HERPES SIMPLEX VIRUS TYPE 1 IGG ELISA TEST

K131334 · Gold Standard Diagnostics · MXJ · Feb 28, 2014 · Microbiology

Device Facts

• Record ID: K131334
• Device Name: HERPES SIMPLEX VIRUS TYPE 1 IGG ELISA TEST
• Applicant: Gold Standard Diagnostics
• Product Code: MXJ · Microbiology
• Decision Date: Feb 28, 2014
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3305
• Device Class: Class 2

Intended Use

The Herpes Simplex Virus Type 1 IgG ELISA Test Kit is intended for the qualitative detection of IgG antibodies to Herpes Simplex Virus Type 1 in human serum. The test is indicated for sexually active individuals and expectant mothers as an aid for the presumptive diagnosis of HSV-1 infection. The predictive value of positive or negative results depends on the population's prevalence and the pretest likelihood of HSV-1. The test is not intended for screening of blood and plasma donors. The performance of this assay has not been established for use in a pediatric population, neonates, or immunocompromised patients.

Device Story

Enzyme-linked immunosorbent assay (ELISA) for qualitative detection of IgG antibodies to HSV-1 in human serum. Microtiter wells coated with recombinant gG1 protein; patient serum added; antibodies bind to antigen. Unbound components washed away; HRP-conjugated goat anti-human IgG added; binds to patient antibody. TMB substrate added; HRP reaction generates color; intensity measured spectrophotometrically at 450nm. Used in clinical laboratory settings by trained technicians. Results aid physicians in presumptive diagnosis of HSV-1 infection. Benefits include rapid, standardized assessment of HSV-1 serological status.

Clinical Evidence

Clinical study evaluated 903 samples (sexually active adults, pregnant women, low prevalence population, and CDC seroconversion panel) across three sites. Compared to predicate immunoblot. Pregnant women (n=185): 96.0% sensitivity, 96.5% specificity. Sexually active adults (n=518): 92.3% sensitivity, 95.5% specificity. Low prevalence (n=100): 93.8% sensitivity, 92.9% specificity. CDC panel (n=100): 97.8% sensitivity, 94.4% specificity. Equivocal results treated as disagreements.

Technological Characteristics

Enzyme-linked immunosorbent assay (ELISA). Solid phase: 96-well polystyrene microtiter plate coated with recombinant HSV-1 gG1 antigen. Detection: HRP-conjugated goat anti-human IgG (Fc specific) with TMB substrate. Readout: Spectrophotometric (colorimetric). Requires external spectrophotometer. Manual/semi-automated processing. Shelf life: 18 months at 2-8°C.

Indications for Use

Indicated for sexually active individuals and expectant mothers as an aid for the presumptive diagnosis of HSV-1 infection. Not for screening blood/plasma donors. Performance not established for pediatric, neonatal, or immunocompromised populations.

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

• HerpeSelect® 1 and 2 Immunoblot IgG (K000238)

Submission Summary (Full Text)

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Image /page/0/Picture/0 description: The image shows the logo for Gold Standard Diagnostics. The logo includes the company name in bold, black letters, with a globe symbol incorporated into the "G". The image also includes the date "FEB 2 8 2014" on the right side of the logo.

# 510(k) Summary

Gold Standard Diagnostics 1) Submitter's Name: 2851 Spafford St. Davis, CA. 95618 Address: Phone Number: 530-759-8000 Fax Number: 530-759-8012 Contact Person: Napoleon Monce Date: February 11, 2014

- 2) Product and Trade Name: Herpes Simplex Virus Type 1 IgG ELISA Test
Common Name: Herpes Simplex Virus, HSV-1

Classification Name: Herpes simplex virus serological assays (Class 2, 21 CFR 866.3305)

Product Code: MXJ

#### 3) Legally marketed device to which the submitter claims equivalence:

Focus Diagnostics HerpeSelect® I and 2 Immunoblot IgG for the qualitative detection of human IgG class antibody to HSV-1 and HSV-2. K000238.

