(141 days)
The Savanna HSV 1+2/VZV Assay is an automated, rapid multianalyte real-time PCR test for the simultaneous qualitative detection and differentiation of herpes simplex virus type 1, herpes simplex virus type 2, and varicella-zoster virus DNA isolated from human 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. This in vitro diagnostic test is intended to aid in the diagnosis of patients with signs or symptoms of herpes simplex virus type 1, herpes simplex virus type 2, and varicella-zoster virus infection.
The Savanna 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 infections. The results of this test should not be used as the sole basis for diagnosis, treatment or other management decisions and must be combined with clinical observations, patient history and/or epidemiological information. Negative results do not preclude herpes simplex virus type 1, herpes simplex virus type 2, or varicella-zoster virus infection that is not detected by a cutaneous or mucocutaneous lesion swab specimen. Positive results do not rule out co-infection with other organisms. Additional laboratory testing (e.g., viral culture, immunoassay, serology) may be necessary for patient evaluation. Savanna HSV 1+2/VZV Assay is for professional use. The Savanna HSV 1+2/VZV Assay is intended for use only with the Savanna instrument.
Warning: The Savanna HSV 1+2/VZV Assay is not intended for use with the cerebrospinal fluid (CSF) or to aid in the diagnosis of HSV or VZV infections of the central nervous system (CNS). The Savanna HSV 1+2/VZV Assay is not intended for use in prenatal screening.
The Savanna HSV 1+2/VZV Assay consists of a single, self-contained assay cartridge employing real-time PCR technology for use with the Savanna instrument to detect and differentiate DNA from herpes simplex virus type 1, herpes simplex virus type 2 and varicella-zoster virus. In approximately 24 minutes, this platform extracts, amplifies and detects DNA present in cutaneous or mucocutaneous lesion swab specimens obtained from symptomatic patients and placed in transport media.
To initiate the assay, a patient cutaneous or mucocutaneous lesion swab specimen in transport medium is transferred via the supplied transfer pipette to the Liguid Sample Port of the Test Cartridge. The user closes the Sample Port and inserts the Test Cartridge into the Savanna instrument, initiating sample processing. The sample containing human DNA is pushed out of the Sample Port by lysis buffer, which then rehydrates the Process Internal Control (IC), and together with the paramagnetic nucleic acid binding particles, are pumped into the extraction chamber. The solution is mixed, and virus and/ or bacteria are further lysed by sonication within the extraction chamber. Specimen and IC DNA are bound to, washed and then eluted off the paramagnetic particles. The purified specimen DNA and IC solution is used to rehydrate four individual lyophilized master mixes. Each master mix is pumped into a PCR chamber and Taq-man® multiplex real-time PCR reactions are carried out under optimized conditions, generating amplicons for the targeted pathogen (if present) and the Process Internal Control (IC).
Each master mix contains primers and dual-labeled probes unique for the pathogen targets and the IC. The probes are labeled with a fluorophore on one end and a quencher on the other end. Target DNA sequences are amplified by pathogen-specific primers and detected by correspondingly specific fluorescence probes. The IC targets are also amplified by specific primers and detected by an IC-specific fluorescence probe. A polymerase included in the master mix cleaves the probes bound to complementary DNA sequences, separating the fluorophore from the quencher. This step generates a signal and if it surpasses multiple defined thresholds, the sample is reported as positive for the detected target sequence.
The Savanna instrument will display the test results (Positive or Invalid) on the main bay screen.
The provided text describes the performance characteristics and clinical studies of the Savanna HSV 1+2/VZV Assay, which is an in vitro diagnostic (IVD) device for the detection and differentiation of herpes simplex virus type 1, herpes simplex virus type 2, and varicella-zoster virus DNA. It is not an AI/ML device in the context of typical FDA AI/ML medical device submissions, as it is a molecular diagnostic test. Therefore, many of the requested points regarding AI/ML device evaluation (like human-in-the-loop, expert consensus for ground truth, MRMC studies, number of experts for ground truth, adjudication methods, and sample size for training set) are not applicable to this type of device.
However, I can extract the acceptance criteria and performance data for this diagnostic assay as presented. The study aims to demonstrate substantial equivalence to a predicate device, the Solana HSV 1+2/VZV Assay (K162451), not to prove performance of an AI model.
1. A table of acceptance criteria and the reported device performance
The document does not explicitly state "acceptance criteria" in a tabulated format for the clinical performance. Instead, it presents the results of the clinical studies with Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) values with their confidence intervals, comparing the Savanna Assay to a commercially available RT-PCR comparator method. For laboratory studies, the acceptance criteria are implied by the results (e.g., >95% positivity for LoD, 100% detection for inclusivity, no interference/cross-reactivity).
I will present the clinical performance results as the "reported device performance" against an implied high standard of agreement with the comparator method.
Table: Reported Device Performance (Clinical Study 1 & 2)
| Analyte | Specimen Type | Study | Reported PPA (95% CI) | Reported NPA (95% CI) |
|---|---|---|---|---|
| HSV-1 | Cutaneous | Clinical Study 1 (Fresh) | 92.00% (75.04% - 97.78%) | 99.45% (96.95% - 99.90%) |
| Mucocutaneous | Clinical Study 1 (Fresh) | 100.00% (95.47% - 100.00%) | 96.36% (93.60% - 97.95%) | |
| Cutaneous | Clinical Study 2 (Frozen) | 100.00% (87.55% - 100.00%) | 96.83% (89.14% - 99.13%) | |
| Mucocutaneous | Clinical Study 2 (Frozen) | 100.00% (88.31% - 100.00%) | 100.00% (90.11% - 100.00%) | |
| HSV-2 | Cutaneous | Clinical Study 1 (Fresh) | 92.86% (68.53% - 98.73%) | 100.00% (98.05% - 100.00%) |
| Mucocutaneous | Clinical Study 1 (Fresh) | 94.34% (84.63% - 98.06%) | 99.09% (97.36% - 99.69%) | |
| Cutaneous | Clinical Study 2 (Frozen) | 100.00% (88.65% - 100.00%) | 100.00% (93.98% - 100.00%) | |
| Mucocutaneous | Clinical Study 2 (Frozen) | 100.00% (79.62% - 100.00%) | 97.96% (89.31% - 99.64%) | |
| VZV | Cutaneous | Clinical Study 1 (Fresh) | 100.00% (90.60% - 100.00%) | 99.41% (96.74% - 99.90%) |
| Mucocutaneous | Clinical Study 1 (Fresh) | 100.00% (56.56% - 100.00%) | 100.00% (98.99% - 100.00%) | |
| Cutaneous | Clinical Study 2 (Frozen) | 100.00% (81.57% - 100.00%) | 100.00% (95.00% - 100.00%) | |
| Mucocutaneous | Clinical Study 2 (Frozen) | 100.01% (51.02% - 100.01%) | 100.01% (93.98% - 100.00%) |
2. Sample size used for the test set and the data provenance
-
Clinical Study 1 (Fresh Samples):
- Sample Size: 590 residual specimens (207 cutaneous, 383 mucocutaneous).
