GTI PF4 ENHANCED® is designed as a solid phase enzyme-linked immunosorbent assay (ELISA). The product is intended to be used as an in vitro diagnostics kit by hematology, (ELIG/Y). The produce is the pathology laboratories to assist in screening patient samples for the presence of heparin-associated antibodies commonly found in patients with heparin induced thrombocytopenia or thrombosis.

Device Description

PF4 ENHANCED® Solid Phase ELISA microwells provide immobilized PF4:PVS complexes as a target for the detection of antibodies associated with Type II HIT which are found in some patients undergoing heparin therapy. The presence of these antibodies has been shown to be associated with heparin induced thrombocytopenia Type II (Type II HIT).

Patient serum is added to microwells coated with platelet factor 4 (PF4) complexed to polyvinyl sulfonate (PVS). If an antibody recognizing a site on PF4:PVS is present, binding will occur. Unbound antibodies are then washed away. An alkaline phosphatase labeled anti-human globulin reagent (Anti-IgG/A/M) is added to the wells and incubated. The unbound Anti-IgG/A/M is washed away and the substrate PNPP (p-nitrophenyl phosphate) is added. After a 30-minute incubation period, the reaction is stopped by addition of a sodium hydroxide solution. The optical density of the color that develops is measured in a spectrophotometer.

AI/ML Overview

The document describes a 510(k) premarket notification for a device called "PF4 ENHANCED® Solid Phase ELISA" and its substantial equivalence to a predicate device, the "GTI-PF4 ELISA". The focus of the provided text is on demonstrating that the new device performs as well as the predicate device, especially considering changes to certain materials.

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

1. Table of Acceptance Criteria and the Reported Device Performance

The document does not explicitly state numerical "acceptance criteria" in a typical table format with specific thresholds (e.g., sensitivity > 90%). Instead, the acceptance criteria are implicitly defined by the goal of demonstrating substantial equivalence to the predicate device, the GTI-PF4 ELISA. The performance data was used to show that the PF4 ENHANCED® device performs "as well as" the predicate.

The reported device performance is a qualitative statement of equivalence rather than specific quantitative metrics against pre-defined thresholds.

Acceptance Criteria (Implicit)	Reported Device Performance (Summary)
Equivalence in assay results after material change (wash buffer)	Data showed the effect of the material change on assay results using known patient samples, demonstrating equivalence to the predicate. (Details of specific results are not provided in the summary.)
Equivalence in kit stability (real-time) after material change (wash buffer)	Data showed the effect of the material change on kit stability (real-time stability), demonstrating equivalence. (Details not provided.)
Equivalence in component stability (accelerated and real-time) after stabilizer added	Data showed the effect of the material change on component stability (accelerated and real-time stability studies on the alkaline phosphatase conjugated anti-IgG/A/M), demonstrating equivalence. (Details not provided.)
Equivalence in kit stability (real-time) after stabilizer added	Data showed the effect of the material change on kit stability (real-time), demonstrating equivalence. (Details not provided.)
Equivalence in assay results after stabilizer added	Data showed the effect of the material change on assay results using known patient samples, demonstrating equivalence to the predicate. (Details not provided.)
Equivalence in assay reproducibility (within run, lot to lot, total)	Data showed the effect of the material change on assay reproducibility (within run precision, lot to lot reproducibility, and total reproducibility), demonstrating equivalence. (Details not provided.)
Equivalence in assay specificity (cross reactivity)	Data showed the effect of the material change on assay specificity (cross reactivity of other antibodies), demonstrating equivalence. (Details not provided.)
Overall Conclusion	The data show that PF4 Enhanced is equivalent to PF4 ELISA. Based on comparison with the legally marketed PF4 ELISA, the data demonstrate that PF4 Enhanced ELISA performs as well as the predicate device and does not present new issues of safety and effectiveness.

