K Number

Device Name

HERPESELECT 2 ELISA IGG, MODEL ELO920G

Manufacturer

FOCUS TECHNOLOGIES, INC.

Date Cleared

2002-08-01

(90 days)

Product Code

MXJ

Regulation Number

866.3305

Intended Use

Focus Technologies' HerpeSelect® 2 ELISA IgG test is intended for qualitatively detecting the presence or absence of human IgG class antibodies to HSV-2 in human sera. In conjunction with the Focus HerpeSelect® I ELISA IgG, the test is indicated for testing sexually active adults or expectant mothers for aiding in the presumptive digenosis of HSV infection. The assay can be used manually or in conjunction with an automated system as outlined in the package insert. The user is responsible for assay performance characteristics when an automated system is used. The performance of this assay has not been established for use in a pediatric population, for neonatal screening, or for testing of immunocompromised patients.

Device Description

In the HerpeSelect 2 ELISA IgG assay, the polystyrene microwells are coated with recombinant gG-2 antigen. Diluted serum samples and controls are incubated in the wells to allow specific antibody present in the samples to react with the antigen. Nonspecific reactants are removed by washing, and peroxidase-conjugated anti-human IgG is added and reacts with specific IgG. Excess conjugate is removed by washing. Enzyme substrate and chromogen are added, and the color is allowed to develop. After adding the Stop Reagent, the resultant color change is quantified by a spectrophotometric reading of optical density (OD). Sample optical density readings are compared with reference cut-off OD readings to determine results.

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Expedited Review

Predicate Devices

HerpeSelect®2 ELISA IgG (manual option)

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description and performance studies detail a standard ELISA assay with spectrophotometric reading and comparison to cut-off values. There is no mention of AI or ML in the text.

Therapeutic

No.
The device is a diagnostic test intended for detecting antibodies, which aids in diagnosis rather than providing therapy or treatment.

Diagnostic

Yes
The "Intended Use / Indications for Use" section explicitly states that the test is "for aiding in the presumptive diagnosis of HSV infection," indicating its role in identifying a potential medical condition.

SaMD (Software as a Medical Device)

The device description clearly outlines a physical ELISA assay kit with microwells, reagents, and a spectrophotometric reading process, indicating it is a hardware-based diagnostic test, not software only.

IVD (In Vitro Diagnostic)

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

Here's why:

Intended Use: The "Intended Use / Indications for Use" section explicitly states that the test is intended for "qualitatively detecting the presence or absence of human IgG class antibodies to HSV-2 in human sera." This involves testing human samples (sera) in vitro (outside the body) to provide information for diagnosis.
Device Description: The description details a laboratory assay (ELISA) performed on serum samples in microwells, involving chemical reactions and spectrophotometric readings. This is a typical description of an in vitro diagnostic test.
Performance Studies: The document describes extensive performance studies conducted on human serum samples to evaluate the device's accuracy (sensitivity, specificity, agreement with reference methods) for diagnostic purposes.
Predicate Device: The mention of a "Predicate Device(s)" which is the "HerpeSelect®2 ELISA IgG (manual option)" further confirms its classification as a medical device, and specifically an IVD, as predicate devices are used for comparison in regulatory submissions for new medical devices, including IVDs.

All these elements align with the definition and characteristics of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

Product codes (comma separated list FDA assigned to the subject device)

MXJ

Device Description

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

sexually active adults or expectant mothers.
The performance of this assay has not been established for use in a pediatric population.

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

Expected Values Study:

Sample Size: 246 sexually active adults (over 14 years old) and 241 expectant mothers.
Data Source: Sera from an outside investigator, masked, archived and unselected.
Annotation Protocol: Reference method was a HSV-2 Western blot from a Pacific Northwest university.

Relative Sensitivity and Relative Specificity with Expectant Mothers:

Sample Size: 241 expectant mothers.
Data Source: Sera sequentially submitted to the laboratory, archived, and masked.
Annotation Protocol: Reference method was a HSV-2 Western blot (WB) from a Pacific Northwest university.

Relative Sensitivity and Relative Specificity with Sexually Active Adults:

Sample Size: 246 sexually active adults over the age of 14.
Data Source: Sera sequentially submitted to the laboratory, archived, and masked.
Annotation Protocol: Reference method was a HSV-2 Western blot from a Pacific Northwest university.

Relative Sensitivity with Culture Positives:

Sample Size: 63 culture positive patients.
Data Source: Sera from culture positive patients.
Annotation Protocol: Reference methods included culture (infection) and a HSV-2 Western blot (antibody) from a Pacific Northwest university.