- Data Provenance: United States, from symptomatic patients suspected of HSV-1, HSV-2, or VZV infection. Retrospective (residual specimens).
-
Clinical Study 2 (Frozen Residual Samples):
- Sample Size: 154 evaluable samples.
- Data Provenance: Not explicitly stated but implies U.S. as it's a supplement to Clinical Study #1. Retrospective (residual frozen samples).
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This is not applicable as this is an IVD device, not an AI/ML device relying on human expert labels for ground truth. The ground truth is established by a comparator FDA-cleared nucleic acid amplification test.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
Not applicable. The ground truth is determined by the results of an FDA-cleared comparator nucleic acid amplification test, not by human adjudication of images.
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
Not applicable. This is an IVD device, not an AI/ML device intended to assist human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
The device is a standalone diagnostic assay (real-time PCR test on the Savanna instrument). Its performance is evaluated independently against a comparator method. The results presented (PPA, NPA) represent this standalone performance.
7. The type of ground truth used
The ground truth for the clinical studies was established by comparison to FDA-cleared nucleic acid amplification tests (comparator method).
8. The sample size for the training set
Not applicable. This is not an AI/ML device that requires a "training set" in the context of machine learning model development. The robust performance of an IVD often relies on extensive analytical studies (LoD, inclusivity, cross-reactivity, precision, etc.) and clinical validation.
9. How the ground truth for the training set was established
Not applicable, as there is no "training set" in the AI/ML sense. The analytical performance was established through various laboratory studies (e.g., Limit of Detection, Inclusivity, Cross-Reactivity, Precision) using well-characterized viral strains and matrices.
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left, there is a symbol representing the Department of Health & Human Services - USA. To the right of the symbol, there is the FDA logo in blue, with the words "U.S. FOOD & DRUG" above the word "ADMINISTRATION".
Quidel Corporation % Selena Liu Senior Regulatory Affairs Specialist QuidelOrtho Corporation 9975 Summers Ridge Road San Diego. California 92121
Re: K232286
Trade/Device Name: Savanna HSV 1+2/VZV Assay, Savanna HSV 1+2/VZV Control Set, Savanna Instrument Regulation Number: 21 CFR 866.3309 Regulation Name: Herpes Virus Nucleic Acid-Based Cutaneous And Mucocutaneous Lesion Panel Regulatory Class: Class II Product Code: PGI Dated: November 21, 2023 Received: November 21, 2023
Dear Selena Liu:
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 (the Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrb/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device"
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(https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review. the OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE(@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely, Ryan C.
Karsner -S Digitally signed by Ryan Date: 2023.12.20
11:54:38 -05'00' Ryan Karsner, MD Deputy Assistant Director Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Ouality Center for Devices and Radiological Health
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Indications for Use
510(k) Number (if known) K232286
Device Name
Savanna HSV 1+2/VZV Assay Savanna HSV 1+2/VZV Assay Control Set, Savanna Instrument
Indications for Use (Describe)
The Savanna HSV 1+2/VZV Assay is an automated, rapid multianalyte real-time PCR test for the simultaneous qualitative detection and differentiation of herpes simplex virus type 1, and varicella-zoster virus DNA isolated from human 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. This in vitro diagnostic test is intended to aid in the diagnosis of patients with signs or symptoms virus type 1, herpes simplex virus type 2, and varicella-zoster virus infection.
The Savanna HSV 1+2/VZV Assay is intended to aid in the diagnosis of herpes simplex virus 2 and varicella-zoster virus active infections. The results of this test should not be used as the sole basis for diagnosis, treatment or other management decisions and must be combined with clinical observations, patient history and/or epidemiological information. Negative results do not preclude herpes simplex virus type 2, or varicella-zoster virus infection that is not detected by a cutaneous lesion swab specimen. Positive results do not rule out co-infection with other organisms. Additional laboratory testing (e.g., viral culture, immunoassay, serology) may be necessary for patient evaluation. Savanna HSV 1+2/VZV Assay is for professional use. The Savanna HSV 1+2/VZV Assay is intended for use only with the Savanna instrument.
Warning: The Savanna HSV 1+2/VZV Assay is not intended for use with the cerebrospinal fluid (CSF) or to aid in the diagnosis of HSV or VZV infections of the central nervous system (CNS). The Savanna HSV 1+2/VZV Assay is not intended for use in prenatal screening.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| ☑ Prescription Use (Part 21 CFR 801 Subpart D) | ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
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Image /page/3/Picture/0 description: The image features the logo for Quidel. The logo consists of a square with rounded corners, filled with a gradient of colors resembling a rainbow spectrum. A smaller, solid blue square is positioned in the upper right corner of the larger square, creating a layered effect. Below the square is the word "QUIDEL" in a simple, sans-serif font.
510(K) SUMMARY
Submitter
Quidel Corporation 10165 McKellar Court San Diego, CA 92121 Telephone: (800) 874-1517
Submission Contact
Selena Liu Senior Regulatory Affairs Specialist (619) 818-6642
Date Prepared
July 31, 2023
Proprietary and Established Names
Savanna HSV 1+2/VZV Assay Savanna HSV 1+2/VZV Control Set Savanna Instrument
Classification
| Product Code | Classificationon | RegulatorySection | Description |
|---|---|---|---|
| PGI | II | 866.3309 | Herpes Virus (Vzv, Hsv1, Hsv2), DNADetection Assay For Cutaneous AndMucocutaneous Lesion Samples |
Panel
Microbiology
Predicate Device
Solana HSV 1+2/VZV Assay (K162451)
Intended Use
The Savanna HSV 1+2/VZV Assay is an automated, rapid multianalyte real-time PCR test for the simultaneous qualitative detection and differentiation of herpes simplex virus type 1, herpes simplex virus type 2, and varicella-zoster virus DNA isolated from human 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. This in vitro diagnostic test is intended to aid in the diagnosis of patients with signs or symptoms of herpes simplex virus type 1, herpes simplex virus type 2, and varicella-zoster virus infection.
