The Trinity Biotech Captia™ Herpes Simplex Virus (HSV) 2 Type Specific IgG kit is an Enzyme-linked Immunosorbent Assay (ELISA) intended for qualitatively detecting the presence or absence of human IgG class antibodies to HSV-2 in human serum. In conjunction with the Trinity Biotech Captia™ Herpes Simplex Virus (HSV) I Type Specific IgG kit, the test is indicated for testing sexually active adults or expectant mothers for aiding in the presumptive diagnosis of HSV infection. Due to the implications of positive results, it is recommended they be confirmed in a low prevalence population with Western blot. The performance of this assay has not been established for use in a pediatric population, for neonatal screening, for testing of immunocompromised patients, or for use with automated equipment. The user is responsible for establishing assay performance in these populations and with automated equipment.

Device Description

The CaptiaTM HSV 2 IgG Type Specific kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for the qualitative determination of IgG antibodies in human serum to Herpes simplex Type 2 antigen. The Captia™ HSV 2 IgG Type Specific assay may be used as an aid in the diagnoses of Herpes infection. Purified recombinant HSV gG2 antigen is attached to a solid phase microtiter well. Diluted test sera is added to each well. If the antibodies are present that recognize the antigen, they will bind to the antigen in the well. After incubation, the wells are washed to remove unbound antibody. An enzyme labeled anti-human IgG is added to each well. If antibody is present, it will bind to the antibody attached to the antigen on the well. After incubation, the wells are washed to remove unbound conjugate. A substrate solution is added to each well. If enzyme is present, the substrate will undergo a color change. After an incubation period, the reaction is stopped and the color intensity is measured photometrically, producing an indirect measurement of specific antibody in the patient specimen.

AI/ML Overview

The provided document details the performance characteristics of the Captia™ HSV 2 IgG Type Specific ELISA Test Kit. Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria (e.g., "The device must achieve X% sensitivity and Y% specificity"). Instead, it presents the performance of the device against a predicate device (Western Blot) and an alternate ELISA. The reported performance is summarized below from different study populations. The predicate device used for comparison is the Western Blot (WB) from a Pacific Northwest university.

Performance Metric	Study Population	Reported Device Performance (Captia™ HSV 2 IgG ELISA)	95% Confidence Interval (CI)
% Agreement Positive to WB	Expectant Mothers	100.00% (43/43)	91.8-100.0%
% Agreement Negative to WB	Expectant Mothers	91.52% (151/165)	86.2-95.3%
% Agreement Positive to WB	Sexually Active Adults	96.72% (59/61)	88.7-99.6%
% Agreement Negative to WB	Sexually Active Adults	90.30% (121/134)	84.0-94.7%
% Agreement Positive to WB	Low Prevalence Population	100.00% (4/4)	39.8-100.0%
% Agreement Negative to WB	Low Prevalence Population	91.06% (163/179)	85.9-94.8%
% Agreement Positive to Culture	Culture Positives	100.00% (56/56)	93.6-100.0%
% Agreement Positive to WB	Culture Positives	100.00% (55/55)	93.5-100.0%
% Positive Agreement vs. Alternate ELISA	Prospectively Collected, Sequential Sera	97.14% (68/70)	90.1-99.7%
% Negative Agreement vs. Alternate ELISA	Prospectively Collected, Sequential Sera	92.13% (117/127)	86.0-96.2%
% Agreement vs. Alternate ELISA	Prospectively Collected, Sequential Sera	92.50% (185/200)	87.9-95.7%
Type-specificity relative to WB	HSV 1 WB Positive, HSV 2 WB Negative Sera	90.75% (265/292)	86.8-93.8%
Type cross-reactivity relative to WB	HSV 1 WB Positive, HSV 2 WB Negative Sera	8.0% (23/292)	5.06-11.6%

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

The document describes several distinct test sets:

Expectant Mothers:
- Sample Size: n = 210
- Data Provenance: Consented, coded, unselected, banked, and masked sera. The reference method (Western Blot) was from a Pacific Northwest university. This suggests retrospective data.
Sexually Active Adults:
- Sample Size: n = 198
- Data Provenance: Consented, unselected, and masked sera. The reference method (Western Blot) was from a Pacific Northwest university. This suggests retrospective data.
Low Prevalence Population:
- Sample Size: n = 184
- Data Provenance: Unselected, banked, and masked sera. The reference method (Western Blot) was from a Pacific Northwest university. This suggests retrospective data.
Culture Positives:
- Sample Size: n = 56
- Data Provenance: Unselected, retrospective, and masked sera from patients at least six weeks but not more than one year post clinical presentation and culture HSV 2 positive. Reference methods (culture and Western Blot) were from a Pacific Northwest university.
Prospectively Collected, Sequential Sera (vs. Alternate ELISA):
- Sample Size: n = 200
- Data Provenance: Prospective, unselected, sequentially submitted specimens. Collected by an outside investigator at a Pacific Northwest University.
Type Specificity with HSV 1 Western Blot Positives:
- Sample Size: n = 292
- Data Provenance: HSV 1 Western Blot positive and HSV 2 Western Blot negative sera from the above described populations (expectant mothers, sexually active adults, low prevalence persons, and HSV 1 culture positives). Collected by an outside investigator at a Pacific Northwest University. This is a retrospective analysis of previously collected samples.

In general, the data seems to be from the United States (Pacific Northwest university) and is predominantly retrospective (banked, unselected, masked, retrospective sera), with one prospective study for comparison against an alternate ELISA.

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

The document does not explicitly mention "experts" in the context of establishing ground truth. The ground truth for comparative studies is established by reference methods, primarily:

Western Blot (WB): From a "Pacific Northwest university." No specific detail on the qualifications of the individuals performing or interpreting the Western Blot.
Culture (for Culture Positives set): Implies standard laboratory procedure for viral culture, not explicitly associated with "experts" in this context.

Therefore, the specific number and qualifications of experts beyond the unspecified standard practices of a university lab for performing Western Blots and cultures are not detailed in the provided information.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method (e.g., 2+1, 3+1). The comparisons are directly between the Captia™ ELISA and the reference method results. There's no mention of a process where multiple readers or experts review discordant results to reach a consensus.

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 (ELISA test kit) and does not involve human readers interpreting images or results, nor does it incorporate AI. Its performance is measured directly against laboratory reference standards.

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

Yes, the studies presented describe the standalone performance of the Captia™ HSV 2 IgG Type Specific ELISA Test Kit. This is an enzymatic immunoassay (ELISA) performed in a laboratory setting, and its efficacy is measured by comparing its outputs directly against established reference methods (Western Blot, culture, or another ELISA). There is no "human-in-the-loop" component in the performance evaluation described, beyond the technical execution of the tests themselves.

7. The type of ground truth used

The primary type of ground truth used across the various studies is:

Reference Standard (Western Blot): The Western Blot (WB) method from a Pacific Northwest university served as the gold standard for serological detection of HSV 2 IgG antibodies in most studies.
Culture: For the "Culture Positives" group, the ground truth for actual infection was established by HSV 2 culture positivity.
Alternate ELISA: In one study, another commercially available HSV 2 type-specific IgG ELISA was used as a comparative reference.

8. The sample size for the training set

The document provides performance data based on comparative studies with clinical samples. It does not mention a "training set" in the context of machine learning or algorithm development. This is a traditional IVD device, not an AI-driven algorithm. The performance evaluation focuses on the device's accuracy against established reference methods using specific test populations.

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

As there is no explicit "training set" described for the development of a machine learning algorithm, this question is not applicable. The device's underlying mechanism is a biochemical ELISA, not an algorithm that learns from data. Its "ground truth" for development would relate to the antigen/antibody interactions it's designed to detect.

Summary

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K033106

JUL 1 3 2004

Summary of Safety and Effectiveness Information Captia™ HSV 2 IgG Type Specific ELISA Test Kit

I. Trinity Biotech USA 2823 Girts Rd. Jamestown, NY 14701 Contact Person: Bonnie B. DeJov Telephone: 716-483-3851 Date of Preparation: July 9, 2004

II. Description of Device

For In Vitro Diagnostic Use Only.

