The HealthTEST® Heparin/Platelet Factor 4 Antibody Assay is an in vitro diagnostic device designed for the detection of antibodies to Platelet Factor 4 complexed to polyanionic compounds such as polystyrene. These antibodies are found in some patients undergoing heparin therapy.

The HEALTHTEST® Heparin/Platelet Factor 4 Antibody Assay is a qualitative in vitro diagnostic device designed for the detection of antibodies to the Platelet Factor 4 complexed to polyanionic compounds such as polystyrene. These antibodies are found in some patients undergoing heparin therapy.

The risk of heparin induced thrombocytopenia (HIT) is greatly increased in patients with recent exposure to heparin. The presence of heparin/PF-4 antibody is associated with patients arisk. for HIT, and is rapidly becoming a standard of care in hematology and cardinlogy. The need for a rapid test to detect these antibodies from serum or plasma in less than 5 minutes is highly desired. This rapid manual assay should be easily performed when STAT results are required,

Device Description

The HealthTEST® Heparin/Platelet Factor 4 Antibody Assay consists of two components: a Mini-reactor device containing a membrane filtration system and a results window, and a dispenser containing reaction reagents.

The Mini-reactor contains a reaction well that allows the sample to react with the reagents. The sample is added to the reaction well followed by the reagents contained in the reagent dispenser. The reagents contain microparticles coated with purified PF-4 protein as well as additional enhancing agents designed to promote rapid agglutination of the particles in the presence of specific antibodies in the test sample.

Once the reagents have reacted with the sample in the reaction well, the reaction mixture automatically collects over the membrane filtration system. This system acts to filter agglutinated particles, while allowing non-agglutinated particles to pass through. Thus, an agglutinated, reactive sample will be trapped within the membrane. Since the dyed particles are trapped by this filter, no particles and hence no color, are able to migrate past the positive/negative line on the results window. Conversely, a nonagglutinated, non-reactive sample will pass through the membrane filter and into the wicking layers, and no color will migrate past the positive/negative line.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the HealthTEST® Heparin/Platelet Factor 4 Antibody Assay:

1. Table of Acceptance Criteria and Reported Device Performance

Measure	Acceptance Criteria (Implied)	HealthTEST® Heparin/Platelet Factor 4 Antibody Assay Performance (Plasma)	HealthTEST® Heparin/Platelet Factor 4 Antibody Assay Performance (Serum)	Predicate Device Performance (Serum)
Specificity	Greater than Predicate (89.9%)	90.1%	98.1%	89.9%
Sensitivity	Comparable to Predicate (95.2%)	91.3%	91.3%	95.2%
Overall Agreement	Not explicitly stated but implied to be high for substantial equivalence	90.3%	97.2%	Not provided

Note: The acceptance criteria are "implied" because they are not explicitly stated as numerical targets. Instead, the submission demonstrates "substantial equivalence" to the predicate device by showing comparable or superior performance, particularly in specificity. The lower sensitivity in both plasma and serum for the HealthTEST® device compared to the predicate's serum sensitivity is noted but not deemed to raise new issues of safety and effectiveness.

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

Study #1 (Plasma):
- Total Samples: 175
- Data Provenance: Fresh samples originating from "field sources." No specific country of origin is mentioned. The study is retrospective in that samples were collected and then tested, but the "fresh samples" suggest they were not archival.
Study #2 (Serum):
- Total Samples: 179
- Data Provenance: Fresh samples originating from "field sources." No specific country of origin is mentioned. The study is retrospective in that samples were collected and then tested, but the "fresh samples" suggest they were not archival.

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

The ground truth was established by comparing the HealthTEST® device's results to a "commercially available, standard laboratory method" which is identified as the GTI PF4 Elisa Assay (K983379). It is implicit that the results from this predicate ELISA assay were considered the reference standard or "ground truth" for the comparison studies. No individual experts were used for adjudication of the test results themselves; the ELISA outcome was the benchmark.