Agreement with CDC Panel:

Sample Size: Not explicitly stated for specific samples in the panel, but it consisted of 37% positive and 63% negative samples.
Data Source: Serum panel obtained from the CDC.
Annotation Protocol: Tested by Focus Technologies, results compared to CDC characterization.

Relative Specificity with a Low Prevalence Population:

Sample Size: 81 college students claiming to lack sexual experience.
Data Source: Sera from a population of college students.
Annotation Protocol: The laboratory reference method was a HSV-2 Western blot from a Pacific Northwest university.

Type Specificity with HSV-1 Western Blot Positives:

Sample Size: 287 HSV-1 Western blot positive and HSV-2 Western blot negative sera.
Data Source: Sera from expectant mothers, sexually active adults, low prevalence persons, and HSV-1 culture positives.
Annotation Protocol: Reference method was HSV-1 Western blot.

Cross-reactivity with Taxonomically Related Viruses:

Sample Size: 27 sera.
Data Source: Sera from individuals HSV sero-negative by another manufacturer's FDA cleared HSV ELISAs, and IFA IgG positive for CMV, EBV VCA, HHV6 and VZV.
Annotation Protocol: Discrepant results between FDA cleared HSV ELISAs and the HerpeSelect 2 ELISA IgG were analyzed using a type specific Western blot from a major university located in the Northwestern United States.

Intra-assay & Inter-assay Reproducibility:

Sample Size: Seven samples, assayed in duplicate.
Data Source: Internal investigator.
Annotation Protocol: Assayed twice a day, for twenty days, for a total of forty runs. Two sets of samples were masked duplicates.

Inter-lot Reproducibility:

Sample Size: Five samples.
Data Source: Internal investigator.
Annotation Protocol: Run on three separate days with three separate lots. For one lot, samples were run in duplicate with the other two lots. Each of the three lots had a different lot of Antigen Wells.

Inter-laboratory Reproducibility:

Sample Size: Seven samples.
Data Source: Internal investigator and two off-site laboratories.
Annotation Protocol: Each of the three laboratories ran seven samples in triplicate on three different days.

% Agreement between the Manual and Automated Methods:

Sample Size: 257 samples.
Data Source: An internal and an external investigator, as part of a CLIA validation for a major clinical laboratory in Southern California. Samples were sequentially selected and manually tested. 255 samples were from the US, and two samples from outside the US. All samples were from adults and submitted for HSV testing.
Annotation Protocol: Agreement between manual and automated methods was assessed.

Reproducibility Using an Automated Instrument:

Sample Size: Ten samples.
Data Source: Internal investigator.
Annotation Protocol: Samples tested in triplicate on three different days.

Stability after Opening Reagents:

Sample Size: Not explicitly stated but refers to samples used in the inter-assay reproducibility study.
Data Source: Internal investigator.
Annotation Protocol: Kit used in inter-assay reproducibility study, re-closed, stored at 2-8C for at least 30 days, then used again to re-test the same samples.

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

Expected Values:

Study Type: Clinical study comparing device performance to a reference method.
Sample Size: 246 sexually active adults, 241 expectant mothers.
Key Results:
- Sexually Active Adults: Hypothetical sensitivity 96.1%, hypothetical specificity 97.0%.
- Expectant Mothers: Hypothetical sensitivity 100%, hypothetical specificity 96.1%.
- Observed prevalence:
  - Sexually Active Adults: WB neg 68.5%, WB pos 31.5%; Focus ELISA neg 67.2%, Focus ELISA pos 32.4%.
  - Expectant Mothers: WB neg 75.6%, WB pos 24.4%; Focus ELISA neg 72.3%, Focus ELISA pos 27.3%.
- Hypothetical Predictive Values based on prevalence were reported in a table for PPV and NPV for both populations.

Relative Sensitivity and Relative Specificity with Expectant Mothers:

Study Type: Clinical performance study.
Sample Size: 241.
Key Results:
- Sensitivity relative to Western blot: 100% (58/58) with 95% CI 93.8-100%.
- Specificity relative to Western blot: 96.1% (172/179) with 95% CI 92.1-98.4%.

Relative Sensitivity and Relative Specificity with Sexually Active Adults:

Study Type: Clinical performance study.
Sample Size: 246.
Key Results:
- Sensitivity relative to Western blot: 96.1% (73/76) with 95% CI 88.9-99.2%.
- Specificity relative to Western blot: 97.0% (159/164) with 95% CI 93.0-99.0%.