2. Sample size used for the test set and the data provenance

The document explicitly states that the studies used "known patient samples." However, it does not provide the specific sample size for the test set or the data provenance (e.g., country of origin, retrospective or prospective nature of the samples). The summary refers to "Section 8: Performance Data Section" for details, which is not included in the provided text.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

The document does not provide information on the number of experts used or their qualifications to establish ground truth for the test set. Given that it's an ELISA for detecting antibodies, the "ground truth" would likely be derived from a combination of clinical diagnosis of Type II HIT and potentially other laboratory tests, rather than expert interpretation of an image or signal that requires adjudication. The document states "known patient samples," implying the status of these samples (e.g., positive or negative for the target antibodies/HIT) was already established.

4. Adjudication method for the test set

The document does not specify an adjudication method. This type of assay (ELISA) typically produces quantitative results (Optical Density) that are then interpreted against cut-offs to yield a qualitative (Positive/Negative) result. Adjudication by multiple readers is less common for such objective assays unless there are borderline results or discrepancies in initial interpretations, which isn't mentioned here.

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, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is an in-vitro diagnostic (IVD) ELISA kit, which is a laboratory assay. It does not involve human readers interpreting images or data directly to make a diagnosis in a way that would be "assisted by AI." Therefore, the concept of "human readers improve with AI vs without AI assistance" is not applicable to this device.

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

The device itself is a "standalone" assay in the sense that it produces an objective result (Optical Density) which leads to a qualitative determination (Positive/Negative). It is an "algorithm only" in the context of the assay's biochemical steps and optical density measurement leading to a result. However, this is not an "AI algorithm" in the common sense of the term. The performance data described are for the assay itself.

7. The type of ground truth used

The ground truth for the "known patient samples" would be based on clinical diagnosis of Type II HIT and potentially confirmatory laboratory tests, which establish whether the patient samples are truly positive or negative for the antibodies associated with Type II HIT. The document refers to "known patient samples," implying this established truth. It's not pathology (as in tissue biopsy) or purely outcomes data from a large cohort, but rather a pre-established clinical and laboratory status.

8. The sample size for the training set

The document does not mention a training set in the context of machine learning or AI. This is an ELISA kit validation, not an AI model development. The "known patient samples" mentioned would be considered the test set for validating the new device against the predicate.

9. How the ground truth for the training set was established

As there is no mention of a training set in the context of AI, there's no information on how its ground truth was established. The "known patient samples" for the performance studies would have their ground truth established as described in point 7.

Summary

{0}------------------------------------------------

Image /page/0/Picture/1 description: The image shows the letters "GTI" in a bold, sans-serif font. The letters are white against a black background, with a grainy texture that gives the image a vintage or distressed look. The letters are large and fill most of the frame, making them the focal point of the image.

510(k) Summary

Submitter: I.

II.

K053559

Owner's Name: GTI 20925 Crossroads Circle. Waukesha, WI 53186 Address: Phone: 262.754.1000 262.754.9831 Fax: Name of Contact Person: Leigh Ann Tidey December 9, 2005 Date Summary Prepared: Name of Device: PF4 ENHANCED®Solid Phase ELISA Device Name: Proprietary Name: PF4 ENHANCED® Solid Phase ELISA

Classification Name: Anti-Platelet Factor IV complex Antibodies, Product Code: 0545

Name of predicate device for claiming equivalence III.

GTI-PF4 ELISA (K983379)

IV. Description of Device:

V. Intended Use

PF4 ENHANCED® is a qualitative solid phase enzyme linked immunosorbent assay (ELISA) designed to detect antibodies reactive with platelet factor 4 (PF4)

Suite 200 20925 Crossroads Circle Waukesha, WI 53186-4054 (262) 754-1000 (800) 233-1843 Fax (262) 754-9831 Ernail gti@gtidiagnostics.com

{1}------------------------------------------------

Image /page/1/Picture/0 description: The image shows the letters "GTI" in a bold, sans-serif font. The letters are white and stand out against a black background. The letters are large and take up most of the image. The image has a slightly grainy texture.

when it is complexed to polyanionic compounds such as Polyvinyl Sulfonate (PVS). These antibodies are found in some patients undergoing heparin therapy.

