HERPES GROUP IGG

K033059 · Trinity Biotech, Inc. · LGC · Nov 26, 2003 · Microbiology

Device Facts

• Record ID: K033059
• Device Name: HERPES GROUP IGG
• Applicant: Trinity Biotech, Inc.
• Product Code: LGC · Microbiology
• Decision Date: Nov 26, 2003
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3305
• Device Class: Class 2

Intended Use

The Trinity Biotech Captia™ Herpes Group IgG ELISA kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for qualitative determination of IgG antibodies in human serum to Herpes simplex virus. The Herpes Group IgG ELISA kit may be used to determine serologic status in females of child bearing age, and to evaluate paired sera for the presence of a seroconversion of IgG as an aid in the diagnosis of Herpes simplex virus infection. It is not intended for determining the type of Herpes simplex virus.

Device Story

The Captia Herpes Group IgG ELISA is an in vitro diagnostic test for human serum. It utilizes purified Herpes Group antigen immobilized on microtiter wells. Patient serum is added; if specific IgG antibodies are present, they bind to the antigen. After washing, enzyme-labeled anti-human IgG is added, followed by a substrate solution. The resulting color change is measured photometrically, providing an indirect quantitative measurement of antibody concentration. The test is performed in clinical laboratories by trained personnel. Results assist clinicians in assessing serologic status and identifying seroconversion in patients suspected of acute infection. It does not differentiate between HSV-1 and HSV-2.

Clinical Evidence

No clinical data provided. Device is a distributor change; performance characteristics were established in the predicate device (K963645).

Technological Characteristics

Enzyme-Linked Immunosorbent Assay (ELISA) using purified Herpes Group antigen immobilized on solid-phase microtiter wells. Employs enzyme-labeled anti-human IgG conjugate and substrate for colorimetric detection. Photometric measurement of optical density. Manual or automated microplate processing. Standard laboratory equipment required.

Indications for Use

Indicated for qualitative determination of IgG antibodies to Herpes simplex virus in human serum. Used to determine serologic status in females of child-bearing age and to evaluate paired sera for IgG seroconversion as an aid in diagnosis. Not intended for HSV typing.

Regulatory Classification

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.

Special Controls

*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).

Predicate Devices

• Herpes Group IgG ELISA Test System (K963645)

Submission Summary (Full Text)

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Summary of Safety and Effectiveness Information Herpes Group IgG ELISA Test Kit

- I. Trinity Biotech 2823 Girts Road Jamestown, NY 14701 Contact person: Bonnie B. DeJoy Telephone: [phone] Date of preparation: Nov. 20, 2003
#### II. Description of Device

The Herpes Group IgG ELISA kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for qualitative determination of IgG antibodies in human serum to Herpes simplex virus. The Herpes Group IgG ELISA kit may be used to evaluate paired sera for the presence of seroconversions of IgG as an aid in the diagnosis of Herpes simplex virus infection.

The Herpes Group IgG ELISA test is an enzyme linked immunosorbent assay to detect IgG antibodies to Herpes simplex virus. Purified Herpes Group antigen is attached to a solid phase microtiter well. Diluted test sera are 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. 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 and indirect measurement of specific antibody in the patient specimen.

#### III. Predicate Device

The Herpes Group IgG ELISA test is substantially equivalent to Clark Laboratories, Inc. (Clark) HSV I and HSV II ELISA tests. Equivalence is demonstrated by the following comparative results:

# Performance Characteristics

1. % Agreement Positive and % Agreement Negative. Four different sites compared the Trinity Biotech Herpes Group IgG ELISA test relative to Clark HSVI ELISA assays. The first site was a R&D laboratory at a commercial company located in Maryland. The frozen sera were from normals with ages from 12-83, with various gender and geographical areas. The results of the study are compiled and summarized in Table 1.

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Please be advised the "% agreement positive" and "% agreement negative" refers to the Note: comparison of this assay's results to that of a similar assay. There was not an attempt to correlate the assay's results with disease presence or absence. No judgment can be made on the comparison assay's accuracy to predict disease.

## Table 1 Comparison of Herpes Group IgG ELISA and Clark HSV 1 and HSV 2 Study 1

## Trinity Biotech Herpes Group IgG ELISA

| | | + | eq | - | Total |
|---------------------------|-------|-----|----|----|-------|
| Clark<br>HSV 1 &<br>HSV 2 | +* | 104 | 1 | 1 | 106 |
| | eq* | 3 | 0 | 0 | 3 |
| | -*** | 4 | 2 | 72 | 78 |
| | Total | 111 | 3 | 73 | 187 |

| % Agreement positive = 104/105 = 99.1% | 95% Confidence interval = 97.2% - 100% |
|----------------------------------------|-----------------------------------------|
| % Agreement negative = 73/76 = 94.7% | 95% Confidence interval = 89.6% - 99.9% |
| % Agreement = 176/181 = 97.2% | 95% Confidence interval = 94.8% - 100% |

Equivocals were not included in the above calculations. The 95% confidence intervals were calculated using the normal method.

* Indicates positive on Clark HSV 1 and/or Clark HSV 2.