Relative Sensitivity with Culture Positives:

Study Type: Clinical performance study.
Sample Size: 63.
Key Results:
- Sensitivity relative to culture: 96.8% (61/63) with 95% CI 89.0-99.6%.
- Sensitivity relative to Western blot: 98.4% (61/62) with 95% CI 91.3-100%.

Agreement with CDC Panel:

Study Type: Performance evaluation against a characterized panel.
Sample Size: Not explicitly given, but the panel consists of 37% positive and 63% negative samples.
Key Results:
- 100% total agreement with the CDC panel.
- 100% agreement with positive CDC results.
- 100% agreement with negative CDC specimens.

Relative Specificity with a Low Prevalence Population:

Study Type: Clinical performance study.
Sample Size: 81.
Key Results:
- Specificity relative to Western blot: 98.7% (77/78) with 95% CI 93.1-100%.
- Sensitivity relative to Western blot: 100% (2/2) with 95% CI 15.8-100%.

Type Specificity with HSV-1 Western Blot Positives:

Study Type: Clinical performance study.
Sample Size: 287.
Key Results:
- Type-specificity relative to Western blot: 96.5% (276/286) with 95% CI 93.7-98.3%.
- Type cross-reactivity relative to Western blot: 3.5% (10/286) with 95% CI 1.7-6.3%.

Cross-reactivity with Taxonomically Related Viruses:

Study Type: Clinical performance study.
Sample Size: 27.
Key Results:
- CMV: 91.7% (11/12) agreement negative, 95% CI 61.5-99.8%.
- EBV VCA: 90.9% (20/22) agreement negative, 95% CI 70.8-98.9%.
- HHV6: 90.9% (20/22) agreement negative, 95% CI 70.8-98.9%.
- VZV: 90.5% (19/21) agreement negative, 95% CI 69.6-98.8%.
- Total: 90.9% (70/77) agreement negative, 95% CI 82.2-96.3%.

Intra-assay & Inter-assay Reproducibility:

Study Type: Reproducibility study.
Sample Size: 7 samples.
Key Results: Intra-assay %CV ranged from 3.0 to 20.5. Inter-assay %CV ranged from 5.5 to 15.9.

Inter-lot Reproducibility:

Study Type: Reproducibility study.
Sample Size: 5 samples.
Key Results: Index %CV ranged from 5.1 to 52.4.

Inter-laboratory Reproducibility:

Study Type: Reproducibility study.
Sample Size: 7 samples.
Key Results: %CV of Lab Means ranged from 3.9 to 33.1. Mean of Lab %CVs ranged from 4.5 to 20.7.

% Agreement between the Manual and Automated Methods:

Study Type: Method comparison study.
Sample Size: 257 samples.
Key Results:
- Agreement for Negative: 99.4% (174/175) with 95% CI 96.4-100%.
- Agreement for Equivocal: 0.0% (0/3) with 95% CI 0.0-70.8%.
- Agreement for Positive: 98.7% (78/79) with 95% CI 93.1-100%.
- Overall Agreement: 98.1% (252/257) with 95% CI 95.5-99.4%.

Reproducibility Using an Automated Instrument:

Study Type: Reproducibility study.
Sample Size: 10 samples.
Key Results: Manual and automated methods agreed 98.9% (89/90). Intra-assay %CV ranged from 0.8 to 51.4. Inter-assay %CV ranged from 0.9 to 105.4 (due to an outlier).

Stability after Opening Reagents:

Study Type: Stability study.
Sample Size: Not explicitly stated but refers to samples from inter-assay reproducibility.
Key Results: 100% agreement with the index when the reagents were opened versus after at least 30 days of storage.

