Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description details a standard ELISA assay which relies on chemical reactions and spectrophotometric measurement, not AI/ML for analysis or interpretation. The summary does not mention any AI/ML components or algorithms.

Therapeutic

No.
This device is an in-vitro diagnostic test intended for the qualitative detection of antibodies to aid in the diagnosis of HSV-1 infection, not to treat or prevent a disease.

Diagnostic

Yes

The device is intended for the qualitative detection of IgG antibodies to Herpes Simplex Virus Type 1 (HSV-1) in human serum, "as an aid for the presumptive diagnosis of HSV-1 infection." This directly indicates its use in diagnosing a condition.

SaMD (Software as a Medical Device)

No

The device is a laboratory test kit that involves physical reagents, incubation steps, and spectrophotometric measurement, indicating it is a hardware-based medical device, not software-only.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use: The intended use explicitly states it's for the "qualitative detection of IgG antibodies to Herpes Simplex Virus Type 1 (HSV-1) in human serum." This involves testing a sample taken from the human body (serum) in vitro (outside the body) to provide information about a medical condition (HSV-1 infection).
Device Description: The description details a laboratory test (ELISA) performed on human serum samples using reagents and equipment. This is characteristic of an in vitro diagnostic test.
Performance Studies: The document describes clinical performance studies conducted on human serum samples to evaluate the test's accuracy (sensitivity, specificity) in diagnosing HSV-1 infection. This is a requirement for IVD devices.
Predicate Device: The mention of a predicate device (Focus Diagnostics HerpeSelect® I and 2 Immunoblot IgG) which is also an IVD, further supports the classification of this device as an IVD.

The entire context of the document describes a test performed on biological samples outside the body to aid in the diagnosis of a disease, which is the definition of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications 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.

Product codes

MXJ

Device Description

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 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.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

The performance of this assay has not been established for use in a pediatric population, neonates, or immunocompromised patients.

Intended User / Care Setting

Not Found

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

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.
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.
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.
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.

Clinical performance:

Performance in the Intended Use Populations: A correlation study was conducted involving 703 samples from pregnant women and sexually active adults. 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 manufactured by Focus Diagnostics. Samples from pregnant women and sexually active adult were prospectively collected, submitted for HSV testing. Equivocal results were treated as the worst case results (disagreement).
- Pregnant Women: Sensitivity = 96.0% (96/100), Specificity = 96.5% (82/85)
- Sexually Active Adults: Sensitivity = 92.3% (275/298), Specificity = 95.5% (210/220)
Performance in a Low Prevalence Population: 100 low prevalence samples (ages 16-19) were prospectively collected in a non-STD setting and tested in-house. Equivocal results were treated as the worst case/disagreement results.
- Sensitivity = 93.8% (15/16), Specificity = 92.9% (78/84)
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. Equivocal results were treated as worst case/disagreement results.
- Sensitivity = 97.8% (45/46), Specificity = 94.4% (51/54)
Expected Values: To determine the prevalence of the test, a total of 703 sera consisting of pregnant women and sexually active adults were tested.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Pregant Women:
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:
Sensitivity = 92.3% (275/298) (95% C.I. = 88.6% - 95.0%)
Specificity = 95.5% (210/220) (95% C.I. = 91.8% - 97.8%)

Low Prevalence Population:
Sensitivity = 93.8% (15/16) (95% C.I. = 69.7% - 99.8%)
Specificity = 92.9% (78/84) (95% C.I. = 85.1% - 97.3%)

CDC Seroconversion Panel:
Sensitivity = 97.8% (45/46) (95% C.I. = 88.5% - 99.9%)
Specificity = 94.4% (51/54) (95% C.I. = 84.6% - 98.8%)

Hypothetical Predictive Values vs. Prevalence:
Sexually Active Adults:
50% Prevalence: PPV 95.4%, NPV 92.5%
40% Prevalence: PPV 93.2%, NPV 94.9%
30% Prevalence: PPV 89.8%, NPV 96.7%
25% Prevalence: PPV 87.2%, NPV 97.4%
20% Prevalence: PPV 83.7%, NPV 98.0%
15% Prevalence: PPV 78.4%, NPV 98.6%
10% Prevalence: PPV 69.5%, NPV 99.1%
5% Prevalence: PPV 51.9%, NPV 99.6%

Pregnant Women:
50% Prevalence: PPV 96.5%, NPV 96.0%
40% Prevalence: PPV 94.8%, NPV 97.3%
30% Prevalence: PPV 92.2%, NPV 98.3%
25% Prevalence: PPV 90.1%, NPV 98.6%
20% Prevalence: PPV 87.3%, NPV 99.0%
15% Prevalence: PPV 82.9%, NPV 99.3%
10% Prevalence: PPV 75.3%, NPV 99.5%
5% Prevalence: PPV 59.1%, NPV 99.8%

Predicate Device(s)

K000238

Reference Device(s)

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information

Not Found

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).