** Indicated equivocal on Clark HSV 1 and/or Clark HSV 2.

*** Indicates negative on both Clark HSV 1 and Clark HSV 2.

The second site was a R&D laboratory at a commercial company located in New York. The frozen sera were from normals with ages from 17-59, with various fender and geographical areas. The results of the study are compiled and summarized in Table 2.

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# Table 2 Comparison of Herpes Group IgG ELISA and Clark HSV 1 and Clark HSV 2 Study 2

## Trinity Biotech Herpes Group IgG ELISA

| | | + | eq | - | Total | |
|--------------------------------------|-------|----|----|----------------------------------------|-------|--|
| Clark<br>HSV 1 and<br>HSV 2 | +* | 92 | 6 | 2 | 100 | |
| | eq** | 1 | 0 | 0 | 1 | |
| | -*** | 0 | 0 | 51 | 51 | |
| | Total | 93 | 6 | 53 | 152 | |
| % Agreement positive = 92/94 = 97.9% | | | | 95% Confidence interval = 94.9% - 100% | | |

95% Confidence interval = 94.2% - 100% % Agreement negative = 51/51 = 100% % Agreement = 143/145 = 98.6% 95% Confidence interval = 96.7% - 100%

Equivocals were not included in the above calculations.

The 95% confidence intervals were calculated using the normal method.

The 95% confidence interval for % agreement positive was calculated assuming one false positive.

* Indicates positive on Clark HSV 1 and/or Clark HSV 2.

** Indicated equivocal on Clark HSV land/or Clark HSV 2.

*** Indicates negative on both Clark HSV 1 Clark HSV 2.

The third site was a clinical laboratory located in Pennsylvania. The sera were prospective samples sent in to the lab for Herpes antibody testing. The results of the studies are compiled and summarized in Table 3.

# Table 3 Comparison of Herpes Group IgG ELISA and Clark HSV 1 and Clark HSV 2 Study 3

## Trinity Biotech Herpes Group IgG ELISA

| | + | eq | - | Total | |
|-----------------------------|------|----|----|-------|---|
| +* | 112 | 0 | 1 | 113 | |
| Clark<br>HSV 1 and<br>HSV 2 | eq** | 1 | 0 | 1 | 2 |
| -*** | 3 | 4 | 54 | 61 | |
| Total | 116 | 4 | 56 | 176 | |

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| % Agreement positive = 112/113 = 99.1% | 95% Confidence interval = 97.4% - 100% |
|----------------------------------------|----------------------------------------|
| % Agreement negative = 54/57 = 94.7% | 95% Confidence interval = 88.8% - 100% |
| % Agreement = 166/170 = 97.7% | 95% Confidence interval = 95.3% - 100% |

Equivocals were not included in the above calculations. The 95% confidence intervals were calculated using the normal method.

The 95% confidence intervals were calculated using the normal method.

* Indicates positive on Clark HSV 1 and/or Clark HSV 2.

** Indicated equivocal on Clark HSV land/or Clark HSV 2.

*** Indicates negative on both Clark HSV 1 Clark HSV 2.

The fourth site was a clinical laboratory located in Wisconsin. The frozen sera were random normal samples. The results of the studies are compiled and summarized in Table 4.

# Table 4 Comparison of Herpes Group IgG ELISA and Clark HSV 1 and Clark HSV 2 Study 4

## Trinity Biotech Herpes Group IgG ELISA

| | | + | eq | - | Total |
|-----------------------------|-------|----|----|----|-------|
| Clark<br>HSV 1 and<br>HSV 2 | +* | 62 | 0 | 0 | 62 |
| | eq** | 0 | 0 | 0 | 0 |
| | -*** | 1 | 0 | 25 | 26 |
| | Total | 63 | 0 | 25 | 88 |

| % Agreement positive = 62/62 = 100% | 95% Confidence interval = 95.3% - 100% |
|---------------------------------------|----------------------------------------|
| % Agreement negative = 25/26 = 96.2% | 95% Confidence interval = 96.2% - 100% |
| % Agreement = 87/88 = 98.9% | 95% Confidence interval = 98.9% - 100% |

Equivocals were not included in the above calculations.

The 95% confidence intervals were calculated using the normal method. The 95% confidence interval for % agreement positive was calculated assuming on false positive.

* Indicates positive on Clark HSV 1 and/or Clark HSV 2.

** Indicated equivocal on Clark HSV 1and/or Clark HSV 2.

*** Indicates negative on both Clark HSV 1 Clark HSV 2.

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The results of the four studies are compiled and summarized in Table 5.

# Table 5 Comparison of Herpes Group IgG ELISA and Clark HSV 1 and Clark HSV 2

# Trinity Biotech Herpes Group IgG ELISA

| | | + | eq | - | Total |
|-----------------------------|-------|-----|----|-----|-------|
| Clark<br>HSV 1 and<br>HSV 2 | +* | 370 | 7 | 4 | 381 |
| | eq** | 5 | 0 | 1 | 6 |
| | -*** | 7 | 6 | 203 | 216 |
| | Total | 382 | 13 | 208 | 603 |

| % Agreement positive = 370/374 = 98.9% | 95% Confidence interval = 97.9% - 100% |
|----------------------------------------|-----------------------------------------|
| % Agreement negative = 203/210 = 96.7% | 95% Confidence interval = 94.2% - 99.1% |
| % Agreement = 573/584 = 98.1% | 95% Confidence interval = 97.0% - 99.2% |

Equivocals were not included in the above calculations.