The Captia™ HSV 2 IgG Type Specific test is an Enzyme-Linked Immunosorbent assay to detect IgG antibodies to Herpes simplex 2 antigen. Purified recombinant HSV gG2 antigen is attached to a solid phase microtiter well. Diluted test sera is added to each well. If the antibodies are present that recognize the antigen, they will bind to the antigen in the well. After incubation, the wells are washed to remove unbound antibody. An enzyme labeled anti-human IgG is added to each well. If antibody is present, it will bind to the antibody attached to the antigen on the well. After incubation, the wells are washed to remove unbound conjugate. A substrate solution is added to each well. If enzyme is present, the substrate will undergo a color change. After an incubation period, the reaction is stopped and the color intensity is measured photometrically, producing an indirect measurement of specific antibody in the patient specimen.

III. Predicate Device

The Captia™ HSV 2 IgG Type Specific test is substantially equivalent to Western Blot. Equivalence is demonstrated by the following comparative results:

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Perfomance Characteristics % Agreement Positive and % Agreement Negative with Expectant Motherst

An outside investigator assessed the % agreement negative with consented, coded, unselected, banked and masked sera from expectant mothers (n = 210). The reference method was an HSV 2 Western Blot (WB) from a Pacific Northwest university. Of 43 WB positives: Trinity ELISA was 43 positive. Of 165 WB negatives: Trinity ELISA was 151 negative, 13 positive and 1 equivocal.

% Agreement Positive and % Agreement Negative with Expectant Mothers (n = 210)†
Characteristic	% (EL/WB)*	95% Confidence Interval (CI)
% agreement positive to WB	100.00% (43/43)	91.8-100.0%
% agreement negative to WB	91.52% (151/165)	86.2-95.3%
* Excludes one atypical Western Blot and one sample that was both atypical Western Blot and ELISA equivocal.† The word “% agreement” refers to comparing this assay's results with those of a similar assay. No attempt was made to correlate the assay results to disease presence or absence. No judgment can be made on the similar assay's accuracy in predicting disease.

% Agreement Positive and % Agreement Negative with Sexually Active Adults t

An outside investigator assessed the % agreement positive and % agreement negative with consented, unselected and masked sera from sexually active adults over the age of 14 (n = 198). The reference method was an HSV 2 Western Blot (WB) from a Pacific Northwest university. Of 61 WB positives: Trinity ELISA was 59 positive and 2 negative. Of 134 WB negatives: Trinity ELISA was 121 negative and 13 positive.

% Agreement Positive and % Agreement Negative with Sexually Active Adults (n = 198)†

Characteristic	% (EL/WB)*	95% Confidence Interval (CI)
% agreement positive to WB	96.72% (59/61)	88.7-99.6%
% agreement negative to WB	90.30% (121/134)	84.0-94.7%

Excludes three atypical Western Blot.

† The word "% agreement" refers to comparing this assay's results with those of a similar assay. No attempt was made to correlate the assay results to disease presence or absence. No judgment can be made on the similar assay's accuracy in predicting disease.

% Agreement Positive and % Agreement Negative with a Low Prevalence Populationt

An outside investigator assessed the % agreement positive and % agreement negative with unselected, banked and masked sera from a low prevalence population (n = 184). The reference method was an HSV 2 Western Blot (WB) from a Pacific Northwest university. Of 179 WB negatives: Trinity ELISA was 163 negative, 14 positive and 2 equivocal. Of 4 WB positives: Trinity ELISA was 4 positive.

% Agreement Positive and % Agreement Negative with a Low Prevalence Population (n = 184)†

Characteristic	% (EL/WB)*	95% Confidence Interval (CI)
% agreement positive to WB	100.00% (4/4)	39.8-100.0%
% agreement negative to WB	91.06% (163/179)	85.9-94.8%

Excludes one atypical Western Blot.

t The word "% agreement" refers to comparing this assay's results with those of a similar assay. No attempt was made to correlate the assay results to disence. No judgment can be made on the similar assure its armilar assay s accuracy in predicting disease.

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% Agreement Positive with Culture Positivest

An outside investigator assessed the % agreement positive using unselected, retrospective and masked sera from patients that were at least six weeks but not more than one year post clinical presentation and culture HSV 2 positive (n = 56). Reference methods included culture (infection) and an HSV 2 Western Blot (WB) (antibody) from a Pacific Northwest university. Of 56 culture positives: 1) Trinity ELISA was 56 positive and, 2) WB was 55 positive and 1 negative.

