SeraQuest HSV Type 2 Specific IgG

K181514 · Quest International, Inc. · MYF · Jun 13, 2019 · Microbiology

Device Facts

• Record ID: K181514
• Device Name: SeraQuest HSV Type 2 Specific IgG
• Applicant: Quest International, Inc.
• Product Code: MYF · Microbiology
• Decision Date: Jun 13, 2019
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3305
• Device Class: Class 2

Intended Use

The SeraQuest® HSV Type 2 Specific IgG assay is an enzyme-linked immunosorbent assay (ELISA) intended for the qualitative detection of human IgG antibodies to type 2 herpes simplex virus (HSV) in human serum. The test is indicated for sexually active individuals and expectant mothers as an aid in the presumptive diagnosis of HSV-2 infection. The predictive value of a positive or negative result depends on the prevalence of HSV-2 infection in the population and the pre-test likelihood of HSV-2 infection. The test is not FDA cleared for screening blood or plasma donors. The performance of this assay has not been established for immunocompromised patients, pediatric patients or matrices other than human serum.

Device Story

SeraQuest HSV Type 2 Specific IgG is an ELISA for qualitative detection of human IgG antibodies to HSV-2 in human serum. The device uses antigen-coated polystyrene microwells; patient samples are incubated; HSV-2 antibodies bind to antigens; conjugate (alkaline phosphatase-labeled anti-human IgG) is added; substrate (p-nitrophenyl phosphate) is converted to a yellow end-product. The device is used with the ChemWell Automated Analyzer to perform the assay steps (incubation, washing, photometric reading at 405 nm). Results are reported as Index values. Healthcare providers use these results as an aid in the presumptive diagnosis of HSV-2 infection. A positive result indicates previous immunologic exposure; it does not determine active infection or disease stage. Equivocal results require re-testing with a new specimen.

Clinical Evidence

Bench testing only. Precision study evaluated within-run, between-run, between-day, and within-lab precision over 12 days. Method comparison study (n=226) compared manual vs. automated performance, showing 100% PPA (95% CI: 97.02-100%) and 99.01% NPA (95% CI: 94.60-99.83%). Linear regression analysis showed a slope of 1.0526 and R² of 0.9770.

Technological Characteristics

Solid-phase ELISA; polystyrene microwells; purified HSV gG 2 antigen; alkaline phosphatase conjugated goat anti-human IgG; p-nitrophenyl phosphate substrate; 0.5 M Trisodium Phosphate stop reagent; spectrophotometric readout at 405 nm. Automated via ChemWell Automated Analyzer. Room temperature incubation.

Indications for Use

Indicated for sexually active individuals and expectant mothers as an aid in the presumptive diagnosis of HSV-2 infection. Not for screening blood/plasma donors. Performance not established for immunocompromised, pediatric patients, or non-serum matrices.

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

• SeraQuest® HSV Type 2 Specific IgG assay (K152353)

Submission Summary (Full Text)

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Image /page/0/Picture/0 description: The image contains the logos of the Department of Health & Human Services and the Food and Drug Administration (FDA). The Department of Health & Human Services logo is on the left, and the FDA logo is on the right. The FDA logo includes the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.

June 13, 2019

Quest International, Inc. Steve Andrus Quality Assurance Manager 1935 SW Martin Highway Palm City, Florida 34990

Re: K181514

Trade/Device Name: SeraQuest HSV Type 2 Specific IgG Regulation Number: 21 CFR 866.3305 Regulation Name: Herpes simplex virus serological assays Regulatory Class: Class II Product Code: MYF Dated: May 13, 2019 Received: May 15, 2019

Dear Steve Andrus:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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

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requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

for

Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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# Indications for Use

510(k) Number (if known) K181514

Device Name

SeraQuest HSV Type 2 Specific IgG

Indications for Use (Describe) Intended Use

The SeraQuest HSV Type 2 Specific IgG assay is an enzyme-linked immunosorbent assay (ELISA) intended for the qualitative detection of human IgG antibodies to type 2 herpes simplex virus (HSV) in human serum. The test is indicated for sexually active individuals and expectant mothers as an aid in the presumptive diagnosis of HSV-2 infection. The predictive value of a positive or negative result depends on the prevalence of HSV-2 infection in the pre-test likelihood of HSV-2 infection.

The test is not FDA cleared for screening blood or plasma donors. The performance of this assay has not been established for immunocompromised patients, pediatric patients or matrices other than human serum.

