Solana HSV 1+2/VZV Assay
Device Facts
| Record ID | K162451 |
|---|---|
| Device Name | Solana HSV 1+2/VZV Assay |
| Applicant | Quidel Corporation |
| Product Code | PGI · Microbiology |
| Decision Date | Nov 28, 2016 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 866.3309 |
| Device Class | Class 2 |
| Attributes | Pediatric |
Indications for Use
The Solana® HSV 1+2/VZV Assay is an in vitro diagnostic test, using isothermal amplification technology (helicase-dependent amplification, HDA), for the qualitative detection and differentiation of herpes simplex virus type 1, herpes simplex virus type 2, and varicella-zoster virus DNA isolated and purified from cutaneous or mucocutaneous lesion samples obtained from symptomatic patients suspected of active herpes simplex virus 1, herpes simplex virus type 2 and/or varicella-zoster infection. The Solana® HSV 1+2/VZV Assay is intended to aid in the diagnosis of herpes simplex virus 1, herpes simplex virus 2 and varicella-zoster virus active cutaneous or mucocutaneous infections. Negative results do not preclude herpes simplex virus 1, herpes simplex virus 2 and varicella-zoster virus infections and should not be used as the sole basis for diagnosis, treatment or other management decisions. The Solana® HSV 1+2/VZV Assay is intended for use only with the Solana® instrument. Warning: The Solana® HSV 1 + 2/VZV Assay is not intended for use with cerebrospinal fluid or to aid in the diagnosis of HSV or VZV infections of the central nervous system (CNS). The Solana® HSV 1 + 2/VZV Assay is not intended for use in prenatal screening.
Device Story
The Solana® HSV 1+2/VZV Assay is an in vitro diagnostic test for the qualitative detection of HSV-1, HSV-2, and VZV DNA. The device uses isothermal helicase-dependent amplification (HDA) to amplify target viral DNA from cutaneous or mucocutaneous lesion swabs. The process involves heat treatment of the specimen at 95°C, followed by rehydration of lyophilized HDA reagents in a reaction tube. The Solana instrument performs the amplification and detection using target-specific fluorescence probes. A competitive process control (PRC) is included to monitor sample processing and inhibition. The instrument measures fluorescent signals and uses on-board algorithms to interpret results, which are displayed to the user. The device is intended for use in clinical settings by healthcare professionals to aid in the diagnosis of active cutaneous or mucocutaneous infections. It provides rapid, automated results, assisting clinicians in patient management and treatment decisions.
Clinical Evidence
Prospective clinical study of 1,062 fresh lesion specimens across three U.S. sites. Comparator: FDA-cleared ELVIS HSV ID/D³ Typing Test (HSV-1/2) and DSFA/culture with DFA (VZV). Sensitivity for HSV-1 ranged 100% (cutaneous/mucocutaneous/uncategorized); HSV-2 sensitivity ranged 92.3%–100%; VZV sensitivity was 100%. Specificity ranged 94.1%–98.6% across targets and lesion types. Bench testing included reproducibility, analytical sensitivity (LOD), inclusivity, cross-reactivity, and interference studies.
Technological Characteristics
Isothermal helicase-dependent amplification (HDA) technology. Uses target-specific primers and fluorescence probes labeled with a fluorophore and quencher. Employs RNaseH2 for probe cleavage. Instrument-based (Solana) detection of fluorescent signals. Lyophilized reagents. Requires heat block (95°C) for sample processing. Standalone instrument operation.
Indications for Use
Indicated for symptomatic patients of all ages suspected of active HSV-1, HSV-2, or VZV cutaneous or mucocutaneous infections. Not for use with CNS samples or prenatal screening.
Regulatory Classification
Identification
A herpes virus nucleic acid-based cutaneous and mucocutaneous lesion panel is a qualitative in vitro diagnostic device intended for the simultaneous detection and differentiation of different herpes viruses in cutaneous and mucocutaneous lesion samples from symptomatic patients suspected of Herpetic infections. Negative results do not preclude infection and should not be used as the sole basis for treatment or other patient management decisions. The assay is not intended for use in cerebrospinal fluid samples.
Special Controls
*Classification.* Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include detailed documentation for the device description, including the device components, ancillary reagents required but not provided, and a detailed explanation of the methodology including primer design and selection. (2) Premarket notification submissions must include detailed documentation from the following analytical and clinical performance studies: Analytical sensitivity (Limit of Detection), reactivity, inclusivity, precision, reproducibility, interference, cross reactivity, carry-over, and cross contamination. (3) Premarket notification submissions must include detailed documentation of a clinical study using lesion samples in which Herpes Simplex Virus 1, Herpes Simplex Virus 2, or Varicella Zoster Virus DNA detection was requested. The study must compare the device performance to an appropriate well established reference method. (4) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling. (5) The device labeling must include a limitation statement that reads: “The device is not intended for use with cerebrospinal fluid or to aid in the diagnosis of HSV or VZV infections of the central nervous system (CNS).” (6) Premarket notification submissions must include quality assurance protocols and a detailed documentation for device software, including, but not limited to, standalone software applications and hardware-based devices that incorporate software. (7) The risk management activities performed as part of the manufacturer's 21 CFR 820.10(c) design and development activities must document an appropriate end user device training program that will be offered as part of efforts to mitigate the risk of failure to correctly operate the instrument.
Predicate Devices
- Lyra® Direct HSV 1+2/VZV Assay (K133448)
Related Devices
- K151046 — illumigene HSV 1&2 DNA Amplification Assay, illumigene HSV 1&2 External Control Kit, illumipro-10 · Meridian Bioscience, Inc. · Jul 17, 2015
Submission Summary (Full Text)
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY
A. 510(k) Number:
K162451
B. Purpose for Submission:
Clearance of new device
C. Measurand:
Target DNA sequences from conserved regions of the herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), and varicella-zoster virus (VZV) genes.
D. Type of Test:
Molecular diagnostic test using isothermal amplification technology (helicase-dependent amplification, HDA), for the qualitative detection and differentiation of HSV-1, HSV-2, and VZV DNA isolated and purified from cutaneous or mucocutaneous lesion samples.
E. Applicant:
Quidel Corporation
F. Proprietary and Established Names:
Solana® HSV 1+2/VZV Assay
G. Regulatory Information:
1. Regulation section:
21 CFR 866.3309
2. Classification:
Class II
3. Product code:
PGI
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4. Panel:
Microbiology (83)
H. Intended Use:
1. Intended use(s):
The Solana® HSV 1+2/VZV Assay is an in vitro diagnostic test, using isothermal amplification technology (helicase-dependent amplification, HDA), for the qualitative detection and differentiation of herpes simplex virus type 1, herpes simplex virus type 2, and varicella-zoster virus DNA isolated and purified from cutaneous or mucocutaneous lesion samples obtained from symptomatic patients suspected of active herpes simplex virus 1, herpes simplex virus 2 and/or varicella-zoster infection. The Solana® HSV 1+2/VZV Assay is intended to aid in the diagnosis of herpes simplex virus 1, herpes simplex virus 2 and varicella-zoster virus active cutaneous or mucocutaneous infections. Negative results do not preclude herpes simplex virus 1, herpes simplex virus 2 and varicella-zoster virus infections and should not be used as the sole basis for diagnosis, treatment or other management decisions. The Solana® HSV 1+2/VZV Assay is intended for use only with the Solana® instrument.