The Savanna HSV 1+2/VZV Assay is intended to aid in the diagnosis of herpes simplex virus 1, herpes
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simplex virus 2 and varicella-zoster virus active infections. The results of this test should not be used as the sole basis for diagnosis, treatment or other management decisions and must be combined with clinical observations, patient history and/or epidemiological information. Negative results do not preclude herpes simplex virus type 1, herpes simplex virus type 2, or varicella-zoster virus infection that is not detected by a cutaneous or mucocutaneous lesion swab specimen. Positive results do not rule out co-infection with other organisms. Additional laboratory testing (e.g., viral culture, immunoassay, serology) may be necessary for patient evaluation. Savanna HSV 1+2/VZV Assay is for professional use. The Savanna HSV 1+2/VZV Assay is intended for use only with the Savanna instrument.
Warning: The Savanna HSV 1+2/VZV Assay is not intended for use with the cerebrospinal fluid (CSF) or to aid in the diagnosis of HSV or VZV infections of the central nervous system (CNS). The Savanna HSV 1+2/VZV Assay is not intended for use in prenatal screening.
Device Description
The Savanna HSV 1+2/VZV Assay consists of a single, self-contained assay cartridge employing real-time PCR technology for use with the Savanna instrument to detect and differentiate DNA from herpes simplex virus type 1, herpes simplex virus type 2 and varicella-zoster virus. In approximately 24 minutes, this platform extracts, amplifies and detects DNA present in cutaneous or mucocutaneous lesion swab specimens obtained from symptomatic patients and placed in transport media.
To initiate the assay, a patient cutaneous or mucocutaneous lesion swab specimen in transport medium is transferred via the supplied transfer pipette to the Liguid Sample Port of the Test Cartridge. The user closes the Sample Port and inserts the Test Cartridge into the Savanna instrument, initiating sample processing. The sample containing human DNA is pushed out of the Sample Port by lysis buffer, which then rehydrates the Process Internal Control (IC), and together with the paramagnetic nucleic acid binding particles, are pumped into the extraction chamber. The solution is mixed, and virus and/ or bacteria are further lysed by sonication within the extraction chamber. Specimen and IC DNA are bound to, washed and then eluted off the paramagnetic particles. The purified specimen DNA and IC solution is used to rehydrate four individual lyophilized master mixes. Each master mix is pumped into a PCR chamber and Taq-man® multiplex real-time PCR reactions are carried out under optimized conditions, generating amplicons for the targeted pathogen (if present) and the Process Internal Control (IC).
Each master mix contains primers and dual-labeled probes unique for the pathogen targets and the IC. The probes are labeled with a fluorophore on one end and a quencher on the other end. Target DNA sequences are amplified by pathogen-specific primers and detected by correspondingly specific fluorescence probes. The IC targets are also amplified by specific primers and detected by an IC-specific fluorescence probe. A polymerase included in the master mix cleaves the probes bound to complementary DNA sequences, separating the fluorophore from the quencher. This step generates a signal and if it surpasses multiple defined thresholds, the sample is reported as positive for the detected target sequence.
The Savanna instrument will display the test results (Positive or Invalid) on the main bay screen.
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Comparison with Predicate
| Features | Predicate Device | New Device |
|---|---|---|
| Solana HSV 1+2/VZV Assay (K162451) | Savanna HSV 1+2/VZV Assay (K232286) | |
| Intended Use | The Solana HSV 1+2/VZV Assay is an in vitrodiagnostic test, using isothermal amplificationtechnology (helicase dependent amplification,HDA), for the qualitative detection anddifferentiation of herpes simplex virus type 1,herpes simplex virus type 2, and varicella-zostervirus DNA isolated and purified from cutaneousor mucocutaneous lesion samples obtained fromsymptomatic patients suspected of active herpessimplex virus 1, herpes simplex virus 2 and/orvaricella-zoster infection. The Solana HSV1+2/VZV Assay is intended to aid in thediagnosis of herpes simplex virus 1, herpessimplex virus 2 and varicella-zoster virus activecutaneous or mucocutaneous infections.Negative results do not preclude herpes simplexvirus 1, herpes simplex virus 2 and varicella-zoster virus infections and should not be used asthe sole basis for diagnosis, treatment, or othermanagement decisions. The Solana HSV1+2/VZV Assay is intended for use only with theSolana instrument.Warning: The Solana HSV 1 + 2/VZV Assay isnot intended for use with cerebrospinal fluid orto aid in the diagnosis of HSV or VZV infectionsof the central nervous system. The Solana HSV1 + 2/VZV Assay is not intended for use inprenatal screening. | The Savanna HSV 1+2/VZV Assay is anautomated, rapid, multianalyte real-time PCRtest for the simultaneous qualitative detectionand differentiation of herpes simplex virus type1, herpes simplex virus type 2, and varicella-zoster virus DNA isolated from humancutaneous or mucocutaneous lesion samplesobtained from symptomatic patients suspected ofactive herpes simplex virus 1, herpes simplexvirus 2 and/or varicella-zoster infection. This invitro diagnostic test is intended to aid in thediagnosis of patients with signs or symptoms ofherpes simplex virus type 1, herpes simplex virustype 2, and varicella-zoster virus infection.The Savanna HSV 1+2/VZV Assay is intendedto aid in the diagnosis of herpes simplex virus 1,herpes simplex virus 2 and varicella-zoster virusactive infections. The results of this test shouldnot be used as the sole basis for diagnosis,treatment or other management decisions andmust be combined with clinical observations,patient history and/or epidemiologicalinformation. Negative results do not precludeherpes simplex virus type 1, herpes simplex virustype 2, or varicella-zoster virus infection that isnot detected by a cutaneous or mucocutaneouslesion swab specimen. Positive results do notrule out co-infection with other organisms.Additional laboratory testing (e.g., viral culture,immunoassay, serology) may be necessary forpatient evaluation. Savanna HSV 1+2/VZVAssay is for professional use. The Savanna HSV1+2/VZV Assay is intended for use only with theSavanna instrument.Warning: The Savanna HSV 1+2/VZV Assay isnot intended for use with the cerebrospinal fluid(CSF) or to aid in the diagnosis of HSV or VZVinfections of the central nervous system (CNS).The Savanna HSV 1+2/VZV Assay is notintended for use in prenatal screening. |
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Image /page/6/Figure/0 description: The image shows the logo for QuidelOrtho Corporation. The logo features a square with a smaller square cut out of the top left corner. The larger square is filled with a gradient of colors, ranging from red and orange at the top to blue and purple at the bottom. The word "QUIDEL" is written in a sans-serif font below the square.