#### 4) Description of the device:

The Gold Standard Diagnostics Herpes Simplex Virus (HSV) Type I IgG ELISA Test is an enzyme linked immunosorbent assay for the qualitative detection of IgG antibodies to HSV-1 in human serum. The assay requires a total of 90 minutes incubation time. The test uses microtiter wells coated with a recombinant gG1 protein of HSV-1. Serum is added to each well and incubated for 30 minutes at 37℃. If antibodies are present they will bind to the antigen in the well. Unbound antibodies are removed by washing the wells three times. A Horse Radish Peroxidase (HRP) conjugated goat anti-human IgG (conjugate) is then added to each well and incubated for 30 minutes at 37°C. If antibodies are present in the patient's serum, the conjugate will bind to the antibody attached to the antigen on the wells are again washed to remove any unbound conjugate. In order to detect the bound conjugate a substrate containing tetramethylbenzidine (TMB) is added to each well and incubated for 30 minutes at 37°C. If conjugate is present, the HRP will react with the substrate to generate a colored product. After the incubation period, the reaction is stopped with a . Stop Solution and the color intensity is measured spectrophotometrically. The kit also includes a Wash Buffer, Diluent, a Negative Control, and a Cutoff Control. The cut-off control is used to determine the validity of the assay and subsequently to determine the result of the

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sample. Positive and Negative controls are provided to determine if the assay is functioning properly. The kit contains 12 x 8well antigen coated microtiter strips in a frame. The reagents are sufficient for 96 determinations.

## 5) Intended Use / Indication for Use:

The Gold Standard Diagnostics Herpes Simplex Virus Type 1 IgG ELISA Test Kit is intended for the qualitative detection of IgG antibodies to Herpes Simplex Virus Type 1 (HSV-1) in human serum. The test is indicated for sexually active individuals and expectant mothers as an aid for the presumptive diagnosis of HSV-1 infection.

The predictive value of positive or negative results depends on the population's prevalence and the pretest likelihood of HSV-1. The test is not intended for screening of blood and plasma donors. The performance of this assay has not been established for use in a pediatric population, neonates, or immunocompromised patients.

#### 6) Comparison with the predicate device:

The Gold Standard Diagnostics Herpes Simplex Virus Type 1 IgG ELISA Test Kit was compared to a commercially manufactured by Focus Diagnostics, the HerpeSelect® 1 and 2 Immunoblot IgG test (K000238). Both kits have the same intended use. Below are tables comparing the reagents provided and the procedural steps performed by each device.

| Gold Standard Diagnostics Herpes Simplex<br>Virus Type 1 IgG ELISA Test Kit | Focus HerpeSelect® 1 and 2<br>Immunoblot IgG |
|-----------------------------------------------------------------------------|----------------------------------------------|
| Antigen coated Microtiter Plate - 96 wells | Antigen coated nitrocellulose strips |
| Wash Solution - 20x | Wash Buffer and Diluent - 10x |
| Diluent - Ready to Use | None |
| IgG Conjugate – Anti Human HRP | IgG Conjugate – Anti Human Peroxidase |
| Substrate - Tetramethylbenzidine (TMB) | Substrate - BCIP/NBT |
| Stop Solution – Acid mixture | Stop Solution – DI water |
| Positive Control | Positive Control |
| Cutoff Control | No Cutoff Control provided |
| Negative Control | Negative Control |

## Table 1: Reagent Comparison

#### Table 2: Procedure Comparison

| Gold Standard Diagnostics Herpes Simplex<br>Virus Type 1 IgG ELISA Test Kit | Focus HerpeSelect® 1 and 2<br>Immunoblot IgG |
|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------|
| Intended Use: Qualitative detection of IgG<br>antibodies to HSV-1 in human serum. The<br>test is indicated for sexually active individuals<br>and expectant mothers as an aid for the | Same |