**Warning:** The Solana® HSV 1 + 2/VZV Assay is not intended for use with cerebrospinal fluid or to aid in the diagnosis of HSV or VZV infections of the central nervous system (CNS). The Solana® HSV 1 + 2/VZV Assay is not intended for use in prenatal screening.
2. Indication(s) for use:
Same as Intended Use
3. Special conditions for use statement(s):
For prescription use only in accordance with 21 CFR 801.109
4. Special instrument requirements:
Solana® instrument
I. Device Description:
The Solana® HSV 1+2/VZV Assay amplifies and detects viral DNA isolated from cutaneous or mucocutaneous lesion samples obtained from symptomatic patients suspected of active
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herpes simplex virus 1, herpes simplex virus 2 and/or varicella-zoster infection.
The assay consists of two (2) major steps: 1) specimen preparation, and 2) amplification and detection of target sequences specific to HSV-1, HSV-2 and/or VZV using isothermal Helicase-Dependent Amplification (HDA) in the presence of target-specific fluorescence probes.
The Solana® HSV 1+2/VZV Assay includes the following components in the kit.
| Component | Quantity | Storage |
| --- | --- | --- |
| Process Buffer Tubes | 48 tubes/kit 1.6 mL | 2°C to 8°C |
| Reaction Tubes | 48 tubes/kit | 2°C to 8°C |
External controls for HSV-1, HSV-2, or VZV (e.g., Quidel Molecular HSV/VZV Control Set, which contains positive and negative controls) serve as external processing and extraction controls.
## J. Substantial Equivalence Information:
1. Predicate device name(s):
Lyra® Direct HSV 1+2/VZV Assay
2. Predicate 510(k) number(s):
K133448
3. Comparison with predicate:
Similarities
| Item | New Device
Solana® HSV 1+2/VZV Assay | Predicate Device
Lyra® Direct HSV 1 + 2/VZV Assay (K133448) |
| --- | --- | --- |
| Intended Use | The Solana® HSV 1+2/VZV Assay is an in vitro diagnostic test, using isothermal amplification technology (helicase-dependent amplification, HDA), for the qualitative detection and differentiation of herpes simplex virus type 1, herpes simplex virus type 2, and varicella-zoster virus | The Lyra® Direct HSV 1 + 2/VZV Assay is an in vitro multiplex Real-Time PCR test for qualitative detection and differentiation of herpes simplex virus type 1, herpes simplex virus type 2, and varicella-zoster virus DNA isolated and purified from cutaneous or mucocutaneous lesion samples obtained from |
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| | DNA isolated and purified from cutaneous or mucocutaneous lesion samples obtained from symptomatic patients suspected of active herpes simplex virus 1, herpes simplex virus 2 and/or varicella-zoster infection. The Solana® HSV 1+2/VZV Assay is intended to aid in the diagnosis of herpes simplex virus 1, herpes simplex virus 2 and varicella-zoster virus active cutaneous or mucocutaneous infections. Negative results do not preclude herpes simplex virus 1, herpes simplex virus 2 and varicella-zoster virus infections and should not be used as the sole basis for diagnosis, treatment or other management decisions. The Solana® HSV 1+2/VZV Assay is intended for use only with the Solana® instrument. Warning: The Solana® HSV 1 + 2/VZV Assay is not intended for use with cerebrospinal fluid or to aid in the diagnosis of HSV or VZV infections of the central nervous system (CNS). The Solana® HSV 1 + 2/VZV Assay is not intended for use in prenatal screening. | symptomatic patients suspected of active herpes simplex virus 1, herpes simplex virus 2 and/or varicella-zoster infection. The Lyra® Direct HSV 1 + 2/VZV Assay is intended to aid in the diagnosis of herpes simplex virus 1, herpes simplex virus 2 and varicella-zoster virus active cutaneous or mucocutaneous infections. Negative results do not preclude herpes simplex virus 1, herpes simplex virus 2 and varicella-zoster virus infections and should not be used as the sole basis for diagnosis, treatment or other management decisions. The Lyra® Direct HSV 1 + 2/VZV Assay is not intended for use with cerebrospinal fluid or to aid in the diagnosis of HSV or VZV infections of the central nervous system (CNS). The Lyra® Direct HSV 1 + 2/VZV Assay is not intended for use in prenatal screening. The device is not intended for point-of-care use. |
| --- | --- | --- |
| Assay Results | Qualitative | Qualitative |
| Detection Techniques | Multiplex assay using different reporter dyes for each target | Multiplex assay using different reporter dyes for each target |
| Identification of HSV-1, HSV-2, and VZV | Yes | Yes |
| Sample Types | Cutaneous or mucocutaneous lesion swab specimens obtained from symptomatic patients | Cutaneous or mucocutaneous lesion swab specimens obtained from symptomatic patients |
| Extraction Method | Not required | Not required |
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Differences
| Item | New Device
Solana® HSV 1+2/VZV Assay | Predicate Device
Lyra® Direct HSV 1 + 2/VZV Assay (K133448) |
| --- | --- | --- |
| Viral Target | HSV-1: US7: glycoprotein I
HSV-2: noncoding region between UL47: VP13/14 and UL48: VP16
VZV: ORF6: DNA-helicase primase | HSV-1: glycoprotein G
HSV-2: glycoprotein G
VZV: ORF6: DNA-helicase primase |
| Assay Methodology | Helicase-Dependent Amplification (HDA) detecting the presence or absence of viral DNA in clinical specimens | PCR-based system for detecting the presence or absence of viral DNA in clinical specimens |
| Instruments | Solana® instrument | Life Technologies QuantStudio™ Dx, the Applied Biosystems® 7500Fast Dx, or the CepheidSmartCycler® II System |
K. Standard/Guidance Document Referenced (if applicable):
Not applicable
L. Test Principle:
The Solana® HSV 1+2/VZV Assay amplifies and detects viral DNA isolated from cutaneous or mucocutaneous lesion samples obtained from symptomatic patients suspected of active herpes simplex virus 1, herpes simplex virus 2 and/or varicella-zoster infection.
The Solana® instrument heats each reaction tube to 64°C. If present, the target sequence is amplified by HSV-1, HSV-2 and/or VZV specific primers and detected by HSV-1, HSV-2 and/or VZV specific fluorescence probes included in the Reaction Tube. Each probe has a fluorescent dye of specific wavelength. The target probes are labeled with a quencher on one end and a fluorophore on the other end. In addition, the target probes carry a ribonucleic acid. Upon annealing to the respective amplicons, the fluorescence probes are cleaved by RNaseH2 and the fluorescence signal increases due to physical separation of fluorophore from quencher. The Solana® instrument measures and interprets the fluorescent signal, using on-board method-specific algorithms. The Solana® instrument will then report the test results to the user on its display screen, and it can print out the results via a printer.
