(79 days)
The AmpliVue® HSV 1+2 Assay is an in vitro diagnostic test for the direct, qualitative detection and differentiation of Herpes Simplex Virus 1 (HSV-1) and Herpes Simplex Virus 2 (HSV-2) DNA in cutaneous or mucocutaneous lesion specimens from symptomatic patients. The test is intended for use as an aid in diagnosis of HSV infection in symptomatic patients.
Warning: The AmpliVue HSV 1+2 Assay is not FDA cleared for use with cerebrospinal fluid (CSF). The assay is not intended for prenatal screening.
The AmpliVue HSV 1+2 Assay consists of three major steps: 1) specimen preparation, 2) isothermal Helicase-Dependent Amplification (HDA) of target amplicons specific to HSV-1 and HSV-2, and 3) detection of the amplified DNA by target-specific hybridization probes via a colorimetric reaction on a lateral-flow strip which is embedded in a self-contained disposable cassette to prevent amplicon contamination.
Specimen preparation involves one simple dilution step in which specimens in viral transport medium are diluted 80-fold in Dilution Tubes.
The diluted samples are transferred into a 0.2 mL Amplification Tube containing lyophilized HDA reagents. Incubation at 64°C for 45 minutes results in the release of the HSV DNA and subsequent isothermal amplification of the target sequence. The amplified DNA is detected by a set of specific detection probes included in the Amplification Tube: HSV-1 target hybridizes to two specific probes labeled with Biotin (BioTEG) and Digoxigenin (DIG) and HSV-2 target hybridizes to two specific probes labeled with Biotin (BioTEG) and Fluorescein isothiocyanate (FITC). A competitive internal control (IC) is included in the Amplification Tube to monitor inhibitory substances in clinical samples, reagent failure or device failure. The IC target is amplified by HSV-2 specific primers and hybridizes to the biotin-labeled HSV-2 probe and a 1C specific probe labeled with 2,4-dinitrophenyl (DNP-TEG).
Detection of the amplified DNA with specific probes is achieved by Type III BEStTM cassettes. The self-contained Type III BESTM cassettes carry lateral-flow DNA detection strips coated with anti-DNP antibodies (C line), anti-DIG antibodies (T1 line) and anti-FITC antibodies (T2 line). HSV-1 amplicon with BioTEG and DIG-labeled probes is captured by anti-DIG antibodies at the TI-Line and HSV-2 amplicon with BioTEG and FITC-labeled probes is captured by anti-FITC antibodies at the T2-Line, while the IC amplicon with BioTEG and DNP-labeled probes is captured by anti-DNP antibodies at the C-Line. The amplicon-probe complexes captures the streptavidin-conjugated color particles for visualization and the test result is shown as colored lines that are visually read.
A positive result for HSV-1 (detection of HSV-1 DNA) is reported when the T1 line is visible through the detection window of the cassette, while a positive result for HSV-2 (detection of HSV-2 DNA) is reported when the T2 line is visible through the detection window of the cassette. A positive result for both HSV-2 (detection of both HSV-1 and HSV-2 DNA) is reported when both the T1 line and the T2 line are visible through the detection window of the cassette. A negative result (no detection of HSV-2 DNA) is reported when only the C line is displayed. The assay result is regarded as invalid when the T1 line, T2 line and C line are not present and the assay should be repeated.
Here's an analysis of the acceptance criteria and study proving the device meets them, based on the provided text:
Device Name: AmpliVue® HSV 1+2 Assay
1. Table of Acceptance Criteria and Reported Device Performance
The provided document primarily focuses on demonstrating the substantial equivalence of the AmpliVue® HSV 1+2 Assay to a predicate device and presenting its analytical and clinical performance. While explicit "acceptance criteria" (numerical thresholds that must be met) are not clearly defined as a separate section with specific targets, the performance studies implicitly set the standard for acceptable performance compared to the gold standard.
Here's a summary of the key performance metrics reported in the document:
| Performance Metric Category | Specific Metric | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|---|
| Reproducibility (Overall) | HSV-1 Low Positive Rate of Detection / Agreement | High (e.g., nearing 100%) | 89/90 (99%) Detection, 94-100% CI |
| HSV-1 Moderate Positive Rate of Detection / Agreement | High (e.g., nearing 100%) | 90/90 (100%) Detection, 96-100% CI | |
| HSV-2 Low Positive Rate of Detection / Agreement | High (e.g., nearing 100%) | 90/90 (100%) Detection, 96-100% CI | |
| HSV-2 Moderate Positive Rate of Detection / Agreement | High (e.g., nearing 100%) | 90/90 (100%) Detection, 96-100% CI | |
| Positive Control Agreement | 100% | 100% (both HSV-1 and HSV-2 sections) | |
| Negative Control Agreement | 100% | 100% (both HSV-1 and HSV-2 sections) | |
| Reproducibility (High Negative) | HSV-1+2 High Negative Rate of Detection / Agreement (HSV-1 calculation) | Undefined (expected low detection, high agreement for negativity) | 45/90 (50%) Detection, 50% Agreement, 40-60% CI |
| HSV-1+2 High Negative Rate of Detection / Agreement (HSV-2 calculation) | Undefined (expected low detection, high agreement for negativity) | 50/90 (44%) Detection, 44% Agreement, 35-55% CI | |
| Repeatability (Within Lab) | HSV-1 Low Positive Agreement | High (e.g., nearing 100%) | 100% (95-100% CI) |
| HSV-1 Moderate Positive Agreement | High (e.g., nearing 100%) | 100% (95-100% CI) | |
| HSV-2 Low Positive Agreement | High (e.g., nearing 100%) | 100% (95-100% CI) | |
| HSV-2 Moderate Positive Agreement | High (e.g., nearing 100%) | 100% (95-100% CI) | |
| Positive Control Agreement | 100% | 100% | |
| Negative Control Agreement | 100% | 100% | |
| Level of Detection (LoD) | Positivity Rate at LoD | ≥95% (as per study definition) | HSV-1: 1.1 x 10^5 TCID50/mL (100% at this level) |
| HSV-2: 1.1 x 10^4 TCID50/mL (100% at this level for MS, 97% for G) | |||
| Analytical Specificity/Cross-Reactivity | No interference/cross-reactivity with specified microorganisms | 100% no interference | None of 89 microorganisms interfered or cross-reacted. |
| Interfering Substances | No interference with specified substances at 3xLoD | 100% no interference | No interference observed with 33 substances and 5 viral transport media. |
| Competitive Inhibition | No inhibition with coinfection at certain concentrations | Undefined, but expected for clinical utility | Not observed with one target at 3xLoD and other up to 300xLoD. Observed at 3000xLoD. Not observed with equal concentrations (3xLoD-3000xLoD). |
| Carry-Over and Cross Contamination | No carry-over in alternating high pos/neg samples | 100% absence | Confirmed no carry-over or cross-contamination. |
| Clinical Performance (Sensitivity) | HSV-1 Cutaneous Lesions | High (Implied by equivalence to gold standard) | 100% (95% CI: 88.6%-100%) |
| HSV-1 Mucocutaneous Lesions | High (Implied by equivalence to gold standard) | 94.9% (95% CI: 90.3%-97.4%) | |
| HSV-2 Cutaneous Lesions | High (Implied by equivalence to gold standard) | 98.3% (95% CI: 91.0%-99.7%) | |
| HSV-2 Mucocutaneous Lesions | High (Implied by equivalence to gold standard) | 97.4% (95% CI: 93.4%-99.0%) | |
| Clinical Performance (Specificity) | HSV-1 Cutaneous Lesions | High (Implied by equivalence to gold standard) | 97.1% (95% CI: 94.6%-98.5%) |
| HSV-1 Mucocutaneous Lesions | High (Implied by equivalence to gold standard) | 96.5% (95% CI: 94.8%-97.7%) | |
| HSV-2 Cutaneous Lesions | High (Implied by equivalence to gold standard) | 95.6% (95% CI: 92.8%-97.3%) | |
| HSV-2 Mucocutaneous Lesions | High (Implied by equivalence to gold standard) | 95.8% (95% CI: 94.2%-97.0%) |
Note on Acceptance Criteria: The document describes the results of the studies and states that they "demonstrate that the AmpliVue® HSV 1+2 Assay is substantially equivalent to the predicate device." This implies that the performance shown met the internal criteria for substantial equivalence, which often means demonstrating non-inferiority or comparable performance to a legally marketed predicate. Specific numerical thresholds for "acceptance" are not explicitly listed in an "Acceptance Criteria" section but are inherent in the successful outcomes of these analytical and clinical studies. For example, for LoD, a positivity rate of ≥95% was defined within the study itself as the criterion for determining the LoD.