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

X Prescription Use (Part 21 CFR 801 Subpart D)

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

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# 510(k) Summary

| Applicant: | Awareness Technology Inc. / Quest International, Inc.<br>1935 SW Martin Highway<br>Palm City, FL 34990 |
|-----------------|--------------------------------------------------------------------------------------------------------------------------------|
| Contact Person: | Steve Andrus<br>Quality Assurance Manager<br>Phone: [phone] ext. 220<br>Fax: [phone]<br>Email: [e-mail] |
| Trade Name: | SeraQuest® HSV Type 2 Specific IgG |
| Common Name: | Enzyme Linked Immunosorbent Assay, Herpes Simplex Virus, Hsv-2 |

| Product Nomenclature | 510(k)<br>Number | Class | Product<br>Code | Regulation<br>Number | Review Panel |
|-------------------------------------------------------------------|------------------|-------|-----------------|----------------------|--------------|
| Enzyme Linked Immunosorbent<br>Assay, Herpes Simplex Virus, Hsv-2 | K181514 | II | MYF | 866.3305 | Microbiology |

# Description

The SeraQuest® HSV Type 2 Specific IgG test is a solid-phase enzyme-linked immunoassay (ELISA), which is performed in microwells, at room temperature, and in three thirty-minute incubations. The test detects IgG antibodies which are directed against HSV 2 type-specific antigens in human serum. The Calibrator in the SeraQuest® HSV Type 2 Specific IgG test set has been assigned Index values based on an in-house standard. Test results are reported as Index values. The following table shows the interpretation of results:

| Index | Result | Interpretation |
|---------------|-----------|------------------------------------------------------------------------------------------------------|
| ≤ 0.9 | Negative | No HSV-2 IgG antibodies detected. Patient is presumed not to have<br>had a previous HSV-2 infection. |
| 0.9 < X < 1.0 | Equivocal | Obtain an additional sample for re-testing |
| ≥ 1.0 | Positive | IgG antibody to HSV-2 detected. |

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Awareness Technology Inc. /Quest International, Inc. 1935 SW Martin Highway Palm City, Florida 3490

Notes:

- 1. A single positive result only indicates previous immunologic exposure; the level of antibody response may not be used to determine active infection or disease stage.
- 2. When equivocal results are obtained, another specimen should be obtained ten to fourteen days later and tested in parallel with the initial specimen. If the second specimen is also equivocal, the patient is negative for primary or recent infection, and equivocal for antibody status. If the second sample is positive, the patient can be considered to have previous experience with HSV-2 infection.
- 3. Values obtained with different manufacturer's assay methods may not be used interchangeably. The magnitude of the reported IgG index value cannot be correlated to an endpoint titer. The magnitude of results above the cut-off is not an indicator of total antibody present.

## Principle:

Diluted patient samples are incubated in antigen-coated wells. HSV Type 2 antibodies, if present in the patient sample, are immobilized in the wells by binding to the antigen. Residual sample is eliminated by washing and draining, and conjugate (enzyme-labeled antibodies to human IgG) is added and incubated. If IgG antibodies to HSV-2 are present, the conjugate will be immobilized in the wells. Residual conjugate is eliminated by washing and draining, and the substrate is added and incubated. In the presence of the conjugate, the substrate is converted to a yellow end-product which is read photometrically.

## Intended Use:

The SeraQuest® HSV Type 2 Specific IgG assay is an enzyme-linked immunosorbent assay (ELISA) intended for the qualitative detection of human IgG antibodies to type 2 herpes simplex virus (HSV) in human serum. The test is indicated for sexually active individuals and expectant mothers as an aid in the presumptive diagnosis of HSV-2 infection. The predictive value of a positive or negative result depends on the prevalence of HSV-2 infection in the population and the pre-test likelihood of HSV-2 infection.

The test is not FDA cleared for screening blood or plasma donors. The performance of this assay has not been established for immunocompromised patients, pediatric patients or matrices other than human serum.

## Predicate Device:

SeraQuest® HSV Type 2 Specific IgG assay 510(k) 152353 manual method.

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Awareness Technology Inc. /Quest International, Inc. 1935 SW Martin Highway Palm City, Florida 34990

#### Predicate Comparison

All reagents, controls, calibrators, and critical procedural steps of the manual and the automatic methods for the SeraQuest HSV Type 2 Specific IgG assay are identical.

