(370 days)
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.
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.
This document describes the performance of the SeraQuest® HSV Type 2 Specific IgG assay when performed on the ChemWell® Automated Analyzer, comparing it to the previously cleared manual method.
Here's the breakdown of the acceptance criteria and study information:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state numerical acceptance criteria in a dedicated section. However, the "Method Comparison Study" presents the core performance metrics (Positive Percent Agreement and Negative Percent Agreement) against the predicate device. For the purpose of this response, we infer that high agreement with the predicate device is the acceptance criterion.
| Acceptance Criterion (Inferred from Study Design) | Reported Device Performance (ChemWell Automated Analyzer vs. Manual Method) |
|---|---|
| High Positive Percent Agreement (PPA) with predicate device | 100% (125/125) |
| High Negative Percent Agreement (NPA) with predicate device | 99.01% (100/101) |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: 226 samples.
- Data Provenance: 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's measuring interval. The country of origin is not specified, but it can be inferred as being related to the applicant's location (Palm City, Florida, USA). The study appears to be a retrospective evaluation using existing or manufactured samples.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
The ground truth for the test set was established by comparison against a predicate device (manual method), not by independent expert interpretation. Therefore, experts were not explicitly used to establish the ground truth for this device in the context of this study. The "ground truth" here is the result obtained from the established manual method.
4. Adjudication Method for the Test Set
No adjudication method using multiple readers or experts is described, as the comparison is between two automated/semi-automated assay methods (the new device vs. the predicate). The "truth" for the comparison was the result generated by the manual method.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No Multi-Reader Multi-Case (MRMC) comparative effectiveness study was done. This study focuses on the equivalence of an automated assay to a manual assay, not on human reader performance.
6. Standalone (Algorithm Only) Performance
Yes, a standalone comparison was done. The study directly compares the performance of the "SeraQuest® HSV Type 2 Specific IgG assay performed by ChemWell® Automated Analyzer" (the new device) against the "SeraQuest® HSV Type 2 Specific IgG assay performed by Manual Method" (the predicate device). This evaluates the algorithm/device performance independently of human interpretation, focusing on concordance between the two methods.
7. Type of Ground Truth Used
The type of ground truth used was comparison to a predicate device (manual assay results). This means the "truth" for evaluating the automated analyzer was the result provided by the already cleared manual method.
8. Sample Size for the Training Set
The document does not explicitly mention a separate training set or its sample size. The study focuses on verifying the performance of the automated analyzer against the predicate manual method using the 226 samples for method comparison and additional samples for precision studies.
9. How the Ground Truth for the Training Set Was Established
Since a separate training set is not explicitly described, the method for establishing its ground truth is also not detailed. The validation approach is based on demonstrating equivalence to an existing, cleared method.
{0}------------------------------------------------
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
{1}------------------------------------------------
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 (DICE@fda.hhs.gov) or phone (1-800-638-2041 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
{2}------------------------------------------------
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.
| ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ | ||
|---|---|---|
| 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)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
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."
{3}------------------------------------------------
510(k) Summary
| Applicant: | Awareness Technology Inc. / Quest International, Inc.1935 SW Martin HighwayPalm City, FL 34990 |
|---|---|
| Contact Person: | Steve AndrusQuality Assurance ManagerPhone: 772.283.6540 ext. 220Fax: 772.283.8020Email: sandrus@awaretech.com |
| Trade Name: | SeraQuest® HSV Type 2 Specific IgG |
| Common Name: | Enzyme Linked Immunosorbent Assay, Herpes Simplex Virus, Hsv-2 |
| Product Nomenclature | 510(k)Number | Class | ProductCode | RegulationNumber | Review Panel |
|---|---|---|---|---|---|
| Enzyme Linked ImmunosorbentAssay, 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 havehad 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. |
{4}------------------------------------------------
Awareness Technology Inc. /Quest International, Inc. 1935 SW Martin Highway Palm City, Florida 3490
Notes:
-
- 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.
-
- 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.
-
- 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.
{5}------------------------------------------------
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 IgGassay performed by Manual Method(Predicate) | SeraQuest ® HSV Type 2 Specific IgGassay performed by ChemWell®Automated Analyzer |
|---|---|---|
| Submission number | K152353 | K181514 |
| Technology | Enzyme Immunoassay | Enzyme Immunoassay |
| Intended Use | The SeraQuest HSV Type 2 Specific IgG assayis an enzyme-linked immunosorbent assay(ELISA) intended for the qualitativedetection of human IgG antibodies to type 2herpes simplex virus (HSV) in human serum.The test is indicated for sexually activeindividuals and expectant mothers as an aidin the presumptive diagnosis of HSV-2infection. The predictive value of a positiveor negative result depends on theprevalence of HSV-2 infection in thepopulation and the pre-test likelihood ofHSV-2 infection.The test is not FDA cleared for screeningblood or plasma donors. The performanceof this assay has not been established forimmunocompromised patients, pediatricpatients or matrices other than humanserum. | The SeraQuest HSV Type 2 Specific IgG assayis an enzyme-linked immunosorbent assay(ELISA) intended for the qualitativedetection of human IgG antibodies to type 2herpes simplex virus (HSV) in human serum.The test is indicated for sexually activeindividuals and expectant mothers as an aidin the presumptive diagnosis of HSV-2infection. The predictive value of a positiveor negative result depends on theprevalence of HSV-2 infection in thepopulation and the pre-test likelihood ofHSV-2 infection.The test is not FDA cleared for screeningblood or plasma donors. The performanceof this assay has not been established forimmunocompromised patients, pediatricpatients or matrices other than humanserum. |
| 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 IncubationDuration | 30 minutes | 30 minutes |
| Incubation Temperature | Room Temperature | Room Temperature |
| Washing Steps | Two | Two |
| Cycles per Washing Step | Four | Four |
| Enzyme-LabeledConjugate | Alkaline Phosphatase Conjugated GoatAnti-Human IgG | Alkaline Phosphatase Conjugated GoatAnti-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 |
{6}------------------------------------------------
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 | MeanValue | 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% |
{7}------------------------------------------------
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 | |||||
|---|---|---|---|---|---|
| ChemWellAutomatedMethod | 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 PercentAgreement (PPA) | 125/125 | 100% | 97.02% to 100% |
| Negative PercentAgreement (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).
§ 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).