The Trinity Biotech Captia™ Herpes Simplex Virus (HSV) 1 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-1 in human serum. In conjunction with the Trinity Biotech Captia™ Herpes Simplex Virus (HSV) 2 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 performanace in these populations and with automated equipment

Device Description

The Captia™ HSV 1 IgG Type Specific kit is an Enzyme-Linked Immunosorbent Assav (ELISA) for the qualitative determination of IgG antibodies in human serum to Herpes simplex Type 1 antigen. The Captia™ HSV 1 IgG Type Specific assay may be used as an aid in the diagnoses of Herpes infection.

For In Vitro Diagnostic Use Only.

The Captia™ HSV 1 IgG Type Specific test is an Enzyme-Linked Immunosorbent assay to detect IgG antibodies to Herpes simplex 1 antigen. Purified recombinant HSV gG1 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

Here's a breakdown of the acceptance criteria and study information for the Captia™ HSV 1 IgG Type Specific ELISA Test Kit, based on the provided text:

Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly defined by the performance characteristics presented in the study. The device is deemed acceptable if its agreement with the predicate device (Western Blot or other ELISA) falls within certain confidence intervals, demonstrated across various patient populations.

Acceptance Criteria (Implied)	Reported Device Performance	95% Confidence Interval (CI)
Expectant Mothers (vs. HSV 1 Western Blot)
% Agreement Positive to WB: Acceptably high	87.74% (136/155)	82.6-92.9%
% Agreement Negative to WB: Acceptably high	98.18% (54/55)	90.3-100.0%
Sexually Active Adults (vs. HSV 1 Western Blot)
% Agreement Positive to WB: Acceptably high	87.93% (102/116)	82.0-93.9%
% Agreement Negative to WB: Acceptably high	100.00% (80/80)	95.5-100.0%
Low Prevalence Population (vs. HSV 1 Western Blot)
% Agreement Positive to WB: Acceptably high	79.25% (42/53)	65.9-89.2%
% Agreement Negative to WB: Acceptably high	97.71% (128/131)	93.5-99.5%
Culture Positives (vs. Culture)
% Agreement Positive to Culture: Acceptably high	69.81% (37/53)	55.7-81.7%
Culture Positives (vs. HSV 1 Western Blot)
% Agreement Positive to WB: Acceptably high	81.82% (36/44)	67.3-91.8%
Alternate HSV 1 Type Specific IgG ELISA
Percent Positive Agreement: Acceptably high	93.88% (92 / 98)	87.2 - 97.7%
Percent Negative Agreement: Acceptably high	97.06% (99 / 102)	91.6 - 99.4 %
Percent Agreement: Acceptably high	95.50% (191 / 200)	91.6 - 97.9 %
Type Specificity with HSV 2 Western Blot Positives
Type-specificity relative to WB: Acceptably high	96.4% (54/56)	87.7-99.6%
Type cross-reactivity relative to WB: Acceptably low	3.6% (2/56)	0.43-12.3%

