This in vitro immunoassay is intended to quantitatively measure OC 125 reactive determinants associated with a high molecular weight glycoprotein in serum of women with primary epithelial invasive ovarian cancer using ADVIA IMS CA125 II Assay on a Bayer ADVIA® IMS™. CA 125 II Assay is indicated as an aid in the management (monitoring) of ovarian cancer patients when used in conjunction with other diagnostics procedures. The CA125 II Assay is also indicated as a one-time test for use as an aid in the detection of residual ovarian carcinoma in patients who have undergone firstline therapy and would be considered diagnostic second-look procedures. This assay is not intended for screening or diagnosis of ovarian cancer or for use on any other system.

The Bayer ADVIA® IMS™CA 125 II Assay is an in vitro diagnostic device intended to quantitatively measure OC 125 reactive determinants associated with a high molecular weight glycoprotein in serum of women with primary epithelial invasive ovarian cancer. The CA 125 II Assay is indicated as an aid in the management (monitoring) of ovarian cancer patients when used in conjunction with other diagnostic procedures. The CA 125 II Assay is also indicated as a one-time test for use as an aid in the detection of residual ovarian carcinoma in patients who have undergone first-line therapy and would be considered for diagnostic second-look procedures. An assay value of greater than 35 UlmL is predictive of residual disease, provided that alrernate causes of elevated CA 125 II Assay values can be excluded. It is recommended that the assessment and treatment of patients with ovarian cancer and the use of this CA 125 II Assay be under the order of a physician trained and experienced in the management of gynecologic cancers. This assay is not intended for screening or diagnosis of ovarian cancer or for use on any other system.

Device Description

AI/ML Overview

The provided documents detail the performance evaluation of the Bayer ADVIA® IMS™ CA 125 II Assay, particularly by comparing it to a predicate device (Immuno 1 CA125 II Assay). This is a technical summary for a 510(k) submission, focusing on establishing substantial equivalence rather than a typical clinical study with acceptance criteria for a new AI device or a novel diagnostic. As such, some of the requested information, such as the number of experts used for ground truth, adjudication methods, or AI-specific details (MRMC, standalone algorithm performance, training set details), are not applicable or provided in this type of submission for an immunoassay.

Here's an interpretation of the available information against your request:

Acceptance Criteria and Device Performance for CA 125 II Assay

1. Table of Acceptance Criteria and Reported Device Performance

Since this is a 510(k) submission for an immunoassay, the "acceptance criteria" are implied by showing the device's performance is comparable to a legally marketed predicate device (Immuno 1 CA125 II Assay) and within acceptable limits for a clinical laboratory test. The document does not explicitly state "acceptance criteria" for each metric in a pass/fail format but rather presents the results of equivalence studies. We can infer the "acceptance criteria" were met because the 510(k) was cleared.

Performance Metric	Implied Acceptance Criteria (relative to predicate)	Reported Device Performance (ADVIA IMS)
Imprecision (Total CV%)	Comparable to predicate device (Immuno 1)	Level 1: 3.0%; Level 2: 1.9%; Level 3: 2.5%
Linearity Recovery	Acceptable range (e.g., 90-110%) and comparable to predicate	96.7% (met specifications, in concordance with Immuno 1)
Parallelism Recovery	Acceptable range and comparable to predicate	95.6% to 109.7% (in concordance with Immuno 1)
Correlation (vs. Immuno 1)	High correlation (R value close to 1), small Syx	R = 0.994, Syx = 13.74 U/mL (Regression: Y = 1.047 * X - 3.94)
Longitudinal Monitoring (Sensitivity)	Clinically relevant sensitivity for detecting change	94.7% (95% CI: 74.0% to 99.9%)
Longitudinal Monitoring (Specificity)	Clinically relevant specificity for detecting no change	22.2% (95% CI: 2.8% to 60.0%)
Interfering Substances (Recovery Bias)	No clinically significant bias	All tested substances showed no clinically significant recovery bias (e.g., Hemoglobin -2.3%, Lipids 0.9%, Bilirubin -2.6%, etc.)
Analytical Range	Defined and clinically relevant	0.5 - 550 U/mL
Minimum Detectable Concentration	Low enough for clinical utility and comparable to predicate	0.5 U/mL (Immuno 1: 0.9 U/mL)

2. Sample Size and Data Provenance for Test Set

Correlation Study (Serum): N = 45 (compared to Immuno 1). The document does not specify the country of origin. This appears to be retrospective, using existing samples for method comparison.
Longitudinal Samples Evaluation: Two examples of serial patient monitoring studies are shown graphically. The table for sensitivity/specificity for clinical status changes has N=28 (total specimens, implies 28 instances of clinical change/no change being assessed). Data provenance (country, retrospective/prospective) is not specified.
Interfering Substances: Low serum pools were spiked. The number of samples for each interference test is not explicitly given, but typically involves a few replicates for each substance. Data provenance is not specified.