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

Hypothetical Sensitivity (Sexually Active Adults): 96.1%
Hypothetical Specificity (Sexually Active Adults): 97.0%
Hypothetical Sensitivity (Expectant Mothers): 100%
Hypothetical Specificity (Expectant Mothers): 96.1%
Relative Sensitivity to Western blot (Expectant Mothers): 100% (95% CI: 93.8-100%)
Relative Specificity to Western blot (Expectant Mothers): 96.1% (95% CI: 92.1-98.4%)
Relative Sensitivity to Western blot (Sexually Active Adults): 96.1% (95% CI: 88.9-99.2%)
Relative Specificity to Western blot (Sexually Active Adults): 97.0% (95% CI: 93.0-99.0%)
Sensitivity relative to culture: 96.8% (95% CI: 89.0-99.6%)
Sensitivity relative to Western blot (Culture Positives): 98.4% (95% CI: 91.3-100%)
Specificity relative to Western blot (Low Prevalence Population): 98.7% (95% CI: 93.1-100%)
Sensitivity relative to Western blot (Low Prevalence Population): 100% (95% CI: 15.8-100%)
Type-specificity relative to Western blot (HSV-1 WB Positives): 96.5% (95% CI: 93.7-98.3%)
Type cross-reactivity relative to Western blot (HSV-1 WB Positives): 3.5% (95% CI: 1.7-6.3%)
Cross-reactivity with CMV (Agreement Negative): 91.7% (95% CI: 61.5-99.8%)
Cross-reactivity with EBV VCA (Agreement Negative): 90.9% (95% CI: 70.8-98.9%)
Cross-reactivity with HHV6 (Agreement Negative): 90.9% (95% CI: 70.8-98.9%)
Cross-reactivity with VZV (Agreement Negative): 90.5% (95% CI: 69.6-98.8%)
Total Cross-reactivity (Agreement Negative): 90.9% (95% CI: 82.2-96.3%)
Intra-assay %CV: Range 3.0-20.5
Inter-assay %CV: Range 5.5-15.9
Inter-lot Index %CV: Range 5.1-52.4
Inter-Laboratory %CV of Lab Means: Range 3.9-33.1
Inter-Laboratory Mean of Lab %CVs: Range 4.5-20.7
Agreement between Manual and Automated Methods (Negative): 99.4% (95% CI: 96.4-100%)
Agreement between Manual and Automated Methods (Equivocal): 0.0% (95% CI: 0.0-70.8%)
Agreement between Manual and Automated Methods (Positive): 98.7% (95% CI: 93.1-100%)
Overall Agreement between Manual and Automated Methods: 98.1% (95% CI: 95.5-99.4%)
Automated Instrument Inter-assay %CV: Range 0.9-105.4 (with outlier)
Automated Instrument Intra-assay %CV: Range 0.8-51.4 (with outlier)

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

HerpeSelect®2 ELISA IgG (manual option)

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

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

1 2002

Image /page/0/Picture/1 description: The image shows the logo for Focus Technologies. The word "FOCUS" is written in large, bold, sans-serif letters. Below the word "FOCUS" is the word "technologies" written in a smaller, sans-serif font. The two crescent moon shapes are placed in the middle of the word FOCUS, replacing the letter "O".

510(k) Summary of Safety and Effectiveness HerpeSelect®2 ELISA IgG Catalog No. EL0920G Prepared July 23, 2002 Page 1 of 9

021486

| Applicant | Focus Technologies, Inc.
10703 Progress Way
Cypress, California 90630
USA |
|-----------------------------------|-------------------------------------------------------------------------------------------------|
| Establishment
Registration No. | 2023365 |
| Contact Person | Michael J. Wagner, Esq.
tel (714) 220-1900
fax (714) 995-6921
mwagner@focusanswers.com |
| Summary Date | July 23, 2002 |
| Proprietary Name | HerpeSelect®2 ELISA IgG (automated option) |
| Generic Name | HSV-2 ELISA IgG |
| Classification | Herpes Simplex Virus Serological Reagents
21 CFR §866.3305
Class III |
| Predicate Device | HerpeSelect®2 ELISA IgG (manual option) |

Device Description

Intended Use

Image /page/1/Picture/1 description: The image shows the logo for Focus Technologies. The logo consists of the word "FOCUS" in a bold, sans-serif font, with a stylized crescent moon shape incorporated into the "O". Below the word "FOCUS" is the word "technologies" in a smaller, sans-serif font with more spacing between the letters. The logo is black and white.

510(k) Summary of Safety and Effectiveness HerpeSelect®2 ELISA IgG Catalog No. EL0920G Prepared July 23, 2002 Page 2 of 9

EXPECTED VALUES

An outside investigator assessed the device with masked, archived and unselected sera from 1) sexually active adults over the age of 14 (n = 246), and 2) from expectant mothers (n = 241). The reference method was a HSV-2 Western blot from a Pacific Northwest university. The observed prevalences and the hypothetical predictive values for the two populations are shown in the tables below. The positive value will decrease proportionally to the prevalence of HSV infection as reflected in the table below. The calculations are based on HerpeSelect 2 ELISA IgG having

I) a hypothetical sensitivity of 96.1% & a hypothetical specificity of 97.0% (sexually active adults), and

a hypothetical sensitivity of 100% and a hypothetical specificity of 96.1% (expectant mothers).

| Population | HSV-2
Serostatus | Observed Prevalence | |
|--------------------------|---------------------|---------------------|-------------|
| | | WB | Focus ELISA |
| Sexually Active Adults * | neg | 68.5% | 67.2% |
| | + | 31.5% | 32.4% |
| Expectant Mothers † | neg | 75.6% | 72.3% |
| | + | 24.4% | 27.3% |

Observed Prevalence with Sexually Active Adults & Expectant Mothers

Excludes 5 atypical Western blots and 1 ELISA equivocal.