2. Sample Size Used for the Test Set and Data Provenance
The primary clinical performance study (test set) involved:
- Sample Size: A total of 1355 specimens from symptomatic male and female patients were tested. 19 tests were considered invalid and removed, resulting in 1336 specimens for the initial analysis. For HSV-1 performance calculation, 211 HSV-2 positive specimens were removed, leaving 1125 specimens.
- Data Provenance:
- Country of Origin: United States.
- Retrospective or Prospective: Not explicitly stated as retrospective or prospective, but the description "evaluated at five geographically diverse locations within the United States" and involving "symptomatic male and female patients" suggests a prospective collection and testing of clinical samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- Number of Experts: Not applicable in the context of this diagnostic assay.
- Qualifications of Experts: The ground truth was established by a "gold standard/reference method" which is the ELVIS® HSV ID and D³ Typing Test System (cell culture using an enzyme linked virus inducible system). This is a laboratory-based reference method, not an expert panel.
4. Adjudication Method for the Test Set
- Adjudication Method: Not applicable. The ground truth was determined by a single reference method (ELVIS® viral culture), not by a panel of human adjudicators. Discrepancies would likely be investigated by re-testing or deeper analysis against the reference method. The document notes that the ELVIS culture inability to detect co-infected specimens led to the removal of HSV-2 positive samples when calculating HSV-1 performance, which served as a form of handling limitations of the ground truth.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
- There was no MRMC comparative effectiveness study done.
- This device is an in vitro diagnostic (IVD) assay for the direct detection of viral DNA, not an AI-assisted diagnostic tool that involves human readers interpreting images or data. Therefore, the concept of human readers improving with AI assistance is not relevant to this device.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
- This question is partially applicable. The AmpliVue® HSV 1+2 Assay is an "algorithm only" in the sense that it is a chemical and molecular diagnostic test with a qualitative visual readout (colored lines). There is no "human-in-the-loop" interpretation beyond reading the positive/negative lines based on established rules.
- The entire clinical performance study (sensitivity and specificity tables) represents the standalone performance of the assay compared to the reference method.
7. The Type of Ground Truth Used
- Ground Truth Type: Expert reference method / Gold standard.
- Specifically, the ground truth was established using the ELVIS® HSV ID and D³ Typing Test System, which is described as the "gold standard/reference method i.e., cell culture using an enzyme linked virus inducible system."
8. The Sample Size for the Training Set
- Sample Size for Training Set: The document does not explicitly mention a separate "training set" as commonly understood in machine learning contexts. This is an IVD assay, and the development process would involve analytical studies (LoD, cross-reactivity, interference, etc.) and then clinical validation. The samples used for initial assay development and optimization (analogous to a training set) are not detailed in terms of specific numbers.
- However, the analytical performance section describes studies that would have informed the assay's design and operational characteristics, such as:
- Level of Detection (LoD): Used serially diluted viral stocks (30 replicates across 3 lots for initial LoD determination, then 20 replicates for confirmation). This involves a number of samples to establish analytical sensitivity.
- Analytical Specificity/Cross-Reactivity: Tested 89 microorganisms (each in triplicate).
- Interfering Substances: Tested 33 substances and 5 viral transport media (each in triplicate).
9. How the Ground Truth for the Training Set was Established
- As noted above, a distinct "training set" with its own ground truth establishment method isn't explicitly described. However, for the analytical studies that would inform assay development (like LoD, specificity, and interference), the ground truth was established by:
- Quantified viral stocks: For LoD studies, Herpes Simplex Virus 1 (HSV-1) and Herpes Simplex Virus 2 (HSV-2) viral stocks were quantified (TCID50/mL). These quantified stocks served as the known "true" concentrations for determining the assay's detection limit.
- Known microorganisms and substances: For analytical specificity and interfering substances studies, known microorganisms (purified genomic DNA, quantified cultures) and specific chemical/biological substances were introduced at known concentrations. The "ground truth" here is the precise identity and concentration of the added components, and the expectation is zero interference or cross-reactivity.
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510(K) SUMMARY
The following information is provided as required by 21 CFR § 807.87 for Quidel Corporation 510(k) premarket notification for the AmpliVue® HSV 1+2 Assay. In response to the Safe Medical Devices Act of 1990, the following is a summary of the information upon which the substantial equivalence determination is based.