The following is a summary of the procedure:
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The patient specimen is transferred to a Process Tube, subjected to heat treatment at $95^{\circ}\mathrm{C}$ for 5 minutes and mixed and vortexed. The processed sample is transferred to a Reaction Tube and mixed. The Reaction Tube contains lyophilized HDA reagents, dNTPs, primers and probes. Once the Reaction Tube contents are rehydrated with the diluted sample, the Reaction Tube is placed in the Solana® instrument for amplification and detection of specific target sequences. In the Solana® instrument, the target sequences are amplified by HSV-1, HSV-2 and/or VZV specific primers and detected by HSV-1, HSV-2 and/or VZV specific fluorescence probes included in the Reaction Tube. A competitive process control (PRC) is included in the Process Tube to monitor sample processing, inhibitory substances in clinical samples, reagent failure or device failure. The PRC target is amplified by specific primers and detected by a PRC specific fluorescence probe. The target and PRC probes are labeled with a quencher on one end and a fluorophore on the other end. In addition, the target and PRC probes carry ribonucleic acid. Upon annealing to HSV-1, HSV-2, VZV or PRC amplicons, the fluorescence probes are cleaved by RNaseH2 and the fluorescence signal increases due to physical separation of fluorophore from quencher. The Solana® instrument measures and interprets the fluorescent signal, using on-board method-specific algorithms. The Solana® instrument will then report the test results to the user on its display screen, and the results can be printed via an attached printer.
Interpretation of Results
| Samples | Assay Result | Interpretation |
| --- | --- | --- |
| Patient specimen | HSV-1 Positive | HSV-1 DNA detected |
| | HSV-1 Negative | No HSV-1 DNA detected and other virus or PRC detected |
| | HSV-2 Positive | HSV-2 DNA detected |
| | HSV-2 Negative | No HSV-2 DNA detected and other virus or PRC detected |
| | VZV Positive | VZV DNA detected |
| | VZV Negative | No VZV DNA detected and other virus or PRC detected |
| | Invalid | No HSV-1, HSV-2, VZV DNA and No PRC detected; for invalid test results, retest the same processed sample first. If the test is invalid upon retesting with the processed sample, re-process another aliquot of the same sample or obtain a new sample and re-test. |
M. Performance Characteristics (if/when applicable):
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1. Analytical performance:
a. Reproducibility:
The reproducibility of the Solana® HSV 1+2/VZV Assay was evaluated at three laboratory sites. A reproducibility panel containing 30 contrived samples, manufactured as high negative samples (n=3; 1/18x or 1/27x LOD (C₂₀ - C₈₀ concentration)) for HSV-1 MacIntyre, HSV-2 G, and VZV Ellen, low positive samples (n=3; near the assay limit of detection) for HSV-1, HSV-2 and VZV, moderate positive samples (n=3; 3x LOD) for HSV-1, HSV-2 and VZV and negative samples (n=3) was used for the study. The samples were randomized and blind-coded within each panel, and the operator tested one (1) panel, together with three (3) positive and three (3) negative external controls, in three runs. The panels were run by two operators at each testing site for five (5) non-consecutive days.
Results of the Reproducibility study for the Solana® HSV 1+2/VZV Assay performed at three sites are presented in the tables below.
Reproducibility Study Summary for HSV-1
| HSV-1 MacIntyre | Site | | | | | | Overall Percent Agreement | 95% Confidence Interval | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Site #1 | | Site #2 | | Site #3 | | | | |
| | Rate of Detection | % Agreement | Rate of Detection | % Agreement | Rate of Detection | % Agreement | Rate of Detection | | % Agreement |
| High Negative (3.50×10³ TCID₅₀/mL) | 11/30 | 36.7 | 5/30 | 16.7 | 14/30 | 46.7 | 30/90 | 33.3 | 24.5 to 43.6 |
| Low Positive (6.30×10² TCID₅₀/mL) | 30/30 | 100 | 30/30 | 100 | 30/30 | 100 | 90/90 | 100 | 95.9 to 100 |
| Moderate Positive (1.89×10³ TCID₅₀/mL) | 30/30 | 100 | 30/30 | 100 | 30/30 | 100 | 90/90 | 100 | 95.9 to 100 |
| Negative | 0/30 | 100 | 0/30 | 100 | 0/30 | 100 | 0/90 | 100 | 95.9 to 100 |
| Positive Control | 30/30 | 100 | 30/30 | 100 | 30/30 | 100 | 90/90 | 100 | 95.9 to 100 |
| Negative Control | 0/30 | 100 | 0/30 | 100 | 0/30 | 100 | 0/90 | 100 | 95.9 to 100 |
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Reproducibility Study Summary for HSV-2
| HSV-2 G | Site | | | | | | Overall Percent Agreement | 95% Confidence Interval | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Site #1 | | Site #2 | | Site #3 | | | | |
| | Rate of Detection | % Agreement | Rate of Detection | % Agreement | Rate of Detection | % Agreement | Rate of Detection | | % Agreement |
| High Negative (3.71 × 10² TCID_{50}/mL) | 12/30 | 40 | 8/30 | 26.7 | 7/30 | 23.3 | 27/90 | 30.0 | 21.5 to 40.1 |
| Low Positive (6.67 × 10³ TCID_{50}/mL) | 30/30 | 100 | 30/30 | 100 | 30/30 | 100 | 90/90 | 100 | 95.9 to 100 |
| Moderate Positive (2.00 × 10⁴ TCID_{50}/mL) | 30/30 | 100 | 30/30 | 100 | 30/30 | 100 | 90/90 | 100 | 95.9 to 100 |
| Negative | 0/30 | 100 | 0/30 | 100 | 0/30 | 100 | 0/90 | 100 | 95.9 to 100 |
| Positive Control | 30/30 | 100 | 30/30 | 100 | 30/30 | 100 | 90/90 | 100 | 95.9 to 100 |
| Negative Control | 0/30 | 100 | 0/30 | 100 | 0/30 | 100 | 0/90 | 100 | 95.9 to 100 |
Reproducibility Study Summary for VZV
| VZV Ellen | | | | | | | Overall Percent Agreement | 95% Confidence Interval | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Site #1 | | Site #2 | | Site #3 | | | | |
| | Rate of Detection | % Agreement | Rate of Detection | % Agreement | Rate of Detection | % Agreement | Rate of Detection | | % Agreement |
| High Negative (5.50 × 10⁻³ TCID_{50}/mL) | 11/30 | 36.7 | 2/30 | 6.7 | 8/30 | 26.7 | 21/90 | 23.3 | 15.8 to 33.1 |
| Low Positive (1.49 × 10⁻¹ TCID_{50}/mL) | 30/30 | 100 | 30/30 | 100 | 30/30 | 100 | 90/90 | 100 | 95.9 to 100 |
| Moderate Positive (4.46 × 10⁻¹ TCID_{50}/mL) | 30/30 | 100 | 30/30 | 100 | 30/30 | 100 | 90/90 | 100 | 95.9 to 100 |
| Negative | 0/30 | 100 | 0/30 | 100 | 0/30 | 100 | 0/90 | 100 | 95.9 to 100 |
| Positive | 30/30 | 100 | 30/30 | 100 | 30/30 | 100 | 90/90 | 100 | 95.9 to 100 |
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| VZV Ellen | | | | | | | | | 95% Confidence Interval |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Site #1 | | Site #2 | | Site #3 | | Agreement | | |
| | Rate of Detection | % Agreement | Rate of Detection | % Agreement | Rate of Detection | % Agreement | Rate of Detection | % Agreement | |
| Control | | | | | | | | | |
| Negative Control | 0/30 | 100 | 0/30 | 100 | 0/30 | 100 | 0/90 | 100 | 95.9 to 100 |
b. Linearity/assay reportable range:
Not applicable
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
The Solana® HSV 1+2/VZV Control Set is available for use with the kit. These controls are manufactured by ZeptoMetrix according to Quidel Corporation specifications. The positive control uses a mixture of highly purified, inactivated strains of HSV-1, HSV-2 and VZV in a HSV-1, HSV-2 and VZV DNA-free matrix. The negative control is the same HSV-1, HSV-2 and VZV DNA-free matrix. The final concentration of HSV-1, HSV-2 and VZV is based on the assay's LOD for the viral strains, and is intended to be near LOD. The controls are used to monitor the assay performance as follows:
i. The process control is used to monitor sample processing, to detect HDA inhibitory specimens and to confirm the integrity of assay reagents and Solana® instrument functionality. The process control is included in the Process Buffer tube.