† Excludes 3 atypical Western blots and 1 ELISA equivocal.

Prevalence vs. Hypothetical Predictive Values
Prevalence	Sexually Active Adults		Expectant Mothers
	PPV	NPV	PPV	NPV
50%	97.0%	97.0%	96.2%	96.1%
40%	95.5%	98.0%	94.5%	97.4%
30%	93.2%	98.7%	91.7%	98.3%
25%	91.4%	99.0%	89.5%	98.7%
20%	88.9%	99.2%	86.5%	99.0%
15%	85.0%	99.5%	81.9%	99.3%
10%	78.1%	99.7%	74.0%	99.6%
5%	62.8%	99.8%	57.4%	99.8%

Prevalence vs. Hynothetical Predictive Values

Note: Sexually active adult and expectant mother populations in different geographic areas may produce different frequency distributions from the table above. Each laboratory should establish frequency distributions for their specific patient populations.

PERFORMANCE CHARACTERISTICS

Image /page/2/Picture/1 description: The image shows the logo for Focus Technologies. The logo is in black and white and features the word "FOCUS" in large, bold letters. Below the word "FOCUS" is the word "technologies" in a smaller, sans-serif font. The two crescent shapes are nested inside the letter O.

510(k) Summary of Safety and Effectiveness HerpeSelect®2 ELISA IgG Catalog No. EL0920G Prepared July 23, 2002 Page 3 of 9

Relative Sensitivity and Relative Specificity with Expectant Mothers †

An outside investigator assessed the device's relative sensitivity and relative specificity with sera from expectant mothers (n = 241). The sera were sequentially submitted to the laboratory, archived, and masked. The reference method was a HSV-2 Western blot (WB) from a Pacific Northwest university. Of 3 atypical Western blots, HerpeSelect® 2 ELISA IgG (EL) was 1 equivocal and 2 negatives. Of 58 Western blot positives, HerpeSelect® 2 ELISA IgG was 58 positive. Of 180 Western blot negatives, HerpeSelect® 2 ELISA IgG was 172 negatives, 7 positives, and 1 equivocal.

Characteristic	% (EL/WB)*	95% CI
Sensitivity relative to Western blot	100% (58/58)	93.8-100%
Specificity relative to Western blot	96.1% (172/179)	92.1-98.4%

Relative Sensitivity and Relative Specificity with Expectant Mothers (n = 241) †

Excludes three atypical Western blots and one ELISA equivocal

The word "relative" refers to comparing this assay's results with those of a similar assay. No attempt was made to correlate the assay results to disease presence or absence. No judgment can be made on the similar assay's accuracy in predicting disease. Assay performed by manual method.

Relative Sensitivity and Relative Specificity with Sexually Active Adults †

An outside investigator assessed the device's relative sensitivity and relative specificity with sera from sexually active adults over the age of 14 (n = 246). The sera were sequentially submitted to the laboratory, archived, and masked. The reference method was a HSV-2 Western blot from a Pacific Northwest university. Of 5 atypical Western blots, HerpeSelect® 2 ELISA IgG was 2 equivocal, 2 negative and 1 positive. Of 76 Western blot positives, HerpeSelect® 2 ELISA IgG was 73 positive. Of 165 Western blot negatives, HerpeSelect® 2 ELISA IgG was 159 negative, 5 positive, and 1 equivocal.

Relative Sensitivity and Relative Specificity with Sexually Active Adults (n = 246) †

Characteristic	% (EL/WB)*	95% CI
Sensitivity relative to Western blot	96.1% (73/76)	88.9-99.2%
Specificity relative to Western blot	97.0% (159/164)	93.0-99.0%

Excludes five atypical Western blots and one ELISA equivocal
The word "relative" refers to comparing this assay's results with those of a similar assay. No attempt was made to correlate the assay results to disease presence or absence. No judgment can be made on the similar assay's accuracy in predicting disease. Assay performed by manual method.

Image /page/3/Picture/1 description: The image shows the logo for Focus Technologies. The logo is black and white and features the word "FOCUS" in large, bold letters. Below the word "FOCUS" is the word "technologies" in smaller letters. The two crescent moon shapes are used to create the letter O in the word FOCUS.