| Features | Predicate DeviceSolana HSV 1+2/VZV Assay (K162451) | New Device Savanna HSV 1+2/VZVAssay (K232286) |
|---|---|---|
| Instrument | Solana | Savanna |
| Qualitative | Yes | Yes |
| Analyte | Viral DNA from HSV-1, HSV-2 and VZV | Viral DNA from HSV-1, HSV-2 and VZV |
| SpecimenTypes | Cutaneous or mucocutaneous lesion swabsin transport medium | Cutaneous or mucocutaneous lesion swabsin transport medium |
| Test Principle | Isothermal Helicase-DependentAmplification (HDA) | PCR |
| AutomatedAnalysis | Yes | Yes |
| DevelopmentTime | 50 min | Within 24 min |
| Kit Storage | 2°C to 8°C | 2°C to 30°C |
| ExternalControls | Positive and Negative Controls (Availableas a separate kit) | Positive and Negative Controls (Availableas a separate kit) |
| QualityControlFeatures | Competitive Process Control (PRC) | Process Internal Control (IC) |
Performance Data
Numerous studies were undertaken to document the performance characteristics and the substantial equivalence of the test to the predicate device. These studies included the following:
Limit of Detection
The limits of detection (LoD) for the Savanna HSV 1+2/VZV Assay were determined using two types/strains of HSV-1, two types/strains of HSV-2 and two types/strains of VZV, serially diluted in negative matrix. The LoD for each pathogen is listed below in Table 1.
| Pathogen | Type/ Strain ID | LoD (TCID50/mL) | LoD (cp/mL) |
|---|---|---|---|
| HSV-1 | Isolate 2 | 1.16E+02 | 6.65E+02 |
| HSV-1 | Macintyre | 1.08E-03 | 2.86E+02 |
| HSV-2 | Strain G | 2.50E+01 | 1.27E+04 |
| MS | 8.51E+00 | 7.64E+01 | |
| VZV | Ellen | N/A | 3.32E+03 |
| VZV | Strain 82 | N/A |
Table 1. Savanna HSV 1+2/VZV Limit of Detection
Co-spike Limit of Detection
Co-spike study demonstrated that multi-analyte preparation does not impact the LoD for the Savanna HSV 1+2/VZV Assay as established in Limit of Detection Study. DNA of one strain of each of HSV-1, HSV-2 and VZV were mixed at 1x LoD level and evaluated with three kit lots. The co-spiked multi-analyte sample mix showed >95% positivity for each target DNA, verifying that the co-spike does not impact the LoD.
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Image /page/7/Picture/0 description: The image shows the logo for QuidelOrtho Corporation. The logo features a square shape with rounded corners, filled with a gradient of colors resembling a color wheel. Below the square is the word "QUIDEL" in a simple, sans-serif font. The logo is clean and modern, suggesting innovation and diversity.
Inclusivity
Inclusivity, or analytical reactivity, for Savanna HSV 1+2/VZV Assay was demonstrated using four additional strains of HSV-1 (Isolate 3, Isolate 11, Isolate 20), four additional strains of HSV-2 (Isolate 6, Isolate 9, Isolate 20) and five additional strains of VZV (AV923L, 9939, Isolate B, 275, Isolate D). All pathogens tested were detected by the assay at the following concentrations (Table 2).
| Virus | Type/Strain | Concentration in UTM(TCID50/mL) | Concentration inUTM (cp/mL) | Inclusive (Yes/No) |
|---|---|---|---|---|
| HSV-1 | Isolate 3 | 4.00E+00 | 8.56E+02 | Yes |
| Isolate 7 | 1.72E+01 | Not Available | Yes | |
| Isolate 11 | 2.53E+01 | Not Available | Yes | |
| Isolate 20 | 5.45E+01 | 1.40E+02 | Yes | |
| HSV-2 | Isolate 6 | 2.94E+00 | 2.54E+03 | Yes |
| Isolate 9 | 2.94E+00 | 3.26E+02 | Yes | |
| Isolate 10 | 2.94E+00 | 1.34E+02 | Yes | |
| Isolate 20 | 2.94E+00 | Not Available | Yes | |
| VZV | AV923L | Not Available | 4.00E+02 | Yes |
| 9939 | 1.05E+01 | 1.09E+03 | Yes | |
| Isolate B | Not Available | 8.20E+02 | Yes | |
| 275 | Not Available | 2.88E+02 | Yes | |
| Isolate D | Not Available | 1.65E+03 | Yes |
In silico Inclusivity Analysis
Specific nucleic acid sequences used in the Savanna HSV 1+2/VZV Assay target the highly conserved regions of each pathogen. The inclusivity of the assay was established through in silico analyses of available HSV-1. HSV-2 and VZV sequences in NCBI databases. The analyses determined that the primer and probe sets for HSV-1, HSV-2 and VZV have high homologies toward their respective target sequences as summarized in Table 3.
| Table 3. Summary of Savanna HSV 1+2/VZV Assay Oligo Homologies | |||
|---|---|---|---|
| ---------------------------------------------------------------- | -- | -- | -- |
| Analyte | Total # Aligned Sequences(%) | Homology Range |
|---|---|---|
| HSV-1 | 136 (100%) | 93.3-100% |
| HSV-2 | 284 (100%) | 93.33-100% |
| VZV | 181 (100%) | 100% |
Cross Reactivity/Microbial Interference
The potential cross reactivity and microbial interference of 22 viral isolates and 38 bacterial and fungal microorganisms were evaluated in the Savanna HSV 1+2/VZV Assay. None of the viruses or microorganisms listed below in Table 4 showed signs of cross reactivity or microbial interference at the concentrations listed, in the presence or absence of the target analytes.
