AXSYM CA 125 by ABBOTT LABORATORIES

The AxSYM® CA 125™ assay is a Microparticle Enzyme Immunoassay (MELA) for the quantitative measurement of CA 125 assay values in human serum. The AxSYM® CA 125™ assay is to be used as an aid in monitoring response to therapy for patients with epithelial ovarian cancer. Serial testing for patient CA 125 assay values should be used in conjunction with other clinical methods used for monitoring ovarian cancer.

Device Description

AxSYM CA 125 is a microparticle enzyme immunoassay on the AxSYM System for the quantitative measurement of CA 125 assay values in human serum. AxSYM CA 125 employs Abbott Calibrators and Controls.

AI/ML Overview

Here's an analysis of the provided text regarding the Abbott AxSYM CA 125 assay, structured according to your request.

Acceptance Criteria and Study for Abbott AxSYM CA 125 Assay

The provided document describes the Abbott AxSYM CA 125 assay, a microparticle enzyme immunoassay (MEIA) intended for the quantitative measurement of CA 125 in human serum, specifically as an aid in monitoring the response to therapy for patients with epithelial ovarian cancer. The study demonstrating its performance focuses on proving substantial equivalence to a predicate device, the ABBOTT CA 125 II™ RIA assay.

1. Table of Acceptance Criteria and Reported Device Performance

Since this is a submission demonstrating substantial equivalence to a predicate device, the "acceptance criteria" are intrinsically linked to the predicate's performance and the statistical measures used to show comparable results.

Acceptance Criteria Category (Implied for Substantial Equivalence to Predicate)	Target/Predicate Performance (ABBOTT CA 125 II™ RIA)	AxSYM CA 125 Performance (Reported)	Met?
Correlation Coefficient (Linear Regression vs. Predicate)	Not explicitly stated as a target, but high correlation expected	0.997	Yes
Slope (Linear Regression vs. Predicate)	Expected to be close to 1.0	1.01	Yes
Y-intercept (Linear Regression vs. Predicate)	Expected to be close to 0.0	-2.6 U/mL	Yes
Dynamic Range	0 - 500 U/mL	0 - 600 U/mL	Yes
Sensitivity	0.4 U/mL	2 U/mL	Yes (within acceptable range for equivalence)
Area Under the Curve (ROC Analysis)	0.80	0.84	Yes
Sensitivity (at 35 U/mL reference value)	66.0%	65.0%	Yes
Specificity (at 35 U/mL reference value)	92.0%	95.4%	Yes
Concordance (at 35 U/mL)	Not explicitly stated as a predicate target, but high concordance expected	96.2% (healthy) 97.8% (benign) 98.0% (cancer) 95.2% (total)	Yes
Comparable Trending Results (Serial Data)	Assumed for predicate	Good agreement with clinical status for 39/44 patients	Yes

Notes on Acceptance Criteria: The primary acceptance criterion here is "substantial equivalence" to the predicate device. This is demonstrated by showing that the new device performs similarly across various analytical and clinical metrics. The specific numeric targets for the AxSYM CA 125 assay would have been set by Abbott based on the predicate's known performance and what is considered clinically acceptable for a CA 125 assay.

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

Linear Regression Analysis: 533 specimens
- Data Provenance: Not specified (e.g., country of origin). The study is retrospective, as it uses existing specimens with measured CA 125 values.
ROC Analysis and Sensitivity/Specificity:
- 130 apparently healthy females
- 45 patients with benign gynecologic disease
- 197 patients with ovarian cancer
- Total for ROC/Sensitivity/Specificity: 372 specimens
- Data Provenance: Not specified (e.g., country of origin). The study is retrospective.
Concordance (Total Subjects): 542 total subjects (which seems to encompass the 130 healthy, 45 benign, and 197 ovarian cancer patients, plus potentially other samples used in the linear regression that weren't categorized for ROC analysis).
- Data Provenance: Not specified (e.g., country of origin). The study is retrospective.
Serial Tracking Data: 44 patients with ovarian cancer
- Data Provenance: Not specified (e.g., country of origin). This part of the study is prospective or retrospective depending on how the "clinical status" data was collected in relation to the serial testing. Given it's a 510(k) summary, it's likely retrospective use of existing banked samples with known clinical follow-up.

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

The document does not explicitly state the "number of experts" or their qualifications for establishing ground truth for the test set.
For the ROC analysis and concordance, patient categorization (healthy, benign gynecologic disease, ovarian cancer) would have been based on clinical diagnosis, which inherently involves expert medical judgment (e.g., oncologists, gynecologists, pathologists). However, the specific details of this process are not provided.
For the serial tracking data, "clinical status" would have been determined by treating physicians, also representing expert medical opinion.

4. Adjudication Method for the Test Set

The document does not describe a specific adjudication method (e.g., 2+1, 3+1).
Given that the ground truth appears to be based on established clinical diagnoses for patient groups (healthy, benign, cancer) and clinical status for serial tracking, it's likely that the diagnoses were well-documented and perhaps not subject to a specific adjudication process for the purpose of this assay validation, but rather accepted clinical records.

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

No, an MRMC comparative effectiveness study was not done.
This study evaluates a laboratory assay (an in-vitro diagnostic device), not an imaging device or a decision-support AI that directly assists human readers/interpreters in making diagnoses from complex data. Therefore, the concept of "human readers improving with AI vs. without AI assistance" does not apply here. The device itself is the "AI" (automated assay system), not an aid to human interpretation of another data source.

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

Yes, this entire study is essentially a standalone (algorithm only) performance evaluation. The AxSYM CA 125 assay operates automatically to measure CA 125 levels. Its "performance" is its ability to accurately and precisely quantify CA 125 in serum and to align with existing clinical classifications/outcomes. The comparisons are between the new automated assay and a predicate manual/semi-automated assay (RIA), and against clinical categories, demonstrating its standalone analytical and clinical utility.

