The DIMERTEST® Latex Assay is intended for the rapid qualitative or semi-quantitative evaluation of circulating derivatives of cross-linked fibrin degradation products (D-dimer) in human plasma.

Device Description

The DIMERTEST® Latex Kit is a qualitative and semi-quantitative latex agglutination slide test for cross-linked fibrin degradation products in human plasma. The active ingredient in the DIMERTEST® product is the latex reagent. This reagent consists of highly specific D-dimer monoclonal antibodies attached to polystyrene latex particles. When mixed with the latex reagent, the presence of antigen (Ddimer) in a plasma sample results in agglutination of the latex particles which can be seen with the unaided eye. A semi-quantitative estimate of the Ddimer concentration can be made by preparing dilutions of a plasma sample. The concentration is determined according to a titration matrix.

Plasma from normal individuals is not expected to agglutinate DIMERTEST® Latex. Reactive fibrinolysis will be demonstrated by latex agglutination at a plasma concentration of approximately 200 ng/mL D-dimer.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:

DIMERTEST® Device Acceptance Criteria and Performance Study

The DIMERTEST® Latex Assay is intended for the rapid qualitative or semi-quantitative evaluation of circulating derivatives of cross-linked fibrin degradation products (D-dimer) in human plasma. The submission K974596 concerns a modified version of the DIMERTEST® product, where American Diagnostica Inc. (ADI) took over manufacturing from AGEN Biomedical Ltd. and made some changes, including a change in the latex supplier and a refined cut-off value.

1. Table of Acceptance Criteria and Reported Device Performance

The provided document doesn't explicitly state "acceptance criteria" with numerical targets in the conventional sense for a new device. Instead, it focuses on demonstrating substantial equivalence to an existing predicate device (DIMERTEST® K882944) by comparing performance characteristics. The implied acceptance criteria are that the modified device's performance (specificity, sensitivity, and analytical characteristics) is comparable to or improved from the predicate device and that the new cut-off is adequately validated.

Criterion/Performance Characteristic	Acceptance Criteria (Implied for Substantial Equivalence to Predicate)	Reported Device Performance (Modified DIMERTEST®)
Precision/Reproducibility	Consistent results within and between runs	Intra-assay: 10 replicates from three plasma pools (D-dimer titers 0 to 4) all had the same values. Inter-assay: 10 plasma pools (D-dimer titers 1 to 16) tested over 10 runs did not vary by more than 1 titer over 28 days.
Reportable Range (Semi-quantitative)	Clearly defined and validated range	200 to 3,200 ng/mL D-dimer
Analytical Specificity	No significant interference from common plasma components	No assay interference detected when plasma samples were spiked with Bilirubin (0.2 mg/dL), Lipids (triglycerides) (30 mg/dL), Hemoglobin (5.0 mg/dL), Protein (gamma globulin) (0.06 g/mL). Reagents are insensitive to rheumatoid factor.
Assay Cut-off	Established and validated diagnostic threshold	New cut-off: 200 ng/mL D-dimer. Validation: Calculated from 145 patient samples (comparison to predicate) and further validated with an additional 373 patient plasmas (comparison to FDA cleared Dimertest Gold EIA K945642).
Specificity (compared to predicate)	Comparable specificity to the predicate device	95.3% negative results in normal blood bank donor samples (n=170) compared to 97.6% negative by the predicate DIMERTEST® reagent.
Sensitivity (compared to predicate)	Comparable sensitivity to the predicate device	145 plasmas from hospital patients with a high probability of thrombotic conditions were analyzed. (The document describes the method for comparison but does not provide a direct single numerical sensitivity metric for the modified device compared to the predicate in this section).

2. Sample Sizes and Data Provenance for Test Set

Specificity Comparison:
- Sample Size: 170 Blood Bank donor plasma samples.
- Data Provenance: In-house comparative study, ostensibly healthy volunteers. The country of origin is not specified but implied to be North America given the submitter's location (Stamford, CT). Retrospective.
Sensitivity Comparison:
- Sample Size: 145 plasmas from hospital patients.
- Data Provenance: In-house comparative study, patients with a high probability of thrombotic conditions. Country of origin not specified, implied North America. Retrospective.
Clinical Cut-off Validation:
- Sample Size: 373 patient plasmas.
- Data Provenance: Not explicitly stated, but these were "patient plasmas." Country of origin not specified, implied North America. Contemporaneous testing with an FDA-cleared EIA method suggests a prospective element to this validation step.

3. Number of Experts and Qualifications for Ground Truth

The document does not specify the use of experts to establish ground truth for the test set. For the normal donor samples, "ostensibly healthy volunteers" serve as the implicit negative ground truth. For the "hospital patients who had a high probability of thrombotic conditions," the "high probability" suggests clinical assessment as the ground truth, but specific details about how this was determined or by whom are not provided.

4. Adjudication Method for Test Set

The document does not describe any adjudication method for the test set. The results are presented as direct comparisons between the modified device and either the predicate device or a separate FDA-cleared EIA method.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No MRMC comparative effectiveness study was done. This device is a biochemical assay (latex agglutination test), not an imaging or diagnostic device that typically involves human readers interpreting results in a complex way that requires AI assistance. The interpretation (agglutination or not) is largely qualitative or semi-quantitative based on visual inspection.