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| presumptive diagnosis of HSV-1 infection.<br>The predictive value of positive or negative<br>results depends on the population's<br>prevalence and the pretest likelihood of HSV-<br>1. The test is not intended for screening of<br>blood and plasma donors. The performance<br>of this assay has not been established for use<br>in a pediatric population, neonates, or<br>immunocompromised patients. | |
|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------|
| Dilute Samples 1:101 in Diluent | Same |
| Add 100ul of Samples and Controls | Add 2ml of Samples and Controls |
| Incubate for 30 minutes at 37°C | Incubate for 60 minutes at RT while rocking |
| Wash four times with reconstituted Wash<br>Solution | Wash three times with Wash Solution with 5<br>minute rocking incubation between washes |
| Add 100ul of Conjugate | Add 2ml of Conjugate |
| Incubate for 30 minutes at 37°C | Incubate for 60 minutes at RT while rocking |
| Wash four times with reconstituted Wash<br>Solution | Wash three times with Wash Solution with 5<br>minute rocking incubation between washes |
| Add 100ul of Substrate | Add 2ml of Substrate |
| Incubate for 30 minutes at 37°C | Incubate for 5 to 30 minutes at RT while<br>rocking |
| Add 50ul of Stop Solution | Rinse with DI water to stop the reaction |
| Read with Spectrophotometer at 450nm | Read visually |

# 7) Analytical performance:

# Precision:

A within-lab precision study was conducted for 12 days, two runs per day, two replicates per run and three lots. Every lot was tested for four days. The mean results are summarized in the table below:

| Sample | N | Units | | Within-Run | Between-<br>Run | Between-<br>Day | Total |
|----------------------|----|--------|----|------------|-----------------|-----------------|-------|
| High<br>Positive | 48 | 58.452 | SD | 1.544 | 1.261 | 5.644 | 7.652 |
| | 48 | | CV | 2.6% | 2.5% | 9.7% | 13.1% |
| Moderate<br>Positive | 48 | 24.955 | SD | 1.290 | 1.088 | 2.982 | 3.653 |
| | 48 | | CV | 5.2% | 5.0% | 11.9% | 14.6% |
| Low<br>Positive | 48 | 18.183 | SD | 0.664 | 0.601 | 1.856 | 2.732 |
| | 48 | | CV | 3.7% | 3.8% | 10.2% | 15.0% |
| Near | 48 | 13.691 | SD | 0.601 | 0.501 | 1.388 | 1.871 |
| | 48 | | CV | | | | |

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| Cutoff | | | CV | 4.4% | 4.2% | 10.1% | 13.7% |
|------------------|----|-------|----|-------|-------|-------|-------|
| High<br>Negative | 48 | 6.565 | SD | 0.388 | 0.343 | 0.579 | 0.950 |
| | | | CV | 5.9% | 6.1% | 8.8% | 14.5% |
| Negative | 48 | 1.899 | SD | 0.153 | 0.133 | 0.256 | 0.342 |
| | | | CV | 8.0% | 8.0% | 13.5% | 18.0% |

#### Reproducibility:

The reproducibility of the assay was performed using six samples (a high positive, a sample near the positive cutoff, a sample near the negative cutoff, a high negative and a negative sample). Each sample was tested for five days, twice a day, at three sites with two technicians per site, each performing one run per day. The mean results of the overall and per site reproducibility are summarized in the tables below:

| Overall | | | | | | | | |
|--------------------|----|-----------------|----------------|-----------------|-----------------|------------------|------------------|-------|
| Sample | N | Mean<br>(Units) | Within-<br>Run | Between-<br>Run | Between-<br>Day | Between-<br>Site | Overall<br>Total | |
| High<br>Positive | 60 | 60.909 | SD | 2.487 | 2.535 | 3.749 | 4.952 | 5.788 |
| | | | CV | 4.1% | 4.2% | 6.2% | 8.1% | 9.5% |
| Low<br>Positive | 60 | 14.754 | SD | 0.775 | 0.758 | 0.957 | 1.369 | 2.156 |
| | | | CV | 5.2% | 5.1% | 6.5% | 9.3% | 14.6% |
| Positive<br>Cutoff | 60 | 11.821 | SD | 0.235 | 0.235 | 0.379 | 0.615 | 0.617 |
| | | | CV | 2.0% | 2.0% | 3.2% | 5.2% | 5.2% |
| Negative<br>Cutoff | 60 | 9.585 | SD | 0.108 | 0.105 | 0.174 | 0.254 | 0.280 |
| | | | CV | 1.1% | 1.1% | 1.8% | 2.7% | 2.9% |
| High<br>Negative | 60 | 7.508 | SD | 0.194 | 0.195 | 0.447 | 0.760 | 0.821 |
| | | | CV | 2.6% | 2.6% | 6.0% | 10.1% | 10.9% |
| Negative | 60 | 1.579 | SD | 0.093 | 0.094 | 0.160 | 0.213 | 0.231 |
| | | | CV | 5.9% | 6.0% | 10.1% | 13.5% | 14.6% |