ii. The external positive control is treated as a patient specimen. The control should be sampled and tested as if it were a specimen and processed as described in the Assay Procedure. The external positive control is intended to monitor substantial reagent and instrument failure.
iv. The external negative control is treated as a patient specimen. The control should be sampled and tested as if it were a specimen and processed as described in the Assay Procedure. The external negative control is used to detect reagent or environmental contamination (or carry-over) by HSV 1+2/VZV DNA or amplicons.
d. Detection limit:
The analytical sensitivity (limit of detection or LOD) of the Solana® HSV 1+2/VZV
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Assay was determined using quantified (TCID50/mL) cultures of two (2) HSV-1 strains, two (2) HSV-2 strains, and two (2) VZV strains, serially diluted in negative matrix. Each dilution was run as 20 replicates in the Solana® HSV 1+2/VZV assay. Analytical sensitivity (LOD) is defined as the lowest concentration at which at least $95\%$ of all replicates tested positive. The LOD for each virus strain tested is shown below:
| LOD | |
| --- | --- |
| Virus Strains | TCID50/mL |
| HSV-1 MacIntyre | 6.30 × 102 |
| HSV-1 316 | 5.47 × 104 |
| HSV-2 G | 6.67 × 103 |
| HSV-2 COMP | 1.62 × 105 |
| VZV Ellen | 1.49 × 10-1 |
| VZV 9939 | 1.65 × 102 |
# e. Analytical Reactivity (Inclusivity):
The inclusivity of the Solana® HSV 1+2/VZV Assay was further evaluated by functional testing of viral strains in addition to those strains used in the LOD study. The clinical panel consisted of two (2) strains of HSV-1, three (3) strains of HSV-2, and five (5) strains of VZV at concentrations near the level of detection (LOD) of the assay.
| Inclusivity Strains | TCID50/mL |
| --- | --- |
| HSV-1 Isolate #1 | 1.26 × 103 |
| HSV-1 Isolate #3 | 1.26 × 103 |
| HSV-2 Strain MS | 1.33 × 104 |
| HSV-2 Isolate #25 | 1.33 × 104 |
| HSV-2 Isolate #32 | 1.33 × 104 |
| VZV Strain 82 | 8.05 × 100 |
| VZV Strain 130 | 2.41 × 101 |
| VZV Strain 275 | 8.05 × 100 |
| VZV Strain B | 2.41 × 101 |
| VZV Strain D | 8.05 × 100 |
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# f. Analytical Specificity/Cross Reactivity:
A study was performed to evaluate the performance of the Solana® HSV 1+2/VZV Assay in the presence of sixty-four (64) microorganisms that could be found in lesion specimens. Each potentially cross-reactive microorganism was tested at a clinically relevant level. There was no cross reactivity observed with the sixty-four (64) microorganisms tested with the Solana® HSV 1+2/VZV Assay.
Cross Reactivity
| Potentially Cross-reactive Organisms | | | |
| --- | --- | --- | --- |
| Ognism | Test Concentration | Ognism | Test Concentration |
| Acholeplasma laidlawi | 7.10E+06 CFU/mL | Klebsiella pneumoniae | 1.61E+06 CFU/mL |
| Acinetobacter calcoaceticus | 9.27E+06 CFU/mL | Lactobacillus acidophilus | 2.49E+06 CFU/mL |
| Adenovirus 7 | 1.58E+05 TCID50/mL | Legionella pneumophila | 1.76E+06 CFU/mL |
| Bacteroides fragilis | 1.19E+06 CFU/mL | Measles virus | 1.95E+05 TCID50/mL |
| Bordetella bronchiseptica | 1.97E+06 CFU/mL | Mobiluncus mulieris | 2.54E+06 CFU/mL |
| Bordetella pertussis | 7.21E+06 CFU/mL | Moraxella cartarrhalis | 1.26E+06 CFU/mL |
| Candida albicans | 2.00E+06 CFU/mL | Mumps virus | 5.89E+05 TCID50/mL |
| Candida glabrata | 3.93E+06 CFU/mL | Mycoplasma hominis | 1.30E+06 CFU/mL |
| Chlamydia trachomatis | 3.00E+06 CFU/mL | Mycoplasma hyorhinis | 6.60E+06 CFU/mL |
| Chlamydophila pneumoniae | 1.25E+06 IFU/mL | Mycoplasma orale | 3.08E+06 CFU/mL |
| Clostridium perfringens | 1.06E+06 CFU/mL | Mycoplasma pneumoniae | 3.16E+06 CFU/mL |
| Coronavirus OC43 | 8.51E+05 TCID50/mL | Mycoplasma salivarium | 1.67E+06 CFU/mL |
| Corynebacterium diphtheriae | 1.51E+06 CFU/mL | Neisseria gonorrhoeae | 1.23E+06 CFU/mL |
| Coxsackievirus B4 | 3.16E+05 TCID50/mL | Parainfluenza Type 1 | 3.97E+05 TCID50/mL |
| Cytomegalovirus Towne VR- | 2.14E+05 TCID50/mL | Parainfluenza Type 2 | 3.15E+05 TCID50/mL |
| Echovirus 11 | 2.14E+05 TCID50/mL | Parainfluenza Type 3 | 2.56E+05 TCID50/mL |
| Enterococcus faecalis | 3.45E+06 CFU/mL | Parainfluenza Type 4 | 1.37E+05 TCID50/mL |
| Enterovirus 70 | 1.78E+05 TCID50/mL | Proteus mirabilis | 1.19E+06 CFU/mL |
| Epstein Barr Virus | 1.34E+05 vp/mL | Pseudomonas aeruginosa | 1.32E+06 CFU/mL |
| Escherichia coli | 8.42E+06 CFU/mL | RSV A Long | 1.95E+05 TCID50/mL |
| Gardnerella vaginalis | 1.20E+06 CFU/mL | RSV B Washington | 3.43E+05 TCID50/mL |
| Haemophilis influenza type A | 5.33E+06 CFU/mL | Rubella Virus | 2.09E+05 TCID50/mL |
| HBV synthetic DNA | 6.80E+05 cp/mL | Salmonella enteritidis | 5.40E+06 CFU/mL |