Study Details

Sample sizes used for the test set and the data provenance:
- Expectant Mothers: n = 210 sera. Data provenance: Consented, coded, unselected, banked, and masked sera. Country of Origin: Not specified beyond "Pacific Northwest university" which references the Western Blot. Retrospective (banked sera).
- Sexually Active Adults: n = 198 sera. Data provenance: Consented, unselected, and masked sera. Country of Origin: Not specified beyond "Pacific Northwest university". Retrospective (masked sera implies pre-collected).
- Low Prevalence Population: n = 184 sera. Data provenance: Unselected, banked, and masked sera. Country of Origin: Not specified beyond "Pacific Northwest university". Retrospective (banked sera).
- Culture Positives: n = 53 sera. Data provenance: Unselected, retrospective, and masked sera from patients at least six weeks but not more than one year post clinical presentation and culture. Country of Origin: Not specified beyond "Pacific Northwest university". Retrospective.
- Alternate HSV 1 Type Specific IgG ELISA Comparison: n = 200 specimens. Data provenance: Prospective, unselected, sequentially submitted specimens. Country of Origin: Not specified beyond "Pacific Northwest University".
- Type Specificity with HSV 2 Western Blot Positives: n = 56 sera. Data provenance: Samples from the "above described populations" (expectant mothers, sexually active adults, low prevalence persons, and HSV 2 culture positives) that were HSV 2 Western Blot positive and HSV 1 Western Blot negative. Country of Origin: Not specified beyond "Pacific Northwest University". Retrospective.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
The document does not explicitly state the number or qualifications of experts used to establish the ground truth. The ground truth (reference method) was established by an "HSV 1 Western Blot (WB) from a Pacific Northwest university" or "culture" for some cases. While Western Blot interpretation requires expertise, no details about the experts are provided.
Adjudication method for the test set:
The document does not mention an adjudication method for the test set. Results from the Trinity ELISA were compared directly against the Western Blot or culture reference method. For the expectant mothers and low prevalence population studies, "equivocal" results from the Trinity ELISA were excluded from the percentage agreement calculations but reported in the raw counts.
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 kit, not an AI-assisted diagnostic tool that would involve human readers interpreting results with or without AI. The evaluation is solely on the performance of the assay itself compared to a reference method.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
Yes, the studies presented are all standalone performance evaluations of the Captia™ HSV 1 IgG Type Specific ELISA kit. The performance metrics (e.g., % agreement positive, % agreement negative) are direct comparisons between the ELISA results and the reference method (Western Blot or culture) without human interpretation being factored in beyond the initial reading of the ELISA and the reference method itself.
The type of ground truth used:
The primary type of ground truth used was:
- Expert Consensus / Established Reference Method: Western Blot (HSV 1 Western Blot, HSV 2 Western Blot). The Western Blot is considered a gold standard for type-specific HSV serology.
- Pathology / Outcomes Data: Culture (for the "Culture Positives" study), indicating active infection.
The sample size for the training set:
The document does not provide information on a training set. The presented studies are performance evaluations of the final device, implying that any training and development would have occurred prior to these validation studies. Therefore, the sample sizes mentioned are for the test sets.
How the ground truth for the training set was established:
Since no training set details are provided, the method for establishing its ground truth is also not mentioned.

Summary

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K0331A5

JUL 1 3 2004

Summary of Safety and Effectiveness Information CaptiaTM HSV 1 IgG Type Specific ELISA Test Kit

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

II. Description of Device

For In Vitro Diagnostic Use Only.

III. Predicate Device

The CaptiaTM HSV 1 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 1 Western Blot ( WB) from a Pacific Northwest university. Of 155 WB positives, Trinity ELISA was 136 positive, 18 negative and 1 equivocal. Of 55 WB negatives, Trinity ELISA was 54 negative and 1 positive.

% Agreement Positive and % Agreement Negative with Expectant Mothers (n = 210)†

Characteristic	% (EL/WB)*	95% Confidence Interval (CI)
% agreement positive to WB	87.74% (136/155)	82.6-92.9%‡
% agreement negative to WB	98.18% (54/55)	90.3-100.0%

† 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 assay's accuracy in predicting disease.

95% CI calculated using the normal approximate method.

% Agreement Positive and % Agreement Negative with Sexually Active Adultst

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 1 Western Blot (WB) from a Pacific Northwest university. Of 116 WB positives, Trinity ELISA was 102 positive and 14 negative. Of 80 WB negatives, Trinity ELISA was 80 negative.

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

Characteristic	% (EL/WB)*	95% Confidence Interval (CI)
% agreement positive to WB	87.93% (102/116)	82.0-93.9%‡
% agreement negative to WB	100.00% (80/80)	95.5-100.0%

Excludes two atypical Western Blots.
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 assay's accuracy in predicting disease,

$ 95% CI calculated using the normal approximate method.