A comparison of the automatic device test procedure and the predicate device test procedure appears below:

| Characteristic | SeraQuest ® HSV Type 2 Specific IgG<br>assay performed by Manual Method<br>(Predicate) | SeraQuest ® HSV Type 2 Specific IgG<br>assay performed by ChemWell®<br>Automated Analyzer |
|-------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Submission number | K152353 | K181514 |
| Technology | Enzyme Immunoassay | Enzyme Immunoassay |
| Intended Use | The SeraQuest HSV Type 2 Specific IgG assay<br>is an enzyme-linked immunosorbent assay<br>(ELISA) intended for the qualitative<br>detection of human IgG antibodies to type 2<br>herpes simplex virus (HSV) in human serum.<br>The test is indicated for sexually active<br>individuals and expectant mothers as an aid<br>in the presumptive diagnosis of HSV-2<br>infection. The predictive value of a positive<br>or negative result depends on the<br>prevalence of HSV-2 infection in the<br>population and the pre-test likelihood of<br>HSV-2 infection.<br><br>The test is not FDA cleared for screening<br>blood or plasma donors. The performance<br>of this assay has not been established for<br>immunocompromised patients, pediatric<br>patients or matrices other than human<br>serum. | The SeraQuest HSV Type 2 Specific IgG assay<br>is an enzyme-linked immunosorbent assay<br>(ELISA) intended for the qualitative<br>detection of human IgG antibodies to type 2<br>herpes simplex virus (HSV) in human serum.<br>The test is indicated for sexually active<br>individuals and expectant mothers as an aid<br>in the presumptive diagnosis of HSV-2<br>infection. The predictive value of a positive<br>or negative result depends on the<br>prevalence of HSV-2 infection in the<br>population and the pre-test likelihood of<br>HSV-2 infection.<br><br>The test is not FDA cleared for screening<br>blood or plasma donors. The performance<br>of this assay has not been established for<br>immunocompromised patients, pediatric<br>patients or matrices other than human<br>serum. |
| Solid Phase | Polystyrene Microwells | Polystyrene Microwells |
| Antigen | Purified HSV gG 2 | Purified HSV gG 2 |
| Incubation Periods | Three 30 minutes | Three 30 minutes |
| Sample Dilution | 1:51 | 1:51 |
| Sample Volume | 100 µL | 100 µL |
| Sample Incubation<br>Duration | 30 minutes | 30 minutes |
| Incubation Temperature | Room Temperature | Room Temperature |
| Washing Steps | Two | Two |
| Cycles per Washing Step | Four | Four |
| Enzyme-Labeled<br>Conjugate | Alkaline Phosphatase Conjugated Goat<br>Anti-Human IgG | Alkaline Phosphatase Conjugated Goat<br>Anti-Human IgG |
| Conjugate Volume | 100 µL | 100 µL |
| Conjugate Incubation | 30 minutes | 30 minutes |
| Enzyme Substrate | p-nitrophenyl phosphate | p-nitrophenyl phosphate |
| Substrate Volume | 100 µL | 100 µL |
| Substrate Incubation | 30 minutes | 30 minutes |
| Stop Reagent | 0.5 M Trisodium Phosphate | 0.5 M Trisodium Phosphate |
| Stop Reagent Volume | 100 µL | 100 µL |
| Drying Step | None | None |
| Readout | Spectrophotometric 405 nm | Spectrophotometric 405 nm |

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Summary of Performance Testing

#### Precision Study

A precision study with a panel of samples was run on the current manual procedure and on the ChemWell® Automated Analyzer. The panel consists of samples in the following categories: true negative, high negative, low positive, and moderate positive. Precision evaluation of within-run, between-run, between-day, and within lab precision was determined over the duration of 12 days, with 2 runs per day, and 2 replicates of each sample per run and 1 replicate per control per run. Data analysis includes calculation of the mean, standard deviation and %CV for each panel.

| The precision Results for HSV Type 2 IgG Method: Manual | | | | | | | | | | |
|---------------------------------------------------------|----|------------|------------|--------|-------------|--------|-------------|--------|------------|--------|
| Sample Description | N | Mean Value | Within-Run | | Between-Run | | Between-Day | | Within Lab | |
| | | | SD | %CV | SD | %CV | SD | CV% | SD | CV% |
| Negative Control | 24 | 0.18 | - | - | 0.03 | 15.75% | 0.03 | 13.84% | 0.04 | 20.96% |
| Positive Control | 24 | 2.66 | - | - | 0.11 | 3.98% | 0.04 | 1.55% | 0.11 | 4.27% |
| True Negative | 48 | 0.19 | 0.03 | 13.48% | 0.03 | 13.48% | 0.01 | 3.32% | 0.04 | 19.35% |
| High Negative | 48 | 0.76 | 0.03 | 4.24% | 0.04 | 5.02% | 0.02 | 2.76% | 0.05 | 6.54% |
| Low Positive | 48 | 1.56 | 0.04 | 2.61% | 0.04 | 2.61% | 0.06 | 3.83% | 0.08 | 5.32% |
| Moderate Positive | 48 | 2.86 | 0.06 | 1.95% | 0.09 | 3.23% | 0.09 | 3.11% | 0.14 | 4.89% |