| HCV synthetic RNA | 1.96E+05 cp/mL | Salmonella typhimurium | 1.01E+06 CFU/mL |
| HHV-6 | 3.30E+05 TCID50/mL | Staphylococcus aureus | 1.02E+06 CFU/mL |
| HHV-7 | 1.15E+05 TCID50/mL | Staphylococcus | 2.00E+06 CFU/mL |
| HHV-8 | 1.26E+05 TCID50/mL | Streptococcus agalactiae | 2.20E+06 CFU/mL |
| HIV purified RNA | 1.60E+05 cp/mL | Streptococcus pneumoniae | 2.18E+06 CFU/mL |
| hMPV AI | 3.66E+05 TCID50/mL | Streptococcus pyogenes | 1.29E+06 CFU/mL |
| HPV | 4.30E+05 cp/uL | Toxoplasma gondii | 1.06E+06 tachyzotes/nL |
| Influenza A/Mexico/ 4108/2009 | 2.88E+05 vp/mL | Trichomonas vaginalis | 1.06E+06 tachyzotes/nL |
| Influenza B Hong Kong VR-791 | 1.91E+05 TCID50/mL | Ureaplasma uralyticum | 1.23E+06 CFU/mL |
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# Microbial Interference:
A study was performed to evaluate the performance of the Solana® HSV 1+2/VZV Assay in the presence of sixty-four (64) microorganisms that could be found in lesion specimens. Each potentially interfering microorganism was tested in the presence of at 2x LOD HSV-1, HSV-2 and VZV viruses, or negative matrix at clinically relevant levels of the microorganisms. The same microorganisms as listed above in the table for the Cross Reactivity Study were evaluated in the Microbial Interference Study and at the same levels listed in the table for Cross Reactivity. There was no interference observed with the sixty-four (64) organisms tested with the Solana® HSV 1+2/VZV Assay.
# g. Analytical Secificity/Interfering Substances:
The performance of Solana® HSV 1+2/VZV Assay was evaluated with potentially interfering substances that may be present in lesion specimens. A panel composed of twenty-six (26) substances was tested in the absence or presence of HSV-1, HSV-2, or VZV (MacIntyre, G, Ellen strains, respectively) at 2X LOD in the Solana® HSV 1+2/VZV Assay. There was no evidence of interference (false positive or false negative results) caused by the substances tested at the concentrations shown below.
| Potentially Interfering Substances | | | |
| --- | --- | --- | --- |
| Substance | Test Concentration | Substance | Test Concentration |
| Abreva | 7% | Female Urine | 7% |
| Acetamidophenol | 10 mg/mL | KY Jelly | 7% |
| Acyclovir | 7 mg/mL | Lanacane | 3.50% |
| Albumin | 3.3 mg/mL | Leukocytes | 2.5x10^5 cells/mL |
| Blood/EDTA | 0.63% | Listerine | 7% |
| Carmex | 7% | Male Urine | 7% |
| Casein | 7 mg/mL | Miconazole 1 | 7% |
| Chlorpheniramine | 5 mg/mL | Miconazole 3 | 7% |
| Colgate | 7% | Mucin | 60 μg/mL |
| Cornstarch | 2.5 mg/mL | Preparation H | 7% |
| Dextromethorphan | 5 mg/mL | Releev | 7% |
| Douche | 7% | Seminal Fluid | 2% |
| Feces | 0.22% | Tioconazole 1 | 7% |
# h. Competitive Interference Study:
A study was performed to demonstrate that detection of near LOD levels of each of HSV-1, HSV-2, or VZV is not impacted by high levels $(\geq 10^{5}\mathrm{TCID}_{50} / \mathrm{mL})$ of the other two viruses when tested with the Solana® HSV 1+2/VZV assay.
{12}
Near LOD HSV-1 (Strain MacIntyre, 2x LOD, $1.26 \times 10^{3} \mathrm{TCID}_{50} / \mathrm{mL}$) detection was not impacted by high levels of HSV-2 (Strain G, $1.00 \times 10^{5} \mathrm{TCID}_{50} / \mathrm{mL}$) or VZV (Isolate D, $1.23 \times 10^{5} \mathrm{TCID}_{50} / \mathrm{mL}$).
Near LOD HSV-2 (Strain G, 2x LOD, $1.26 \times 10^{3} \mathrm{TCID}_{50} / \mathrm{mL}$) detection was not impacted by high levels of HSV-1 (Isolate #17, $1.15 \times 10^{5} \mathrm{TCID}_{50} / \mathrm{mL}$), but was impacted by high levels of VZV (Isolate D, $1.23 \times 10^{5} \mathrm{TCID}_{50} / \mathrm{mL}$). Near LOD HSV-2 detection was observed after a 100-fold reduction of the VZV test concentration ($1.23 \times 10^{5} \mathrm{TCID}_{50} / \mathrm{mL}$).
Near LOD VZV (Strain Ellen, 2x LOD, $2.97 \times 10^{-1} \mathrm{TCID}_{50} / \mathrm{mL}$) detection was not impacted by high levels of HSV-1 (Isolate #17, $1.15 \times 10^{5} \mathrm{TCID}_{50} / \mathrm{mL}$) or HSV-2 (Strain G, $1.00 \times 10^{5} \mathrm{TCID}_{50} / \mathrm{mL}$).
i. Assay cut-off:
Not applicable
j. Sample Stability Studies:
## Transport Media (Swab) Compatibility and Stability:
HSV-1, HSV-2, and VZV virus stocks (HSV-1 MacIntyre, HSV-2 G, and VZV Ellen) were diluted to their respective 2x LOD concentrations in each of five (5) transport medium pooled negative matrix (Remel M4, Remel M4-RT, Remel M5, Remel M6, or UTM transport medium).
The transport media systems containing the contrived samples were stored at three different conditions: Condition 1) = room temperature $(30 \pm 2^{\circ} \mathrm{C})$ for 50 hours, Condition 2) = $2^{\circ}$ to $8^{\circ} \mathrm{C}$ for 8 days, and Condition 3) = $-20^{\circ} \mathrm{C}$ for 8 days.