Applicant:
Quidel Corporation 10165 McKellar Court San Diego, California 92121 Telephone: 858-552-7910 Fax: 858-646-8045
Contact Information:
Ronald H. Lollar, Senior Director Clinical and Regulatory Affairs 2005 East State Street Suite 100 Athens, Ohio 45701 740-589-3300 - Corporate number 740-589-3373 - Desk phone 740-593-8437 - Fax Ron.Lollar@quidel.com
Date of preparation of 510(k) summary:
December 30, 2013
Device Name:
| Trade name: | AmpliVue® HSV 1+2 Assay |
|---|---|
| Classification name: | Herpes Simplex Virus Nucleic Acid Amplification Assay |
| Product Code: | OQO |
| Class: | II |
| Regulation: | 21 CFR 866.3305 Herpes simplex virus serological assays |
| Panel: | Microbiology (83) |
Substantial Equivalency
The AmpliVue® HSV 1+2 Assay is substantially equivalent in principle to the currently marketed IsoAmp HSV Assay for the direct, qualitative detection of Herpes Simplex Virus 1 (HSV-1) and
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Herpes Simplex Virus 2 (HSV-2) nucleic acids. The clinical performance of the AmpliVue™ HSV 1+2 Assay for the differentiation of Herpes Simplex Virus 1 (HSV-1) and Herpes Simplex Virus 2 (HSV-2) nucleic acids was compared with the ELVIS® HSV ID and D³ Typing Test System which is the gold standard/reference method i.e., cell culture using an enzyme linked virus inducible system.
| Features | AmpliVue® HSV 1+2 AssayQuidel Corporation | IsoAmp® HSV AssayBioHelix Corporation(K111951) |
|---|---|---|
| Intended Use | The AmpliVue® HSV 1+2Assay is an in vitro diagnostictest for the direct, qualitativedetection and differentiation ofHerpes Simplex Virus 1(HSV-1) and Herpes SimplexVirus 2 (HSV-2) DNA incutaneous or mucocutaneouslesion specimens fromsymptomatic patients. The testis intended for use as an aid indiagnosis of HSV infection insymptomatic patients.Warning: The AmpliVueHSV 1+2 Assay is not FDAcleared for use withcerebrospinal fluid (CSF). Theassay is not intended forprenatal screening. | The IsoAmp® HSV Assay isan in vitro diagnostic test forthe direct, qualitative detectionof the Herpes Simplex Virus(HSV-1 + HSV-2) DNA inmale and female genital andoral lesions. The test isintended for use as an aid indiagnosis of HSV infection insymptomatic patients.Warning: The IsoAmp®HSVAssay is not FDA cleared foruse with cerebrospinal fluid(CSF). The assay does notprovide specific typinginformation to differentiateHSV-1 and HSV-2. The assayis not intended to be used forprenatal screening. |
| Assay Results | Qualitative | Qualitative |
| Detection of HSV-1 andHSV-2 | Yes | Yes |
| Typing of HSV-1 and HSV-2 | Yes | No |
| Methodology | HDA (Helicase-DependentAmplification) | HDA (Helicase-DependentAmplification) |
| Packaging | Supplied as a kit; 16 tests perkit1. Amplification-related KitComponents (ARKC)2. Non-amplification relatedKit Components (NKC) | The product is supplied as twoseparate labeled boxes.1. Amplification-related KitComponents (ARKC)2. Non-amplification relatedKit Components (NKC) |
| Kit Reagent StorageConditions | ARKC: 2°C to 8°CNKC: 2°C to 30°C | ARKC: <-15°CNKC: 15-30°C |
| Comparison of New Device with Predicate Device | ||||
|---|---|---|---|---|
| ------------------------------------------------ | -- | -- | -- | -- |
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Indications for Use and Intended Use
The AmpliVue® HSV 1+2 Assay is an in vitro diagnostic test for the direct, qualitative detection and differentiation of Herpes Simplex Virus 1 (HSV-1) and Herpes Simplex Virus 2 (HSV-2) DNA in cutaneous or mucocutaneous lesion specimens from symptomatic patients. The test is intended for use as an aid in diagnosis of HSV infection in symptomatic patients.
Warning: The AmpliVue HSV 1+2 Assay is not FDA cleared for use with cerebrospinal fluid (CSF). The assay is not intended for prenatal screening.
Methodology
The AmpliVue HSV 1+2 Assay consists of three major steps: 1) specimen preparation, 2) isothermal Helicase-Dependent Amplification (HDA) of target amplicons specific to HSV-1 and HSV-2, and 3) detection of the amplified DNA by target-specific hybridization probes via a colorimetric reaction on a lateral-flow strip which is embedded in a self-contained disposable cassette to prevent amplicon contamination.
Specimen preparation involves one simple dilution step in which specimens in viral transport medium are diluted 80-fold in Dilution Tubes.
The diluted samples are transferred into a 0.2 mL Amplification Tube containing lyophilized HDA reagents. Incubation at 64°C for 45 minutes results in the release of the HSV DNA and subsequent isothermal amplification of the target sequence. The amplified DNA is detected by a set of specific detection probes included in the Amplification Tube: HSV-1 target hybridizes to two specific probes labeled with Biotin (BioTEG) and Digoxigenin (DIG) and HSV-2 target hybridizes to two specific probes labeled with Biotin (BioTEG) and Fluorescein isothiocyanate (FITC). A competitive internal control (IC) is included in the Amplification Tube to monitor inhibitory substances in clinical samples, reagent failure or device failure. The IC target is amplified by HSV-2 specific primers and hybridizes to the biotin-labeled HSV-2 probe and a 1C specific probe labeled with 2,4-dinitrophenyl (DNP-TEG).
Detection of the amplified DNA with specific probes is achieved by Type III BEStTM cassettes. The self-contained Type III BESTM cassettes carry lateral-flow DNA detection strips coated with anti-DNP antibodies (C line), anti-DIG antibodies (T1 line) and anti-FITC antibodies (T2 line). HSV-1 amplicon with BioTEG and DIG-labeled probes is captured by anti-DIG antibodies at the TI-Line and HSV-2 amplicon with BioTEG and FITC-labeled probes is captured by anti-FITC antibodies at the T2-Line, while the IC amplicon with BioTEG and DNP-labeled probes is captured by anti-DNP antibodies at the C-Line. The amplicon-probe complexes captures the streptavidin-conjugated color particles for visualization and the test result is shown as colored lines that are visually read.
A positive result for HSV-1 (detection of HSV-1 DNA) is reported when the T1 line is visible through the detection window of the cassette, while a positive result for HSV-2 (detection of HSV-2 DNA) is reported when the T2 line is visible through the detection window of the cassette. A positive result for both HSV-2 (detection of both HSV-1 and HSV-2 DNA) is reported when both the T1 line and the T2 line are visible through the detection window
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of the cassette. A negative result (no detection of HSV-2 DNA) is reported when only the C line is displayed. The assay result is regarded as invalid when the T1 line, T2 line and C line are not present and the assay should be repeated.
Analytical Performance
Reproducibility
The reproducibility of the AmpliVue® HSV 1+2 Assay was evaluated at three test sites using a panel consisting of four panel members: HSV 1+2 High Negative; HSV-1 Low Positive; HSV-2 Low Positive; and HSV 1+2 Moderate Positive members. The HSV-1 Low Positive member served as a HSV-2 Negative member and the HSV-2 Low Positive member served as a HSV-1 Negative member. The panel members were prepared in HSV Negative Matrix that consisted of a pool of HSV negative cheek swabs in M4 medium. HSV Negative Matrix was spiked with quantified HSV 1 and 2 viral stocks at pre-determined TCIDso concentrations. The HSV viral stock was diluted in the HSV Negative Matrix to three (3) different concentration levels, defined as High Negative member (0.3 x LoD), Low Positive member (1 x LoD) and Moderate Positive member (3 x LoD level).
