K981698

4. Statement of Intended Use

unknown

6. Summary of Technological Characteristics

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7. Performance Data

Sensitivity

The ACS:Centaur BR assay measures CA 27.29 concentrations up to 450 U/mL with a minimum detectable concentration (analytical sensitivity) of 3.5 U/mL.

Accuracy

For 225 samples in the range of 6.54 to 448.94 U/mL, the relationship of the ACS:Centaur BR assay to the ACS:180 BR assay is described by the following equation:

ACS:Centaur BR = 1.00 (ACS:180 BR) - 0.94 U/mL Correlation coefficient (r) = 0.99

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Image /page/2/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus symbol, which is a staff with a serpent entwined around it. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES (USA)" is arranged in a circular pattern around the symbol.

OCT 1 5 1998

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. William J. Pignato Director of Requlatory Affairs Chiron Diaqnostics Corporation 63 North Street Medfield, Massachusetts 02052

Re: K982680 ACS:Centaur BR Immunoassay Trade Name: Requlatory Class: İI Product Code: MOI Dated: July 28, 1998 Received: July 31, 1998

Dear Mr. Pignato:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Requlations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Requlation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Druq Administration (FDA) will verify such assumptions. Failure to comply with the GMP requlation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obliqation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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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 requlation (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" (21 CFR 807.97). Other qeneral information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers 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 Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Company Confidential

Page of

510(k) Number (if known): h 953680

Device Name: Chiron Diagnostics ACS:Centaur BR Immunoassay

Indications for Use:

The Chiron Diagnostics ACS:Centaur BR assay is an in vitro diagnostic test for the quantitative serial determination of cancer antigen CA 27.29 in human serum using the Chiron Diagnostics ACS:Centaur" Automated Chemiluminescence System. The test is intended for use as an aid in monitoring patients previously treated for Stage III breast cancer. Serial testing for CA 27.29 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 breast cancer patients with metastatic disease by monitoring the progression of disease in response to treatment.

Peter E. Maher

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

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

1 Prescription Use (Per 21 CFR 801.109)

Over-The-Counter Use (Optional Format 1-2-96)

ACS:Centaur BR 510(k)

28 July, 1998

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.