The Chiron Diagnostics ACS:180 BR 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:180® Automated Chemiluminescence Systems. The test is intended for use as an aid in monitoring patients previously treated for Stage II or 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 or regression of disease in response to treatment.

Device Description

The Chiron Diagnostics ACS:180 BR assay is a fully automated, competitive, chemiluminescent assay. One reagent, designated Lite Reagent, is composed of a mouse monoclonal 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 breast cancer antigen (CA 27.29) which is covalently coupled to paramagnetic particles (PMP). After onboard pretreatment, the patient serum sample is incubated with both reagents simultaneously for 7.5 minutes.

The ACS: 180 system automatically performs the following steps:

dispenses sample and Pretreatment Reagent into a cuvette .
dispenses Lite Reagent and Solid Phase and incubates for 7.5 minutes u
separates, aspirates and washes the cuvettes
dispenses reagents which initiate the chemiluminescent reaction
= reports results

An inverse relationship exists between the concentration of CA27.29 in a sample and the relative light units (RLU) detected by the system.

AI/ML Overview

The provided text describes a 510(k) premarket notification for a modified in vitro diagnostic device, the ACS:180 BR, which is an automated chemiluminescence system for detecting cancer antigen CA 27.29 in human serum.

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" but rather focuses on demonstrating "substantial equivalence" to a predicate device. The primary performance metric reported is the correlation between the modified assay and the predicate device.

Performance Metric	Acceptance Criteria (Implied by Substantial Equivalence Goal)	Reported Device Performance	Comments
Correlation ($r^2$)	A high coefficient of determination, ideally close to 1, demonstrating a strong linear relationship with the predicate device.	$>0.99$	This indicates a very strong positive linear correlation between the modified and predicate assays.
Slope	A slope close to 1, indicating that the modified assay measures values very similarly to the predicate device across the range.	$1.0408$	Close to 1, suggesting good agreement in the rate of change between the two methods.
Y-intercept	A Y-intercept close to 0, indicating minimal constant bias between the modified assay and the predicate device.	$0.9907$ U/mL	Relatively close to 0, suggesting a small positive bias but overall good agreement with the predicate.
Assay Range	Must match the predicate device to ensure comparable applicability.	$3.5$ U/mL to $450$ U/mL	Matches the predicate device.
Upper Limit of Normal	Must match the predicate device, as it defines the clinical cutoff.	$38.6$ U/mL	Matches the predicate device, with a note that individual labs should determine their own reference ranges.

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

Sample Size: Over 875 specimens.
Data Provenance: The document does not specify the country of origin. It does not explicitly state whether the data was retrospective or prospective, but it implies a retrospective comparison of previously collected specimens, given the statement "These specimens had CA 27.29 levels that spanned the range from 3.68 U/mL to 420 U/mL."

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

The study described is a method comparison study between a modified device and a predicate device, not typically requiring expert-established "ground truth" in the same way an imaging or diagnostic AI device would. The "ground truth" here is the measurement provided by the existing, legally marketed predicate device. Therefore, no information is provided regarding expert qualifications or the number of experts used to establish ground truth in this context.

4. Adjudication Method for the Test Set

Not applicable. This was a direct comparison of measurements between two diagnostic assays, not a study requiring adjudication of interpretations.

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

No, an MRMC comparative effectiveness study was not done. This is a comparison between two automated diagnostic assays, not a study involving human readers or AI assistance for interpretation.

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

Yes, this was a standalone performance comparison study of the device (an automated chemiluminescence system) against its predicate device. The results reported are for the device (modified assay) performing on its own, without human intervention in the measurement process beyond standard laboratory procedures.

7. The Type of Ground Truth Used

The "ground truth" for this comparative study was the results obtained from the predicate device (the original ACS:180 BR assay). The objective was to show that the modified assay yielded results substantially equivalent to the established predicate.

8. The Sample Size for the Training Set

The document does not mention a "training set" in the context of machine learning or AI. This is a traditional in vitro diagnostic device modification, where performance is typically validated through comparison to a well-established method, not through machine learning training and testing paradigms. Therefore, information on a training set size is not applicable/provided.

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

Not applicable, as no training set (in the machine learning sense) is described or implied for this type of device validation.

Summary

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SUMMARY OF SAFETY AND EFFECTIVENESS - ACS:180 BR

This summary of safety and effectiveness information is being submitted in This Sunmary of Salety and Onotanonison of The Safe Medical Devices Act of 1990 (SMDA 1990) and 21 CFR part 807.92.