510(k) Summary of Safety and Effectiveness HerpeSelect®2 ELISA IgG Catalog No. EL0920G Prepared July 23, 2002 Page 4 of 9

Relative Sensitivity with Culture Positives +

An outside investigator assessed the device's relative sensitivity using sera from culture positive patients (n = 63). Reference methods included culture (infection) and a HSV-2 Western blot (antibody) from a Pacific Northwest university. Of 5 atypical Western blots, HerpeSelect®2 ELISA IgG was 2 equivocal, 2 negative and 1 positive. Of 63 culture positives, HerpeSelect® 2 ELISA IgG was 61 positive and 2 negative, and Western blot was 62 positive and 1 negative. Of 62 Western blot positives, HerpeSelect® 2 ELISA IgG was 61 positive and 1 negative.

| Characteristic | % (EL/WB or
Culture) | 95% CI |
|--------------------------------------|-------------------------|------------|
| Sensitivity relative to culture | 96.8% (61/63)* | 89.0-99.6% |
| Sensitivity relative to Western blot | 98.4% (61/62)* | 91.3-100% |

*Of the 2 ELISA negatives, one was WB positive and the other WB negative.

The word "relative" refers to comparing this assay's results with those of a similar assay. No attempt was made to correlate the assay results to disease presence or absence. No judgment can be made on the similar assay's accuracy in predicting disease. Assay performed by manual method.

Agreement with CDC Panel +

The following information is from a serum panel obtained from the CDC and tested by Focus Technologies. 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 37% positive and 63% negative samples. The HerpeSelect® 2 ELISA IgG demonstrated 100% total agreement with the Of the results obtained by Focus Technologies, there was 100% agreement with the positive CDC results. specimens and 100% agreement with the negative specimens.

Assay performed by manual method.

Relative Specificity with a Low Prevalence Population *

An outside investigator assessed the device's relative specificity using sera from a population of college students claiming to lack sexual experience (n = 81), and having a published HSV-2 antibody prevalence of 2% (4/186) ** The laboratory reference method was a HSV-2 Western blot from a Pacific Northwest university. One atypical Western blot was an HerpeSelect® 2 ELISA IgG negative. Of 78 Western blot negatives, HerpeSelect® 2 ELISA IgG was 77 negative and 1 positive. Of 2 Western blot negatives, HerpeSelect® 2 ELISA IgG was 2 positive.

Characteristic	% (EL/WB)*	95% CI
Specificity relative to Western blot†	98.7% (77/78)	93.1-100%
Sensitivity relative to Western blot†	100% (2/2)	15.8-100%

Relative Specificity with a Low Prevalence Population (n = 81) +

Excludes one atypical Western blot.

** Corey, L. A. Wald, New Developments in the Biology of Genital Herpes, in Clinical Management of Herpes Viruses, p.46.

The word "relative" refers to comparing this assay's results with those of a similar assay. No attempt was made to correlate the assay results to disease presence or absence. No judgment can be made on the similar assay's accuracy in predicting disease. Assay performed by manual method.

Image /page/4/Picture/1 description: The image shows the logo for Focus Technologies. The logo is black and white and features the word "FOCUS" in large, bold letters. Below the word "FOCUS" is the word "technologies" in smaller letters. The two crescent moon shapes are used in place of the letter "O" in the word "FOCUS".

510(k) Summary of Safety and Effectiveness HerpeSelect®2 ELISA IgG Catalog No. EL0920G Prepared July 23, 2002 Page 5 of 9

Type Specificity with HSV-1 Western Blot Positives †

An outside investigator assessed the device's type specificity using HSV-1 Western blot positive and HSV-2 Western Blot negative sera from the above described populations (n = 287): expectant mothers, sexually active adults, low prevalence persons, and HSV-1 culture positives. Of 287 HSV-1 Western blot positive and HSV-2 Western blot negative samples, HerpeSelect® 2 ELISA IgG was 276 negatives, 1 equivocal and 10 positives.

Characteristic	% (EL/WB)*	95% CI
Type-specificity relative to Western blot	96.5% (276/286)	93.7-98.3%
Type cross-reactivity relative to Western blot	3.5% (10/286)	1.7-6.3%

		Type Specificity with HSV-1 Western Blot Positives (n = 287) †

Excludes one equivocal ELISA result.