HSV-1, HSV-2, and VZV samples at 2x LOD were stable when stored in M4, M4-RT, M5, M6, and UTM negative matrix for up to 50 hours at $30^{\circ}\mathrm{C} \pm 2^{\circ}\mathrm{C}$. HSV-1, HSV-2, and VZV samples were stable when stored in M4, M4-RT, M5, M6, and UTM negative matrix for up to 8 days at $2^{\circ}$ to $8^{\circ}\mathrm{C}$. HSV-1, HSV-2, and VZV samples were stable when stored in M4, M4-RT, M5, M6, and UTM negative matrix for up to 8 days at $-20^{\circ}\mathrm{C}$.
These stability data support the claim in the Package Insert that specimens can be stored at room temperature (up to $30^{\circ}\mathrm{C}$) for up to 48 hours, $2^{\circ}$ to $8^{\circ}\mathrm{C}$ or $-20^{\circ}\mathrm{C}$ for up to 7 days prior to processing.
## Processed Specimen Stability:
HSV-1, HSV-2, and VZV virus stocks (HSV-1 MacIntyre, HSV-2 G, and VZV
{13}
Ellen) were diluted to their respective 2x LOD concentrations in negative matrix. Each sample was added to Process Buffer tubes, which were stored at 2° to 8°C either before or after heat lysis and tested at 0, 24, 48, 72, and 73 hours post-storage.
Samples are stable in process buffer up to 73 hours at 2° to 8°C before and after the heat step.
These data support the claim in the Package Insert that specimens in Process Buffer Tubes may be stored at 2°C to 8°C for up to 72 hours before and after the heat step.
## Processed Specimen Stability - 95°C Lysis Time Flex Study:
HSV-1, HSV-2, and VZV virus stocks (HSV-1 MacIntyre, HSV-2 G, and VZV Ellen) were diluted to their respective 2x LOD concentrations in pooled negative matrix and tested in 3 replicates for each condition. The heat time conditions were 2 minutes, 3 minutes, 5 minutes, 10 minutes and 11 minutes.
HSV-1, HSV-2, VZV and the process control were detected for 3 of 3 replicates with all tested heat lysis times, indicating that the Solana® HSV 1+2/VZV Assay tolerates heat lysis times between 2 to 11 minutes at 95°C.
## Processed Specimen Stability - 95°C Lysis Temperature Flex Study:
HSV-1, HSV-2, and VZV virus stocks (HSV-1 MacIntyre, HSV-2 G, and VZV Ellen) were diluted to their respective 2x LOD concentrations in pooled negative matrix and tested in 3 replicates for each condition. The heat lysis temperature conditions were 92°C, 93°C, 95°C, 97°C and 98°C.
HSV-1, HSV-2, VZV and the process control were detected for 3 of 3 replicates with all tested heat lysis temperatures, indicating that the Solana® HSV 1+2/VZV tolerates heat lysis temperatures between 92° to 98°C for 5 minutes.
## 2. Comparison studies:
a. Method comparison with predicate device:
Not Applicable. Refer to the Clinical Section below.
b. Matrix comparison:
Not Applicable.
## 3. Clinical studies:
a. Clinical Sensitivity:
14
{14}
Not Applicable.
# b. Clinical specificity:
Not Applicable.
c. Other clinical supportive data (when a. and b. are not applicable):
# Clinical Performance:
Performance characteristics of the Solana® HSV 1+2/VZV Assay were established during a prospective study. One thousand and sixty-two (1062) fresh lesion specimens, collected for herpes simplex/varicella-zoster detection and identification, were tested at three (3) sites across the United States. A single specimen was collected per patient. The specimens were processed and tested with the Solana® HSV 1+2/VZV Assay on the Solana® instrument at the sites. Each specimen was also processed and inoculated into two (2) different cell culture systems within 72 hours of collection. The isolation and identification of HSV-1 and HSV-2 was performed using the FDA-cleared ELVIS HSV ID and D³ Typing Test. This testing was performed according to the manufacturer's product insert. The detection and isolation of VZV was performed by staining cells present in the specimen with an FDA-cleared VZV detection reagent (DSFA) and by culturing the specimen for 96-hours using commercially available mixed cell culture (H&V mixed cells from Diagnostic Hybrids, a Quidel Company) consisting of MRC-5 cells (human diploid fibroblast) and CV-1 cells (african green monkey kidney), and staining the cultures with the same FDA-cleared reagent used for DSFA. A specimen was considered positive for VZV if either the DSFA or the culture with DFA was positive. Testing of the comparator methods (culture with DFA) were performed at one central location.
The gender and age demographics of the patients enrolled in the study are shown below.
| Combined Study – Age and Gender Distribution (Cutaneous) | | |
| --- | --- | --- |
| Gender | Female | Male |
| Total | 111 | 164 |
| Age/Years | | |
| ≤ 5 | 4 | 5 |
| 6 to 21 | 10 | 33 |
| 22 to 59 | 68 | 112 |
| ≥ 60 | 29 | 14 |
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| Combined Study – Age and Gender Distribution (Mucocutaneous) | | |
| --- | --- | --- |
| Gender | Female | Male |
| Total | 552 | 69 |
| Age/Years | | |
| ≤ 5 | 5 | 16 |
| 6 to 21 | 141 | 18 |
| 22 to 59 | 366 | 22 |
| ≥ 60 | 40 | 13 |
| Combined Study – Age and Gender Distribution (Uncategorized Lesion Source) | | |
| --- | --- | --- |
| Gender | Female | Male |
| Total | 129 | 37 |
| Age/Years | | |
| ≤ 5 | 5 | 6 |
| 6 to 21 | 20 | 8 |
| 22 to 59 | 75 | 14 |
| ≥ 60 | 29 | 9 |
## Cutaneous Lesions
HSV-1: Two-hundred and seventy-five (275) active cutaneous lesion specimens were cultured for HSV-1, using the FDA-cleared ELVIS cell culture system and were also tested with the subject device for HSV-1 viral DNA. Samples which gave HSV-2 positive results from the ELVIS method were excluded from the HSV-1 performance calculation because of the inability of the ELVIS method to distinguish an HSV-1 positive sample when HSV-2 was detected first (n=26). The table below details the HSV-1 results for the remaining two-hundred and forty-nine (249) specimens.
| HSV-1 Results | | | |
| --- | --- | --- | --- |
| | Comparator: ELVIS® HSV ID and D³ Typing Test | | |
| Solana® HSV 1 + 2/VZV Assay | Positive | Negative | Total |
| Positive | 22 | 5* | 27 |
| Negative | 0 | 222 | 222 |
| Total | 22 | 227 | 249 |
| 95% CI | | | |
| Sensitivity | 22/22 | 100% | 85.1% to 100% |
| Specificity | 222/227 | 97.8% | 95.0% to 99.1% |
* Three (3) of the five (5) positives was positive by an additional RT-PCR assay.