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| Condition Description | Virus/Bacteria/FungusConcentration | Condition Description | Virus/Bacteria/FungusConcentration |
|---|---|---|---|
| Acholeplasma laidlawi | 1.00E+06 CFU/mL | Haemophilus influenzaeType B | 1.00E+06 CFU/mL |
| Acinetobactercalcoaceticus | 1.00E+06 CFU/mL | Hepatitis A virus | 2.70E+05 cp/mL |
| Acinetobacter lwoffii | 1.01E+06 CFU/mL | Hepatitis B virus | 2.45E+05 cp/mL |
| Adenovirus 7 | 1.04E+05 TCID50/mL | Hepatitis C virus | 4.15E+05 cp/mL |
| Bacteroides fragilis | 1.00E+06 CFU/mL | HIV-1 Type 1 | 1.95E+05 cp/mL |
| Bordetellabronchiseptica | 1.06E+06 CFU/mL | Human Herpes virusHHV6 | ≥ 1.01E+05 TCID50/mL |
| Bordetella pertussis | 1.01E+06 CFU/mL | Human Herpes virusHHV7 | 2.34E+04 TCID50/mL |
| Candida albicans | 1.00E+06 CFU/mL | Human Herpes virusHHV8 | 1.01E+05 TCID50/mL |
| Candida glabrata | 1.03E+06 CFU/mL | HumanMetapneumovirus A1 | 1.90E+05 TCID50/mL |
| Candida krusei | 1.14E+06 CFU/mL | Human papillomavirusHPV-16 | 2.85E+05 cp/mL |
| Candida parapsilosis | 1.20E+06 CFU/mL | Human papillomavirusHPV-18 | 2.60E+05 cp/mL |
| Candida tropicalis | 1.04E+06 CFU/mL | Klebsiella pneumoniae | 1.00E+06 CFU/mL |
| Chlamydia trachomatis | 1.06E+06 CFU/mL | Lactobacillusacidophilus | 1.04E+06 CFU/mL |
| Chlamydophilapneumoniae | 1.13E+06 CFU/mL | Measles virus | 1.04E+05 TCID50/mL |
| Clostridium perfringens | 1.00E+06 CFU/mL | Mobiluncus mulieris | 1.00E+06 CFU/mL |
| Coronavirus OC43 | 1.00E+05 TCID50/mL | Moraxella catarrhalis | 1.34E+06 CFU/mL |
| Coxsackievirus B1 | 1.00E+05 TCID50/mL | Mycoplasma orale | 1.00E+06 CFU/mL |
| Cutibacterium acnes | 1.00E+06 CFU/mL | Mycoplasmapneumoniae | 1.00E+06 CFU/mL |
| Cytomegalovirus | 1.00E+05 TCID50/mL | Neisseria gonorrhoeae | 1.00E+06 CFU/mL |
| Cytomegalovirus Towne | 8.00E+04 TCID50/mL | Neisseria meningitidis | 1.09E+06 CFU/mL |
| Echovirus 11 | 1.40E+05 TCID50/mL | Prevotellamelaninogenica | 1.20E+06 CFU/mL |
| Enterobacter cloacae | 1.04E+06 CFU/mL | Proteus mirabilis | 1.04E+06 CFU/mL |
| Enterococcus faecalis | 1.04E+06 CFU/mL | Rubella virus; Strain:RA 27/3 | 1.00E+05 TCID50/mL |
| Enterovirus 70 | 1.00E+05 TCID50/mL | Staphylococcus aureus | 1.15E+06 CFU/mL |
| Epstein Barr (EBV) | 6.05E+06 cp/mL | Staphylococcus aureus(MRSA) | 1.03E+06 CFU/mL |
| Escherichia coli | 1.00E+06 CFU/mL | Staphylococcussaprophyticus | 1.15E+06 CFU/mL |
| Fusobacteriumnucleatum | 1.07E+06 CFU/mL | Streptococcusagalactiae | 1.13E+06 CFU/mL |
| Gardnerella vaginalis | 1.03E+06 CFU/mL | Streptococcuspneumoniae | 1.20E+06 CFU/mL |
| Haemophilus ducreyi | 1.00E+06 CFU/mL | Streptococcus pyogenes | 3.17E+06 CFU/mL |
| Haemophilus influenzae(Type A) | 1.00E+06 CFU/mL | Streptococcussalivarius | 1.00E+06 CFU/mL |
Table 4. Potential-Cross-Reacting and Interfering Viruses and Microorganisms evaluated
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Interfering Substances
The performance of Savanna HSV 1+2/VZV Assay was evaluated with potentially interfering substances that may be present in lesion specimens. Several endogenous substances, over the counter (OTC) products, and prescription medications were evaluated with the Savanna HSV 1+2/VZV Assay. None of the substances in Table 5 interfered with the assay at the levels listed below.
| Substance | Active Ingredient | Test Concentration |
|---|---|---|
| Blood/EDTA | N/A | 0.63% |
| Casein | Casein Bovine Milk | 7 mg/mL |
| Feces | N/A | 2.5 mg/mL |
| Female Urine | Urea | 7% |
| Leukocytes | N/A | 2.5x105 cells/mL |
| Male Urine | Urea | 3.5% |
| Mucus (Mucin, bovine submaxillary gland, type I-S) | Mucin | 5% (w/v) |
| Seminal fluid | Semen | 2% |
| Abreva Docosanol | Docosanol | 3.5% (w/v) |
| Acetaminophen | Acetaminophen | 1.75% (w/v) |
| Anti-itch cream | Benzalkonium chloride | 3.5% (w/v) |
| Balneol Hygienic Cleansing Lotion | N/A | 3.5% (w/v) |
| Carmex Cold Sore Lip Balm | Benzocaine, White Petrolatum | 3.5% (w/v) |
| Chlor-Trimeton | Chlorpheniramine maleate | 1.25 mg/mL |
| Clotrimazole 3 Vaginal Cream | Clotrimazole | 3.5% (w/v) |
| Cornstarch | N/A | 1.25 mg/mL |
| Dextromethorphan hydrobromide (i.e. Mucinex) | Dextromethorphan, Guaifenesin, Phenylephrine | 5 mg/mL |
| Douche | Decyl Glucoside; Octoxynol-9 | 7% (w/v) |
| K-Y Brand Jelly | Glycerol | 7% (w/v) |
| Lanacane | 3% w/w Benzocaine | 3.5% (w/v) |
| Lip Clear Lysine+ | Menthol | 3.5% (w/v) |
| Listerine | Thymol | 7% (w/v) |
| Miconazole 1 | N/A | 7% (w/v) |
| Miconazole 3 | N/A | 7% (w/v) |
| Monistat 1 | N/A | 7% (w/v) |
| Monistat 3 | N/A | 7% (w/v) |
| Preparation H | Witch Hazel | 3.5% (w/v) |
| Releev | Benzalkonium chloride | 3.5% (w/v) |
| Toothpaste | Sodium Fluoride | 7% (w/v) |
| Triconazole 1 | Tioconazole | 7% (w/v) |
Table 5. Potential Interfering Substances evaluated
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| Substance | Active Ingredient | Test Concentration |
|---|---|---|
| Vagisil Cream | Benzocaine, Resorcinol | 7% (w/v) |
| YeastGard | Sodium Borate | 7% (w/v) |
| Acyclovir | Acyclogauanosine | 7 mg/mL |
| Cidofovir | Cidofovir Hydrate | 2.5 mg/mL |
| Foscarnet | Foscarnet Sodium | 1.25 mg/mL |
| Ganciclovir | Ganciclovir | 2.5 mg/mL |
Competitive Interference
A competitive interference study was conducted to evaluate the performance of the Savanna HSV 1+2/VZV Assay using samples containing 2 target analytes at different combination of high and low analyte concentrations. Each sample was prepared with one of the analytes at 3X LoD and the other analytes at 10X, 500X or 1000X LoD in negative buccal matrix. Five replicates per sample were evaluated. When competitive interference was observed (shaded in Table 6), titration of the high-level analyte was done and tested. Results are listed in Table 6.