Each run tested the four member panel of four members in triplicate and also included three each of HSV-1 + HSV-2 positive control, and negative control. Two (2) operators per test site each carried out one run of the four member panel plus controls per test day for five (5) days using one lot of the AmpliVue® HSV 1+2 Assay.
Results of the Reproducibility study for the AmpliVue® HSV 1+2 Assay performed at three sites are presented in the tables below.
| Site | Overall | 95%ConfidenceInterval | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Category | Site #1 | Site #2 | Site #3 | Rate ofDetection | PercentAgreement | ||||
| Rate ofDetection | PercentAgreement | Rate ofDetection | PercentAgreement | Rate ofDetection | PercentAgreement | Detection | Agreement | ||
| HSV 1+2HighNegative | 16/30 | 47% | 9/30 | 70% | 20/30 | 33% | 45/90 | 50% | 40% - 60% |
| HSV-1LowPositive | 30/30 | 100% | 29/30 | 97% | 30/30 | 100% | 89/90 | 99% | 94% -100% |
| HSV 1+2ModeratePositive | 30/30 | 100% | 30/30 | 100% | 30/30 | 100% | 90/90 | 100% | 96% -100% |
| HSV-2Low | 0/30 | 100% | 0/30 | 100% | 0/30 | 100% | 0/90 | 100% | 96% -100% |
Reproducibility Study Summary for HSV-1
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Reproducibility Study Summary for HSV-1
| Category | Site | Rate ofDetection | OverallPercentAgreement | 95%ConfidenceInterval | |||||
|---|---|---|---|---|---|---|---|---|---|
| Site #1 | Site #2 | Site #3 | |||||||
| Rate ofDetection | PercentAgreement | Rate ofDetection | PercentAgreement | Rate ofDetection | PercentAgreement | ||||
| PositiveHSV-1+2PositiveControl | 30/30 | 100% | 30/30 | 100% | 30/30 | 100% | 90/90 | 100% | 96% -100% |
| NegativeControl | 0/30 | 100% | 0/30 | 100% | 0/30 | 100% | 0/90 | 100% | 96% -100% |
Reproducibility Study Summary for HSV-2
.
| Category | Site | Rate ofDetection | OverallPercentAgreement | 95%ConfidenceInterval | |||||
|---|---|---|---|---|---|---|---|---|---|
| Site #1 | Site #2 | Site #3 | |||||||
| Rate ofDetection | PercentAgreement | Rate ofDetection | PercentAgreement | Rate ofDetection | PercentAgreement | ||||
| HSV1+-2HighNegative | 20/30 | 33% | 17/30 | 43% | 13/30 | 57% | 50/90 | 44% | 35% - 55% |
| HSV-2LowPositive | 30/30 | 100% | 30/30 | 100% | 30/30 | 100% | 90/90 | 100% | 96% -100% |
| HSV 1+- 2ModeratePositive | 30/30 | 100% | 30/30 | 100% | 30/30 | 100% | 90/90 | 100% | 96% -100% |
| HSV-1LowPositive | 0/30 | 100% | 0/30 | 100% | 0/30 | 100% | 0/90 | 100% | 96% -100% |
| HSV-1+2PositiveControl | 30/30 | 100% | 30/30 | 100% | 30/30 | 100% | 90/90 | 100% | 96% -100% |
| NegativeControl | 0/30 | 100% | 0/30 | 100% | 0/30 | 100% | 0/90 | 100% | 96% -100% |
: · ·
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Repeatability
For the Precision/Within Laboratory Repeatability study, a blinded four-member panel consisting of medium positive and low positive, high negative 3x, 1x, ≤0.3x LoD, respectively) and negative HSV-1 and HSV-2 samples were tested in triplicate by two (2) operators, twice a day (2X) for twelve (12) days on all three instruments (triplicate testing x 2 operators x 12 days = 72 results per level for each virus). Positive and negative controls were run in triplicate with each test run. Results of the Precision/Within Laboratory Repeatability study for the AmpliVue® HSV 1+2 Assay performed are presented in the tables below.
| Category | Rate ofDetection | OverallPercentAgreement | તે રેજી જેવી જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામનાં લોકોનો મુખ્ય વ્યવસાય ખેતી, ખેતમજૂરી તેમ જ પશુપાલન છે. આ ગામનાં મુખ્યત્વે ખેતConfidenceInterval |
|---|---|---|---|
| HSV-1+2 High Negative | 35/72 | ર્સ I % | 40 - 63% |
| HSV-1 Low Positive | 72/72 | 100% | 95 - 100% |
| HSV 1+2 Moderate Positive | 72/72 | 100% | 95 - 100% |
| HSV-1 Negative Sample | 0/72 | 100% | 95 - 100% |
| HSV-1+2 Positive Control | 72/72 | 100% | તેરે – 100% |
| Assay Negative Control | 0/72 | 100% | 95 - 100% |
Repeatability Study Summary for HSV-1
Repeatability Study Summary for HSV-2
| Category | Rate ofDetection | OverallPercentAgreement | 95%ConfidenceInterval |
|---|---|---|---|
| HSV-1+2 High Negative | 43/72 | 40% | 30 - 52% |
| HSV-2 Low Positive | 72/72 | 100% | 95 - 100% |
| HSV-1+2 Moderate Positive | 72/72 | 100% | 95 - 100% |
| HSV-2 Negative Sample | 0/72 | 100% | 95 – 100% |
| HSV-1+2 Positive Control | 72/72 | 100% | 95 – 100% |
| Assay Negative Control | 0/72 | 100% | 95 - 100% |
Level of Detection (LoD)
A Limit of Detection (LoD) study was performed to evaluate the analytical sensitivity of AmpliVue HSV 1+2 Assay using a two representative viral strains of HSV-1 (McIntyre & HF) and two representative strains of HSV-2 (G & MS). Quantified (TCID5/mL) cultures of the HSV-1 and HSV-2 strains were serially diluted to five (5) concentrations in HSVnegative matrix pools and tested in replicates of ten (10) on three reagent lots. The observed LoD of a HSV strain was determined as the lowest concentration level that had a positivity rate of ≥95%. The observed limit of detection of HSV-1 and HSV-2 were determined to be 1.1 x 105 TCID50/mL and 1.1 x 104 TCID50/mL, respectively.
