IMX CA 15-3 by ABBOTT LABORATORIES

The IMx® CA 15-3™ assay is a Microparticle Enzyme Immunoassay (MEIA) for the quantitative measurement of CA 15-3 assay values in human serum and plasma (EDTA) to aid in the management of Stage II and III breast cancer patients. Serial testing for patient CA 15-3 assay values should be used in conjunction with other clinical methods for monitoring breast cancer.

Device Description

IMx CA 15-3 is a microparticle enzyme immunoassay for the quantitative measurement of CA 15-3 assay values in human serum and EDTA plasma on the IMx System. IMx CA 15-3 employs Abbott Calibrators and Controls.

AI/ML Overview

Table of Acceptance Criteria and Reported Device Performance:

Metric	Acceptance Criteria (Predicate Device: TRUQUANT® BR™ RIA)	Reported Device Performance (IMx® CA 15-3™)
Correlation Coefficient (R-value)	Implied to be high for substantial equivalence	0.910 (vs. TRUQUANT BR RIA for 561 specimens) 0.989 (vs. AxSYM CA 15-3 for 2337 specimens)
Slope	Implied to be close to 1	0.69 (vs. TRUQUANT BR RIA) 1.04 (vs. AxSYM CA 15-3)
Y-intercept	Implied to be close to 0	3.1 U/mL (vs. TRUQUANT BR RIA) -0.30 U/mL (vs. AxSYM CA 15-3)
Dynamic Range	0 - 200 U/mL	0 - 250 U/mL
Sensitivity (of assay measurement)	7.0 U/mL	0.2 U/mL
Area Under the Curve (ROC)	0.70 (for 160 healthy + 30 benign vs. 228 malignant breast patients)	0.71 (for 160 healthy + 30 benign vs. 228 malignant breast patients)
Sensitivity (at reference value)	30.3% (TRUQUANT BR RIA at 37.7 U/mL) 62% (TRUQUANT BR RIA at 37.7 U/mL for relapse prediction)	29.8% (IMx CA 15-3 at 31.3 U/mL) 54% (IMx CA 15-3 at 31.1 U/mL for relapse prediction, 95% CI=25-81)
Specificity (at reference value)	98.4% (TRUQUANT BR RIA at 37.7 U/mL) 91% (TRUQUANT BR RIA at 37.7 U/mL for relapse prediction)	97.4% (IMx CA 15-3 at 31.3 U/mL) 94% (IMx CA 15-3 at 31.1 U/mL for relapse prediction, 95% CI=85-99)
Concordance (total subjects)	Implied to be high for substantial equivalence	98.8% (160 healthy females) 100% (30 benign breast patients) 93.4% (228 malignant breast patients) 98.4% (629 total subjects) 91% (359 specimens from 77 evaluable patients at respective reference values for relapse prediction)
Serial Tracking	Comparable trending results with predicate	Comparable trending results for 24 malignant breast patients

Study Information:

Sample sizes used for the test set and the data provenance:
- Substantial Equivalence Study (IMx CA 15-3 vs. TRUQUANT BR RIA):
  - Linear Regression: 561 specimens with IMx CA 15-3 values ranging from 4.0 to 246.7 U/mL.
  - ROC Analysis: 160 apparently healthy females, 30 benign breast patients, 228 malignant breast patients (total 418 subjects).
  - Concordance: 160 apparently healthy females, 30 benign breast patients, 228 malignant breast patients, and 629 total subjects (the 629 total subjects likely include the previously mentioned groups and potentially additional ones for the overall concordance calculation).
  - Serial Tracking: 24 malignant breast patients.
- Blinded Study (AxSYM CA 15-3 vs. TRUQUANT BR RIA):
  - 79 Stage II and Stage III breast cancer patients.
  - 359 specimens from 77 of the evaluable patients for concordance and sensitivity/specificity at relapse.
- Comparison Study (IMx CA 15-3 vs. AxSYM CA 15-3):
  - 2337 specimens with IMx CA 15-3 values ranging from 3.0 to 250.0 U/mL.
- Data Provenance: Not explicitly stated but clinical specimens from patients with breast cancer, benign breast conditions, and apparently healthy individuals. Given the context of a 510(k) submission, it's highly likely to be retrospective analysis of collected human serum and EDTA plasma samples. Country of origin is not specified.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not applicable/Not mentioned. For an immunoassay device, "ground truth" is typically established by patient diagnosis (e.g., "malignant breast cancer patient," "benign breast patient," "apparently healthy female") and potentially clinical outcomes (e.g., "relapse" for serial tracking of Stage II/III patients), not by expert interpretation of images or other subjective data. The reference values for the assays are predetermined cut-offs.
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- Not applicable/Not mentioned. Adjudication methods like 2+1 or 3+1 are typically used for subjective diagnostic tasks (e.g., image interpretation) where multiple human experts provide opinions that need reconciliation to establish ground truth. This is an immunoassay, and the ground truth relies on physician diagnoses and clinical status.
If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- Not applicable. This is a submission for an in vitro diagnostic (IVD) immunoassay device, not an AI-assisted diagnostic tool that helps human readers interpret data. Therefore, an MRMC study and analysis of human reader improvement with/without AI assistance are not relevant.
If a standalone (i.e. algorithm only, without human-in-the-loop performance) was done:
- Yes, the performance characteristics (e.g., correlation, sensitivity, specificity, dynamic range) represent the standalone performance of the IMx CA 15-3 assay in comparison to the predicate device and another Abbott assay. The device itself is an automated immunoassay system that provides a quantitative result.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The ground truth for the classification studies (ROC, sensitivity/specificity, concordance) appears to be based on clinical diagnosis (e.g., "malignant breast patients," "benign breast patients," "apparently healthy females") and for the serial tracking, it's based on clinical outcomes/status (e.g., "relapse" in Stage II and III breast cancer). For the linear regression and overall correlation, the ground truth is the quantitative measurement provided by the predicate immunoassay (TRUQUANT BR RIA) or another Abbott immunoassay (AxSYM CA 15-3).
The sample size for the training set:
- Not explicitly mentioned. For IVD submissions, internal method development and optimization would constitute a "training" phase, but specific regulated training set sizes are typically not reported in the 510(k) summary as they are for AI/ML devices. The "test sets" described above are used for performance validation against the predicate.
How the ground truth for the training set was established:
- Not explicitly mentioned. Similar to the test set, it would have been established through clinical diagnoses and comparison to existing reference methods during assay development.

