BIOPHEN Antithrombin 2.5 and 5 kit, is an in vitro diagnostic test for the quantitative determination of Antithrombin in human plasma, as an aid in the diagnosis of thrombophilia (a congenital deficiency of Antithrombin).

Device Description

Biophen Antithrombin 2.5 and 5 kit, an in vitro diagnostic test for the quantitative determination of Antithrombin in human plasma to monitor the Antithrombin concentration in human plasma, in instances of recurrent thrombosis resulting from a congenital or acquired deficiency of Antithrombin.

AI/ML Overview

The provided text describes the Biophen Antithrombin device and its performance relative to a predicate device, Coamatic® Antithrombin. The study presented here is focused on demonstrating substantial equivalence to the predicate device, not on establishing de novo clinical utility or a standalone performance against a clinical ground truth.

Here's an analysis based on your questions:

1. Table of Acceptance Criteria and Reported Device Performance

The core acceptance criterion for substantial equivalence in this context is a strong correlation with the predicate device and acceptable reproducibility (intra-assay and inter-assay variability).

Acceptance Criteria	Reported Device Performance (Biophen® Antithrombin)
Correlation with Predicate Device (Coamatic® Antithrombin)	0.99
Intra-Assay Reproducibility	Sample 1: 0.73% CV
	Sample 2: 0.66% CV
	Sample 3: 0.92% CV
Inter-Assay Reproducibility	Sample 1: 2.57% CV
	Sample 2: 2.49% CV
	Sample 3: 3.72% CV

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

Sample Size for Test Set: 21 samples
Data Provenance: The plasma samples were "received from hospital," implying they are clinical samples. The country of origin is not explicitly stated, but the submission is from Hyphen Biomed, France, and the FDA review process is for the US market. It is retrospective as samples were "received from hospital" and tested.

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

This type of study does not involve establishing ground truth by human experts in the typical sense for diagnostic imaging or subjective assessments. Instead, the performance of the new device (Biophen Antithrombin) is compared to the results obtained by a predicate device (Coamatic® Antithrombin), which serves as the "reference" or "ground truth" for the comparison of analytic performance. Therefore, no human experts were used to establish the "ground truth" for the test set in this context. The "truth" is established by the measurements of the predicate device.

4. Adjudication Method for the Test Set

Not applicable. As described in point 3, there was no expert adjudication process. The comparison was directly between the quantitative results of two laboratory devices.

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 is an in vitro diagnostic (IVD) device for quantitative determination of Antithrombin, not an imaging AI or a device that assists human readers. Therefore, an MRMC study or assessment of human reader improvement with AI assistance is not relevant.

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

Yes, in a way. The "performance data" provided clearly represents the standalone analytical performance of the Biophen Antithrombin device. It measures the Antithrombin concentration directly from plasma samples. There is no human "in the loop" impacting the quantitative measurement itself, beyond handling the samples and operating the automated system (ACL, BCS). The comparison to the predicate device is also a standalone comparison of two device-generated results.

7. The Type of Ground Truth Used

The "ground truth" for this study is not a clinical outcome or pathology report, but rather the results obtained from the legally marketed predicate device, Coamatic® Antithrombin. The study aims to demonstrate that Biophen Antithrombin produces results substantially equivalent to an already approved device.

8. The Sample Size for the Training Set

The document does not provide information about a "training set" for the Biophen Antithrombin device itself. This is an IVD kit, not a machine learning algorithm that requires a training set in the conventional sense. The development of such a kit would involve internal validation and optimization, but these details are not part of this 510(k) summary.

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

Not applicable, as there is no mention of a training set for a machine learning algorithm. The "training" of an IVD device like this would involve internal R&D to define reagents and protocols, but this is not disclosed in the summary.

Summary

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Section Q. Biophen Antithrombin - 510(k ) Summary (Summary of Safety and Effectiveness)

Submitted by:

Hyphen Biomed 95000 Neuville sur oise. France Phone # 01 34 40 6510 Fax# 301 34 48 72 36

Contact Person:

Dr. Jean Amiral, President & Scientific Director

Summary prepared by:

14" Oct 2004

Name of the Device:

Biophen Antithrombin

Classification Name:

Antithrombin III Assay, Class II

Regulation # 864.7060

Product Code: 81JBQ

Identification of Predicate device:

K 915083 Coamatic ® Antithrombin ( Originaly named Coamatic Antithrombin)

Description of the Device/Intended use:

Statement of How the technological Characteristics of the Device Compare to the Predicate Device:

Biophen Antithrombin uses the same principle as the predicate Coamatio® Antithrombin and is substantially equivalent in performance, intended use and safety and effectiveness.

Summary of performance Data:

The assay performance of Biophen Antithrombin was compared to Coamatic ® Antithrombin using plasma received from hospital on automated BCS. The Biophen Antithrombin ®2.5 & 5 રવ 510(k) # K043007

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correlation was 0.99 between the results obtained with the two devices. Overall 21 samples were tested on both the devices.

The intra-assay and Inter assay reproducibility's obtained for samples with variable Antithrombin concentration on ACL is given below:

sample	AT concentration%	Intra Assay(CV %)	N	Inter-Assay(CV %)	N
1	109	0.73%	10	2.57%	12
2	69	0.66%	10	2.49%	12
3	51	0.92%	10	3.72%	12

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Image /page/2/Picture/1 description: The image shows the logo for the Department of Health & Human Services USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" written around the perimeter. Inside the circle is a stylized image of an eagle.

NOV - 7 2005

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

HYPHEN Biomed c/o Mr. Ola Anderson President Aniara Corporation 6560 Gove Court Mason, Ohio 45040

Re: K043007

Trade Name: Biophen® Antithrombin 2.5 and Biophen® Antithrombin 5 Regulation Number: 21 CFR § 864.7060 Regulation Name: Antithrombin III Assay Regulatory Class: II Product Code: JBQ Dated: September 14, 2005 Received: September 15, 2005

Dear Mr. Anderson:

We have reviewed your Scction 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalcnt (for the indications for use stated in the enclosure) to legally marketed predicate 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) that do not require approval of a premarket approval application (PMA). 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 adultcration.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 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.

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If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html

Sincerely yours,

lobetz Beckerh

Robert L. Becker, Jr., MD, Pa Director Division of Immunology and Hematology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): 043007

Device Name: Biophen ® Antithrombin 2.5 &5

Indications for Use:

Prescription Use _____________________________________________________________________________________________________________________________________________________________

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

Concurrepes of CDRH, Office of Device Eyaluation (ODE)

Josephine Bautista

Division/Sign Off

Office of In Vitro Diagnostic Device Evaluation and Safe

510(k) K043007

Regulation Number and Section

§ 864.7060 Antithrombin III assay.

(a)
Identification. An antithrombin III assay is a device that is used to determine the plasma level of antithrombin III (a substance which acts with the anticoagulant heparin to prevent coagulation). This determination is used to monitor the administration of heparin in the treatment of thrombosis. The determination may also be used in the diagnosis of thrombophilia (a congenital deficiency of antithrombin III).(b)
Classification. Class II (performance standards).