OPUS D-Dimer is an in vitro fluorogenic enzyme immunoassay (ELISA) for the quantitative measurement of cross-linked fibrin degradation products (XL-FDP) containing D-Dimer in human plasma, used in the diagnosis of thromboembolic events. OPUS D-Dimer is intended for use with the OPUS analyzers.

Device Description

OPUS D-Dimer is a set of reagents intended to be used together with the OPUS immunoassay analyzers for the quantitative measurement of cross-linked fibrin degradation products containing D-Dimer in human plasma.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Behring Diagnostics Inc. OPUS® D-Dimer device, based on the provided text:

Acceptance Criteria and Device Performance

The document does not explicitly state pre-defined "acceptance criteria" in the format of pass/fail thresholds for the device's performance. Instead, it presents performance characteristics determined through several studies. The underlying acceptance is implied by the FDA's "substantial equivalence" determination, meaning the performance is considered comparable and safe/effective relative to the predicate device.

However, we can infer the reported device performance from the "Device Performance Characteristics" section.

Table of Performance Characteristics:

The document doesn't provide a typical "acceptance criteria" table with specific targets. Instead, it reports the resulting performance metrics from the studies conducted.

Performance Metric	Reported Device Performance (OPUS D-Dimer)
Precision
Intra-assay %CV	7.3% to 8.9% (at two control levels)
Inter-assay %CV	8.6% to 10.3% (at two control levels)
Accuracy
Recovery (pooled human serum spiked)	85% to 95% (across five D-Dimer levels)
Correlation with predicate device (ASSERACHROM D-Di)	Correlation Coefficient: 0.93
	Y-intercept: 0.34
	Slope: 0.89

Study Details

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

Accuracy by Correlation: 321 human plasma samples.
Data Provenance: The document does not explicitly state the country of origin for the data or whether the samples were collected retrospectively or prospectively. It refers to "human plasma samples."

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

This information is not provided in the document. For in vitro diagnostic devices like D-Dimer assays, "ground truth" is typically established by comparing the device's results to a recognized reference method or a legally marketed predicate device. The document uses the "ASSERACHROM® D-Di" as the comparator for accuracy by correlation, implying its results served as the reference. There's no mention of human experts establishing ground truth for the D-Dimer levels in the plasma samples.

4. Adjudication Method for the Test Set

This information is not applicable/provided. The evaluation methods described (precision studies, recovery studies, and correlation with a predicate device) do not involve adjudication by multiple human readers in the way typically seen for medical imaging or clinical decision support AI devices. The comparison is between the new device and a reference method.

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

No, an MRMC comparative effectiveness study was not performed. This type of study is relevant for AI-powered diagnostic aids that assist human interpretation (e.g., radiologists reading images). The OPUS D-Dimer is a standalone in vitro diagnostic assay that quantitatively measures a biomarker, not a device that assists human readers in interpreting clinical cases.

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

Yes, the OPUS D-Dimer is an in vitro diagnostic standalone device. Its performance characteristics (precision, recovery, and correlation with another assay) are reported for the device itself, without human-in-the-loop interpretation being part of the primary performance evaluation. It's an automated fluorometric immunoassay system.

7. The Type of Ground Truth Used

For the "Accuracy by Correlation" study, the ground truth was effectively the results obtained from the legally marketed predicate device, ASSERACHROM® D-Di, which is a "commercially available D-Dimer assay." For precision and recovery studies, the ground truth was based on pre-defined control materials or spiked samples with known concentrations.

8. The Sample Size for the Training Set

This document does not mention a "training set" in the context of machine learning or AI models. The OPUS D-Dimer is an immunoassay system. While the system would have undergone internal development, calibration, and validation, the concept of a separate "training set" and "test set" for an AI algorithm is not applicable here. The reported studies describe analytical performance evaluation, not AI model deployment.

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

As mentioned above, the concept of a "training set" for an AI model is not applicable to this device. For the development and calibration of the immunoassay, ground truth would have been established through highly characterized reference materials and established laboratory methods. The document does not provide details on the specific methods used for establishing these intrinsic reference values during product development.