| Site 1 | | | | | | | |
|--------------------|----|--------|----|------------|-------------|-------------|------------------|
| Sample | N | Mean | | Within-Run | Between-Run | Between-Day | Overall<br>Total |
| High<br>Positive | 20 | 59.224 | SD | 2.569 | 2.643 | 3.370 | 4.360 |
| | | | CV | 4.3% | 4.5% | 5.7% | 7.4% |
| Low<br>Positive | 20 | 13.302 | SD | 0.868 | 0.845 | 0.942 | 1.303 |
| | | | CV | 6.5% | 6.3% | 7.1% | 9.8% |
| Positive<br>Cutoff | 20 | 11.759 | SD | 0.133 | 0.138 | 0.291 | 0.585 |
| | | | CV | 1.1% | 1.2% | 2.5% | 5.0% |
| Negative<br>Cutoff | 20 | 9.432 | SD | 0.131 | 0.121 | 0.192 | 0.239 |
| | | | CV | 1.4% | 1.3% | 2.0% | 2.5% |

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| | | | SD | | | | |
|------------------|----|-------|-------|-------|-------|-------|------|
| High<br>Negative | 20 | 7.944 | 0.205 | 0.199 | 0.451 | 0.752 | |
| | | | CV | | | | |
| | | | 2.6% | 2.5% | 5.7% | 9.5% | |
| Negative | 20 | 1.693 | SD | 0.079 | 0.082 | 0.165 | 0.22 |
| | | | CV | | | | |
| | | | 4.7% | 4.8% | 9.8% | 12.9% | |

| Site 2 | | | | | | | |
|--------------------|----|--------|----|------------|-------------|-------------|------------------|
| Sample | N | Mean | | Within-Run | Between-Run | Between-Day | Overall<br>Total |
| High<br>Positive | 20 | 58.440 | SD | 2.596 | 2.662 | 4.218 | 5.583 |
| | | | CV | 4.4% | 4.6% | 7.2% | 9.6% |
| Low<br>Positive | 20 | 13.875 | SD | 0.787 | 0.767 | 0.990 | 1.462 |
| | | | CV | 5.7% | 5.5% | 7.1% | 10.5% |
| Positive<br>Cutoff | 20 | 11.846 | SD | 0.213 | 0.210 | 0.285 | 0.671 |
| | | | CV | 1.8% | 1.8% | 2.4% | 5.7% |
| Negative<br>Cutoff | 20 | 9.712 | SD | 0.102 | 0.104 | 0.193 | 0.249 |
| | | | CV | 1.1% | 1.1% | 2.0% | 2.6% |
| High<br>Negative | 20 | 7.282 | SD | 0.223 | 0.230 | 0.324 | 0.760 |
| | | | CV | 3.1% | 3.2% | 4.5% | 10.4% |
| Negative | 20 | 1.473 | SD | 0.10 | 0.10 | 0.15 | 0.20 |
| | | | | CV | 6.6% | 6.6% | 10.1% |