Summary

0

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

1. 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

1

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

2

| 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-

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. | |
|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------|
| 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
Solution | Wash three times with Wash Solution with 5
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
Solution | Wash three times with Wash Solution with 5
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
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-
Run | Between-
Day | Total |
|----------------------|----|--------|----|------------|-----------------|-----------------|-------|
| High
Positive | 48 | 58.452 | SD | 1.544 | 1.261 | 5.644 | 7.652 |
| | 48 | | CV | 2.6% | 2.5% | 9.7% | 13.1% |
| Moderate
Positive | 48 | 24.955 | SD | 1.290 | 1.088 | 2.982 | 3.653 |
| | 48 | | CV | 5.2% | 5.0% | 11.9% | 14.6% |
| Low
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 | | | | |

3

Cutoff			CV	4.4%	4.2%	10.1%	13.7%
High
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
(Units)	Within-
Run	Between-
Run	Between-
Day	Between-
Site	Overall
Total
High
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
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
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
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
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
Total
High
Positive	20	59.224	SD	2.569	2.643	3.370	4.360
			CV	4.3%	4.5%	5.7%	7.4%
Low
Positive	20	13.302	SD	0.868	0.845	0.942	1.303
			CV	6.5%	6.3%	7.1%	9.8%
Positive
Cutoff	20	11.759	SD	0.133	0.138	0.291	0.585
			CV	1.1%	1.2%	2.5%	5.0%
Negative
Cutoff	20	9.432	SD	0.131	0.121	0.192	0.239
			CV	1.4%	1.3%	2.0%	2.5%

4

			SD
High
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
Total
High
Positive	20	58.440	SD	2.596	2.662	4.218	5.583
			CV	4.4%	4.6%	7.2%	9.6%
Low
Positive	20	13.875	SD	0.787	0.767	0.990	1.462
			CV	5.7%	5.5%	7.1%	10.5%
Positive
Cutoff	20	11.846	SD	0.213	0.210	0.285	0.671
			CV	1.8%	1.8%	2.4%	5.7%
Negative
Cutoff	20	9.712	SD	0.102	0.104	0.193	0.249
			CV	1.1%	1.1%	2.0%	2.6%
High
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
Total
High
Positive	20	65.062	SD	2.296	2.300	3.660	4.913
			CV	3.5%	3.5%	5.6%	7.6%
Low
Positive	20	17.085	SD	0.669	0.663	0.939	1.341
			CV	3.9%	3.9%	5.5%	7.8%
Positive
Cutoff	20	11.857	SD	0.359	0.356	0.561	0.588
			CV	3.0%	3.0%	4.7%	5.0%
Negative
Cutoff	20	9.610	SD	0.090	0.091	0.138	0.275
			CV	0.9%	0.9%	1.4%	2.9%
High
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:

5

| Positive For | Number
Tested | Number
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

6

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
Line Blot | |
|-------------------------------------------------|-----------|--------------------------------------|----------|
| | | Positive | Negative |
| Gold Standard
Diagnostics HSV-1
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 | | Focus Diagnostics HSV-1
Line Blot | |
|----------------------------------------------------------|-----------|----------------------------------------------|----------|
| | | Positive | Negative |
| Gold Standard
Diagnostics HSV-1
IgG ELISA | 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
Line Blot | |
|-------------------------------------------------|-----------|--------------------------------------|----------|
| | | Positive | Negative |
| Gold Standard
Diagnostics HSV-1
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)
Specificity = 94.4% (51/54)		(95% C.I. = 88.5% - 99.9%)
(95% C.I. = 84.6% - 98.8%)

7

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
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)

8

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).

9

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.

10

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 (800) 638 2041 or (301) 796-7100 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 (800) 638-2041 or (301) 796-7100 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

11

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'

This section applies only to requirements of the Paperwork Reduction Act of 1995.

*DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW."

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."