| Low Analyte | High Analyte | HSV-1Positivity | HSV-2Positivity | VZV Positivity | |
|---|---|---|---|---|---|
| 1 | HSV-1 (3x LoD) | HSV-2 (1000x LoD) | 0.0% (0/5) | 100.0% (5/5) | 0% (0/5)* |
| 2 | HSV-1 (3x LoD) | HSV-2 (500x LoD) | 0.0% (0/5) | 100.0% (5/5) | 0% (0/5)* |
| 3 | HSV-1 (3x LoD) | HSV-2 (250x LoD) | 20.0% (1/5) | 100.0% (5/5) | 0% (0/5)* |
| 4 | HSV-1 (3x LoD) | HSV-2 (100x LoD) | 60.0% (3/5) | 100.0% (5/5) | 0% (0/5)* |
| 5 | HSV-1 (3x LoD) | HSV-2 (10x LoD) | 100.0% (5/5) | 100.0% (5/5) | 0% (0/5)* |
| 6 | HSV-1 (3x LoD) | VZV (500x LoD) | 100.0% (5/5) | 0% (0/5)* | 100.0% (5/5) |
| 7 | HSV-2 (3x LoD) | HSV-1 (1000x LoD) | 100.0% (5/5) | 60.0% (3/5) | 0% (0/5)* |
| 8 | HSV-2 (3x LoD) | HSV-1 (500x LoD) | 100.0% (5/5) | 100.0% (5/5) | 0% (0/5)* |
| 9 | HSV-2 (3x LoD) | HSV-1 (250x LoD) | 100.0% (5/5) | 100.0% (5/5) | 0% (0/5)* |
| 10 | HSV-2 (3x LoD) | HSV-1 (100x LoD) | 100.0% (5/5) | 100.0% (5/5) | 0% (0/5)* |
| 11 | HSV-2 (3x LoD) | HSV-1 (10x LoD) | 100.0% (5/5) | 100.0% (5/5) | 0% (0/5)* |
| 12 | HSV-2 (3x LoD) | VZV (500x LoD) | 0% (0/5)* | 100.0% (5/5) | 100.0% (5/5) |
| 13 | VZV (3x LoD) | HSV-1 (1000x LoD) | 100.0% (5/5) | 0% (0/5)* | 100.0% (5/5) |
| 14 | VZV (3x LoD) | HSV-2 (1000x LoD) | 0% (0/5)* | 100.0% (5/5) | 100.0% (5/5) |
- Analyte not present in the sample, the negative results are not due to competitive interference. The negative results are true negative.
Repeatability/ Within-Lab Precision
A 20-day within laboratory precision study was performed with two testing events per day, each testing had two replicates of a three- member test panel on three product lots. The test panel was prepared in negative buccal cell matrix comprised of a negative sample, a co-spiked low positive sample (at LoD for each pathogen), and a co- spiked moderate positive sample (at 4 times the LoD for each pathogen). The negative sample had an overall 99.6% (239/240) expected agreement for HSV-1, 99.6% (239/240) expected agreement for HSV-2 and 100.0% (242/242) expected agreement for VZV across all lots. The
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low positive sample had an overall 99.2% (237/239) expected agreement for HSV-1, 100.0% (239/239) expected agreement for HSV- 2 and 99.6% (238/239) expected agreement for VZV across all lots. The moderate positive sample had an overall 99.6% (239/240) expected agreement for HSV-1, 100.0% (240/240) expected agreement for HSV- 2 and 99.6% (240/241) expected agreement for VZV across all lots. Results are presented in Table 7.