The word "relative" refers to comparing this assay's results with those of a similar assay. No attempt was made to correlate the assay results to disease presence or absence. No judgment can be made on the similar assay's accuracy in predicting disease. Assay performed by manual method. Assay performed by manual method.

Cross-reactivity with Taxonomically Related Viruses *

Focus Technologies assessed the device's cross-reactivity using sera (n = 27) from 1) HSV sero-negative by another manufacturer's FDA cleared HSV ELISAs, and 2) IFA IgG positive for taxonomically similar viruses including CMV, EBV VCA, HHV6 and VZV. Discrepants between the FDA cleared HSV ELISAs and the HerpeSelect" 2 ELISA IgG were analyzed using a type specific Western blot from a major university located in the Northwestern United States.

Cross-reactivity with Taxonomically Related Viruses (n = 27) †
IFA IgG Pos	% Agreement
Negative*	95% CI
CMV	91.7% (11/12)	61.5-99.8%
EBV VCA	90.9% (20/22)	70.8-98.9%
HHV6	90.9% (20/22)	70.8-98.9%
VZV	90.5% (19/21)	69.6-98.8%
Total	90.9% (70/77)	82.2-96.3%

Cross-reactivity with Taxonomically Related Viruses (n

Excludes 3 Western blot positives, and one discrepant that was not analyzed with the Western blot because of insufficient volume

Assay performed by manual method.

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Intra-assay & Inter-assay Reproducibility †

An internal investigator assessed the device's intra-assay reproducibility by assaying seven samples in duplicate, twice a day, for twenty days, for a total of forty runs. Two sets of samples were masked duplicates.

Inter-lot Reproducibility †

An internal investigator assessed the device's inter-lot reproducibility. Five samples were run on three separate days with three separate lots. For one lot, the samples were run in duplicate with the other two lots. Each of the three lots had a different lot of Antigen Wells.

Inter-laboratory Reproducibility †

An internal investigator and two off-site laboratories assessed the device's inter-laboratory reproducibility. Each of the three laboratories ran seven samples in triplicate on three different days. Three points were excluded because an incorrect sample (instead of sample 27) was run one day.

Sample	Inter- & Intra-assay			Inter-lot		Inter-Laboratory
	Index
Mean	Intra-
assay
%CV	Inter-
assay
%CV	Index
Mean	Index
%CV	Index
Mean	%CV of
Lab
Means	Mean of
Lab
%CVs
21*	0.2	20.5	15.9	0.3	52.4	0.2	19.6	17.3
26*	0.2	12.2	12.4	NA	NA	0.3	33.1	20.7
22**	1.2	6.3	6.2	1.2	5.1	1.2	3.9	7.8
27**	1.2	5.2	6.3	NA	NA	1.1	14.1	8.8
23	1.8	4.7	5.5	1.8	5.4	1.7	5.2	7.
24	3.4	3.2	7.9	3.2	16.7	2.8	11.0	10.8
25	8.2	3.0	6.9	8.0	7.4	6.8	18.6	4.5

Reproducibility †

#21 & #26 are same material.

** #22 & #27 are same material.

ート Assay performed by manual method.

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510(k) Summary of Safety and Effectiveness HerpeSelect®2 ELISA IgG Catalog No. EL0920G Prepared July 23, 2002 Page 7 of 9

% Agreement between the Manual and Automated Methods (n = 257)

An internal and an external investigator compared % agreement between the HerpeSelect automated ws. the manual method as part of a CLIA validation for a major clinical laboratory located in Southern California. The external investigator sequentially selected and manually tested 257 sample was from an adult, and was submitted for HSV testing. 255 samples were from the US, and two samples from outside the US. Of the 257 samples, the manual method detected 175 negatives, 3 equivocals, and 79 positives. Of the 175 negatives by the manual method, the automated method agreed with 99.4% (174/175). Of the 3 equivocals by the manual method, the automated method agreed with 0% (0/3). Of the 79 positives by the manual method, the automated method agreed with 98.7% (78/79). Overall, the two methods agreed 98.1% (252/257). Of the five discrepants, two resolved in favor of the automated method, and the other three did not resolve.

Interpretation*	% Agreement	95% CI
Negative	99.4% (174/175)	96.4-100%
Equivocal	0.0% (0/3)	0.0-70.8%
Positive	98.7% (78/79)	93.1-100%
Overall	98.1% (252/257)	95.5-99.4%

% Agreement between Manual and Automated Methods

Interpretation by manual method.