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| Strain | ConcentrationTCID50/mL | Positive/Total | Positivityrate | 95% CI |
|---|---|---|---|---|
| HSV-1McIntyre | 1.00 x106 | 30/30 | 100.0% | 88.65% 100.00% |
| 3.33 x106 | 30/30 | 100.0% | 88.65% 100.00% | |
| 1.1 x105 | 30/30 | 100.0% | 88.65% 100.00% | |
| 3.70 x104 | 24/30 | 80.0% | 62.69% 90.50% | |
| 1.23 x104 | 8/30 | 26.7% | 14.18% 44.45% | |
| HSV-1HF | 1.00 x105 | 30/30 | 100.0% | 88.65% 100.00% |
| 3.33 x105 | 30/30 | 100.0% | 88.65% 100.00% | |
| 1.11 x105 | 30/30 | 100.0% | 88.65% 100.00% | |
| 3.70 x104 | 23/30 | 76.7% | 59.07% 88.21% | |
| 1.23 x104 | 9/10 | 30.0% | 16.66% 47.88% | |
| HSV-2G | 1.00 x105 | 30/30 | 100.0% | 88.65% 100.00% |
| 3.33 x104 | 30/30 | 100.0% | 88.65% 100.00% | |
| 1.11 x104 | 29/30 | 100.0% | 88.30% 100.00% | |
| 3.70 x103 | 28/30 | 93.3% | 78.68% 98.15% | |
| 1.23 x103 | 24/30 | 73.3% | 55.55% 85.82% | |
| HSV-2MS | 1.00 x105 | 30/30 | 100.0% | 88.65% 100.00% |
| 3.33 x104 | 30/30 | 100.0% | 88.65% 100.00% | |
| 1.11 x104 | 30/30 | 100.0% | 88.65% 100.00% | |
| 3.70 x103 | 30/30 | 100.0% | 88.65% 100.00% | |
| 1.23 x103 | 27/30 | 90.0% | 74.38% 96.54% |
Results obtained with each HSV LoD panels:
The LoD was confirmed with the same two (2) HSV-1 and two (2) HSV-2 reference strains diluted to the observed LoD and tested with twenty (20) replicates using three (3) lots of AmpliVue HSV 1+2 Assay. Since all HSV-1 and HSV-2 strains show positivity rates of ≥95% with all three (3) validation lots, the observed LoD is confirmed for both HSV-1 and HSV-2. In addition, twenty (20) HSV-1 and twenty (20) HSV-2 clinical isolates were cultured and quantified in TCIDsymL. Each isolate was diluted to the corresponding LoD in HSV-negative matrix and tested in triplicate. AmpliVue HSV 1+2 Assay was able to detect all 20 HSV-1 and 20 HSV-2 clinical isolates.
Assay LoD: _The final assay LoD claim is 1.1 x 105 TCIDsofmL for HSV-1 and 1.1 x 10 TCID50/mL for HSV-2.
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Analytical Specificity/Cross-Reactivity
A study was performed to evaluate the performance of the AmpliVue® HSV 1+2 Assay in the presence of eighty-nine (89) microorganisms that might be found in lesion specimens. The panel members were obtained from suppliers as purified genomic DNA (GD) or quantified cultures (QC), or prepared in house (IHC) by growing each organism and quantifying the culture. Each potentially interfering or cross-reactive microorganism was tested in three (3) replicates the presence of negative matrix or 3x LoD HSV-2. Clinically relevant levels of viruses and bacteria are typically 10 cfulml or higher for bacteria and 10 pfu/ml or higher for viruses. Purified and quantified DNA or RNA was used for seven (7) of the microorganisms. For these microorganisms 106 copies per ml (cp/ml) or higher was used.
None of the eighty-nine (89) microorganisms that might be found in lesion specimens interfere or cross-react with the assay.
| Microorganism | Member Type(GD,QC, IHC ) | Test concentration |
|---|---|---|
| Bacteria (N=52) | ||
| Acholeplasma laidlawi PG8 | QC | 7.1 x 106 cfu/mL |
| Acinetobacter calcoaceticus | QC | 9.80 x 106 cfu/mL |
| Acinetobacter lwoffi | IHC | 4.55 x 106 cfu/mL |
| Bacteroides fragilis Z029 | QC | 8.8 x 106 cfu/mL |
| Bordetella bronchiseptica | QC | 1.17 x 106 cfu/mL |
| Bordetella pertussis E431 | QC | 1.73 x 106 cfu/mL |
| Chlamydia trachomatis VR-347 | QC | 3.00 x 106 cfu/mL |
| Chlamydia trachomatis D-UW3 | QC | 7.83 x 107 IFU/mL |
| Chlamydia trachomatis | GD | 1.5 x 107 cp/mL |
| LGV-II 434 DNA | ||
| Chlamydophila pneumoniae DNA | GD | 1.6 x 106 cp/mL |
| Clostridium difficile NAP1 | QC | 6.77 x 106 cfu/mL |
| Clostridium perfringens Type A | QC | 1.06 x 106 cfu/mL |
| Corynebacterium diphtheriae | QC | 3.44 x 106 cfu/mL |
| Enterobacter cloacae Z101 | QC | 5.70 x 106 cfu/mL |
| Enterococcus faecalis VSE | QC | 8.60 x 106 cfu/mL |
| Escherichia coli ATCC 43895 | QC | 1.13 x 106 cfu/mL |
| Fusobacterium nucleatum | IHC | 8.05 x 106 cfu/mL |
| Gardnerella vaginalis | QC | 1.20 x 106 cfu/mL |
| Haemophilis influenzae type A | QC | 4.00 x 106 cfu/mL |
| Haemophilus ducreyi Class I DNA | GD | 2.97 x 106 cp/mL |
| Microorganism | Member Type(GD,QC, IHC ) | Test concentration |
| Klebsiella pneumoniae | QC | 9.75 x 106 cfu/mL |
| Lactobacillus acidophilus Z048 | QC | 2.00 x 106 cfu/mL |
| Legionella pneumophila | QC | 1.42 x 106 cfu/mL |
| Mobiluncus curtisii V125 [DSM 2711] ATCC43063 | QC | 3.2 x 106 cfu/mL |
| Mobiluncus mulieris ATCC 35240 | QC | 1.76 x 106 cfu/mL |
| Moraxella cartarrhalis Ne11 | QC | 9.90 x 106 cfu/mL |
| Mycoplasma hominis LBD-4 | QC | 1.30 x 106 cfu/mL |
| Mycoplasma hyorhinis BTS-7 | QC | 6.6 x 106 cfu/mL |
| Mycoplasma orale CH 19299 | QC | 3.08 x 106 cfu/mL |
| Mycoplasma pneumoniae M129 | QC | 3.16 x 106 CCU/mL |
| Mycoplasma salivarium H110 | QC | 1.67 x 106 cfu/mL |
| Neisseria gonorrhoeae Z017 | QC | 5.73 x 106 cfu/mL |
| Neisseria meningitidis SerogroupA | QC | 7.07 x 106 cfu/mL |