4. Adjudication Method for the Test Set

No explicit human adjudication method (e.g., 2+1, 3+1) was used for the test set. The HealthTEST® device's results were directly compared against the results of a single reference method, the GTI PF4 Elisa Assay.

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

No MRMC comparative effectiveness study was described. This device is an in vitro diagnostic assay, where the output is directly generated by the device based on a chemical reaction, rather than being interpreted by human readers.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

Yes, the described studies are standalone performance evaluations. The specificity and sensitivity percentages are for the device (HealthTEST® Heparin/Platelet Factor 4 Antibody Assay) itself, without human interpretation of the results beyond reading the positive/negative line on the device.

7. Type of Ground Truth Used

The ground truth used was based on the results from a predicate laboratory assay (GTI PF4 Elisa Assay). This is a form of comparative gold standard where a well-established and legally marketed diagnostic device's results are used as the benchmark.

8. Sample Size for the Training Set

The document does not provide information on a specific "training set" for the HealthTEST® Heparin/Platelet Factor 4 Antibody Assay. Diagnostic assays like this often undergo an extensive development and optimization phase, but the presented data focuses on performance verification (test set) against a predicate, rather than a separate training and validation split as might be seen with AI/machine learning models.

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

As no explicit training set is mentioned for the HealthTEST® device itself (it's a chemical assay rather than a predictive algorithm in the modern AI sense), the concept of "ground truth for the training set" as it applies to AI models is not directly applicable here. The development of such assays typically involves iterative formulation and testing, where the "ground truth" in development would stem from clinical diagnosis or an accepted reference method, guiding the optimization of the assay's reagents and detection mechanism.

Summary

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MAY 2 8 2004

Akers Laboratories, Inc. HealthTEST® Heparin/Platelet Factor 4 Antibody Assay 510(k) Notification

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

The assigned 510(k) number is K040293.

807.92 (a)(1): Name:	Akers Laboratories, Inc.
Address:	201 Grove Road
	Thorofare, NJ 08086
Phone:	(856) 848-8698
FAX:	(856) 848-0269
Contact:	Barbara A. Bagby

807.92 (a)(2): Device Name - trade name and common name, and classification

Trade name:	HealthTEST® Heparin/Platelet Factor 4Antibody Assay
Common name:	Platelet Factor 4 Assay
Classification:	21 CFR 864.7695Product Code: LCO

807.92 (a)(3): Identification of the legally marketed predicate device

HealthTEST® Heparin/Platelet Factor 4 Antibody Assay is substantially equivelant to the GTI PF4 Elisa Assay, Genetic Testing Institute, Waukesha, WI; K983379

807.92 (a)(4): Device Description

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Akers Laboratories, Inc. HealthTEST® Heparin/Platelet Factor 4 Antibody Assay 510(k) Notification

807.92 (a)(4): Device Description (continued)

807.92 (a)(5): Intended use

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Akers Laboratories, Inc. HealthTEST® Heparin/Platelet Factor 4 Antibody Assay 510(k) Notification

807.92 (a)(6): Technological Similarities and Differences to Predicate

The following chart exhibits similarities and differences between the HealthTEST® Heparin/Platelet Factor 4 Antibody Assay and the GTI PF4 Elisa Assay:

CHARACTERISTIC	HealthTEST®Heparin/Platelet Factor 4Antibody Assay	GTI PF4 ELISAK983379
Intended Use	Detects antibodies to theHeparin/PF4 complex in patient'scirculation	Detects antibodies to theHeparin/PF4 complex inpatient's circulation
Indications for Use	Used as an in vitro diagnostic kit byhematology, coagulation or otherpathology laboratories to assist inscreening patient samples for thepresence of heparin-associatedantibodies commonly found inpatients with heparin-inducedthrombocytopenia or thrombosis.	Used as an in vitro diagnostic kitby hematology, coagulation orother pathology laboratories toassist in screening patientsamples for the presence ofheparin-associated antibodiescommonly found in patients withheparin-inducedthrombocytopenia or thrombosis.
Assay type	Serology	Serology
Sample Matrix	Serum, plasma	Serum
Methodology	Immunoassay,Particulate ImmunoFiltrationAssay (PIFA)	Immunoassay,Enzyme-linked ImmunosorbentAssay (ELISA)
Testing Environment	Professional	Professional
Analyte Detection	Antibody to PF-4 complexed withpolyanionic compounds	Antibody to PF-4 complexedwith polyanionic compounds
Specificity	90.1% (plasma)98.1% (serum)	89.9% (serum)
Sensitivity	91.3% (serum & plasma)	95.2% (serum)
Throughput	Individual	Batch testing
Risk to Patient	Minimal to moderate, interpretedwith other clinical findings	Minimal to moderate, interpretedwith other clinical findings

The differences in the two testing platforms do not raise new issues of safety and effectiveness.

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Akers Laboratories, Inc. HealthTEST® Heparin/Platelet Factor 4 Antibody Assay 510(k) Notification

807.92 (b)(1): Brief Description of Non-clinical data

Two studies were performed to evaluate the performance of the HealthTEST® Heparin/Platelet Factor 4 Antibody Assay compared to commercially available, standard laboratory methods using fresh samples originating from field sources.

Specificity and Sensitivity
Study #1 Plasma	ELISA
		Positive	Negative
HealthTEST Positive		21	15
Negative		2	137
Specificity = 90.1%Sensitivity = 91.3%Overall Agreement = 90.3%
Study #2 Serum	ELISA
		Positive	Negative
HealthTEST Positive		21	3
Negative		2	153

Specificity = 98.1% Sensitivity = 91.3% Overall Agreement = 97.2%

807.92 (b)(2): Brief Description of Clinical Data

Not applicable, all testing performed via bench by independent laboratory and/or internally.

807.92 (b)(3): Conclusions from Non-clinical and Clinical Testing

The HealthTEST® Heparin/Platelet Factor 4 Antibody Assay was evaluated for non-clinical and clinical performance characteristics in comprehensive studies. These studies demonstrated that the test is safe and effective for intended use.

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Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus symbol, which is a staff with two snakes coiled around it, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" arranged in a circular pattern around the symbol. The text is in all caps and appears to be in a sans-serif font.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

MAY 2 8 2004

Ms. Barbara A. Bagby Director, Quality Assurance & Regulatory Affairs Akers Laboratories, Inc 201 Grove Rd. Thorofare, NJ 08086

Re: K040293

Trade/Device Name: HEALTHTEST® Heparin/Platelet Factor 4 Antibody Assay Regulation Number: 21 CFR 864.7695 Regulation Name: Platelet Factor 4 radioimmunoassay Regulatory Class: Class II Product Code: LCO Dated: April 30, 2004 Received: May 3, 2004

Dear Ms. Bagby:

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).

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Page 2

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.

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 (301) 594-3084. 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/dsma/dsmamain.html.

Sincerely yours,

Joseph L. Hackett

Joseph L. Hackett, Ph.D. Acting 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): K040293

Device Name: HEALTHTEST® Heparin/Platelet Factor 4 Antibody Assay

Indications for Use:

Prescription Use L (Part 21 CFR 801 Subpart D)

Over-the-Counter Use (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE – CONTINUE ON ANOTHER PAGE AS NEEDED)

Concurrence of CDRH, Office of Device Evaluation (OD

Division Sign-Off

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Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) Ko Yo293

Regulation Number and Section

§ 864.7695 Platelet factor 4 radioimmunoassay.

(a)
Identification. A platelet factor 4 radioimmunoassay is a device used to measure the level of platelet factor 4, a protein released during platelet activation by radioimmunoassay. This device measures platelet activiation, which may indicate a coagulation disorder, such as myocardial infarction or coronary artery disease.(b)
Classification. Class II (performance standards).