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HSV-2: Two-hundred and seventy-five (275) active cutaneous lesion specimens were cultured for HSV-2, using the FDA-cleared ELVIS cell culture system and were also tested with the subject device for HSV-2 viral DNA. The table below details the HSV-2 results for the two-hundred and seventy-five (275) specimens.
| HSV-2 Results | | | |
| --- | --- | --- | --- |
| | Comparator: ELVIS® HSV ID and D³ Typing Test | | |
| Solana® HSV 1 + 2/VZV Assay | Positive | Negative | Total |
| Positive | 24 | 14* | 28 |
| Negative | 2** | 235 | 237 |
| Total | 26 | 249 | 275 |
| 95% CI | | | |
| Sensitivity | 24/26 | 92.3% | 75.9% to 97.9% |
| Specificity | 235/249 | 94.4% | 90.8% to 96.6% |
*Thirteen (13) of the fourteen (14) positives were positive by an additional RT-PCR assay.
** Two (2) of the two (2) negatives were positive by an additional RT-PCR assay.
VZV: Two-hundred and seventy-five (275) active cutaneous lesion specimens were cultured for VZV using the H&V mixed cells with DFA cell culture systems and were also tested with the subject device for VZV viral DNA. Due to the presence of either HSV-1 or HSV-2, fifty-one (51) specimens were excluded from analysis. Two (2) specimens were contaminated or had toxic cultures. These fifty-three (53) specimens have been excluded from analysis. The table below details the VZV results for the remaining two-hundred and twenty-two (222) specimens.
| VZV Results | | | |
| --- | --- | --- | --- |
| | Comparator: DSFA and Culture with DFA | | |
| Solana® HSV 1 + 2/VZV Assay | Positive | Negative | Total |
| Positive | 22 | 7* | 29 |
| Negative | 0 | 193 | 193 |
| Total | 22 | 200 | 222 |
| 95% CI | | | |
| Sensitivity | 22/22 | 100% | 85.1% to 100% |
| Specificity | 193/200 | 96.5% | 93.0% to 98.3% |
* Six (6) of the seven (7) positives were positive by an additional RT-PCR assay.
## Mucocutaneous Lesions
HSV-1: Six-hundred and twenty-one (621) active mucocutaneous lesion specimens were cultured for HSV-1, using the FDA-cleared ELVIS cell culture system and were also tested with the subject device for HSV-1 viral DNA. Seven (7) specimens were
{17}
contaminated in the ELVIS cell culture. Two (2) specimens were invalid in the Solana® HSV 1 + 2/VZV Assay. Two (2) specimens were contaminated and invalid. Samples which gave HSV-2 positive results from the ELVIS method were excluded from the HSV-1 performance calculation because of the inability of the ELVIS method to distinguish an HSV-1 positive sample when HSV-2 was detected first (n=109). Thus, one hundred and twenty (120) specimens were excluded from further analysis. The table below details the HSV-1 results for the remaining five hundred and one (501) specimens.
| HSV-1 Results | | | |
| --- | --- | --- | --- |
| | Comparator: ELVIS® HSV ID and D³ Typing Test | | |
| Solana® HSV 1 + 2/VZV Assay | Positive | Negative | Total |
| Positive | 113 | 14* | 127 |
| Negative | 0 | 374 | 374 |
| Total | 113 | 388 | 501 |
| 95% CI | | | |
| Sensitivity | 113/113 | 100% | 96.7% to 100% |
| Specificity | 374/388 | 96.4% | 94.0% to 97.8% |
* Six (6) of the fourteen (14) positives were positive by an additional RT-PCR assay.
HSV-2: Six-hundred and twenty-one (621) active mucocutaneous lesion specimens were cultured for HSV-2, using the FDA-cleared ELVIS cell culture system and were also tested with the subject device for HSV-2 viral DNA. Seven (7) specimens were contaminated in the ELVIS cell culture. Two (2) specimens were invalid in Solana® HSV 1 + 2/VZV Assay. Two (2) specimens were contaminated and invalid. These eleven (11) specimens were excluded from further analysis. The table below details the HSV-2 results for the remaining six-hundred ten (610) specimens.
| HSV-2 Results | | | |
| --- | --- | --- | --- |
| | Comparator: ELVIS® HSV ID and D³ Typing Test | | |
| Solana® HSV 1 + 2/VZV Assay | Positive | Negative | Total |
| Positive | 108 | 14* | 122 |
| Negative | 1** | 487 | 488 |
| Total | 109 | 501 | 610 |
| 95% CI | | | |
| Sensitivity | 108/109 | 99.1% | 95.0% to 99.8% |
| Specificity | 487/501 | 97.2% | 95.4% to 98.3% |
* Eleven (11) of the fourteen (14) positives were positive by an additional RT-PCR assay.
** One (1) of one (1) negative was positive by an additional RT-PCR assay.
VZV: Six-hundred twenty and one (621) active mucocutaneous lesion specimens
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were cultured for VZV using the H&V mixed cells with DFA cell culture system and were also tested with the subject device for VZV viral DNA. Due to the presence of either HSV-1 or HSV-2, two hundred and thirty-six (236) specimens were excluded from analysis. Nine (9) specimens were contaminated in culture, and four (4) specimens were invalid in the Solana® HSV 1 + 2/VZV Assay. These two hundred forty-nine (249) specimens have been excluded from analysis. The table below details the VZV results for the remaining three hundred and seventy-two (372) specimens.
| VZV Results | | | |
| --- | --- | --- | --- |
| | Comparator: DSFA and Culture with DFA | | |
| Solana® HSV 1 + 2/VZV Assay | Positive | Negative | Total |
| Positive | 4 | 5* | 9 |
| Negative | 0 | 363 | 363 |
| Total | 4 | 368 | 372 |
| 95% CI | | | |
| Sensitivity | 4/4 | 100% | 51.0% to 100% |
| Specificity | 363/368 | 98.6% | 96.9% to 99.4% |
* One (1) of the five (5) positives was positive by an additional RT-PCR assay.
Note: The data presented for the detection of VZV is consistent with the limited presence of VZV in mucocutaneous lesions. The use of mucocutaneous lesions has no discernible impact on the performance characteristics of Solana® HSV 1 + 2/VZV Assay.
# Uncategorized Lesions
HSV-1: One hundred and sixty-six (166) active lesion specimens (not categorized as cutaneous or mucocutaneous) were cultured for HSV-1, using the FDA-cleared ELVIS cell culture system and were also tested with the subject device for HSV-1 viral DNA. Samples which gave HSV-2 positive results from the ELVIS method were excluded from the HSV-1 performance calculation because of the inability of the ELVIS method to distinguish an HSV-1 positive sample when HSV-2 was detected first $(n = 18)$ . The table below details the HSV-1 results for the remaining one hundred and forty-eight (148) specimens.
| HSV-1 Results | | | |
| --- | --- | --- | --- |
| | Comparator: ELVIS® HSV ID and D3 Typing Test | | |
| Solana® HSV 1 + 2/VZV Assay | Positive | Negative | Total |
| Positive | 25 | 3* | 28 |
| Negative | 0 | 120 | 120 |
| Total | 25 | 123 | 148 |
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20
| 95% CI | | | |
| --- | --- | --- | --- |
| Sensitivity | 22/22 | 100% | 86.7% to 100% |
| Specificity | 120/123 | 97.6% | 93.1% to 99.2% |
* Three (3) of the three (3) positives was positive by an additional RT-PCR assay.
