PREMIER HSV PLUS

K953839 · Meridian Diagnostics, Inc. · LGC · May 23, 1996 · Microbiology

Device Facts

• Record ID: K953839
• Device Name: PREMIER HSV PLUS
• Applicant: Meridian Diagnostics, Inc.
• Product Code: LGC · Microbiology
• Decision Date: May 23, 1996
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3305
• Device Class: Class 2

Indications for Use

The Premier HSV is a qualitative enzyme immunoassay designed for detection of herpes simplex virus (HSV). The test is intended to be used for direct detection from genital or other skin vesicles/ulcerated lesions or asymptomatic genital specimens to rapidly confirm the presence of HSV. The test can also be used in conjunction with cell cultures inoculated with these specimens.

Device Story

Premier HSV Plus is a microwell-based sandwich enzyme immunoassay (EIA) for detecting herpes simplex virus (HSV) antigens. Input consists of clinical specimens (genital/skin vesicles, ulcerated lesions, or asymptomatic genital swabs) or cell culture inoculates. The assay uses capture antibody-coated microwells; samples are incubated with extraction buffer, followed by enzyme conjugate, wash steps, and substrate addition. The reaction produces a colorimetric change measured via spectrophotometry at 450/630nm. Performed in clinical laboratory settings by trained personnel. Output is a qualitative determination of HSV presence based on optical density readings. Results assist clinicians in confirming HSV infection, facilitating timely diagnosis and management.

Clinical Evidence

Clinical performance evaluated against culture with FA confirmation in 556 specimens. Direct EIA demonstrated 92.7% relative sensitivity and 100% relative specificity across all specimen types (genital symptomatic/asymptomatic, oral, other). Spin-Amp EIA procedure demonstrated 99.0% relative sensitivity and 99.7% relative specificity. Reproducibility studies (intra-assay and inter-assay) provided for HSV-1 and HSV-2 samples at high, medium, and low concentrations.

Technological Characteristics

Microwell-based sandwich enzyme immunoassay (EIA). Components include capture antibody-coated microwells, extraction buffer, enzyme conjugate, wash buffer, substrate, and stop solution. Detection via spectrophotometric reading at 450/630nm. Sensitivity limits: 10 TCID50 (HSV-1) and 30 TCID50 (HSV-2).

Indications for Use

Indicated for qualitative detection of HSV antigens in patients with genital or other skin vesicles/ulcerated lesions or asymptomatic genital specimens. Applicable to both symptomatic and asymptomatic 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

• Premier HSV

Submission Summary (Full Text)

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MAY 23 1996
K953839

Meridian Diagnostics, Inc.
Cincinnati, OH 45244

510(k) Notification
Premier HSV Plus

## APPENDIX A - 510(k) Summary

### A. Identification Information

1. Submitter's Information:

a. Submitter's Name and Address:

Meridian Diagnostics, Inc.
3471 River Hills Drive
Cincinnati, Ohio 45244

b. Phone Number: 1-513-271-3700

c. Contact Person: Allen D. Nickol, Ph.D.
Director, Scientific & Regulatory Affairs

d. Date Summary Prepared: August 11, 1995

2. Name of Device: Premier HSV Plus

a. Classification Name: Enzyme Linked Immunosorbent Assay, Herpes Simplex Virus (83LGC)

3. Predicate Equivalent Device: Premier HSV

178

{1}

Meridian Diagnostics, Inc.
Cincinnati, OH 45244
510(k) Notification
Premier HSV Plus

4. Description of Device: The Premier HSV Plus assay system is a microwell-based sandwich EIA for the detection of herpes simplex virus. Each kit contains the following components:

| a. | Capture Antibody-coated microwells | 1 x 96 |
| --- | --- | --- |
| b. | Positive Control | 6.5ml |
| c. | Negative Control | 6.5ml |
| d. | Extraction Buffer | 15ml |
| e. | Enzyme Conjugate | 10ml |
| f. | 20X Wash Buffer | 50ml |
| g. | Substrate | 10ml |
| h. | Stop Solution | 10ml |
| i. | Transfer Pipet | 96 |
| j. | Microwell Strip Holder | 1X |
| k. | Microwell Strip Sealer | 2X |

The assay is performed by adding two free drops (or 50μl) of Extraction Buffer to all wells. Then add four free drops (200μl) each of positive and negative control to the control wells, or 200μl of sample into appropriate wells and incubate 90 minutes at 37-39°C. Wash 5X with wash buffer. Add two free drops (100μl) of enzyme conjugate to each well, cover and incubate 30 minutes at 37-39°C. Then wash 5X with a five minute soak. Add two free drops (100μl) of substrate to all wells and incubate ten minutes at room temperature. Add two free drops (50μl) of Stop Solution to each well. Wait two minutes and read at 450/630nm.