| Site 3 | | | | | | | |
|--------------------|----|--------|----|------------|-------------|-------------|------------------|
| Sample | N | Mean | | Within-Run | Between-Run | Between-Day | Overall<br>Total |
| High<br>Positive | 20 | 65.062 | SD | 2.296 | 2.300 | 3.660 | 4.913 |
| | | | CV | 3.5% | 3.5% | 5.6% | 7.6% |
| Low<br>Positive | 20 | 17.085 | SD | 0.669 | 0.663 | 0.939 | 1.341 |
| | | | CV | 3.9% | 3.9% | 5.5% | 7.8% |
| Positive<br>Cutoff | 20 | 11.857 | SD | 0.359 | 0.356 | 0.561 | 0.588 |
| | | | CV | 3.0% | 3.0% | 4.7% | 5.0% |
| Negative<br>Cutoff | 20 | 9.610 | SD | 0.090 | 0.091 | 0.138 | 0.275 |
| | | | CV | 0.9% | 0.9% | 1.4% | 2.9% |
| High<br>Negative | 20 | 7.298 | SD | 0.153 | 0.155 | 0.565 | 0.770 |
| | | | CV | 2.1% | 2.1% | 7.7% | 10.5% |
| Negative | 20 | 1.571 | SD | 0.10 | 0.10 | 0.17 | 0.22 |
| | | | CV | 6.5% | 6.6% | 10.5% | 13.9% |

# Cross Reactivity:

Potential cross reactivity was evaluated for infectious diseases and conditions. The samples were obtained from serum brokers who confirmed positivity for each respective disease and conditions using FDA cleared tests. Samples were tested on the Gold Standard Diagnostics Herpes Simplex Virus Type 1 IgG ELISA Test as well as on the predicate device. The results are summarized in the following table:

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| Positive For | Number<br>Tested | Number<br>Reactive |
|------------------------------|------------------|--------------------|
| Cytomegalovirus (CMV) | 10 | 0 |
| Epstein-Barr Virus (EBV) | 10 | 1* |
| Varicella-zoster Virus (VZV) | 10 | 1* |
| Chlamydia trachomatis | 10 | 0 |
| Treponema pallidum | 10 | 0 |
| Human papilloma virus (HPV) | 10 | 0 |
| Rubella Virus | 10 | 0 |
| Toxoplasma gondii | 10 | 3* |
| Candida albicans | 10 | 2* |
| Neisseria gonorrhea | 10 | 0 |
| Rheumatoid Factor | 10 | 0 |
| ANA | 10 | 0 |
| Measles | 10 | 0 |
| HSV-2 | 10 | 0 |
| HIV | 10 | 4* |
| Bacteroides | 1 | 0 |

* Samples were also reactive with the predicate device assay

#### Interfering Substances:

The effect of potential interfering substances on samples using the Gold Standard Diagnostics Herpes Simplex Virus Type 1 IgG ELISA Test was evaluated. High levels of hemoglobin, bilirubin, cholesterol. Triglycerides, and albumin in serum samples were tested at the assay cutoff in triplicate. The recommended concentrations from the guideline "Interference Testing In Clinical Chemistry" from the Clinical and Laboratory Standards Institute were used (CLSI EP7-A2). An acceptance criterion of ±20% was used. The tested substances did not affect the performance of the Gold Standard Diagnostics Herpes Simplex Virus Type 1 IgG ELISA Test if tested in the following concentration:

| Substance | Concentration |
|---------------|---------------|
| Hemoglobin | 2 g/L |
| Bilirubin | 342 µmol/L |
| Cholesterol | 13 mmol/L |
| Triglycerides | 37 mmol/L |
| Albumin | 60 g/L |

#### Clinical performance:

#### Performance in the Intended Use Populations

The performance of the Gold Standard Diagnostics Herpes Simplex Virus Type 1 IgG ELISA assay was determined by conducting a correlation study tested at three different sites using a total of 703 samples representative of the intended use population, pregnant women and sexually active adults at risk. The samples were tested on both the Gold Standard Herpes Simplex Virus Type 1 IgG ELISA assay and a commercially available Herpes Simplex Virus Line Blot test being manufactured by