3. Number of Experts and Qualifications for Ground Truth

Not applicable for this immunoassay submission. For this type of device, "ground truth" is established by the reference measurement method (the predicate device, Immuno 1) or by the expected analytical performance characteristics for laboratory tests, rather than expert interpretation of images or clinical cases.
The longitudinal evaluation references "guidelines by Bast et al," which suggests clinical experts defined what constitutes disease progression (doubling of CA125 II values) and response to therapy (50% decrease). However, no specific number or qualifications of experts involved in the study's ground truth assessment are provided.

4. Adjudication Method for the Test Set

Not applicable for this immunoassay submission. Adjudication methods like 2+1 or 3+1 are typically used for subjective assessments (e.g., image-based diagnosis) where multiple readers provide initial interpretations. For an immunoassay, the result is a quantitative value, and comparisons are made against a reference method or clinical outcome definitions, not expert reconciliation of interpretations.

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

No, not performed. An MRMC study is not relevant for an immunoassay that produces a quantitative numerical result. This type of study assesses human reader performance with and without an AI assistant, which is not applicable here.

6. Standalone (Algorithm Only) Performance Study

Yes, in essence. The entire submission describes the standalone performance of the ADVIA® IMS™ CA 125 II Assay. It is an automated in vitro diagnostic device, and its performance characteristics (imprecision, linearity, correlation, etc.) are intrinsically "algorithm only" in the context of it being a laboratory instrument and assay, without a human-in-the-loop interacting with its fundamental measurement principle. The output is a quantitative value, not a diagnostic interpretation that would then be reviewed by a human.

7. Type of Ground Truth Used

Reference Method/Predicate Device: For analytical performance (imprecision, linearity, parallelism, correlation), the Immuno 1 CA125 II Assay served as the primary reference for comparison, indicating "substantial equivalence" as the ground truth.
Clinical Definitions: For longitudinal monitoring, "ground truth" for clinical status change (progression, response) was based on established guidelines (Bast et al.) related to CA125 II value changes correlating with disease progression or response to therapy.
Spiking/Known Concentrations: For interfering substances and analytical range, ground truth was based on known concentrations of spiked substances or samples with pre-determined high/low CA125 levels.

8. Sample Size for the Training Set

Not applicable. This is an immunoassay, not an AI/machine learning device that requires a "training set" in the conventional sense. The assay's chemical and mechanical parameters are developed through standard laboratory procedures and optimization, not machine learning model training.

9. How Ground Truth for the Training Set Was Established

Not applicable. As above, there is no "training set" or "ground truth" for it in the context of an AI/ML algorithm. The assay's development involves optimizing reagent formulations, instrument settings, and calibration processes, which are guided by established analytical chemistry principles and empirical testing.

Summary

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NOV 2 7 2002

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CA 125 II ASSAY CA 125 II (06/18/02)

510(k) SUMMARY OF SAFETY AND EFFECTIVENESS CA125 II Assay for Bayer ADVIA® Integrated Modular System (IMS)™

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and 21 CFR 807.92.

The assigned 510(k) number is: K00033399

1. Intended Use

2. Predicate Device

Product Name	Reagent Part #	Calibrator Part #
Immuno 1 CA125 II Assay	T01-3560-51	T03-3562-01

3. Device / Method

Product Name	Reagent Part # /BAN Number	Calibrator Part # /BAN Number
ADVIA IMS CA 125 II Assay	B42-3893-21 /03692807	B43-3925-01 /06578142

4. Performance

Imprecision
ADVIA IMS	Immuno 1
Level(U/mL) TotalCV(%) 26.8 3.0 74.1 1.9 169.8 2.5									Level(U/mL) TotalCV(%) 30.2 2.4 80.6 2.5 200.2 2.6

Linearity

Linearity was evaluated by diluting a high CA 125 II serum sample with a serum pool containing low CA 125 II level. Recovery was acceptable ranging from 96.7%, meeting specifications and in concordance with the Immuno 1 (predicate).

Parallelism

Parallelism was evaluated by diluting a serum sample with a high CA125 II level, with Immuno 1 Sample Diluent B. Recovery was acceptable ranging from 95.6% to 109.7% in concordance with the Immuno 1 (predicate)

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CA 125 II ASSAY CA 125 II (06/18/02)

Correlation (Y = ADVIA IMS, X=comparison system)
Specimen type	Comparison System (X)	N	Regression Equation	Syx (U/mL)	R	Sample Range (U/mL)
Serum	Immuno 1	45	$1.047 * X - 3.94$	13.74	0.994	5.1-509.2

Longitudinal Samples Evaluation

Two examples of serial patient monitoring studies using Bayer ADVIA IMS assay results in comparison to results obtained for another marketed device are shown in the following figures.

Image /page/1/Figure/7 description: The image contains two line graphs titled "Longitudinal Sample 1" and "Longitudinal Sample 2". Both graphs depict the levels of CA125 [U/mL] over time, with the x-axis representing the date and the y-axis representing the CA125 levels. Each graph contains two lines, labeled "ADVIA IMS" and "Immuno 1", showing the CA125 levels measured by each method. In the first graph, the CA125 levels for both methods increase from approximately 20 to around 90 between April 1998 and November 1998, while in the second graph, the CA125 levels decrease from around 500 to approximately 80 between April 1996 and December 1996, then increase to around 200 by July 1997.