Summary

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Behring Diagnostics Inc. OPUS® D-Dimer 510(k) Notification

SEP 9 1997

510(k) Summary for OPUS D-Dimer

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:

June 19, 1997

Device Name/ Classification: 2.
OPUS D-Dimer: Classification Number:

Fibrinogen/fibrin degradation products assay Class II (864.7320)

3 . marketed device: Identification of the legally
ASSERACHROM® D-Di

Description: 4 . Device

5. Device Intended Use:

OPUS D-Dimer is an in vitro fluorogenic enzyme immunoassay (ELISA) for the quantitative measurement of cross-linked fibrin degradation products containing D -Dimer in human plasma. OPUS D-Dimer is intended for use with the OPUS analyzers.

CONFIDENTIAL

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Behring Diagnostics Inc. OPUS® D-Dimer 510(k) Notification

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

The OPUS D-Dimer assay is substantially equivalent in intended use to the ASSERACHROM® D-Di. The ASSERACHROM® D-Di, like the proposed product, employs the principle of two site or sandwich immunoassay. The OPUS D-Dimer and ASSERACHROM D-Di both quantitatively measure cross-linked fibrin degradation products that contain D-Dimer in human plasma.

The OPUS D-Dimer differs from the ASSERACHROM® D-Di in that the enzyme labeled antibody is a rabbit polyclonal in the ASSERACHROM® D-Di while the enzyme labeled antibody is a mouse monoclonal in the OPUS test. Also, the OPUS D-Dimer includes a bilevel control, where as the ASSERACHROM® D-Di test does not include a control. Additionally, the OPUS D-Dimer is used with a fully automated fluorometric instrument system which includes a stored calibration curve while the ASSERACHROM® D-Di is a manual assay and uses a calibration curve with each run. Also, the OPUS D-Dimer does not require sample pretreatment for plasma samples while the ASSERACHROM® D-Di requires a predilution of the plasma samples. EDTA, heparinized and citrated plasma samples may be used with the OPUS D-Dimer, but only citrated plasma samples with the ASSERACHROM® D-Di.

Device Performance Characteristics: 7 .

Precision

Intra-assay precision was determined by the evaluation of two levels of control material in replicates of twenty (20) each. %CV ranged from 7.3% to 8.9%.

Inter-assay precision was determined by the evaluation of two levels of control material in duplicate, assayed over a five day period to total 20 replicates. %CV ranged from 8.6% to 10.3%.

Accuracy by Recovery

Recovery was determined by spiking previously assayed and pooled human serum matrix with five different levels of D-Dimer. The samples were assayed using OPUS D-Dimer in duplicate. Percent recovery ranged from 85 to 95%.

Accuracy by Correlation

OPUS D-Dimer was compared to a commercially available D-Dimer assay by evaluation of 321 human plasma samples ranging from 37 to 8480 ng/ml. A correlation coefficient of 0.93 was obtained, with a y-intercept value of 0.34 and a slope of 0.89.

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Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is circular and contains the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol that resembles an eagle or a bird in flight, composed of three stylized lines.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

SEP 9 1997

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

Re : K972316 OPUS® D-Dimer Test System Regulatory Class: II Product Code: GHH Dated: June 19, 1997 Received: June 20, 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 regulations affecting your device can be found in the Code of Federal Requlations, Title 21, Parts 800 to 895. ਰ substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, 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 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 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 (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html".

Sincerely yours,
Steven Sutman

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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Diagnostics Inc. Behring OPUS® D-Dimer 510(k) Notification

Page of

510(k) Number (if known): K972316

OPUS D-Dimer Test System

Device Name: J

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 Devifes
510(k) Number. K972316

Prescription Use (Per 21 CFR 801.109) OR

Over-The Counter Use

(Optional Format 1-2-96)

00026

Regulation Number and Section

§ 864.7320 Fibrinogen/fibrin degradation products assay.

(a)
Identification. A fibrinogen/fibrin degradation products assay is a device used to detect and measure fibrinogen degradation products and fibrin degradation products (protein fragments produced by the enzymatic action of plasmin on fibrinogen and fibrin) as an aid in detecting the presence and degree of intravascular coagulation and fibrinolysis (the dissolution of the fibrin in a blood clot) and in monitoring therapy for disseminated intravascular coagulation (nonlocalized clotting in the blood vessels).(b)
Classification. Class II (performance standards).