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Focus Diagnostics. Samples from pregnant women and sexually active adult were prospectively collected, submitted for HSV testing. The combined results from all three sites are summarized in the following tables, sorted according to the intended use population tested. Equivocal results were treated as the worst case results (disagreement):

| Pregnant Women | | Focus Diagnostics HSV-1<br>Line Blot | |
|-------------------------------------------------|-----------|--------------------------------------|----------|
| | | Positive | Negative |
| Gold Standard<br>Diagnostics HSV-1<br>IgG ELISA | Positive | 96 | 1 |
| | Equivocal | 1 | 2 |
| | Negative | 3 | 82 |
| Sensitivity = 96.0% (96/100) | | (95% C.I. = 90.1% - 98.9%) | |
| Specificity = 96.5% (82/85) | | (95% C.I. = 90.0% - 99.3%) | |

| Sexually Active Adults | | <b>Focus Diagnostics HSV-1<br/>Line Blot</b> | |
|----------------------------------------------------------|-----------|----------------------------------------------|----------|
| | | Positive | Negative |
| <b>Gold Standard<br/>Diagnostics HSV-1<br/>IgG ELISA</b> | Positive | 275 | 8 |
| | Equivocal | 3 | 2 |
| | Negative | 20 | 210 |
| Sensitivity = 92.3% (275/298) | | (95% C.I. = 88.6% - 95.0%) | |
| Specificity = 95.5% (210/220) | | (95% C.I. = 91.8% - 97.8%) | |

#### Performance in a Low Prevalence Population

The low prevalence samples were prospectively collected in a non-STD setting from sera ages 16-19 years old. They were only tested in-house. Equivocal results were treated as the worst case/disagreement results.

| Low Prevalence | | Focus Diagnostics HSV-1<br>Line Blot | |
|-------------------------------------------------|-----------|--------------------------------------|----------|
| | | Positive | Negative |
| Gold Standard<br>Diagnostics HSV-1<br>IgG ELISA | Positive | 15 | 3 |
| | Equivocal | 0 | 3 |
| | Negative | 1 | 78 |
| Sensitivity = 93.8% (15/16) | | (95% C.I. = 69.7% - 99.8%) | |
| Specificity = 92.9% (78/84) | | (95% C.I. = 85.1% - 97.3%) | |

#### Performance with a CDC Seroconversion Panel

A seroconversion panel consisting of well-characterized HSV I serum samples was obtained from the CDC and tested on the Gold Standard Herpes Simplex Virus Type 1 IgG ELISA test in an in-house study. The results are summarized in the table below. Equivocal results were treated as worst case/disagreement results.

| A 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 | CDC | | |
|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------|----------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | | Positive | Negative |
| Gold Standard | Positive | ર્વ રે | |
| Diagnostics HSV-1 | Equivocal | () | 0 |
| IgG ELISA | Negative | | રી તેમને છે. આ ગામના લોકોનો મુખ્ય વ્યવસાય ખેતી, ખેતમજૂરી તેમ જ પશુપાલન છે. આ ગામમાં મુખ્યત્વે ખેત-ઉત્પાદની ખેતી, ખેતમજૂરી તેમ જ પશુપાલન છે. આ ગામમાં મુખ્યત્વે ખેત-ઉત્પાદની ખે |
| Sensitivity = 97.8% (45/46)<br>Specificity = 94.4% (51/54) | | (95% C.I. = 88.5% - 99.9%)<br>(95% C.I. = 84.6% - 98.8%) | |

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# Expected Values

To determine the prevalence of the test, a total of 703 sera consisting of pregnant women and sexually active adults were tested. The observed prevalence and the hypothetical prevalence for the two intended use populations are summarized below.