HSV-2: One hundred and sixty-six (166) active lesion specimens (not categorized as cutaneous or mucocutaneous) were cultured for HSV-2, using the FDA-cleared ELVIS cell culture system and were also tested with the subject device for HSV-2 viral DNA. The table below details the HSV-2 results for the one hundred sixty-six (166) specimens.
| HSV-2 Results | | | |
| --- | --- | --- | --- |
| | Comparator: ELVIS® HSV ID and D³ Typing Test | | |
| Solana® HSV 1 + 2/VZV Assay | Positive | Negative | Total |
| Positive | 18 | 5* | 23 |
| Negative | 0 | 143 | 143 |
| Total | 18 | 148 | 166 |
| 95% CI | | | |
| Sensitivity | 18/18 | 100% | 82.4% to 100% |
| Specificity | 143/148 | 96.6% | 92.3% to 98.6% |
* Five (5) of the five (5) positives were positive by an additional RT-PCR assay.
VZV: One hundred sixty-six (166) active lesion specimens (not categorized as cutaneous or mucocutaneous) were cultured for VZV using the H&V mixed cells with DFA cell culture systems and were also tested with the subject device for VZV viral DNA. Due the presence of either HSV-1 or HSV-2, forty-six (46) specimens have been excluded from analysis. One (1) specimen was contaminated in culture. These forty-seven (47) specimens have been excluded from analysis. The table below details the VZV results for the remaining one hundred nineteen (119) specimens.
| VZV Results | | | |
| --- | --- | --- | --- |
| | Comparator: DSFA and Culture with DFA | | |
| Solana® HSV 1 + 2/VZV Assay | Positive | Negative | Total |
| Positive | 17 | 6* | 23 |
| Negative | 0 | 96 | 96 |
| Total | 17 | 102 | 119 |
| 95% CI | | | |
| Sensitivity | 17/17 | 100% | 81.6% to 100% |
| Specificity | 96/102 | 94.1% | 87.8% to 97.3% |
*Five (5) of the six (6) positives were positive by an additional RT-PCR assay.
4. Clinical cut-off:
{20}
Not Applicable.
# 5. Expected Values:
The expected values of the Solana® HSV 1+2/VZV Assay were established during a prospective study conducted between February and May 2016. One thousand and sixty-two (1062) specimens were included in this study at three (3) sites across the United States. A single specimen was collected per patient. The specimens were processed and tested with the Solana® HSV 1+2/VZV Assay on the Solana® instrument at the sites.
The expected values for HSV-1, HSV-2, and VZV with the Solana® HSV 1+2/VZV Assay were calculated for the combined sites based on the category of specimen (cutaneous, mucocutaneous, or unknown lesion source) and the age of the patient.
| Combined Study – Expected Values (Cutaneous) (N=275) | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Age/Years | HSV-1 | | | HSV-2 | | | VZV | | |
| | Total # | Total Positive | Prevalence | Total # | Total Positive | Prevalence | Total # | Total Positive | Prevalence |
| ≤ 5 | 9 | 1 | 11.1% | 9 | 0 | N/A | 9 | 4 | 44.4% |
| 6 to 21 | 43 | 10 | 23.3% | 43 | 4 | 9.3% | 43 | 0 | N/A |
| 22 to 59 | 180 | 16 | 8.9% | 180 | 26 | 14.4% | 180 | 19 | 10.6% |
| ≥ 60 | 43 | 0 | N/A | 43 | 8 | 18.6% | 43 | 6 | 14.0% |
| Expected Values (Cutaneous) (N=275) | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Specimen Source | HSV-1 | | | HSV-2 | | | VZV | | |
| | Total # | Total Positive | Prevalence | Total # | Total Positive | Prevalence | Total # | Total Positive | Prevalence |
| Skin lesion | 105 | 10 | 9.5% | 105 | 19 | 18.1% | 105 | 1 | 1.0% |
| Genital | 170 | 17 | 10.0% | 170 | 19 | 11.2% | 170 | 28 | 16.5% |
| Combined Study – Expected Values (Mucocutaneous) (N=617)* | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Age/Years | HSV-1 | | | HSV-2 | | | VZV | | |
| | Total # | Total Positive | Prevalence | Total # | Total Positive | Prevalence | Total # | Total Positive | Prevalence |
| ≤ 5 | 21 | 4 | 19.0% | 21 | 0 | N/A | 21 | 1 | 4.8% |
| 6 to 21 | 158 | 41 | 25.9% | 158 | 29 | 18.4% | 158 | 0 | N/A |
| 22 to 59 | 385 | 74 | 19.2% | 385 | 89 | 23.1% | 385 | 8 | 2.1% |
| ≥ 60 | 53 | 11 | 20.8% | 53 | 5 | 9.4% | 53 | 1 | 1.9% |
* Four (4) specimens were invalid and removed from analysis
| Combined Study – Expected Values (Mucocutaneous) (N=617)* | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Specimen Source | HSV-1 | | | HSV-2 | | | VZV | | |
| | Total # | Total Positive | Prevalence | Total # | Total Positive | Prevalence | Total # | Total Positive | Prevalence |
| Skin lesion | 105 | 10 | 9.5% | 105 | 19 | 18.1% | 105 | 1 | 1.0% |
| Genital | 170 | 17 | 10.0% | 170 | 19 | 11.2% | 170 | 28 | 16.5% |
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| Anorectal | 26 | 7 | 26.9% | 26 | 7 | 26.9% | 26 | 1 | 3.8% |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Genital – vaginal/ cervical | 449 | 80 | 17.8% | 449 | 112 | 24.9% | 449 | 5 | 1.1% |
| Nares | 23 | 5 | 21.7% | 23 | 1 | 4.3% | 23 | 3 | 13.0% |
| Ocular | 7 | 2 | 28.6% | 7 | 0 | N/A | 7 | 1 | 14.3% |
* Four (4) specimens were invalid and removed from analysis
| Combined Study – Expected Values (Uncategorized Lesion Source) (N=166) | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Age/Years | HSV-1 | | | HSV-2 | | | VZV | | |
| | Total # | Total Positive | Prevalence | Total # | Total Positive | Prevalence | Total # | Total Positive | Prevalence |
| ≤ 5 | 11 | 1 | 9.1% | 11 | 0 | N/A | 11 | 0 | N/A |
| 6 to 21 | 28 | 10 | 35.7% | 28 | 0 | N/A | 28 | 2 | 7.1% |
| 22 to 59 | 89 | 15 | 16.9% | 89 | 18 | 20.2% | 89 | 14 | 15.7% |
| ≥ 60 | 38 | 2 | 5.3% | 38 | 5 | 13.2% | 38 | 8 | 21.1% |
## N. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.
## O. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