Date of Summary Preparation:	May 13, 1998
Company Name:	Chiron Diagnostics Corporation333 Coney StreetEast Walpole, MA 02032
Company Contact:	Nancy A. HornbakerRegulatory AffairsChiron DiagnosticsChiron Corporation4560 Horton StreetEmeryville, CA 94608Telephone Number: 510.923.2758FAX: 510.923.3703
Device Name:	ACS:180 BRAutomated Chemiluminescence System
Common or Usual Name:	Automated Tumor Associated Antigen
Classification:	Class II device
Predicate Device:	ACS:180 BR

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Intended Use and Indications for Use:

Description of the Device:

The ACS: 180 system automatically performs the following steps:

dispenses sample and Pretreatment Reagent into a cuvette .
dispenses Lite Reagent and Solid Phase and incubates for 7.5 minutes u
separates, aspirates and washes the cuvettes
dispenses reagents which initiate the chemiluminescent reaction
= reports results

An inverse relationship exists between the concentration of CA27.29 in a sample and the relative light units (RLU) detected by the system.

Comparison to the Predicate Device

The performance of the modified ACS:180 BR assay was compared to that of the predicate device in studies of over 875 specimens from breast cancer patients. These specimens had CA 27.29 levels that spanned the range from 3.68 U/mL to 420 U/mL. The results of the linear regression analysis indicated that the two methods were correlated. The coefficient of determination (r2) was greater than 0.99, the slope was 1.0408 and the y-intercept was 0.9907 U/mL.

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Comparison of Features

Feature	ACS:180 BR(predicate device)	ACS:180 BR(modified assay)
Specimen type	Serum	Serum
Antigen	CA 27.29	CA 27.29
Antibody	MAb B27.29	MAb B27.29
Antibody Label	Acridinium Ester	Acridinium Ester
Assay Principle	Competitive Immunoassay	Competitive Immunoassay
Detection Method	Chemiluminescence	Chemiluminescence
Calibration	Master Curve Card + 2calibrators	Master Curve Card + 2calibrators
Assay Range	3.5 U/mL to 450 U/mL	3.5 U/mL to 450 U/mL
Upper Limit of Normal*	38.6 U/mL	38.6 U/mL
Population to be tested	Patients previously treatedfor State II and Stage IIIbreast cancer; patients withmetastatic disease	Patients previously treatedfor State II and Stage IIIbreast cancer; patients withmetastatic disease
Assay Protocol(Automated)	Dispense 25 µL sample	Dispense 25 µL sample +22 µL PretreatmentReagent
	Dispense 50 µL LiteReagent + 250 µL solidPhase	Dispense 50 µL LiteReagent + 250 µL solidPhase
	Incubate 7.5 minutes	Incubate 7.5 minutes
	Separate, aspirate, washcuvettes	Separate, aspirate, washcuvettes
	Dispense 300 µL reagentswhich initiate thechemiluminescent reactionReport results	Dispense 300 µL reagentswhich initiate thechemiluminescent reactionReport results

*This ULN was determined during well-controlled clinical studies. As stated in the product's package insert, each laboratory should determine its own reference range(s).

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Image /page/3/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 curved lines representing its body and wings. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" are arranged in a circular pattern around the eagle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUL 10 1998

Ms. Nancy A. Hornbaker Director Regulatory Affairs Chiron Corporation 4560 Horton St. Emeryville, California 94608

K981698 Re : ACS:180 BR Trade Name: Requlatory Class: II Product Code: MOI Dated: May 13, 1998 Received: May 14, 1998

Dear Ms. Hornbaker:

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 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 Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the current Good Manufacturing Practice requirement, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic (QS) inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in requlatory action. In addition, FDA may publish further announcements concerning your device in the Federal Reqister. Please note: this response to your premarket notification submission does not affect any obligation 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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Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770)488-7655.

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" (21 CFR 807.97). Other general 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 at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/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__________________________________________________________________________________________________________________________________________________________________________

510(k) Number (if known):	K981698
Device Name:	ACS: 180 BR

Indications For Use:

CHIRON DIAGNOSTICS, CHIRON CORPORATION PREMARKET NOTIFICATION, ACS:180 BR May 1998

K981698

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Signature

(Div!
Divi
510	evices K981698

Prescription Use (Per 21 CFR 801.109)	OR Over-The-Counter Use (Optional Format 1-2-96)
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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.