| Observed Prevalence with Pregnant Women | | | | | |
|-----------------------------------------|-----|-----|-----|-------|------------|
| Age (years) | Pos | Equ | Neg | Total | Prevalence |
| 16-19 | 7 | 0 | 11 | 18 | 38.9% |
| 20-24 | 20 | 0 | 11 | 31 | 64.5% |
| 25-29 | 23 | 0 | 18 | 41 | 56.1% |
| 30-34 | 26 | 2 | 28 | 56 | 46.4% |
| 35-39 | 16 | 1 | 14 | 31 | 51.6% |
| >40 | 5 | 0 | 3 | 8 | 62.5% |
| Totals | 97 | 3 | 85 | 185 | 53.5% |

| Observed Prevalence with Sexually Active Adults | | | | | |
|-------------------------------------------------|-----|-----|-----|-------|------------|
| Age (years) | Pos | Equ | Neg | Total | Prevalence |
| 16-19 | 22 | 0 | 26 | 48 | 45.8% |
| 20-24 | 27 | 1 | 50 | 78 | 34.6% |
| 25-29 | 55 | 1 | 63 | 119 | 46.2% |
| 30-34 | 58 | 1 | 30 | 89 | 65.2% |
| 35-39 | 28 | 1 | 22 | 51 | 54.9% |
| >40 | 93 | 1 | 39 | 133 | 69.9% |
| | | | | | |
| Totals | 283 | 5 | 230 | 518 | 55.0% |

| Hypothetical Predictive Values vs. Prevalence | | | | |
|-----------------------------------------------|---------------------------|-------|----------------|-------|
| | Sexually Active<br>Adults | | Pregnant Women | |
| Prevalence | PPV | NPV | PPV | NPV |
| 50% | 95.4% | 92.5% | 96.5% | 96.0% |
| 40% | 93.2% | 94.9% | 94.8% | 97.3% |
| 30% | 89.8% | 96.7% | 92.2% | 98.3% |
| 25% | 87.2% | 97.4% | 90.1% | 98.6% |
| 20% | 83.7% | 98.0% | 87.3% | 99.0% |
| 15% | 78.4% | 98.6% | 82.9% | 99.3% |
| 10% | 69.5% | 99.1% | 75.3% | 99.5% |
| 5% | 51.9% | 99.6% | 59.1% | 99.8% |

(Results are the worst case/disagreement results)

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# 8) Conclusion:

From the data, we find that the Gold Standard Diagnostics Herpes Simplex Virus Type 1 IgG ELISA assay is substantially equivalent to the commercially available Herpes Simplex Virus Line Blot test being manufactured by Focus Diagnostics (K000238).

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/9/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle or bird-like symbol with three curved lines representing its wings or body. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the symbol. The logo is in black and white.

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

February 28, 2014

GOLD STANDARD DIAGNOSTICS NAPLEON MONCE DIRECTOR OF PRODUCT DEVELOPMENT 2851 SPAFFORD ST · DAVIS CA 95618

Re: K131334

Trade/Device Name: Herpes Simplex Virus Type 1 IgG Elisa Test Regulation Number: 21 CFR 866.3305 Regulation Name: Herpes simplex virus serological assays Regulatory Class: II Product Code: MXJ Dated: January 29, 2014 Received: January 30, 2014

Dear Mr. Monce:

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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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Page 2-Mr. Monce

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact 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/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

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 [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

# Stephen J. Lovell -S for

Sally A. Hojvat, M.Sc., PhD. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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#### DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

## Indications for Use

510(k) Number (if known) K131334

Device Name

Herpes Simplex Virus Type 1 IgG ELISA Test

#### Indications for Use (Describe)

The Gold Standard Diagnostics Herpes Simplex Virus Type 1 IgG ELISA Test Kit is intended for the qualitative detection of IgG antibodies to Herpes Simplex Virus Type 1 (HSV-1) in human serum. The test is indicated for sexually active individuals and expectant mothers as an aid for the presumptive diagnosis of HSV-1 infection.

The predictive value of positive or negative results depends on the population's prevalence and the pretest likelihood of HSV-1. The test is not intended for screening of blood and plasma donors. The performance of this assay has not been established for use in a pediatric population, neonates, or immunocompromised patients.

Type of Use (Select one or both, as applicable)

2 Prescription Use (Part 21 CFR B01 Subpart D)

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

#### PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

#### FOR FDA USE ONLY

Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

# Stephen J. Lovell -S 2014.02.28 10:53:31 -05'00'

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