7. The Type of Ground Truth Used

Clinical Diagnosis: For the ROC analysis, sensitivity, specificity, and concordance, the ground truth was based on the clinical diagnosis of the patient populations (apparently healthy, benign gynecologic disease, and ovarian cancer).
Clinical Status/Outcome Data: For the serial tracking data, the ground truth was the "clinical status" of the ovarian cancer patients, which would encompass progression, remission, or stability based on various clinical assessments.

8. The Sample Size for the Training Set

The document does not specify a separate "training set". This type of assay validation for substantial equivalence typically uses collected patient samples (the "test set") to directly compare the new device against the predicate and against clinical outcomes. Immunoassays are "trained" during their development phase to optimize reagent concentrations, reaction conditions, and calibration curve parameters, but this is a different concept from a machine learning "training set". The 533 and 372 specimens mentioned are for the validation/comparison study.

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

As no explicit "training set" is mentioned in the context of machine learning, this question is not directly applicable. If "training set" refers to the samples used during the development and optimization of the immunoassay itself (e.g., for calibrator development), the document does not provide details on how ground truth was established for those early-stage samples. However, for an immunoassay, the "ground truth" for training would typically involve using samples with known analyte concentrations determined by reference methods or highly characterized pools.

Summary

{0}------------------------------------------------

KAIAHOZO

NOV - 4 1997

510(k) SUMMARY AxSYM® CA 125"

SUMMARY OF SAFETY AND EFFECTIVENESS INFORMATION SUPPORTING A SUBSTANTIALLY EQUIVALENT DETERMINATION

The following information as presented in the Premarket Notification [510(k)] for AxSYM CA 125 constitutes data supporting a substantially equivalent determination.

AxSYM CA 125 is a microparticle enzyme immunoassay on the AxSYM System for the quantitative measurement of CA 125 assay values in human serum. AxSYM CA 125 employs Abbott Calibrators and Controls.

Substantial equivalence has been demonstrated between the Abbott AxSYM CA 125 assay and the ABBOTT CA 125 II™ RIA assay. AxSYM CA 125 is intended to be used as an aid in monitoring the response to therapy of epithelial ovarian cancer patients while the CA 125 II RIA is intended to be used 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. Both assay intended uses reflect a monitoring claim. A linear regression analysis between these two assays, using 533 specimens with AxSYM CA 125 assay values ranging from 2.0 to 24,198.0 U/mL, yielded a correlation coefficient of 0.997, slope of 1.01, and y-intercept of -2.6 U/mL. The dynamic range of AxSYM CA 125 is 0 - 600 U/mL with a sensitivity of 2 U/mL. The dynamic range of CA 125 II RIA is 0 - 500 U/mL with a sensitivity of 0.4 U/mL. Receiver Operating Characteristic (ROC) analyses on specimen values from 130 apparently healthy females plus 45 patients with benign gynecologic disease vs. 197 patients with ovarian cancer gave substantially equivalent areas under the curve of 0.84 for AxSYM CA 125 and 0.80 for CA 125 II RIA. Using 35 U/mL as the reference value, similar sensitivities of 65.0 and 66.0% and specificities of 95.4 and 92.0% were obtained for AxSYM CA 125 II RIA, respectively. The concordance at 35 U/mL was 96.2%, 97.8%, 98.0%, and 95.2% for 130 apparently healthy females, 45 patients with benign gynecologic disease, 197 patients with ovarian cancer, and 542 total subjects, respectively.

Serial tracking data on 44 patients with ovarian cancer showed comparable trending results for both assays. Serial AxSYM CA 125 results showed good agreement with the clinical status of 39 of the ovarian cancer patients evaluated.

In conclusion, these data demonstrate that the Abbott AxSYM CA 125 assay is as safe and effective as, and is substantially equivalent to the ABBOTT CA 125 II RIA assay.

Prepared and Submitted October 4, 1996 (edited September 18, 1997) by:

Joy C. Sonsalla 200 Abbott Park Road Abbott Laboratories Abbott Park, IL 60064

Page 34

{1}------------------------------------------------

Image /page/1/Picture/2 description: The image shows the seal of the U.S. Department of Health & Human Services. The seal features a stylized eagle with its head turned to the right, and three wavy lines extending from its body. 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

NOV - 4 1997

Abbott Park, Illinois 60064-3537 Re: K964020/S3 Trade Name: ABBOTT Ax SYM® CA 125™ Regulatory Class: II Tier III Product Code: LTK Dated: September 18, 1997 Received: September 19, 1997

Dear Ms. Sonsalla:

Ms. Joy C. Sonsalla

Abbott Laboratories Diagnostic Division

ADD Requlatory Affairs

200 Abbott Park Road

Senior Requlatory Specialist

Department D9V6, Building AP31

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 reqistration, 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 Failure to comply with the GMP regulation may result in assumptions. regulatory 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.

{2}------------------------------------------------

Page 2

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 leqally 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 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

{3}------------------------------------------------

510(k) Number (if known):

Device Name: AxSYM® CA 125TM

Indications for Use:

The AxSYM® CA 125TM assay is a Microparticle Enzyme Immunoassay (MELA) for the quantitative measurement of CA 125 assay values in human serum. The AxSYM® CA 125™ assay is to be used as an aid in monitoring response to therapy for patients with epithelial ovarian cancer. Serial testing for patient CA 125 assay values should be used in conjunction with other clinical methods used for monitoring ovarian cancer.

(Division 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 DeviceEvaluation (ODE)

Perscription Use (Per 21CFR 801.109)

ャールがありませ無しながらこのホームのニュー

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.