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

An outside investigator assessed the % agreement negative with unselected, banked and masked sera from a low prevalence population (n = 184). The reference method was an HSV 1 Western Blot (WB) from a Pacific Northwest university. Of 131 WB negatives, Trinity ELISA was 128 negative, 1 positive and 2 equivocal. Of 53 WB positives, Trinity ELISA was 42 positive, 8 negative and 3 equivocal.

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

Characteristic	% (EL/WB)*	95% Confidence Interval (CI)
% agreement positive to WB	79.25% (42/53)	65.9-89.2%
% agreement negative to WB	97.71% (128/131)	93.5-99.5%

f The word "% agreement" refers to comparing this assay's results with those of a similar assay. No attempt was nade to correlate the assay results to disence. No judgment can be made on the similar 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 (n = 53). Reference methods included culture (infection) and an HSV 1 Western Blot (WB) (antibody) from a Pacific Northwest university. Of 53 culture positives: 1) Trinity ELISA was 37 positive and 4 equivocal and, 2) WB was 44 positive and 9 negative. Of 44 WB positives: Trinity ELISA was 36 positive, and 2 equivocal.

Characteristic	% (EL/WB or Culture)	95% Confidence Interval (CI)
% agreement positive to culture	69.81% (37/53)	55.7-81.7%
% agreement positive to WB	81.82% (36/44)	67.3-91.8%

% Agreement Positive with Culture Positives (n = 53)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 assay's accuracy in predicting disease.

% Agreement Positive and % Agreement Negative to Alternate HSV 1 Type Specific IgG ELISA

An outside investigator at a Pacific Northwest University assessed the 10 % agreement negative of the Trinity Biotech Captia™ HSV 1 Type Specific IgG kit and an alternate HSV 1 type specific IgG ELISA test with 200 prospective, unselected, sequentially submitted specimens.

	Prospectively Collected, Sequential Sera	Alternate HSV 1 Type Specific IgG
		+	-	E
Trinity Biotech CaptiaHSV 1 Type Specific	+	92	3	0
	-	6	99	0
	E	0	0	0

Characteristic	% (TBU ELISA / Alt.ELISA)	95% ConfidenceInterval (CI)
Percent PositiveAgreement	93.88% (92 / 98)	87.2 - 97.7%
Percent NegativeAgreement	97.06% (99 / 102)	91.6 - 99.4 %
Percent Agreement	95.50% (191 / 200)	91.6 - 97.9 %

Type Specificity with HSV 2 Western Blot Positives

An outside investigator at a Pacific Northwest University assessed the type specificity using HSV 2 Western Blot positive and HSV 1 Western Blot negative sera from the above described populations (n = 56): expectant mothers, sexually active adults, low prevalence persons, and HSV 2 culture positives. Of 56 HSV 2 Western Blot positive and HSV 1 Western Blot negative samples, Trinity ELISA was 54 negative and 2 positive.

Characteristic	% (EL/WB)	95% Confidence Interval (CI)
Type-specificity relative to WB	96.4% (54/56)	87.7-99.6%
Type cross-reactivity relative to WB	3.6% (2/56)	0.43-12.3%

Type Specificity with HSV 2 Western Blot Positives (n = 56)

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Image /page/3/Picture/2 description: The image shows the seal of the U.S. Department of Health & Human Services. The seal features a stylized eagle with three tail feathers, representing the department's mission to protect the health of all Americans and provide essential human services. The eagle is encircled by the words "DEPARTMENT OF HEALTH & HUMAN SERVICES U.S.A."

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

Re: K033105

Trade/Device Name: CaptiaTM HSV 1 IgG Type Specific ELISA Regulation Number: 21 CFR 866.3305 Regulation Name: Herpes Simplex Virus Serological Reagents Regulatory Class: Class III Product Code: MXJ 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: K033105 Device Name: Captia™ HSV 1 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)

Reeder Jr. Poole

Division Sign Off

Division Sign-Off

Office of to Vitro Diagnostic Device Evaluation and Safe

510(k) KD33105/51

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).