Correspondence of ADVIA IMS CA125II Assay levels with the clinical course of disease was evaluated using guidelines by Bast et al, whereby a doubling of CA125 II values reflect disease progression and a 50% decrease in CA125 II values reflects response to therapy.

Clinical Status	Change	NoChange	Total
Change	18	7	25
NoChange	1	2	3
Total	19	9	28
	Estimate	95% CI
Sensitivity	94.7%	74.0%	to 99.9%
Specificity	22.2%	2.8%	to 60.0%
Positive predictive value	72.0%
Negative predictive value	66.7%
Concordance	71.4%

Interfering Substances

Separate low serum pools were spiked with the following materials: triglycerides (1000 mg/dL), hemoglobin (1000 mg/dL), bilirubin (25 mg/dL), albumin (6.5 g/dL), immunoglobulin (6.0 g/dL), over the counter medications, vitamins, caffeine and drug pools (two times lethal dose). In all cases the observed recovery bias was found to be of no clinical significance.

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			CA 125 II ASSAY
			CA 125 II (06/18/02)
and the comments of the comments of the comments of the comments of the comments of the comments of the comments of the comments of the comments of the comments of the commen

InterferingSubstance	Interfering SubstanceConcentrationmg/dL	CA125Concentration(U/mL)	CA 125 II (06/18/Effect(% change)
Hemoglobin	1000	19.9	-2.3
Lipids (Triglycerides)	1000	18.5	0.9
Bilirubin	25	22.5	-2.6
IgG	6000	25.1	-4.0
Albumin	6500	22.2	4.3
Acetaminophen	200 µg/mL	30.9	-0.5
Aspirin	500 µg/mL	23.8	-2.2
Ibuprofen	400 µg/mL	23.8	-0.8
Caffeine	100 µg/mL	24.5	1.2
Vitamin A	10 U/mL	21.6	0.1
Vitamin B₁	3 µg/mL	23.4	-1.2
Vitamin B₂	3.4 µg/mL	21.6	-1.3
Vitamin B₆	4 µg/mL	20.6	-0.4
Vitamin B₁₂	12 ng/mL	21.6	9.5
Vitamin C	30 µg/mL	24.5	1.4
Vitamin D₂	0.8 U/mL	20.6	3.7
Vitamin E	0.06 U/mL	20.6	2.5
Folic Acid	0.8 µg/mL	21.6	7.0
Niacin	40 µg/mL	21.6	4.4
Vincristine Sulfate	13.5	20.6	4.1
Vinblastine	5.11	20.6	4.1
Mitomycin C	73	21.6	0.9
Tamoxifen - Free	60	20.6	4.1
Tamoxifen - Citrate	60	20.6	4.1
Etoposide	415	22.5	4.1
5-Fluorouracil	1600	21.6	3.5
CyclophosphamideMonohydrate	800	21.6	0.9
Doxorubicin HCl	51.8	21.6	0.9
Diethylstibestrol	23	20.6	4.1
Methotrexate	450	22.5	5.6
Cis-Platinum	173	20.6	4.1
Lupron	15	25.9	-5.8
Megestrol Acetate	243	21.6	0.9

Analytical Range

0.5 -- 550 U/mL

Minimum Detectable Concentration

ADVIA IMS(U/mL)	Immuno 1(U/mL)
0.5	0.9

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CA 125 II ASSAY CA 125 II (06/18/02)

4. Conclusion

Performance of the ADVIA IMS CA125 II Assay on a Bayer ADVIA® IMS™ is equivalent to the performance of the CA125 II Assay on the predicate device (Immuno 1) and is within proposed specifications. No safety and effectiveness issues have been raised.

Date

K. Edds Director Regulatory Affairs Bayer Corporation 511 Benedict Avenue Tarrytown, New York 10591-5097

PROPRIETARY and CONFIDENTIAL Bayer Corporation 511 Benedict Avenue Tarrytown, NY 10591-5097 USA

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DEPARTMENT OF HEALTH & HUMAN SERVICES

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Food and Drug Administration 2098 Gaither Road Rockville MD 20850

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

K022329 Re: Trade/Device Name: CA 125 II Assay for the ADVIA® IMSTM Regulation Number: 21 CFR 866.6010 Regulation Name: Tumor-associated antigen immunological test system Regulatory Class: Class II Product Code: LTK Dated: October 25, 2002 Received: October 29, 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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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). 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 Sutman

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: KO22329

Device Name: CA125 II Assay for the ADVIA® IMS™

Indications for Use:

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

J.L. Reeves for J. Bautista

Division of Clinical Laboratory Devices

510(k) Number: 1022329

510(k) Number

Prescription Use (Per 21 CFR 801.109) OR

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.