The 95% confidence intervals were calculated using the normal method.

* Indicates positive on Clark HSV 1 and/or Clark HSV 2.

** Indicated equivocal on Clark HSV 1and/or Clark HSV 2.

*** Indicates negative on both Clark HSV 1 Clark HSV 2.

2. Precision. Seven sera were assayed ten times each on three different assays at three different sites. The intersite precision is shown in Table 6. With appropriate technique the user should obtain precision of <15% CV.

## Table 6 Herpes Group IgG ELISA inter Site Precision Study

| | | (n = 90) | |
|--------|------|----------|-------|
| Sera # | X | SD | CV |
| 1. | 3.81 | 0.351 | 9.21% |
| 2. | 2.03 | 0.255 | 12.6% |
| 3. | 3.16 | 0.287 | 9.08% |
| 4. | 2.01 | 0.272 | 13.5% |
| 5. | 1.31 | 0.198 | 15.1% |
| 6. | 0.09 | 0.109 | 121% |
| 7. | 0.03 | 0.045 | 150% |

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#### Paired Serum Study

Twenty serum pairs tested by CF from patients suspected of having acute Herpes simplex infection were assayed on the Trinity Biotech Herpes Group IgG ELISA assay. Each serum pair was evaluated to determine a seroconversion. Six serum pairs could not be evaluated due to the acute being positive. Three serum pairs could not be evaluated due to the convalescent being negative. The remaining eleven pairs all demonstrated a seroconversion thus giving a 100% agreement positive versus CF for showing a seroconversion in antibody for serum meeting the paired sera criteria.

### Cross-Reactivity

Serum containing IgG antibody detectable by ELISA to Epstein Barr virus, Cytomegalovirus, and Varicella-zoster virus were assayed. The data summarized in Table 8 indicate that antibodies to these Herpes Viruses do not cross-react with the Trinity Biotech Herpes Group IgG ELISA kit.

### Table 7

### Cross-Reactivity

| SERUM | Trinity<br>Herpes Group<br>IgG | EBV VCA | CMV | VZV |
|-------|--------------------------------|----------|----------|-----|
| 1 | 0.17 | 2.6 | Negative | 2.7 |
| 2 | 0.05 | 2.3 | Negative | 1.6 |
| 3 | 0.00 | Negative | Negative | 2.2 |
| 4 | 0.00 | 1.8 | Negative | 2.0 |
| 5 | 0.14 | 6.3 | 1.2 | 2.1 |
| 6 | 0.08 | 2.4 | Negative | 3.3 |
| 7 | 0.09 | 1.1 | Negative | 2.1 |
| 8 | 0.12 | 7.2 | 1.1 | 3.2 |
| 9 | 0.18 | Negative | 2.9 | 3.0 |

Sera ≥ 1.10 were considered positive. Sera ≤ 0.90 were considered negative.

The following information is from a serum panel obtained from the Centers for Disease Control (CDC) and tested by the Trinity Biotech Herpes Group IgG ELISA. The results are presented as a means to convey further information on the performance of this assay with a masked, characterized serum panel. This does not imply an endorsement of the assay by the CDC.

The panel consists of 72% positive and 28% negative samples. Excluding two equivocals, the Trinity Biotech Herpes Group IgG ELISA demonstrated 96.9% total agreement with the CDC results. Of the results obtained by the Trinity Biotech Herpes Group IgG ELISA, there was 95.7% aggreement with the positive specimens, and 100% agreement with the negative specimens.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

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Public Health Service

NOV 26 2003

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Bonnie B. DeJoy Director, Quality Systems Trinity Biotech USA P.O. Box 1059 Jamestown. NY 14702-1059

Re: k033059

> Trade/Device Name: Captia Herpes Group IgG ELISA Regulation Number: 21 CFR 866.3305 Regulation Name: Herpes Simplex Virus Serological Reagents Regulatory Class: Class III Product Code: LGC Dated: September 17, 2003 Received: September 29, 2003

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 (OS) 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 [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Steven Sutman

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Page 1 of 1

510(k) Number: K033059

Device Name: Trinity Biotech Captia™ Herpes Group IgG ELISA

Indications For Use: The Trinity Biotech Captia™ Herpes Group IgG ELISA kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for qualitative determination of IgG antibodies in human serum to Herpes simplex virus. The Herpes Group IgG ELISA kit may be used to determine serologic status in females of child bearing age, and to evaluate paired sera for the presence of a seroconversion of IgG as an aid in the diagnosis of Herpes simplex virus infection. It is not intended for determining the type of Herpes simplex virus.

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|----------------------|---------------------------------------------------------------|----|-----------------------------|
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