VI. Support of substantial equivalence based on comparison of features, characteristics and components to the predicate device:

The characteristics of the two devices can be summarized as follows:

Features/Characteristics	PF4 ELISA Assay	PF4 ENHANCED®
Type of Test	Qualitative	Qualitative
Intended Use	PF4® ELISA Assay is aqualitative solid phaseenzyme linkedimmunosorbent assay(ELISA) designed todetect antibodies reactivewith platelet factor 4(PF4) when it iscomplexed topolyanionic compoundssuch as PolyvinylSulfonate (PVS). Theseantibodies are found insome patientsundergoing heparintherapy.	PF4 ENHANCED® is aqualitative solid phaseenzyme linkedimmunosorbent assay(ELISA) designed todetect antibodies reactivewith platelet factor 4(PF4) when it iscomplexed topolyanionic compoundssuch as PolyvinylSulfonate (PVS). Theseantibodies are found insome patientsundergoing heparintherapy.
Technology Used inAssay	ELISA	ELISA
Detection Method	Optical Density	Optical Density

In addition, these products have the same:

. indications for use
performance characteristics .
assay protocol .
labeling (except for name) .
scientific technology .

The differences between the two products are related to changes of materials within existing reagents:

1. A different wash buffer is used in PF4 Enhanced
1. A stabilizer was added to the storage buffer used in the alkaline phosphatase conjugated anti-IgG/A/M of PF4 Enhanced.

Suite 200 20925 Crossroads Circle Waukesha, WI 53186-4054 (262) 754-1000 (800) 233-1843 Fax (262) 754-9831 Email gti@gtidiagnostics.com

{2}------------------------------------------------

Image /page/2/Picture/0 description: The image shows the letters "GTI" in a bold, sans-serif font. The letters are large and take up most of the image. The letters are black, and the background is white. The letters appear to have a slightly rough or textured appearance.

Risk analysis did not identify any new issues of safety or effectiveness.

VII. Support of substantial equivalence with performance data:

The performance data used to validate the of the wash buffer change includes:

a) Data showing the effect of the material change on assay results using known patient samples.
b) Data showing the effect of the material change on kit stability (real time stability).

The performance data used to validate the stabilizer added to the storage buffer used in the alkaline phosphatase conjugated anti-IgG/A/M includes:

Data showing the effect of the material change on component stability a) (accelerated and real time stability studies on the alkaline phosphatase conjugated anti-IgG/A/M.)
b) Data showing the effect of the material change on kit stability (real time).
Data showing the effect of the material change on assay results using c) known patient samples.
Data showing the effect of the material change on assay reproducibility d) (within run precision, lot to lot reproducibility, and total reproducibility).
Data showing the effect of the material change on assay specificity e) (cross reactivity of other antibodies).

The details of each of these studies along with results and analysis can be found in Section 8: Performance Data Section.

Summary:

The data show that PF4 Enhanced is equivalent to PF4 ELISA.

VIII. Conclusion:

Based on comparison with the legally marketed PF4 ELISA, the data demonstrate that PF4 Enhanced ELISA performs as well as the predicate device and does not present new issues of safety and effectiveness.

Suite 200 20925 Crossroads Circle Waukesha, WI 53186-4054 (262) 754-1000 (800) 233-1843 Fax (262) 754-9831 Email gti@gtidiagnostics.com

{3}------------------------------------------------

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image shows the logo for the Department of Health & Human Services USA. The logo features a stylized eagle with three stripes extending from its head, symbolizing health and human services. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the eagle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Leigh Ann Tidey, MS, MT(ASCP)SBB Quality Assurance Manager Genetic Testing Institute, Inc. 20925 Crossroads Circle Waukesha, WI 53186

JAN 2 0 2006

K053559 Re: Trade/Device Name: PF4 ENHANCED® Regulation Number: 21 CFR § 864.7695 Regulation Name: Platelet factor 4 radioimmunoassay Regulatory Class: II Product Code: LCO Dated: December 19, 2005 Received: December 21, 2005

Dear Ms. Tidey:

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 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.

{4}------------------------------------------------

Page 2 -

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,

lobatz 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

{5}------------------------------------------------

Indications for Use

510(k) Number (if known):

K053559

Device Name:_PF4 ENHANCED®

Indications For Use:

Prescription Use
(Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Josephine Bautista

Division Sign/Off

Office of In Vitro Diagnostic Device Evaluation and Safety

Page 1 of 1

01083 h053559

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).