| Prevotella melaninogenica ATCC 25845 | QC | 7.3 x 106 cfu/mL |
| Proteus mirabilis | QC | 1.19 x 106 cfu/mL |
| Pseudomonas aeruginosa | QC | 1.32 x 106 cfu/mL |
| Salmonella enteriditis | QC | 5.40 x 106 cfu/mL |
| Salmonella typhimurium | QC | 4.60 x 106 cfu/mL |
| Staphylococcus aureus MRSA | IHC | 7.52 x 106 cfu/mL |
| Staphylococcus aureus MSSA | IHC | 7.02 x 106 cfu/mL |
| Staphylococcus epidermidis MRSE | IHC | 1.75 x 106 cfu/mL |
| Staphylococcus saprophyticus | QC | 3.00 x 106 cfu/mL |
| Streptococcus agalactiae | QC | 2.20 x 106 cfu/mL |
| Streptococcus mitis | QC | 2.43 x 106 cfu/mL |
| Streptococcus mutans Z072 | QC | 1.17 x 106 cfu/mL |
| Streptococcus pneumonia | QC | 2.8 x 106 cfu/mL |
| Streptococcus pyogenes ATCC 9898 | QC | 6.38 x 106 cfu/mL |
| Streptococcus salivarius | IHC | 2.75 x 106 cfu/mL |
| Toxoplasma gondii | QC | 6.6 x 106 tachyzoites/mL |
| Treponema pallidum Nichols | QC | 2.0 x 106 Tp/mL |
| Trichomonas vaginalis Z070 | QC | 1.65 x 106trophozoites/mL |
| Ureaplasma uralyticum NCTC 10177 DNA | GD | 1.23 x 106 cp/mL |
| Candida albicans | QC | 2.00 x 106 cfu/mL |
| Microorganism | Member Type(GD, QC, IHC) | Test concentration |
| Candida glabrata Z007 | QC | 9.73 x 106 cfu/mL |
| Candida guilliermondii Z008 | QC | 9.96 x 106 cfu/mL |
| Candida krusei Z009 | QC | 5.33 x 106 cfu/mL |
| Candida lusitaniae Z010 | QC | 6.56 x 106 cfu/mL |
| Candida parapsilosis Z011 | QC | 1.24 x 106 cfu/mL |
| Candida tropicalis Z012 | QC | 1.0 x 106 cfu/mL |
| Virus (N=30) | ||
| Influenza A/Mexico/4108/2009 H1N1 | QC | 4.08 x 106 TCID50/mL |
| Adenovirus 2 | QC | 1.02 x 105 TCID50/mL |
| Adenovirus 7 VR-7 | QC | 1.58 x 105 TCID50/mL |
| Coronavirus OC43 VR-1558 | QC | 2.42 x 105 TCID50/mL |
| Coxsackievirus B4 | QC | 1.08 x 105 TCID50/mL |
| Cytomegalovirus AD-169 | QC | 9.55 x 105 TCID50/mL |
| Echovirus 11 ODH-37285 | QC | 2.14 x 105 TCID50/mL |
| Enterovirus Type 71 | QC | 1.00 x 105 TCID50/mL |
| Epstein-Barr Virus B95-8 | GD | 2.22 x 105 cp/mL |
| Influenza B Hong Kong VR-791 | QC | 9.53 x 106 TCID50/mL |
| Hepatitis B Virus | QC | 3.44 x 103 IU/mL |
| Hepatitis C Virus | QC | 7.58 x 103 IU/mL |
| HHV-8 | QC | 1.26 x 105 TCID50/mL |
| HIV-1 Subtype B RNA | GD | 1.14 x 105 cp/mL |
| hMPV (Italy) A1 | QC | 3.66 x 105 TCID50/mL |
| Human Herpes 6 virus Z29 strain | QC | 1.95 x 105 TCID50/mL |
| Human Herpes 7 virus SB strain | QC | 1.15 x 105 TCID50/mL |
| Human papilloma virus 16 DNA | GD | 4.3 x 103 cp/mL |
| Human papilloma virus 18 DNA | GD | 1.8 – 3.6 x 105 cp/mL |
| Measles virus | QC | 1.95 x 105 TCID50/mL |
| Mumps virus | QC | 5.89 x 105 TCID50/mL |
| Parainfluenza Type 1 #2 | QC | 3.97 x 105 TCID50/mL |
| Parainfluenza Type 2 | QC | 3.15 x 105 TCID50/mL |
| Parainfluenza Type 3 NY14 | QC | 2.36 x 105 TCID50/mL |
| Parainfluenza Type 4B VR-1377 | QC | 1.37 x 105 TCID50/mL |
| RSV A Long VR-26 | QC | 4.36 x 104 TCID50/mL |
| RSV B Washington VR-1401 | QC | 3.43 x 105 TCID50/mL |
| Rubella virus | QC | 4.17 x 105 TCID50/mL |
| Simian Virus type 40 Pa-57 ATCC strain VR- | QC | 3.16 x 105 TCID50/mL |
Cross Reactivity Panel
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and the comments of the country of
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{10}------------------------------------------------
| Microorganism | Member Type(GD,QC , IHC ) | Test concentration |
|---|---|---|
| 239 | ||
| VZV DNA | GD | 1.5 x 105 cp/mL |
Interfering Substances
This study was performed to evaluate potential interference with Ampli Vue HSV 1+2 Assay with a panel of thirty-three (33) substances and five different viral transport media and microorganisms from cross reactivity panel that may be present in clinical specimens.
The study was carried out in the presence of HSV-1 and HSV-2 at 3 x LoD to evaluate potential interference to the detection of the HSV target. The study was also carried out in the absence of HSV to evaluate potential interference to the detection of internal control of AmpliVue HSV 1+2 Assay. Each potential interfering substance was tested in triplicate.
Interfering Substances
The analytical performance of AmpliVue HSV 1+2 Assay was characterized in the presence of interfering substances at potentially highest ("the worst case") concentrations to evaluate the susceptibility of the HSV assay to interference. By "worst case," each interfering substance was introduced into the assay by directly wetting a clean, dry Remel M4 kit swab with the substance and placing the swab directly in transport media. Calculated concentrations are based on an estimated volume of 200µL of substance introduced by the swab. Each panel member was tested in triplicate spiked with HSV-1 HF and HSV-2 G strains separately at 3 x LoD. The panel was also tested in triplicate in the absence of HSV transport media to see if the potentially interfering substances interfere with the detection of the internal control. No interference was observed in the presence of the potential interfering substances tested.