% Agreement Positive with Culture Positives (n = 56)t

Characteristic	% (EL/WB or Culture)	95% Confidence Interval (CI)
% agreement positive to culture	100.00% (56/56)	93.6-100.0%
% agreement positive to WB	100.00% (55/55)	93.5-100.0%
† The word "% agreement" refers to comparing this assay's results with those of a similar assay. No attempt was made tocorrelate the assay results to disease presence or absence. No judgment can be made on the similar assay's accuracy inpredicting disease.

% Agreement Positive and % Agreement Negative with Alternate HSV 2 Type Specific IgG ELISA

An outside investigator at a Pacific Northwest University assessed the % agreement positive of the Trinity Biotech Captia™ HSV 2 Type Specific IgG kit and alternate HSV 2 type specific IgG ELISA test with 200 prospective, unselected, sequentially submitted specimens.

Prospectively Collected, SequentialSera	Alternate HSV 2 Type SpecificIgG
	+	-	E
Trinity Biotech CaptiaTMHSV 2 Type Specific	+	68	10	2
	-	2	117	0
	E	0	1	0

Characteristic	% (TBU ELISA / Alt. ELISA)	95% Confidence Interval (CI)
Percent Positive Agreement	97.14% (68 / 70)	90.1 – 99.7%
Percent Negative Agreement	92.13% (117 / 127)	86.0 – 96.2%
Percent Agreement	92.50% (185 / 200)	87.9 – 95.7%

Type Specificity with HSV 1 Western Blot Positives

An outside investigator at a Pacific Northwest University assessed the type specificity using HSV 1 Western Blot positive and HSV 2 Western Blot negative sera from the above described populations (n = 292); expectant mothers, sexually active adults, low prevalence persons, and HSV 1 culture positives. Of 292 HSV 1 Western Blot positive and HSV 2 Western Blot negative samples: ELISA was 265 negative, 23 positive and 4 equivocal.

Characteristic	% (EL/WB)	95% Confidence Interval (CI)
Type-specificity relative to WB	90.75% (265/292)	86.8-93.8%
Type cross-reactivity relative to WB	8.0% (23/292)	5.06-11.6%

Type Specificity with HSV 2 Western Blot Positives (n = 292)

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Public Health Service

Image /page/3/Picture/2 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 words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged in a circular pattern around the symbol. The caduceus is a common symbol associated with healthcare and medicine.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUL 1 3 2004

Ms. Bonnie B. DeJoy Director of Quality Systems Trinity Biotech USA 2823 Girts Road Jamestown, NY 14701

K033106 Re:

Trade/Device Name: CaptiaTM HSV2 IgG Type Specific ELISA Regulation Number: 21 CFR 866.3305 Regulation Name: Herpes Simplex Virus Serological Reagents Regulatory Class: Class III Product Code: MYF Dated: April 20, 2004 Received: April 21, 2004

Dear Ms. DeJoy:

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,

Salartys

Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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510(k) Number: K033106 Device Name: Captia™ HSV2 IgG Type Specific ELISA

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 Device Evaluation (ODE)

Luddi Cole

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K033106

Page 1 of 1

Regulation Number and Section

§ 866.3305 Herpes simplex virus serological assays.

(a)
Identification. Herpes simplex virus serological assays are devices that consist of antigens and antisera used in various serological tests to identify antibodies to herpes simplex virus in serum. Additionally, some of the assays consist of herpes simplex virus antisera conjugated with a fluorescent dye (immunofluorescent assays) used to identify herpes simplex virus directly from clinical specimens or tissue culture isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by herpes simplex viruses and provides epidemiological information on these diseases. Herpes simplex viral infections range from common and mild lesions of the skin and mucous membranes to a severe form of encephalitis (inflammation of the brain). Neonatal herpes virus infections range from a mild infection to a severe generalized disease with a fatal outcome.(b)
Classification. Class II (special controls). The device is classified as class II (special controls). The special control for the device is FDA's revised guidance document entitled “Class II Special Controls Guidance Document: Herpes Simplex Virus Types 1 and 2 Serological Assays.” For availability of the guidance revised document, see § 866.1(e).