Summary

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K964407

510(k) SUMMARY IMx® CA 15-3™

0 1997 សូក្រប់

SUMMARY OF SAFETY AND EFFECTIVENESS INFORMATION SUPPORTING A SUBSTANTIALLY EQUIVALENT DETERMINATION

The following information as presented in the Premarket Notification [510(k)] for IMx CA 15-3 constitutes data supporting a substantially equivalent determination.

Substantial equivalence has been demonstrated between the Abbott IMx CA 15-3 assay and the BIOMIRA Diagnostics Inc. TRUQUANT® BR™ RIA assay. Both assays are intended to be used as an aid in the management of stage II and stage III breast cancer patients. A linear regression analysis between these two assays, using 561 specimens with IMx CA 15-3 assay values ranging from 4.0 to 246.7 U/mL, yielded a correlation coefficient of 0.910, slope of 0.69, and y-intercept of 3.1 U/mL. The dynamic range of IMx CA 15-3 is 0 - 250 U/mL with a sensitivity of 0.2 U/mL. The dynamic range of TRUQUANT BR RIA is 0 - 200 U/mL with a sensitivity of 7.0 U/mL. Receiver Operating Characteristic (ROC) analyses on 160 apparently healthy females plus 30 benign breast patients vs. 228 malignant breast patients gave substantially equivalent areas under the curve of 0.71 for IMx CA 15-3 and 0.70 for TRUQUANT BR RIA. At the claimed reference values for the assays (31.3 U/mL for IMx CA 15-3 and 37.7 U/mL for TRUQUANT BR RIA), similar sensitivities of 29.8% and 30.3% and specificities of 97.4% and 98.4% were obtained for IMx CA 15-3 and TRUQUANT BR RIA, respectively. Based on the claimed reference values for the two assays, concordance was 98.8%, 100%, 93.4%, and 98.4% for 160 apparently healthy females, 30 benign breast patients, 228 malignant breast patients, and 629 total subjects, respectively. Serial tracking data on 24 malignant breast patients showed comparable trending results for both assays.

Seventy nine Stage II and Stage III breast cancer patients were evaluated in a blinded study using the AxSYM CA 15-3 assay and the TRUQUANT BR RIA. 359 specimens from 77 of the evaluable patients gave a concordance(agreement) between the two assays of 91% at their respective reference values. At the claimed reference values for the assays (31.1 U/mL for AxSYM CA 15-3 and 37.7 U/mL for TRUQUANT BR RIA), when using values obtained within 6 months of relapse, similar sensitivities of 54% (95% CI=25-81) and 62% (95% CI=32-86) and specificities of 94% (95% CI=85-99) and 91% (95% CI=80-97) were obtained for AxSYM CA 15-3 and TRUQUANT BR RIA, respectively. The IMx CA 15-3 assay was compared to the AxSYM CA 15-3 assay on 2337 specimens with IMx CA 15-3 assay values ranging from 3.0 to 250.0 U/mL, yielded a correlation coefficient of 0.989, slope of 1.04, and y-intercept of -0.30 U/mL.

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In conclusion, these data demonstrate that the Abbott IMx CA 15-3 assay is as safe and effective as, and is substantially equivalent to the BIOMIRA Diagnostics Inc. TRU-QUANT BR RIA assay.

Prepared and Submitted November 1, 1996 (edited September 15, 1997) by:

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

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Image /page/2/Picture/2 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. Inside the circle is an abstract symbol that resembles three human profiles facing right, stacked on top of each other.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Joy C. Sonsalla Requlatory Affairs Section Leader ADD Regulatory Affairs Abbott Laboratories D49C AP31 200 Abbott Park Road Abbott Park, Illinois 60064-3537

NOV 10 19:

Re: K964407 Trade Name: Abbott IMz® CA 15-3™ Tier III Requlatory Class: II Product Code: MOI Dated: September 16, 1997 Received: September 17, 1997

Dear Ms. Sonsalla:

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 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 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 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 requlation 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 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): K#964407

Device Name:

Indications For Use:

Peter E. Madine

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

(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)

IMx CA 15-3 510(k) Response to FDA Letter dated 1/13/97 mdril 53 lwp

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.