Interfering Substance Panel
| Substance | Test conc. |
|---|---|
| Seminal Fluid | 7% |
| Cornstarch | 1.25 mg/mL |
| Acetamidophenol | 5 mg/mL |
| Feces | 7% |
| Acetylsalicylic Acid | 10 mg/mL |
| Chlorpheniramine | 5 mg/mL |
| Dextromethorphan | 10 mg/mL |
| Whole blood with EDTA | 7% |
| Female Urine | 7% |
| Male Urine | 7% |
| Acyclovir (Acycloguanosine) | 7 mg/mL |
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| Substance | Test conc. |
|---|---|
| Albumin | 3.3 mg/mL |
| Casein | 7 mg/mL |
| K-Y Brand Jelly | 7% |
| Douche | 7% |
| Monistat 1 | 7% |
| Monistat 3 | 7% |
| Tioconazole 1 | 7% |
| Preparation H | 7% |
| Lanacane | 7% |
| Listerine | 7% |
| Abreva | 7% |
| Carmex Cold Sore Lip Balm | 7% |
| Releev cold sore treatment | 7% |
| Crest | 7% |
| Mucin (Bovine Submaxillary Gland, type I-S) | 60 µg/mL |
| Buffy coat | 7% |
| YeastGard | 7% |
| Vagisil Crème | 7% |
| Lip clear Lysine | 7% |
| Clotrimazole 3 Vaginal Cream | 7% |
| Balneol Hygienic Cleansing Lotion | 7% |
| Ortho Options Gynol II Extra Strength Vaginal | 7% |
| Contraceptive Jelly | 7% |
Viral Transport Media
The performance of the AmpliVue HSV 1+2 Assay was assessed with Remel M5, Remel M4RT, Bartels VTM, and BD Universal Viral Transport (UVT)/ Copan UTM. (Remel M4 had previously been assessed and found to not interfere with the assay). Each medium was tested after spiking with HSV-1 HF and HSV-2 G strain to a final concentration of approximately 3 x LoD to determine if the viral transport media interferes with the detection of HSV targets in positive samples. The media were tested in the absence of HSV-2 (medium only) to see if the viral transport media interfere with the detection of the internal control in negative samples.
There was no interference observed with the Remel M4RT, Remel M5, Bartels VTM, and BD UVT/Copan UTM media for the detection of HSV-1 and HSV- 2 target or the internal control. Remel M4RT, Remel M5, Bartels VTM, and BD UVT/Copan UTM did not interfere with the detection of HSV-1 and HSV-2 target or the internal control.
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Cross-Reactivity Panel Members
The performance of the AmpliVue HSV 1+2 Assay was characterized by testing the eighty-nine (89) microorganisms that were evaluated for analytical specificity and cross reactivity in the presence of HSV-1 HF and HSV-2 G at 3 x LoD separately to see if the presence of these organisms interferes with the detection of HSV targets. Each panel member was tested in triplicate. None of the cross reactivity panel members interfered with the detection of HSV-1 and HSV-2 targets.
Specimen Stability
A study was performed to confirm the stability of HSV-1 and HSV-2 in viral transport media in accordance with recommended storage and handling specifications of each medium tested. The five media described above were spiked with HSV-1 or HSV-2 at 3 x LoD and stored at 2 - 8°C or -70°C. The media was tested by AmpliVue HSV 1+2 Assay at multiple time points. Based on this study at 3x LoD, HSV-1 and HSV-2 are stable in all five (5) media for 7 days at 2 - 8°C, and for 34 days at -70°C.
Competitive Inhibition
The performance of the AmpliVue HSV 1+2 Assay was assessed for competitive interference using simulated samples in two studies mimicking co-infections. The first study used simulated samples with one target at a concentration near the LoD (3 x LoD) and the other target at higher concentrations (30x LoD to 3000 x LoD). The second study used simulated samples that had equal concentrations of HSV-1 virus and HSV-2 virus (3 x LoD to 3000 x LoD).
In the first study competitive inhibition was not observed with simulated samples containing one target at a concentration near the LoD (3 x LoD) and the other target at up to 300 x LoD. However, competitive inhibition was observed for both HSV-1 and HSV-2 with simulated samples containing one target at a concentration near the LoD (3 x LoD) and the other target at 3000 x LoD.
In the second study competitive inhibition was not observed with simulated samples containing equal concentrations of HSV-1 virus and HSV-2 virus, from 3 x LoD to 3000 x LoD.
Carry-Over and Cross Contamination
Test results confirm that carry-over and cross contamination does not occur with AmpliVue HSV 1+2 Assay. High HSV-1 (HSV-2) positive samples were tested in series alternating with negative samples. In order to challenge the device, cultured and quantified viral stock served as high positive sample. HSV-1 HF (7.96 x 108 TCID30mL) and HSV-2 G (2.27 x 10' TCIDs6/mL) viral stocks were used directly without dilution, for the highest concentration available. Remel M4 viral transport media was used as negative sample. Ten (10) replicates of negative sample together with assay controls were run by two (2) operators to confirm that negative samples (Remel M4 viral transport media) generate a negative result 100% of the time. Five (5) replicates of high-concentration positive and negative samples were tested in a series, alternating sample types. All HSV-1 and HSV-2 high positive samples gave positive results and all the negative samples gave HSV negative results.
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Expected Results
The prevalence of HSV-1 and HSV-2 with the AmpliVue® HSV 1 +2 Assay in cutaneous (skin lesion, genital - penis), or mucocutaneous (anorectal, genital - vaginal/cervical, nares, ocular, oral lesion and urethral) was estimated for the one thousand three hundred forty-three (1343) specimens with valid AmpliVue® HSV 1 + 2 Assay results. Seven of 1343 specimens were not included in the performance analysis due to contamination or invalid data by reference method.
The prevalence of HSV-1 and HSV-2 with the AmpliVue® HSV 1 + 2 Assay was calculated for the combined sites based on the age of the patient and the specific source of specimen and are presented below.
