MDA® D-Dimer is a homogeneous latex particle based immunoassay (LIA) for the quantitative determination of cross-linked fibrin degradation products containing the D-dimer domain in citrated human plasma. The assay is designed for use on the MDA® 180 automated coagulation analyzer.

D-dimer is elevated in disseminated intravascular coagulation (DIC), deep venous thrombosis (DVT), and pulmonary omboliom and pulmonary embolism.

Device Description

Organon Teknika's MDA®D-Dimer is a homogeneous latex particle based immunoassay (LIA) for the quantitative determination in human plasma of cross-linked fibrin degradation products containing the D-Dimer domain in human plasma.

D-Dimer containing fibrin degradation products (FbDP) fragments are released when cross-linked fibrin is degraded by plasmin. Cross-linked fibrin is formed when fibrinogen is cleaved by thrombin to form fibrin monomers, which then spontaneously polymerize and are cross-linked by Factor XIIIa. Thrombin is required to cleave fibrinogen as well as to activate Factor XIII. Plasmin-formation is triggered when a fibrin clot is formed. Plasmin degrades some of the cross-linked fibrin and the resulting level of D-Dimer is, therefore, an indirect measure of thrombin generation and subsequent clot formation.

D-Dimer is elevated in disseminated intravascular coagulation (DIC), deep venous thrombosis (DVT), pulmonary embolism. Also, D-Dimer has been reported in the literature to be elevated in other thrombotic conditions.

MDA®D-Dimer is a quantitative homogeneous-phase immunoassay using latex microparticles to photooptically detect binding of specific monoclonal antibody to D-Dimer. These latex particles aggregate only in the presence of fibrin derivatives containing the D-Dimer domain. The rate of latex microparticle aggregation is proportional to the concentration of D-Dimer in the sample. D-Dimer concentration may be interpolated from a reference curve.

AI/ML Overview

Here's a summary of the acceptance criteria and study details for the MDA® D-Dimer device, based on the provided 510(k) submission:

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as distinct numerical targets in this document. Instead, the study aims to demonstrate "substantial equivalence" to predicate devices, focusing on accuracy (correlation) and precision.

Performance Metric	Acceptance Criteria (Implied)	Reported Device Performance (MDA® D-Dimer)
Accuracy	Demonstrates strong correlation with predicate device (Fibrinostika® FbDP EIA)	Slope: 1.005, Intercept: 0.293, Correlation: 0.91 (compared to Fibrinostika® FbDP EIA)
Precision	Low within-run and total variability for positive and normal controls
	Positive Control (1.51 µg FEU/ml)	SD (within-run): 0.06 µg FEU/ml, CV (within-run): 3.83%, SD (total): 0.10 µg FEU/ml, CV (total): 6.67%
	Normal Control (0.28 µg FEU/ml)	SD (within-run): 0.02 µg FEU/ml, CV (within-run): 6.97%, SD (total): 0.04 µg FEU/ml, CV (total): 12.65%
Specificity	Aggregates in the presence of cross-linked fibrin degradation products D-dimer and D-dimer E	Achieved (stated that "MDA D-Dimer Latex Reagent aggregates in the presence of cross-linked fibrin degradation products D-dimer and D-dimer E.")

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

Sample Size: For accuracy testing, 175 samples were used ("Reference Method Fibrinostika® FbDP EIA, n=175").
Data Provenance: Not explicitly stated. The document does not specify the country of origin of the data or whether it was retrospective or prospective.

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

This device is an in-vitro diagnostic (IVD) assay. The "ground truth" for the test set is established by comparison to a legally marketed predicate device (Fibrinostika® FbDP EIA). Therefore, no human experts were used to establish ground truth in the way one would for image-based diagnostic AI. The predicate device's results served as the reference.

4. Adjudication Method for the Test Set

Not applicable as the ground truth was established by another device (predicate device), not through human expert consensus requiring adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size

No, an MRMC comparative effectiveness study was not done. This is an IVD device, not a diagnostic imaging AI requiring human reader performance evaluation.

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

Yes, a standalone performance evaluation was done. The MDA® D-Dimer device's performance (accuracy, precision, specificity) was evaluated directly against a predicate device and its own internal controls. The results presented are for the device operating independently.

7. The Type of Ground Truth Used

The ground truth for the accuracy study was established by comparison to a legally marketed predicate device, specifically the Fibrinostika® FbDP EIA. For precision, internal controls with established values were used.

8. The Sample Size for the Training Set

This document describes the validation of a laboratory assay, not a machine learning algorithm that typically has a distinct training set. Therefore, the concept of a "training set" in the context of AI is not applicable here. The device is an immunoassay, the "training" would be the initial assay development and calibration performed by the manufacturer. No specific "training set" size for an algorithm is provided or relevant.

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

Again, since this is a laboratory immunoassay validation and not an AI algorithm, the concept of establishing ground truth for a "training set" is not applicable in the same way. The assay is developed and manufactured to detect specific analytes (D-dimer) with established chemical and biological principles. The "ground truth" during development would rely on known D-dimer concentrations and biological samples to ensure the assay performs as expected.

Summary

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K974776

510(k) SUMMARY

APR 1 6 1998

MDA®D-Dimer

This summary of safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and the final rule under 21 CFR 807.92 published December 14, 1994.