6. Standalone Performance (Algorithm Only)

This device is a standalone diagnostic kit (a latex agglutination assay) that produces a direct result. It does not involve an "algorithm" in the computational sense nor human-in-the-loop performance with an AI system. The performance characteristics described (precision, linearity, analytical specificity, cut-off validation, and method comparison) represent its standalone performance.

7. Type of Ground Truth Used

Specificity Study: Implicitly, "normal individuals" from Blood Bank donor plasma samples served as the negative ground truth.
Sensitivity Study: Implicitly, "hospital patients who had a high probability of thrombotic conditions" served as the positive ground truth.
Cut-off Validation: The FDA cleared Dimertest Gold EIA method (K945642) served as a comparative reference for determining and validating the new cut-off. This could be considered a reference method ground truth.

8. Sample Size for the Training Set

The document does not explicitly mention a separate "training set" for the device's development or performance evaluation in the context of machine learning. The studies described are performance validation studies for the modified device. The 145 patient samples were used to calculate the new clinical cut-off and the 373 patient plasmas were used to validate it. These samples effectively functioned as the data used to refine and confirm a key aspect of the device's operation.

9. How Ground Truth for the Training Set Was Established

As there's no explicit "training set" in the machine learning sense, the ground truth for the data used to establish or validate the cut-off was as follows:

For the 145 patient plasmas used to calculate the new cut-off, the comparison was made against the D-dimer values determined by the predicate DIMERTEST® reagent.
For the 373 patient plasmas used to validate the new cut-off, the comparison was made against the results from the FDA cleared Dimertest Gold EIA method (K945642).

Summary

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K080069

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510(k) SUMMARY

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of the Safe Medical Device Act (SMDA) of 1990 and 21 CFR part 807.92.

A. 510(k) Number: K974596

B. Purpose for the Submission:

To seek clearance for the existing DIMERTEST® product that was manufactured by AGEN Biomedical Ltd., but is now manufactured by American Diagnostica Inc. (ADI) due to the transfer of ownership of the DIMERTEST® product-line to ADI. The performance characteristics of the modified DIMERTEST® product and a summary of the modifications made to the DIMERTEST® product that had been cleared in 1988 (K882944) are described in the DIMERTEST® 510(k) submission K974596.

C. Measurand: D-Dimer

D. Type of Test: Latex Immuno Assay

E. Applicant:

Submitted by: American Diagnostica Inc. 500 West Avenue Stamford, CT 06902 Tel. 203 602-7777 Ext. 14 Fax 203 602-5553

Contact: Leigh Avres Director of Regulatory Affairs and Quality Assurance 203-602-7777 x 14

Summary Prepared: December 17, 2007

F. Proprietary and Established Name: DIMERTEST®

500 West Avenue, P.O. Box 110215, Stamford, CT 06911-0215 USA · Tel. +1.203.602.7777 · Fax +1.203.602.5553 2007DEC17 DIMERTEST® 510(K) Summary.doc Page 1 of 5

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G. Regulatory Information:

1. Regulation section: 864.7320
1. Classification: Class II
1. Product code: DAP
1. Panel: Hematology

H. Intended Use:

The DIMERTEST® Latex Assay is intended for the rapid qualitative or semi-quantitative evaluation of circulating derivatives of cross-linked fibrin degradation products (D-dimer) in human plasma.

I. Device Description:

J. Substantial Equivalence Information:

1. Predicate device name(s): DIMERTEST®
1. Predicate 510(k) number: K882944

3. Comparison of the Modified DIMERTEST® Kit to the Predicate DIMERTEST® Kit:

SEQ	Kit Component	Is there adifference fromthe PredicateDIMERTEST® kit?	Description of the Change that Was Madeto the Modified DIMERTEST® Kit
1	Latex Reagent	Yes	The supplier for the latex starting materialwas changed, the latex reagent in the kitis now supplied with a dropper bottle, andthe cut-off value was changed from 250ng/mL to 200 ng/mL.

500 West Avenue, P.O. Box 110215, Stamford, CT 06911-0215 USA · Tel. +1.203.602.7777 · Fax +1.203.602.5553 2007DEC17 DIMERTEST® 510(K) Summary.doc Page 2 of 5

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SEQ	Kit Component	Is there adifference fromthe PredicateDIMERTEST® kit?	Description of the Change that Was Madeto the Modified DIMERTEST® Kit
2	Positive Control	Yes	The formulation was not changed, but thebottle in the kit is now provided with adropper tip.
3	NegativeControl	Yes	This was not provided in the predicateDIMERTEST® kit. It is a liquid formulationready to use and it has a dropper tip.
4	Buffer Solution	No	No changes
5	Dropper Pipette	Yes	Deleted from the modifiedDIMERTEST® kit. No longer necessarybecause the latex reagent is now suppliedwith a dropper tip.
6	Reading Cards	Yes	Changed to a pack of 10 disposable blackbackground cards with 8 reaction wellsmarked on each card.
7	Plastic Stirrers	Yes	There was a minor change to the shape ofthe stirrers.
8	Intended Use	No	No changes
9	OperatingPrinciple	No	No changes
10	CaptureAntibody	No	No changes
11	Assay Sample	No	No changes

