OPUS Progesterone is an in vitro fluorogenic enzyme immunoassay (ELISA) for the quantitative measurement of progesterone in human serum or heparanized plasma. OPUS Progesterone is intended for use with the OPUS analyzers.

OPUS Progesterone is an in vitro fluorogenic enzyme immunoassay (ELISA) for the quantitative measurement of progesterone in serum or heparanized plasma, used in the diagnosis and treatment of disorders of the ovaries or placenta. OPUS Progesterone is intended for use with the OPUS analyzers.

Device Description

OPUS Progesterone is a set of reagents intended to be used together with the OPUS immunoassay analyzers for the quantitative measurement of progesterone in human serum or heparanized plasma.

AI/ML Overview

Here's an analysis of the provided 510(k) notification, focusing on the acceptance criteria and the study details:

Device: OPUS® Progesterone Test System

1. Table of Acceptance Criteria and Reported Device Performance

Performance Characteristic	Acceptance Criteria (Implied/General Industry Practice)	Reported Device Performance (OPUS Progesterone)
Precision
Intra-assay %CV	Typically < 15-20% for immunoassay, lower for higher concentrations	8.2% to 14.4% (for three control levels)
Inter-assay %CV	Typically < 15-20% for immunoassay, lower for higher concentrations	9.7% to 14.4% (for three control levels)
Accuracy by Recovery	Generally 80-120% recovery	80% to 111%
Accuracy by Correlation	Correlation coefficient (R) > 0.95, slope near 1, y-intercept near 0	R = 0.97, slope = 0.99, y-intercept = -0.19

Note on Acceptance Criteria: The provided document does not explicitly state pre-defined acceptance criteria values for each performance metric. The "Acceptance Criteria" column above is based on typical industry standards and expectations for immunoassay performance for such devices at the time of submission (mid-1990s). The reported device performance generally falls within these commonly accepted ranges, suggesting the device met the implicit or expected criteria for clearance.

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

Precision (Intra-assay): 3 levels of control material, 20 replicates each.
Precision (Inter-assay): 3 levels of control material, duplicate assays over 5 days (totaling 20 replicates).
Accuracy by Recovery: 5 different levels of Progesterone spiked into previously assayed human serum, assayed in duplicate.
Accuracy by Correlation: 83 serum samples.
Data Provenance: The document does not explicitly state the country of origin. It indicates human serum and heparanized plasma were used as sample matrices. The study appears to be prospective in the sense that the samples were analyzed using the OPUS system for the purpose of demonstrating performance. It's unclear if the samples themselves were collected prospectively or retrospectively from a larger bank.

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

This type of in-vitro diagnostic (IVD) device (immunoassay for quantitative measurement of a biomarker) typically does not rely on expert review of images or clinical cases for ground truth. Instead, the ground truth for performance characteristics like accuracy and precision is established through:

Reference materials/standards: For precision, control materials with known concentrations are used.
Spiked samples with known analyte concentrations: For recovery studies, a known amount of progesterone is added to a sample, and the device's ability to measure that addition is assessed.
Comparison to a legally marketed predicate device: For accuracy by correlation, the predicate device (DPC Coat-a-Count® Progesterone) serves as the "truth" or reference method against which the new device's measurements are compared.

Therefore, the concept of "experts establishing ground truth" in the way it applies to image-based diagnostics is not directly relevant here.

4. Adjudication Method for the Test Set

Not applicable for this type of IVD performance study. Adjudication (e.g., 2+1, 3+1) is typically used in clinical studies or image-based diagnostic evaluations where multiple reviewers resolve discrepancies in interpretations.

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

Not applicable. This device is an automated immunoassay for measuring progesterone levels. It does not involve human readers interpreting AI outputs or images.

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

Yes, the performance studies described (Precision, Accuracy by Recovery, Accuracy by Correlation) are all standalone performance studies for the OPUS Progesterone system. The device itself is an automated system designed for quantitative measurement. Human intervention is limited to sample loading, running the assay, and interpreting the reported numerical result, not in the direct "performance" of the measurement itself or its internal analytical process.

7. The Type of Ground Truth Used

Precision: Established using control materials with known reference ranges.
Accuracy by Recovery: Established by spiking samples with known quantities of progesterone.
Accuracy by Correlation: Established by comparison to a legally marketed predicate device (DPC Coat-a-Count® Progesterone), which serves as the reference method or "truth" for comparative purposes.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of machine learning or AI models, as this is an immunoassay device. Immunoassays are based on biochemical reactions and calibrated using a calibrator system, not typically "trained" in the AI sense.

Calibrator System: The OPUS Progesterone uses a six-point calibrator system. This calibrator system is crucial for establishing the standard curve against which unknown samples are measured. While not a "training set" in the ML sense, these calibrators are fundamental to the device's ability to provide quantitative results.