(a) (1) The submitter's name, address, telephone number, a contact person, and the date the summary was prepared;

Submitter's Name: Submitter's Address: Submitter's Telephone: Submitter's Fax: Submitter's Contact: Date 510(k) Summmary Prepared: Organon Teknika Corporation 100 Akzo Avenue, Durham, North Carolina 27712, USA (919) 620-2373 (919) 620-2548 Ron Sanyal, M. Pharm, CQE, RAC December 19, 1997

The name of the device, including the trade or proprietary name if applicable, the common or (a) (2) usual name, and the classification name, if known;

Trade/Proprietary Name: Common/ Usual Name: Classification Name:

MDA® D-Dimer Fibrin Degradation Product Fibrin Degradation Product

An identification of the legally marketed device to which the submitter claims substantial (a) (3) equivalence.

Device Equivalent to: 1.

Fibrinostika® FbDP Microelisa System (K912876)

Dimertest® Gold EIA (K945642)

(a) (4) A description of the device(System)

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(a) (5) A statement of the intended use of the device.

Device Intended Use:

Organon Teknika's MDA®D-Dimer is a homogeneous latex particle based immunoassay (LLA) for the quantitative determination of cross-linked fibrin degradation products containing the D-Dimer domain in human plasma.

D-dimer is elevated in disseminated intravascular coagulation (DIC), deep venous thrombosis (DVT), and pulmonary embolism.

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A summary of the technological characteristics of the new device in comparision to those of the (a) (6) predicate device.
The technological characteristics of the new device in comparison to those of the device ((Fibrinostika® FbDP Microelisa System (K912876) and (Dimertest® Gold ELA (K945642))] are given in the table 1 below.

Table 1

	MDA ® D-Dimer	FibrinostikaFbDP EIA	DimertestGOLD EIA
Presentation	Automated LatexImmunoassay	Microelisa	Microelisa
Format	Quant.	Quant.	Quant.
Pre-WashPlate	*NA	No	Yes
SamplePre-Treatment	No	Yes	No
Sample Vol.	50 µl	100µl	25 µl
Latex Vol.	50 µl	NA	NA
Conjugate Vol.	NA	100 µl	50 µl
Wash Steps	NA	2	3
Substrate	NA	TMB	ABTS
TotalIncubationTime	12 min.	40 Min.	45 min. withshaking; 140 min.without shaking
Sensitivity	0.25 µg FEU /ml	0.011 µg FEU /ml	0.032 µg/mlD-Dimer
Reference CurveRange	0 - 4µg FEU /ml	0 - 0.9 µg FEU /ml	0-2.0 µg/mlD-Dimer

Not Applicable

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(b) (1) A brief discussion of the nonclinical tests submitted, reference, or relied on in the premarket notification submission for a determination of substantial equivalency.

Not Applicable

A brief discussion of the clinical tests submitted, reference, or relied on in the premarket (b)(2) notification submission for a determination of substantial equivalency.

Comparison Data:

Performance Characteristics

Specíficity

MDA D-Dimer Latex Reagent aggregates in the presence of cross-linked fibrin degradation products D-dimer and D-dimer E.

Accuracy

Results from MDA D-Dimer reagents obtained on an MDA were compared with a commercially available assay (Fibrinostika® FbDP EIA)for detection of crosslinked fibrin degradation product containing the D-dimens were tested in duplicate according to NCCLS Approved Guideline EP9-A. 3 The following results for slope, intercept and correlation were observed for linear least squares regression comparing MDA D-Dimer (y-axis) and the reference method (x-axis):

Reference Method"Specificant of the contribution of the consisted to the control of the comments of the comments	0	Slope	Intercept
Fibrinostika® FbDP EIA	175	1.005	0.293	0.91

Precision

Total precision and within-run precision for the MDA D-Dimer assay were determined in accordance with NCCLS Tentative Guideline EP5-T2.30 Controls were tested in duplicate on an MDA instrument twice daily. Data were collected for 20 days, with a minimum of 40 runs and 80 measurements at each control level. The following precision was observed:

Sample	Mean(µg FEU/ml)	SD (within-run)(µg FEU/ml)	CV (within-run)(%)	SD(total)(µg FEU/ml)	CV(total)(%)
Positive Control	1.51	0.06	3.83	0.10	6.67
MDA Verify 1(Normal Control)	0.28	0.02	6.97	0.04	12.65

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(b) (3) The conclusion drawn from the nonclinical tests that demonstrate that the device is as safe, as effective, and performed as well or better than the legally marketed device identified in (a) (3).

In concusion, the MDA® D-Dimer has sucessfully met all aspects of non clinical and clinical testing and have demonstrated that the device is safe and effective and has performed well and is substantially equivalent to the legally marketed device Fibrinostika® FbDP Microelisa System (K912876) and Dimertest® Gold EIA (K945642).

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Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract image of an eagle with three lines representing its wings and body. The logo is black and white.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

APR 1 6 1998

Ron Sanyal, M. Pharm, CQE, RAC Requlatory Affairs Administrator Organon Teknika Corporation 100 Akzo Avenue Durham, North Carolina 27712

Re : K974776 MDA® D-Dimer Requlatory Class: II Product Code: DAP, GHH Dated: February 27, 1998 March 2, 1998 Received:

Dear Mr. Sanyal:

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 reqistration, 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. ಗ್ 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 In addition, FDA may publish further announcements action. 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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Page 2

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 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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. .

Page ol ……

510(k) Number (if known): K974776

Device Name:__________________________________________________________________________________________________________________________________________________________________ MDA D-Dimer

Indications For Use:

D-dimer is elevated in disseminated intravascular coagulation (DIC), deep venous thrombosis (DVT),
and pulmonary omboliom and pulmonary embolism.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Laboratory Devices

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

(Optional Format 1-2-96)

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number
2974276

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).