| Analyte | Sample | Agreement withExpected Results | DetectedMeanCt | Repeatability | BetweenRuns | BetweenDays | Between Lot | Total | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SD | % CV | SD | % CV | SD | % CV | SD | % CV | SD | % CV | ||||
| Negative | 239/240(99.6%) | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | |
| HSV-1 | LowPositive | 237/239(99.2%) | 36.4 | 1.50 | 4.1 | 0.07 | 0.2 | 0.19 | 0.5 | 0.50 | 1.4 | 1.60 | 4.4 |
| ModeratePositive | 239/240(99.6%) | 34.3 | 1.06 | 3.1 | 0.70 | 2.0 | 0.00 | 0.0 | 0.41 | 1.2 | 1.33 | 3.9 | |
| Negative | 239/240(99.6%) | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | |
| LowPositive | 239/239(100%) | 33.9 | 0.95 | 2.8 | 0.49 | 1.5 | 0.05 | 0.2 | 0.42 | 1.3 | 1.16 | 3.4 | |
| HSV-2 | ModeratePositive | 240/240(100%) | 31.9 | 0.98 | 3.1 | 0.46 | 1.5 | 0.00 | 0.0 | 0.00 | 0.0 | 1.09 | 3.4 |
| Negative | 242/242(100%) | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | |
| LowPositive | 238/239(99.6%) | 35.7 | 0.77 | 2.2 | 0.11 | 0.3 | 0.20 | 0.6 | 0.19 | 0.5 | 0.83 | 2.3 | |
| VZV | ModeratePositive | 240/241(99.6%) | 34.1 | 0.54 | 1.6 | 0.00 | 0.0 | 0.11 | 0.3 | 0.18 | 0.5 | 0.58 | 1.7 |
| Table 7. Repeatabilitv/Within-Laboratory Precision | |
|---|---|
Reproducibility
A five-day, multi-site reproducibility study was conducted at three healthcare facilities. Each day, two operators at each site ran two replicates of a three-member test panel prepared in negative buccal cell matrix comprised of a negative sample, a co-spiked low positive sample (at LoD for each pathogen), and a co-spiked moderate positive sample (at 4 times the LoD for each pathogen). The negative sample had an 100% (179/179) expected agreement across all sites for all three analytes. The low positive samples were called positive 99.4% (179/180) of the time for HSV-1, 100% (180/180) of the time for HSV-2 and 100% (180/180) of the time for VZV. The moderate positive samples were called positive 99.4% (179/180) of the time for HSV-1, 100% (180/180) HSV-2 and 99.4% (179/180) for VZV. Results are in Table 8.
| Analyte | Sample | Agreement withExpectedResults | DetectedMeanCt | Repeatability | BetweenDay | BetweenSite | BetweenLot | BetweenOperator | Reproducibility | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | ||||
| Negative | 179/179(100%) | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | |
| HSV-1 | LowPositive | 179/180(99.4%) | 36.22 | 1.31 | 3.6 | 0.35 | 1.0 | 0.06 | 1.36 | 1.36 | 0.4 | 0.00 | 0.0 | 1.36 | 3.8 |
| ModeratePositive | 179/180(99.4%) | 34.38 | 1.05 | 3.1 | 0.00 | 0.0 | 0.27 | 1.23 | 1.23 | 1.6 | 0.14 | 0.4 | 1.23 | 3.6 |
Table 8. Reproducibility Study Results (3 Sites)
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| Analyte | Sample | Agreement withExpected | DetectedMean | Repeatability | BetweenDay | BetweenSite | BetweenLot | BetweenOperator | Reproducibility |
|---|---|---|---|---|---|---|---|---|---|
| Negative | 179/179(100%) | N/A | N/A | N/A | N/A | N/A | N/A | N/A | |
| HSV-2 | LowPositive | 180/180(100%) | 33.73 | 1.19 | 0.25 | 0.00 | 1.23 | 0.00 | 1.23 |
| ModeratePositive | 180/180(100%) | 31.86 | 0.96 | 0.00 | 0.19 | 1.10 | 0.5 | 0.14 | |
| Negative | 179/179(100%) | N/A | N/A | N/A | N/A | N/A | N/A | N/A | |
| VZV | LowPositive | 180/180(100%) | 35.79 | 1.29 | 0.00 | 0.34 | 1.34 | 0.00 | 1.34 |
| ModeratePositive | 179/180(99.4%) | 33.99 | 0.52 | 1.5 | 0.00 | 0.25 | 0.6 | 0.17 |
External Control Performance
The Savanna HSV 1+2/VZV External Control Set, comprised of a pouched positive control swab and a negative control, was evaluated with the Savanna HSV 1+2/VZV Assay at 30 replicates each on three device lots for a total of 180 tests. The positive control produced 100% agreement to the expected positive results on all three device lots. The negative control produced 96.8% agreement to the expected results on one device lot and 100% agreement on the other two device lots.
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Transport Media and Specimen Stability/Storage
Specimen stability in various Transport Media (Copan UTM, Remel M4RT, Remel M6) was evaluated. The following Co-spike samples were used in the test: Negative, Low Positive (2x LoD), and High Positive (4x LoD). Specimens collected in transport medium are stable when stored according to the conditions specified in Table 9.
| Transport Medium | Room Temperature (15-30°C) | Refrigerated (4°C) |
|---|---|---|
| Copan UTM | Up to 24 hours | Up to 48 hours |
| Remel M4RT | Up to 96 hours | Up to 96 hours |
| Remel M5 | Up to 48 hours | Up to 96 hours |
| Remel M6 | Up to 72 hours | Up to 72 hours |
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Clinical Performance
Performance characteristics of the Savanna HSV 1+2/VZV Assay were established through 2 multi-site clinical studies, testing cutaneous and mucocutaneous lesions from symptomatic individuals, as described below. Clinical Study 1 evaluated assay performance from fresh samples while clinical study 2 evaluated performance after residual samples were stored frozen.
Clinical Study #1
A multi-site study was conducted in the United States to evaluate the Savanna HSV 1+2/VZV Assay using cutaneous or mucocutaneous lesion samples in transport media. Five hundred and ninety (590) residual specimens were randomly selected from subjects with signs and symptoms of HSV-1, HSV-2 or VZV infection that were tested and for whom samples were collected in an all-comers fashion. A single replicate of each specimen was tested with both the candidate assay, Savanna HSV 1+2/VZV Assay and the comparator assay. Testing was split across three clinical sites and 44 Savanna instruments. Savanna HSV 1+2/VZV Control Sets were tested each day by the clinical sites during sample testing. The clinical performance of the Savanna HSV 1+2/VZV Assay was established by comparing to FDA-cleared nucleic acid amplification tests.