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

Given that this is an immunoassay and not an AI/ML device, the concept of "ground truth for the training set" doesn't directly apply. Instead, the "ground truth" for the calibrator system (used to establish the standard curve) would be based on:

Highly purified progesterone standards: The concentrations of progesterone in the calibrator materials would be precisely determined using gravimetric methods or other highly accurate analytical techniques, often traceable to international reference standards.
Manufacturing QC: The calibrators would be manufactured and verified for their specified concentrations and stability according to strict quality control procedures.

Summary

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K971725

Behring Diagnostics Inc. OPUS® Progesterone 510(k) Notification

JUN 18 1997

Summary for 510(k) OPUS Progesterone

Manufactures Name, Address, Telephone, and contact person, date of 1 . preparation:

Manufacturer:

Behring Diagnostics Inc. 151 University Avenue Westwood. MA 02090 617-320-3117 Attn: Ruth Forstadt

Preparation date:

May 8, 1997

Name/ Classification: 2. Device

OPUS Progesterone: Progesterone Test System Class | (862.1620) Classification Number:

Identification of the legally marketed device: 3.

DPC Coat-a-Count® Progesterone

Proposed Device Description: 4 .

OPUS Progesterone is a set of reagents intended to be used together with the OPUS immunoassay analyzers for the quantitative measurement of progesterone in human serum or heparanized plasma.

Proposed Device Intended Use: 5.

CONFIDENTIAL

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Behring Diagnostics Inc. OPUS® Progesterone 510(k) Notification

Medical device to which equivalence is claimed and comparison 6. information:

The OPUS Progesterone assay is substantially equivalent in intended use to the DPC Coata-Count® Progesterone. The DPC Coat-a-Count® Progesterone, like the proposed product, use a labeled antibody for the quantitative measurement of progesterone in human serum or heparanized plasma.

The OPUS Progesterone differs from the DPC Coat-a-Count® Progesterone in the technique employed for the quantitative measurement of progesterone. While the DPC Coat-a-Count® Progesterone employs competitive immunassay, the OPUS Progesterone test system is one of sequential binding. Progesterone is labeled with 1185 in the DPC Coat-a-Count® Progesterone, while in the OPUS Progesterone test the antibody is an enzyme labeled mouse monoclonal. Also, the OPUS Progesterone includes a six-point calibrator sytem, whereas the DPC Coat-a-Count® Progesterone includes a seven-point calibrator system. Additionally, the OPUS Progesterone is used with a fully automated fluorometric instrument system, while the DPC Coat-a-Count® Progesterone uses a gamma counter.

Proposed Device Performance Characteristics: 7 .

Precision

Intra-assay precision was determined by the evaluation of three levels of control material in replicates of twenty (20) each. %CV ranged from 8.2% to 14.4%.

Inter-assay precision was determined by the evaluation of three levels of control material in duplicate, assaved over a five day period to total 20 replicates. %CV ranged from 9.7% to 14.4%.

Accuracy by Recovery

Recovery was determined by spiking previously assayed and pooled human serum matrix with five different levels of Progesterone. The samples were assayed using OPUS Progesterone in duplicate. Percent recovery ranged from 80 to 111%.

Accuracy by Correlation

OPUS Progesterone was compared to a commercially available Progesterone assay by evaluation of 83 serum samples ranging from 0.44 to 37.92 ng/ml. A correlation coefficient of 0.97 was obtained, with a y-intercept value of -0.19 and a slope of 0.99.

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Image /page/2/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized symbol resembling a bird or an abstract human figure with three curved lines. The symbol is positioned to the right of the text, which is arranged in a circular fashion around the symbol. The text reads "DEPARTMENT OF HEALTH & HUMAN SERVICES USA".

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUN 18 1997

Ruth Forstadt Regulatory Affairs Associate Behring Diagnostics Inc. 151 University Avenue Westwood, Massachusetts 02090

K971725 Re: OPUS® Progesterone Test System Requlatory Class: I Product Code: JLS Dated: May 8, 1997 Received: May 9, 1997

Dear Ms. Forstadt:

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 The general controls provisions of the Act 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 requlations affecting your device can be found in the Code of Federal Requlations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Good Manufacturing Practice for Medical Devices: General (GMP) requlation (21 CFR Part 820) and that, through periodic GMP 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 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 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 regulation entitled, "Misbranding by reference to
premarket notification" (21 CFR 807.97). Other gener 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 (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html".

Sincerely yours,
Steven Gutman

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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Behring Diagnostics Inc. OPUS® Progesterone 510(k) Notification

Page of of

K971725 510(k) Number (if known): ____________________________________________________________________________________________________________________________________________________

Device Name:_

参

OPUS Progesterone Test System

Indications For 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 2171725

Prescription Use_ (Per 21 CFR 801.109)

Over-The-Counter Use__________________________________________________________________________________________________________________________________________________________

(Optional Format 1-2-96)

DOCCC

Confidential

Regulation Number and Section

§ 862.1620 Progesterone test system.

(a)
Identification. A progesterone test system is a device intended to measure progesterone (a female hormone) in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of disorders of the ovaries or placenta.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 862.9.