5. Intended Use: The Premier HSV is a qualitative enzyme immunoassay designed for detection of herpes simplex virus (HSV). The test is intended to be used for direct detection from genital or other skin vesicles/ulcerated lesions or asymptomatic genital specimens to rapidly confirm the presence of HSV. The test can also be used in conjunction with cell cultures inoculated with these specimens.

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Meridian Diagnostics, Inc. Cincinnati, OH 45244

510(k) Notification Premier HSV Plus

6. Comparison with Predicate Devices:

a. Both assays employ enzyme immunoassay technology
b. Both methodologies are specific for detection of HSV antigens.

7. Clinical Trial Results: Comparison of the performance of Premier HSV Plus Direct EIA and Spin-Amp EIA procedure to culture with FA confirmation of positives

Direct EIA vs Culture with FA Confirmation

| Specimen Type | N | Relative Sensitivity | | Relative Sensitivity | |
| --- | --- | --- | --- | --- | --- |
| | | Initial | Resolved | Initial | Resolved |
| Genital Symptomatic | 393 | 88.9% (152/171) | 93.1% (161/173) | 98.2% (218/222) | 100% (220/220) |
| Genital Asymptomatic | 78 | 80% (4/5) | 83.3% (5/6) | 98.6% (72/73) | 100% (72/72) |
| Oral | 42 | 92.9% (13/14) | 92.9% (13/14) | 100% (28/28) | 100% (28/28) |
| Others* | 43 | 92.3% (12/13) | 92.3% (12/13) | 100% (30/30) | 100% (30/30) |
| Total | 556 | 89.2% (181/203) | 92.7% (191/206) | 98.6% (348/353) | 100% (350/350) |

*Skin lesion specimens other than genital, oral, and ocular.

Spin-Amp EIA vs Culture with FA Confirmation

| Specimen Type | N | Relative Sensitivity | | Relative Sensitivity | |
| --- | --- | --- | --- | --- | --- |
| | | Initial | Resolved | Initial | Resolved |
| Genital Symptomatic | 393 | 98.3% (168/171) | 99.4% (173/174) | 97.3% (216/222) | 99.5% (218/219) |
| Genital Asymptomatic | 78 | 100% (5/5) | 100% (6/6) | 98.6% (72/73) | 100% (72/72) |
| Oral | 42 | 92.9% (13/14) | 92.9% (13/14) | 100% (28/28) | 100% (28/28) |
| Others* | 43 | 100% (13/13) | 100% (13/13) | 100% (30/30) | 100% (30/30) |
| Total | 556 | 98.0% (199/203) | 99.0% (205/207) | 98.0% (346/353) | 99.7% (348/349) |

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Meridian Diagnostics, Inc. Cincinnati, OH 45244

510(k) Notification Premier HSV Plus

# B. Additional Information/Nonclinical Test Results

# 1. Reproducibility

# a. Intra-assay variability

Intra-assay Variation

| Sample | Mean O.D. Range | C.V. Range |
| --- | --- | --- |
| HSV-1 (H) | 1.01 - 1.55 | 1.8 - 17.4% |
| HSV-1 (M) | 0.52 - 0.92 | 1.5 - 13.5% |
| HSV-1 (L) | 0.33 - 0.44 | 3.9 - 13.4% |
| HSV-2 (H) | 1.36 - 1.61 | 1.4 - 13.9% |
| HSV-2 (M) | 0.33 - 0.48 | 1.3 - 12.4% |
| HSV-2 (L) | 0.17 - 0.33 | 1.9 - 14.1% |
| Negative Control | 0.08 - 0.12 | 2.4 - 18.7% |

# b. Inter-assay variability

Inter-Assay Variation

| Sample | Mean O.D. Range | C.V. Range |
| --- | --- | --- |
| HSV-1 (H) | 1.26 - 1.48 | 8.8 - 29.9% |
| HSV-1 (M) | 0.54 - 0.62 | 0.8 - 21.9% |
| HSV-1 (L) | 0.37 - 0.44 | 14.7 - 22.0% |
| HSV-2 (H) | 1.36 - 1.46 | 0.8 - 16.0% |
| HSV-2 (M) | 0.39 - 0.40 | 18.6 - 32.7% |
| HSV-2 (L) | 0.21 - 0.29 | 6.9 - 18.4% |
| Negative Control | 0.09 - 0.10 | 12.0 - 29.5% |

2. Sensitivity Limits: The sensitivity of Premier HSV Plus for HSV-1 and HSV-2 is 10 TCID $_{50}$ units and 30 TCID $_{50}$ units respectively.