The specimens have been categorized as cutaneous (skin lesion, genital), or mucocutaneous (anorectal, genital, nares, ocular, oral and urethral). The gender and age demographics for each category are listed below.
| Specimen | Age | Female | Male | Total |
|---|---|---|---|---|
| Cutaneous Lesion | <= 5 years | 5 | 10 | 15 |
| 6 to 21 years | 13 | 10 | 23 | |
| 22 to 59 years | 57 | 39 | 96 | |
| >= 60 years | 50 | 23 | 73 | |
| Total | 125 | 82 | 207 | |
| Mucocutaneous Lesion | <= 5 years | 8 | 3 | 11 |
| 6 to 21 years | 50 | 24 | 74 | |
| 22 to 59 years | 185 | 56 | 241 | |
| >= 60 years | 43 | 14 | 57 | |
| Total | 286 | 97 | 383 | |
| Total | <= 5 years | 13 | 13 | 26 |
| 6 to 21 years | 63 | 34 | 97 | |
| 22 to 59 years | 242 | 95 | 337 | |
| >= 60 years | 93 | 37 | 130 | |
| Total | 411 | 179 | 590 |
Table 10. Subject Demographics - Clinical Study #1
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The clinical performance results commercially available RT-PCR comparator method are shown in Tables 11 to 13, for cutaneous and mucocutaneous lesions separately.
| HSV1 Results | |||||
|---|---|---|---|---|---|
| Cutaneous (N=207) | Mucocutaneous (N=383) | ||||
| Comparator | Comparator | ||||
| Positive | Negative | Positive | Negative | ||
| Savanna HSV1+2/VZV AssayResults | Positive | 23 | 1 | 81 | 11 |
| Negative | 2 | 181 | 0 | 291 | |
| Total | 25 | 182 | 81 | 302 | |
| PPA= 92.00%(23/25)(75.04% -97.78%) | NPA= 99.45%(181/182)(96.95% - 99.90%) | PPA= 100.00%(81/81)(95.47% - 100.00%) | NPA= 96.36%(291/302)(93.60% - 97.95%) |
Table 11: HSV1 Clinical performance for the Savanna HSV 1+2/VZV Assay in cutaneous fresh specimens
Table 12: HSV2 Clinical performance for the Savanna HSV 1+2/VZV Assay in cutaneous fresh specimens
| HSV2 Results | |||||
|---|---|---|---|---|---|
| Cutaneous (N=207) | Mucocutaneous (N=383) | ||||
| Comparator | Comparator | ||||
| Positive | Negative | Positive | Negative | ||
| Savanna HSV1+2/VZV AssayResults | Positive | 13 | 0 | 50 | 3 |
| Negative | 1 | 193 | 3 | 327 | |
| Total | 14 | 193 | 53 | 330 | |
| PPA= 92.86%(13/14)(68.53% -98.73%) | NPA= 100.00%(193/193)(98.05% - 100.00%) | PPA= 94.34%(50/53)(84.63% - 98.06%) | NPA= 99.09%(327/330)(97.36% - 99.69%) |
Table 13: VZV Clinical performance for the Savanna HSV 1+2/VZV Assay in cutaneous and mucocutaneous fresh specimens
| VZV Results | |||||
|---|---|---|---|---|---|
| Cutaneous (N=207) | Mucocutaneous (N=383) | ||||
| Comparator | Comparator | Comparator | Comparator | ||
| Positive | Negative | Positive | Negative | ||
| Savanna HSV1+2/VZV AssayResults | Positive | 37 | 1 | 5 | 0 |
| Negative | 0 | 169 | 0 | 377 | |
| Total | 37 | 170 | 5 | 377 | |
| PPA= 100.00%(37/37)(90.60% - 100.00%) | NPA= 99.41%(169/170)(96.74% - 99.90%) | PPA= 100.00%(5/5)(56.56% - 100.00%) | NPA= 100.00%(377/377)(98.99% - 100.00%) |
Clinical Study #2
Analysis of frozen residual cutaneous and mucocutaneous swab samples in transport medium was performed in July 2023 to supplement Clinical Study #1. The samples were residual specimens left over
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from patients with signs and symptoms of HSV-1, HSV-2 or VZV infection. The total number of evaluable samples was one hundred fifty-four (154). The clinical study #2 performance results compared to commercially available RT- PCR comparator method(s) are shown in Tables 14 to 16.
Table 14: HSV1 Clinical performance for the Savanna HSV 1+2V Assay in cutaneous and mucocutaneous residual frozen specimens
| HSV1 Results | |||||
|---|---|---|---|---|---|
| Cutaneous (N=90) | Mucocutaneous (N=64) | ||||
| Comparator | Comparator | ||||
| Positive | Negative | Positive | Negative | ||
| Savanna HSV1+2/VZV AssayResults | Positive | 27 | 2 | 29 | 0 |
| Negative | 0 | 61 | 0 | 35 | |
| Total | 27 | 63 | 29 | 35 | |
| PPA= 100.00%(27/27)(87.55% -100.00%) | NPA= 96.83%(61/63)(89.14% -99.13%) | PPA= 100.00%(29/29)(88.31% - 100.00%) | NPA= 100.00%(35/35)(90.11% - 100.00%) |
Table 15: HSV2 Clinical performance for the Savanna HSV 1+2/VZV Assay in cutaneous and mucocutaneous residual frozen specimens
| HSV2 Results | ||||||
|---|---|---|---|---|---|---|
| Cutaneous (N=90) | Mucocutaneous (N=64) | |||||
| Comparator | Comparator | |||||
| Positive | Negative | Positive | Negative | |||
| Savanna HSV1+2/VZV AssayResults | Positive | 30 | 0 | 15 | 1 | |
| Negative | 0 | 60 | 0 | 48 | ||
| Total | 30 | 60 | 15 | 49 | ||
| PPA= 100.00%(30/30)(88.65% -100.00%) | NPA= 100.00%(60/60)(93.98% -100.00%) | PPA= 100.00%(15/15)(79.62% - 100.00%) | NPA= 97.96%(48/49)(89.31% - 99.64%) |
Table 16: VZV Clinical performance for the Savanna HSV 1+2/VZV Assay in cutaneous residual frozen specimens
| VZV Results | ||||||
|---|---|---|---|---|---|---|
| Cutaneous (N=90) | Mucocutaneous (N=64) | |||||
| Comparator | Comparator | |||||
| Positive | Negative | Positive | Negative | |||
| Savanna HSV1+2/VZV AssayResults | Positive | 17 | 0 | 4 | 0 | |
| Negative | 0 | 73 | 0 | 60 | ||
| Total | 17 | 73 | 4 | 60 | ||
| PPA= 100.00%(17/17)(81.57% -100.00%) | NPA= 100.00%(73/73)(95.00% - 100.00%) | PPA= 100.01%(4/4)(51.02% - 100.01%) | NPA= 100.01%(60/60)(93.98% - 100.00%) |
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Conclusion
These studies demonstrated equivalent performance of the Savanna HSV 1+2/VZV Assay to the predicate product, the Solana HSV 1+2/VZV Assay.
§ 866.3309 Herpes virus nucleic acid-based cutaneous and mucocutaneous lesion panel.
(a)
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.(b)
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 820.30 design controls 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.