(88 days)
The DiaSorin Molecular Simplexa™ VZV Swab Direct assay is intended for use on the LIAJSON® MDX instrument for the qualitative detection of varicella-zoster virus (VZV) DNA present in cutaneous and mucocutaneous lesion swabs from patients with signs and symptoms of VZV infection. This test is intended as an aid in the diagnosis of VZV infection. Negative results do not preclude VZV infection and should not be used as the sole basis for treatment or other patient management decisions.
The Simplexa™ VZV Positive Control Pack is intended to be used as a control with the Simplexa™ VZV Direct kit and the Simplexa™ VZV Swab Direct kit on the LIAISON® MDX Instrument. It is not intended for use with other assays or systems.
The Simplexa™ VZV Swab Direct assay is a real-time PCR system that enables the direct amplification and detection of VZV DNA from unprocessed cutaneous and mucocutaneous lesion swab specimens without nucleic acid extraction. The system consists of the Simplexa™ VZV Swab Direct assay, the LIAISON® MDX (with LIAISON® MDX Studio Software), the Direct Amplification Disc (DAD) and associated accessories.
In the Simplexa™ VZV Swab Direct assay, fluorescent probes are used together with corresponding forward and reverse primers to amplify VZV and internal control targets. A well-conserved region of the VZV DNA polymerase gene is targeted to identify VZV DNA in the specimen. An internal control is used to detect PCR failure and/or inhibition.
This document describes the validation of the DiaSorin Molecular Simplexa™ VZV Swab Direct assay. The assay is intended for the qualitative detection of varicella-zoster virus (VZV) DNA directly from cutaneous and mucocutaneous lesion swabs.
1. Table of Acceptance Criteria and Reported Device Performance:
The document implicitly defines acceptance criteria through the results of the clinical and analytical studies, which consistently demonstrate high agreement and sensitivity/specificity.
| Study Type | Acceptance Criterion (Implicit) | Reported Device Performance |
|---|---|---|
| Clinical Agreement (Prospective) | High Sensitivity and Specificity with Composite Reference Method (CRM) | All (N=452): Sensitivity 97.8% (95% CI: 92.2% - 99.4%), Specificity 99.2% (95% CI: 97.6% - 99.7%) |
| Mucocutaneous (N=179): Sensitivity 87.5% (95% CI: 52.9% - 97.8%), Specificity 100.0% (95% CI: 97.8% - 100.0%) | ||
| Cutaneous (N=245): Sensitivity 98.8% (95% CI: 93.3% - 99.8%), Specificity 98.2% (95% CI: 94.8% - 99.4%) | ||
| Clinical Agreement (Retrospective) | High Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) with Composite Reference Method 2 (CRM 2) | All (N=180): PPA 98.4% (95% CI: 91.4% - 99.7%), NPA 99.2% (95% CI: 95.4% - 99.9%) |
| Mucocutaneous (N=73): PPA 90.0% (95% CI: 59.6% - 98.2%), NPA 100.0% (95% CI: 94.3% - 100.0%) | ||
| Cutaneous (N=107): PPA 100.0% (95% CI: 93.1% - 100.0%), NPA 98.2% (95% CI: 90.4% - 99.7%) | ||
| Clinical Agreement (Contrived) | 100% PPA and NPA with CRM 2 | All (N=120): PPA 100.0% (95% CI: 94.0% - 100.0%), NPA 100.0% (95% CI: 94.0% - 100.0%) |
| Reproducibility | 100% Agreement with Expected Results across sites, runs, and operators for positive and negative controls. Consistent Ct values across sites. | All positive samples (LP, MP for both strains, and PC): 100.0% agreement with expected results (90/90 replicates). |
| Negative Control (UTM): 0.0% agreement with expected results (0/90 replicates). | ||
| Low %CV for Ct values indicating good precision (e.g., typically |
§ 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.