TRUQUANT® BR™ RIA is an in vitro diagnostic device indicated for the quantitative determination of CA 27.29 antigen in serum or EDTA plasma of patients previously treated for stage II or stage III breast cancer. Serial testing for CA 27.29 antigen with TRUQUANT® BR™ RIA in patients who are clinically free of disease should be used in conjunction with other clinical methods used for the early detection of recurrence. In addition, quantitation of CA 27.29 antigen in conjunction with other clinical methods can be used as an aid in monitoring response to therapy in patients with stage IV breast cancer.

Device Description

TRUQUANT® BR™ RIA quantitates CA 27.29 by competitive inhibition RIA. 125(iodine-labelled monoclonal antibody, specific for CA 27.29, is added to antigen-coated polystyrene tubes with the specimen in the form of plasma or serum. Antigen (CA 27.29) in the specimen inhibits the antibody from binding to the CA 27.29 antigen on the tube and after a subsequent wash step, bound radioactivity is determined. A calibration curve, generated from standards containing known quantities of CA 27.29, is used to determine the amount of antigen in the specimen.

AI/ML Overview

The TRUQUANT® BR™ RIA device is indicated for the quantitative determination of CA 27.29 antigen in serum or EDTA plasma for two main purposes:

Monitoring for recurrence in patients previously treated for stage II or stage III breast cancer who are clinically free of disease (used in conjunction with other clinical methods).
Monitoring response to therapy in patients with stage IV breast cancer (used in conjunction with other clinical methods).

The provided text focuses on the clinical studies supporting the device's use in monitoring remission and progression in breast cancer patients with stage IV disease.

Here's the detailed breakdown based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for the TRUQUANT® BR™ RIA in the context of monitoring stage IV breast cancer patients appear to be based on its ability to predict disease progression or remission using a 50% change in CA27.29 values. The presented data reflects the device's performance in these specific scenarios.

Acceptance Criteria (Implicit from Study Findings)	Reported Device Performance (for Stage IV Breast Cancer Monitoring)
Statistically significant prediction of disease progression with a ≥50% increase in CA27.29 from baseline.	Cox regression analysis of prospective study data indicates that a 50% or greater increase in CA27.29 values from baseline, detected at least one examination prior to clinical assessment, is a statistically significant predictor of disease progression. Positive Predictive Value (PPV) for disease progression: 71% (17/24). A marker increase of 50% or more suggests a high probability of treatment failure and likelihood of disease progression.
Statistically significant prediction of disease remission with a ≥50% decrease in CA27.29 from baseline.	Cox regression analysis of prospective study data indicates that a 50% or greater decrease in CA27.29 values from baseline, detected at least one examination prior to clinical assessment, is a statistically significant predictor of disease remission. Negative Predictive Value (NPV) for disease remission: 78% (54/69).
Ability to predict disease remission in patients with progressive or stable disease (mucin-producing subset).	Sensitivity: 25% (5/20) Specificity: 87% (54/62) Accuracy: 72% (59/82)
Ability to detect disease progression in patients with complete or partial remission or with stable disease (mucin-producing subset).	Sensitivity: 52% (17/33) Specificity: 59% (10/17) Accuracy: 54% (27/50) A marker decrease of less than 50% is also associated with ineffective therapy and failure to induce remission.
Provide clinically useful information in the management of late-stage breast cancer.	The positive and negative predictive values (71% for progression and 78% for remission) provide clinically useful information. The device can facilitate clinical decisions through surveillance of soluble marker levels in metastatic breast cancer patients whose tumors produce and secrete mucin (CA27.29).

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

The text explicitly mentions a "prospective study data."

Sample Size for predicting disease remission in patients with progressive or stable disease: 82 patients (20 true remissions, 62 true non-remissions based on clinical assessment).
Sample Size for detecting disease progression in patients with complete or partial remission or with stable disease: 50 patients (33 true progressions, 17 true non-progressions based on clinical assessment).
Data Provenance: The study was a prospective study. The geographical origin of the data is not specified in the provided text.

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

The text states that changes in CA27.29 values were compared against "clinical assessment of status change." It does not specify the number of experts, their qualifications (e.g., specific medical specialties, years of experience), or the precise methodology used for the clinical assessment that served as the ground truth.

4. Adjudication Method for the Test Set

The text does not explicitly describe an adjudication method for establishing the clinical assessment (ground truth). It simply refers to "clinical assessment of status change," implying that this was the established clinical determination made by healthcare providers.

5. 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

This section is not applicable. The TRUQUANT® BR™ RIA is an in vitro diagnostic (IVD) device that quantitates a molecular marker (CA 27.29) by competitive inhibition RIA. It is not an AI-powered image analysis tool or a device that involves "human readers" in the typical sense of interpreting medical images or complex data where AI assistance would be measured in an MRMC study. The device provides a quantitative measurement, which clinicians then incorporate into their decision-making, along with other clinical methods.

6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done

Yes, the performance metrics (sensitivity, specificity, accuracy, PVs) presented for the TRUQUANT® BR™ RIA are standalone performance of the assay itself, demonstrating its ability to correlate with clinical outcomes based on its quantitative output. The device generates a numerical value (CA 27.29 concentration) independently of human interpretation of that specific assay output. The interpretation of the clinical significance of that numerical output is then made by a clinician.