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510(k) Summary of Safety and Effectiveness HerpeSelect®2 ELISA IgG Catalog No. EL0920G Prepared July 23, 2002 Page 8 of 9

Reproducibility Using an Automated Instrument

An internal investigator assessed the device's inter-assay reproducibility with an automated instrument. Ten samples were tested in triplicate on three different days. The manual and automated methods agreed 98.9% (89/90). One point from Sample 3 was an outlier (162 standard deviations from the mean).

| Sample | Mean Index | Intra-assay
%CV | Inter-assay
%CV |
|----------------------|------------|--------------------|--------------------|
| 6 | 0.06 | 27.2 | 20.8 |
| 3 (without outlier)* | 0.45 | 8.8 | 4.6 |
| 8 | 0.10 | 28.3 | 25.2 |
| 3 (with outlier)* | 1.18 | 51.4 | 105.4 |
| 10 | 1.39 | 6.0 | 5.5 |
| 9 | 1.87 | 4.8 | 2.5 |
| 5 | 5.23 | 2.8 | 0.9 |
| 1 | 6.38 | 1.3 | 3.5 |
| 4 | 7.14 | 3.0 | 3.3 |
| 7 | 7.97 | 6.4 | 10.8 |
| 2 | 8.21 | 0.8 | 4.6 |

*One point from Sample 3 was an outlier (162 standard deviations from the mean).

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510(k) Summary of Safety and Effectiveness HerpeSelect®2 ELISA IgG Catalog No. EL0920G Prepared July 23, 2002 Page 9 of 9

Stability after Opening Reagents

An internal investigator assessed stability after the reagents had been opened and used with an automated instrument. The kit was used in the inter-assay reproducibility study (above), re-closed, stored at 2-8C for at least 30 days, and then used again to re-test the same samples. There was 100% agreement with the index when the reagents were opened.

| Sample | Index when
Opened | After at Least
30 Days (Run 1) | After at Least
30 Days (Run 2) |
|---------------------|----------------------|-----------------------------------|-----------------------------------|
| 6 | 0.06 | 0.06 | 0.07 |
| 3 (without outlier) | 0.45* | 0.43 | 0.48 |
| 8 | 0.10 | 0.14 | 0.10 |
| 10 | 1.39 | 1.60 | 1.76 |
| 9 | 1.87 | 2.03 | 2.11 |
| 5 | 5.23 | 5.13 | 5.10 |
| 1 | 6.38 | 6.79 | 6.57 |
| 4 | 7.14 | 7.67 | 7.26 |
| 7 | 7.97 | 8.16 | 8.29 |
| 2 | 8.21 | 8.38 | 8.35 |

Stability after Opening Reagent

*One point from Sample 3 was an outlier, it was 162 SDs from the mean. The values without the outlier are used here.

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Food and Drug Administration 2098 Gaither Road Rockville MD 20850

AUG 0 1 2002

Michael J. Wagner, Esq. Senior Regulatory Affairs Specialist Focus Technologies, Inc. 10703 Progress Way Cypress, CA 90630

Re: K021486 Trade/Device Name: HerpeSelect ™ 2 ELISA IgG Regulation Number: 21 CFR 866.3305 Regulation Name: Herpes Simplex Virus Serological Reagents Regulatory Class: Class III Product Code: MXJ Dated: May 2, 2002 Received: May 3, 2002

Dear Mr. Wagner:

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. Iisting 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 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 Part 801); 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.

Page 2 -

This letter will allow you to begin marketing your device as described in your 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 advice for your device on our labeling regulation (21 CFR Part 801 and ' additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device. please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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 (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrb/dsma/dsmamain.html".

Sincerely yours,

Steven Butman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory-Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

510(k) Number (if known): K021486

Device Name:

HerpeSelect® 2 ELISA IgG

Indications for Use:

Focus Technologies' HerpeSelect® 2 ELISA IgG test is intended for qualitatively detecting the presence or absence of human IgG class antibodies to HSV-2 in human sera. In conjunction with the Focus HerpeSelect® 1 ELISA IgG, the test is indicated for testing sexually active adults or expectant mothers for aiding in the presumptive diagnosis of HSV infection. The assay can be used manually or in conjunction with an automated system as outlined in the package insert. The user is responsible for assay performance characteristics when an automated system is used. The performance of this assay has not been established for use in a pediatric population, for neonatal screening, or for testing of immunocompromised patients.

(PLEASE DO NOT WRITE BELOW THIS LINE CONTINUE ON ANOTHER PAGE IF NEEDED) Concurrence of CDRH, Office of Device Evaluation (ODE)

Woody Duboer

0(k) Number

For PRESCRIPTION USE_X

(Optional Format 3-10-98)