#### The precision results for HSV Type 2 IgG Method: Manual

#### The precision results for HSV Type 2 IgG

Method: ChemWell® Automated Analyzer

| | | | Within Run | | Between-Run | | Between-Day | | Within Lab | |
|--------------------|----|---------------|------------|--------|-------------|--------|-------------|--------|------------|--------|
| Sample Description | N | Mean<br>Value | SD | %CV | SD | CV% | SD | CV% | SD | CV% |
| Negative Control | 24 | 0.13 | - | - | 0.05 | 35.34% | 0.01 | 6.74% | 0.05 | 35.97% |
| Positive Control | 24 | 2.52 | - | - | 0.11 | 4.36% | 0.01 | 0.35% | 0.11 | 4.37% |
| True Negative | 48 | 0.13 | 0.04 | 31.61% | 0.01 | 11.17% | 0.02 | 12.38% | 0.05 | 35.74% |
| High Negative | 48 | 0.75 | 0.05 | 7.20% | 0.05 | 6.09% | 0.02 | 3.31% | 0.07 | 9.99% |
| Low Positve | 48 | 1.59 | 0.07 | 4.54% | 0.09 | 5.37% | 0.05 | 3.35% | 0.12 | 7.79% |
| Moderate Positive | 48 | 2.68 | 0.08 | 3.14% | 0.10 | 3.57% | 0.07 | 2.78% | 0.15 | 5.51% |

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Awareness Technology Inc. /Quest International, Inc. 1935 SW Martin Highway Palm City, Florida 3490

#### Method Comparison Study

The percent agreement between the manual and the ChemWell® Automated Analyzer was evaluated by testing a total of 226 samples with both methods. Samples were developed from remnants of patient samples and samples from vendors. Additional samples were prepared by spiking negative samples with positive samples or dilution with diluent reagent to span the range of the assay measuring interval. All samples were tested with the assay performed with - manual method and the ChemWell Automated Analyzer.

The concordance analysis for the manual and the ChemWell Automated Analyzer are summarized in the table below.

Percent Agreement (PPA) and Negative Percent Agreement (NPA) between the SeraQuest HSV Type 2 Specific IgG assay manual method and the ChemWell Automated Analyzer

| | Manual Method | | | | |
|---------------------------------|---------------|----------|-----------|----------|-------|
| ChemWell<br>Automated<br>Method | | Positive | Equivocal | Negative | Total |
| | Positive | 125 | 0 | 1 | 126 |
| | Equivocal | 0 | 0 | 0 | 0 |
| | Negative | 0 | 0 | 100 | 100 |
| | Total | 125 | 0 | 101 | 226 |

| | Absolute | Relative | Two-sided 95% CI |
|-------------------------------------|----------|----------|------------------|
| Positive Percent<br>Agreement (PPA) | 125/125 | 100% | 97.02% to 100% |
| Negative Percent<br>Agreement (NPA) | 100/101 | 99.01% | 94.60% to 99.83% |

#### Ordinary Linear Regression - All Points

| Parameter | Slope | Intercept | R² | Range | n |
|-----------|--------|-----------|--------|-------|-----|
| HSV-2 | 1.0526 | -0.0364 | 0.9770 | 0-3.7 | 226 |

Image /page/7/Figure/10 description: This image is a scatter plot titled "Method Comparison". The x-axis is labeled "Manual Method Index Value" and ranges from -0.5 to 4.5. The y-axis is labeled "ChemWell Method Index Value" and ranges from -0.5 to 4.5. There are many blue data points scattered around a black trend line.

## Conclusions

Analysis of the performance for assay on the manual method and the ChemWell Automated Analyzer in this 510(k) including data collected for precision and correlation demonstrates that the SeraQuest ® HSV Type 2 Specific IgG assay performed by ChemWell® Automated Analyzer is substantially equivalent to the predicate device (manual method).