7. The Type of Ground Truth Used

The ground truth used in the study was clinical assessment of status change (disease progression or remission). This implies that the ground truth was based on a comprehensive clinical evaluation of the patients, which would typically include imaging, physical examination, and other laboratory tests, not just the CA 27.29 levels.

8. The Sample Size for the Training Set

The provided text does not specify a separate "training set" or its sample size. The analysis described appears to be based on a single prospective study for evaluating the device's performance against clinical outcomes. For an IVD assay like this, "training set" is not typically referenced in the same way as for machine learning algorithms. The development of the assay itself involves internal validation and calibration, but the clinical study described is for performance evaluation.

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

As no "training set" is explicitly mentioned in the context of this clinical study, this question is not applicable based on the provided information.

Summary

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KQ65141

OCT 31 1997

BIOMIRA Diagnostics Inc. 30 Meridian Road Rexdale, Ontario M9W 4Z7 Canada

ITEM 1.0 510(k) SUMMARY TRUQUANT® BR™ RIA

This 510(k) summary of safety and effectiveness information is being submitted in accordance with the requirements of the Safety Medical Devices Act of 1990.

Submitter :

BIOMIRA Diagnostics Inc.30 Meridian RoadRexdale, Ontario, CanadaM9W 4Z7
Telephone: (416) 674-0863Facsimile: (416) 674-2992
Official Contact:	Bo HollasManager QA/RegulatoryBIOMIRA Diagnostics Inc.
Designated Alternate:	Marilyn OlsonDirector, Regulatory AffairsBIOMIRA Inc.Edmonton Research Park2011-94 StreetEdmonton, AlbertaCanada T6N 1H1Telephone: (403) 450-3761Facsimile: (403) 463-0871
Authorized US Representative:	Jillian CastrucciManager, Regulatory AffairsBIOMIRA USA Corp.1002 East Park Blvd.Cranberry, New Jersey08512Telephone: (609) 655-5300Facsimile: (609) 655-1755

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Date Submitted:

December 20, 1996

Device Name:

Trade Name: TRUQUANT® BR™ RIA

Generic Name: This device does not have an official generic name.

Classificati Class II

Predicate Device: TRUQUANT® BR™ RIA

Device Description:

TRUQUANT® BR™ RIA quantitates CA 27.29 by competitive inhibition RIA. 12ª(odinelabelled monoclonal antibody, specific for CA 27.29, is added to antigen-coated polystyrene tubes with the specimen in the form of plasma or serum. Antigen (CA 27.29) in the specimen inhibits the antibody from binding to the CA 27.29 antigen on the tube and after a subsequent wash step, bound radioactivity is determined. A calibration curve, generated from standards containing known quantities of CA 27.29, is used to determine the amount of antigen in the specimen.

Intended Use:

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Summery and Conclusion

The clinical studies support the safety and effectiveness of TRUQUANT® BR™ RIA for monitoring remission and progression in breast cancer patients with stage IV disease. Cox regression analysis of the prospective study data indicates that a 50% or greater increase or decrease in CA27.29 values from baseline, detected at least one examination prior to clinical assessment of status change, is a statistically significant predictor of disease progression or remission, respectively. The operating characteristics of the assay in the mucin-producing subset of patients (baseline marker levels above the upper limit of normal, 37.7 U/mL) provide evidence for the utility of TRUQUANT® BR™ RIA in determining response to therapy in patients with metastatic breast cancer. TRUQUANT® BR™ RIA exhibited a sensitivity of 25% (5/20) and specificity of 87% (54/62), for an accuracy of 72% (59/82), in predicting disease remission in patients with progressive or stable disease. In patients with complete or partial remission or with stable disease, TRUQUANT® BR™ RIA demonstrated a sensitivity of 52% (17/33), a specificity of 59% (10/17) and accuracy of 54% (27/50) in detecting disease progression. Furthermore, the positive and negative predictive values of 71% (17/24) and 78% (54/69) for disease progression and remission, respectively, provide clinically useful information in the management of late stage breast cancer. A marker increase of 50% or more suggests a high probability of treatment failure and likelihood of disease progression; a marker decrease of less than 50% is also associated with ineffective therapy and failure to induce remission.

In medical practice, the premature withdrawl of effective therapy or prolonged maintenance of ineffective treatment are critical consequences predicated on accurate assessment of patient status. TRUQUANT® BR™ RIA can facilitate important clinical decisions through surveillance of soluble marker levels in metastatic breast cancer patients whose turnors produce and secrete mucin (CA27.29).

Conclusion: TRUQUANT® BR™ RIA, when used in conjunction with other clinical criteria, can assist the clinician in determining response to therapy and in management of breast cancer patients with stage IV disease.

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. . . . . .

Image /page/3/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is a circular emblem with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" arranged around the top half of the circle. Inside the circle is a stylized image of an eagle with its wings spread, facing to the left.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Bo Hollas Manager QA/Regulatory Biomira Diagnostics, Inc. 30 Meridian Road Rexdale, Ontario, CANADA

OCT 31 1997

Re: K965141 TRUQUANT® BR™ RIA Trade Name: Requlatory Class: II Product Code: MOI October 16, 1997 Dated: Received: October 17, 1997

Dear Ms. Hollas:

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 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 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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Page	of

510(k) Number (if known):_ K96514 L___________________________________________________________________________________________________________________________________________

Device Name:_

Indications For Use:

2.3 Intended Use

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

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

Prescription Use	OR	Over-The-Counter Use
(Per 21 CFR 801.109)		(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.