K. Standard/Guidance Document Referenced (if applicable): N/A

L. Test Principle:

The assay is based on a visible agglutination that occurs when a patient plasma containing D-Dimer is mixed with latex particles coated with monoclonal antibodies.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Intra-assay (within run) reproducibility was determined by testing 10 replicates from three plasma pools that contained D-dimer titers ranging from 0 to 4. The test results for all ten replicates from each pool had the same values.

Inter-assay (run-to-run) reproducibility was determined by testing 10 plasma pools that had Ddimer titers ranging from 1 to 16. The assay values of the replicates from 10 runs of each plasma pool tested over a 28-day period did not vary by more than 1 titer.

500 West Avenue, P.O. Box 110215, Stamford, CT 06911-0215 USA · Tel. +1.203.602.7777 · Fax +1.203.602.5553 2007DEC17 DIMERTEST® 510(K) Summary.doc Page 3 of 5

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b. Linearity/assay reportable range:

The reportable range for the semi-quantitative assay is 200 to 3,200 ng/mL Ddimer.

c. Traceability, Stability, and Expected Values:

The DIMERTEST® kit contains a positive control and a negative control.

The vial labels contain the expiration dates. Reagents are stored between 20 C and 8 €.

Normal plasma samples give negative results.

d. Analytical specificity:

The DIMERTEST® reagent showed no assay interference when plasma samples were spiked with interferents at the following concentrations:

Bilirubin 0.2 mg/dL Lipids (triglycerides) 30 mg/dL Hemoglobin 5.0 mg/dL Protein (gamma globulin) 0.06 g/mL

The DIMERTEST® reagents are insensitive to rheumatoid factor.

e. Assay cut-off:

200 ng/mL D-dimer

Comparison studies:

a. Method Comparison of the Modified DIMERTEST® Reagent versus the Predicate DIMERTEST® Reagent:

Specificity Comparison

An in-house comparative study of 170 Blood Bank donor plasma samples from ostensibly healthy volunteers was performed. 95.3% of the normal results were negative by the modified DIMERTEST® reagent compared to 97.6% negative by the predicate DIMERTEST® reagent.

Sensitivity Comparison

145 plasmas from hospital patients who had a high probability of thrombotic conditions were analyzed in an in-house comparative study.

500 West Avenue, P.O. Box 110215. Stamford, CT 06911-0215 USA · Tel. +1.203.602.7777 · Fax +1.203.602.5553 2007DEC17 DIMERTEST® 510(K) Summary.doc Page 4 of 5

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Clinical Cut-off Change

The new value of the diagnostic cut-off for the modified DIMERTEST® reagent was calculated to be 200 ng/ml. D-dimer with the linear curve generated from the N=145 sensitivity study plasma samples. The D-dimer values that were determined with the predicate DIMERTEST® reagent were plotted as the x-axis and the D-dimer values that were determined with the modified DIMERTEST® reagent were plotted as the y-axis. With a slope of 1.19, the new cutoff was calculated to be approximately 20% less than the predicate DIMERTEST® reagent cut-off of 250 ng/mL D-dimer.

The new cut-off value was validated with an additional 373 patient plasmas that were tested by the modified DIMERTEST® reagent and also tested concurrently by the FDA cleared Dimertest Gold ElA method (K945642).

N. Conclusion

The modified DIMERTEST® product is substantially equivalent to the predicate DIMERTEST® product based on the comparison summary and the performance characteristics.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

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Public Health Service

FEB 1 8 2008

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

American Diagnostica, Inc. C/O Leigh Ayres 500 West Avenue Stamford, Connecticut 06902

Re: K080069 Trade/Device Name: Dimertest Regulation Number: 21 CFR 864.7320 Regulation Name: Fibrinogen/Fibrin Degradation Products Assay Regulatory Class: Class II Product Code: DAP Dated: December 19, 2007 Received: January 11, 2008

Dear Ms. Ayres:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (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 adulteration.

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

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Page 2 -- American Diagnostica

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), plcase contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (240) 276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at (240) 276-3464. 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 (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Katt Beckerl

Robert L. Becker, Jr., MA., Ph.D. 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 STATEMENT

510(k) Number:

K080069

K974596

Device name:

DIMERTEST®

Indications for Use:

The DIMERTEST® Latex Assay is intended for the rapid qualitative or semi-quantitative evaluation of circulating derivatives of cross-linked fibrin degradation products (D-dimer) in human plasma.

Concurrence of CDRH, Office of Device Evaluation (ODE)

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Prescription Use (Per Title 21 CFR part 801.109)

Over-The-Counter-Use

Josephine Bautista

Office of In Vitro Diagnostic Device Evaluation and Sai

510(k) KD80069

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).