| Combined Study - Cutaneous Prevalence by Age | ||||||
|---|---|---|---|---|---|---|
| HSV-1 | HSV-2 | |||||
| Age | Total # | Total Positive | Prevalence | Total # | Total Positive | Prevalence |
| ≤ 5 years | 37 | 2 | 5.4% | 37 | 1 | 2.7% |
| 6 to 21 years | 68 | 13 | 19.1% | 68 | 6 | 8.8% |
| 22 to 59 years | 225 | 20 | 8.9% | 225 | 49 | 21.8% |
| ≥ 60 years | 70 | 5 | 7.1% | 70 | 18 | 25.7% |
| Percent | 95% CI | Percent | 95% CI | |||
| Positive PredictiveValue | 76.9% | 88.6% to 100% | 79.5% | 68.8% to 87.1% | ||
| Negative PredictiveValue | 100% | 94.6% to 98.5% | 99.7% | 98.3% to 99.9% |
| Combined Study - Cutaneous Prevalence by Specific Source | ||||||
|---|---|---|---|---|---|---|
| HSV- 1 | HSV-2 | |||||
| Source | Total # | TotalPositive | Prevalence | Total # | TotalPositive | Prevalence |
| Skin lesion | 271 | 27 | 10.0% | 271 | 48 | 17.7% |
| Genital - penis | 129 | 13 | 19.1% | 129 | 26 | 20.2% |
| Combined Study - Mucocutaneous Prevalence by Age | ||||||
|---|---|---|---|---|---|---|
| HSV-1 | HSV-2 | |||||
| Age | Total # | TotalPositive | Prevalence | Total # | TotalPositive | Prevalence |
| ≤ 5 years | 39 | 10 | 25.6% | 39 | 1 | 2.6% |
| 6 to 21 years | 190 | 42 | 22.1% | 190 | 34 | 17.9% |
| 22 to 59 years | 606 | 104 | 17.2% | 606 | 132 | 21.8% |
| > 60 years | 107 | 16 | 15.0% | 107 | 17 | 15.9% |
| Not provided | 1 | 1 | 100% | 1 | 0 | 0% |
| Percent | 95% CI | Percent | 95% CI | |||
| PositivePredictive Value | 87.1% | 81.3% to 91.3% | 81.8% | 75.5% to 86.7% | ||
| NegativePredictive Value | 98.7% | 97.5% to 99.3% | 99.5% | 98.6% to 99.8% |
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| Combined Study - Mucocutaneous Prevalence by Specific Source | ||||||
|---|---|---|---|---|---|---|
| HSV- 1 | HSV-2 | |||||
| Source | Total # | Total Positive | Prevalence | Total # | Total Positive | Prevalence |
| Anorectal | 35 | 2 | 5.7% | 35 | 8 | 22.9% |
| Genital -vaginal/cervical | 691 | 109 | 15.9% | 691 | 168 | 24.3% |
| Nasal | 16 | 5 | 31.3% | 16 | 2 | 12.5% |
| Ocular | 18 | 3 | 16.7% | 18 | 1 | 5.6% |
| Oral lesion | 165 | 54 | 32.7% | 165 | 2 | 1.2% |
| Urethral | 18 | 0 | N/A | 18 | 3 | 16.7% |
Clinical Performance
The performance of the AmpliVue HSV 1 + 2 Assay was evaluated at five geographically diverse locations within the United States. A total of one thousand three hundred fifty-five (1355) specimens from symptomatic male and female patients were tested. Patient population ranged from ≤ 5 years to ≥ 60 years. The swab specimens have been categorized as cutaneous (skin lesion, genital - penis), or mucocutaneous (anorectal, genital - vaginal/cervical, nares, ocular, oral lesion and urethral). Nineteen (19) tests were considered invalid and were removed from the performance analysis.
The reference ELVIS viral culture used in this study was unable to detect co-infected specimens. Due to this, if a specimen was positive for HSV-2 it was removed from the calculation of the HSV-1 clinical performance. Two hundred eleven (211) specimens identified as HSV-2 positive by ELVIS have been removed from the initial one thousand three hundred thirty-six (1336) specimens. The data below is for the remaining one thousand one hundred twenty-five (1125) specimens.
| Combined Sites - HSV-1 Cutaneous Lesions (N=340) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| ReferenceMethod | ૭૨% Cl | ||||||||||
| POS | NEG | Total | Sensitivity | 100% | 88.6% | 100% | |||||
| AmpliVue HSV | POS | 30 | ರ | ਤੇ ਹੋ | Specificity | 97.1% | 94.6% | 98.5% | |||
| 1+2 Assay | NEG | 0 | 301 | 301 | |||||||
| Total | 30 | 310 | 340 |
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| Combined Sites – HSV-1 Mucocutaneous Lesions (N=785) | ||||||||
|---|---|---|---|---|---|---|---|---|
| Reference Method | 95% CI | |||||||
| POS | NEG | Total | Sensitivity | 94.9% | 90.3% | 97.4% | ||
| AmpliVue HSV1+2 Assay | POS | 149 | 22 | 171 | Specificity | 96.5% | 94.8% | 97.7% |
| NEG | 8 | 606 | 614 | |||||
| Total | 157 | 628 | 785 |
The table below details the HSV-2 results for the one thousand three hundred thirty-six (1336) specimens.
| Combined Sites - HSV-2 Cutaneous Lesions (N=399) | ||||||||
|---|---|---|---|---|---|---|---|---|
| Reference Method | 95% CI | |||||||
| POS | NEG | Total | Sensitivity | 98.3% | 91.0% | 99.7% | ||
| AmpliVue HSV1+2 Assay | POS | 58 | 15 | 73 | Specificity | 95.6% | 92.8% | 97.3% |
| NEG | 1 | 325 | 326 | |||||
| Total | 59 | 340 | 399 |
| Combined Sites – HSV-2 Mucocutaneous Lesions (N=937) | ||||||||
|---|---|---|---|---|---|---|---|---|
| Reference Method | 95% CI | |||||||
| POS | NEG | Total | Sensitivity | 97.4% | 93.4% | 99.0% | ||
| AmpliVue HSV1+2 Assay | POS | 148 | 33 | 181 | Specificity | 95.8% | 94.2% | 97.0% |
| NEG | 4 | 752 | 756 | |||||
| Total | 152 | 785 | 937 |
Statement of Performance
The results of the analytical and clinical performance studies submitted in this pre-market notification are complete and demonstrate that the AmpliVue® HSV 1+2 Assay is substantially equivalent to the predicate device. The AmpliVue® HSV 1+2 Assay performs as well as the gold standard/reference method for the differentiation of Herpes Simplex Virus 1 (HSV-1) and Herpes Simplex Virus 2 (HSV-2) nucleic acids.
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Image /page/16/Picture/0 description: The image shows the logo for the Department of Health & Human Services (HHS). The logo consists of a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES. USA" around the perimeter. Inside the circle is an abstract symbol resembling an eagle or bird in flight, composed of three curved lines.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
March 26, 2014
QUIDEL CORPORATION RONALD H. LOLLAR SENIOR DIRECTOR, CLINICAL AND REGULATORY AFFAIRS 2005 EAST STATE STREET, SUITE 100 ATHENS, OH 45701 USA
Re: K140029
Trade/Device Name: AmpliVue™ HSV 1+ 2 Assay Regulation Number: 21 CFR §866.3305 Regulation Name: Herpes Simplex Virus Nucleic Amplification Assay Regulatory Class: II Product Code: OQO Dated: December 30, 2013 Received: January 6, 2014
Dear Mr. Lollar:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
{17}------------------------------------------------
Page 2-Mr. Lollar
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.goy/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Stephen J. Lovell -S for
Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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510(k) Number (if known): K140029
Device Name: AmpliVue® HSV 1+2 Assay
Indication for Use:
The AmpliVue® HSV 1+2 Assay is an in vitro diagnostic test for the direct, qualitative detection and differentiation of Herpes Simplex Virus 1 (HSV-1) and Herpes Simplex Virus 2 (HSV-2) DNA in cutaneous or mucocutaneous lesion specimens from symptomatic patients. The test is intended for use as an aid in diagnosis of HSV infection in symptomatic patients.
Warning: The AmpliVue HSV 1+2 Assay is not FDA cleared for use with cerebrospinal fluid (CSF). The assay is not intended for prenatal screening.
Prescription Use Over-The-Counter Use AND/OR X (21 CFR 801 Subpart C) (Part 21 CFR 801 Subpart D)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED
Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)
Stephen J. Lovell -S 2014.03.26 09:55:34 -04'00'
§ 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).