(242 days)
The HSV 1&2 ELITe MGB® Assay is a real-time polymerase chain reaction (PCR) based qualitative in vitro diagnostic test for the direct detection and differentiation of Herpes Simplex Virus 1 and 2 (HSV-2) DNA in cutaneous or mucocutaneous lesion swab specimens from patients with signs and symptoms of HSV-2 infection. This test is an aid in the differential diagnosis of HSV-1 and HSV-2 infections.
The HSV 1&2 ELITe MGB Assay is not FDA cleared for use with cerebrospinal fluid (CSF) specimens. The assay is not intended to be used for prenatal screening or for screening blood or blood products.
The HSV 1&2 ELITe MGB Assay is a qualitative in vitro diagnostic Real-Time PCR Assay for the direct detection of Herpes Simplex Virus (HSV) DNA (glycoprotein D gene for HSV-1 and glycoprotein G gene for HSV-2) in symptomatic male and female patients using DNA purified from swab specimens collected from individuals with cutaneous or mucocutaneous herpetic lesions.
The HSV 1&2 ELITe MGB Assay system is comprised of three major processes: (1) automated preparation of unprocessed sample to extract nucleic acids from primary swab specimens using the ELITe InGenius SP 200 Extraction Cartridge, (2) PCR amplification of target DNA sequences using HSV-1 and HSV-2 specific primers, and (3) real-time detection of fluorescent-labeled HSV-1 and HSV-2 specific oligonucleotide detection probes.
An Internal Control (IC), containing unrelated randomized DNA sequence, is added to all samples prior to extraction and monitors the integrity of the reagents, equipment function, and the presence of inhibitors in the samples. A positive signal in the Internal Control channel in the absence of HSV DNA indicates that the PCR has not been inhibited.
The amplification reagents, Positive Control and Internal Control are packaged as part of the HSV 1&2 ELITe MGB Assay.
Here's a breakdown of the acceptance criteria and study information for the HSV 1&2 ELITe MGB Assay, based on the provided text:
Acceptance Criteria and Reported Device Performance
The acceptance criteria for the HSV 1&2 ELITe MGB Assay are presented in terms of Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) against a composite reference method.
| Metric | Acceptance Criteria (Implied by achieved performance and regulatory clearance) | Reported Device Performance (95% CI) - Cutaneous Lesion Samples | Reported Device Performance (95% CI) - Mucocutaneous Lesion Samples |
|---|---|---|---|
| HSV-1 PPA | High (e.g., typically >90-95%) | 98.7% (93.2-99.8%) | 99.2% (95.7-99.9%) |
| HSV-1 NPA | High (e.g., typically >90-95%) | 98.5% (96.9-99.3%) | 97.6% (95.8-98.6%) |
| HSV-2 PPA | High (e.g., typically >90-95%) | 96.2% (91.3-98.3%) | 97.6% (94.0-99.1%) |
| HSV-2 NPA | High (e.g., typically >90-95%) | 98.6% (96.9-99.3%) | 98.2% (96.6-99.1%) |
Study Information
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Sample Size Used for the Test Set and Data Provenance:
- Test Set Sample Size: 1,174 prospectively collected archived swab samples were initially collected. After exclusions:
- 1,171 samples were analyzed for HSV-1.
- 1,170 samples were analyzed for HSV-2.
- A separate contrived oral panel study involved 75 individual negative cheek swab samples spiked with HSV-2, plus 10 HSV-1 positive samples and 15 HSV-1/HSV-2 negative oral samples.
- Data Provenance: The samples were "left-over prospectively collected archived swab samples" from symptomatic patients. The country of origin is not explicitly stated, but the context of an FDA submission generally implies US-based data.
- Test Set Sample Size: 1,174 prospectively collected archived swab samples were initially collected. After exclusions:
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Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
- The document does not explicitly state the number of experts or their qualifications for establishing the ground truth. The ground truth was established using a composite reference method.
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Adjudication Method for the Test Set:
- The adjudication method for the test set was a "composite reference method" defined as: "an FDA cleared assay and a validated HSV 1&2 PCR followed by bi-directional sequencing of gel electrophoresis-positive samples."
- "A positive result by the composite reference method is defined as a positive by the FDA cleared PCR or the validated sequencing. Two negative results are needed to confirm a negative." This implies a type of adjudicted consensus, where the "truth" is determined by agreement or hierarchical resolution between different methods, rather than human experts per se.
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If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done:
- No. This document describes the analytical and clinical performance of an in vitro diagnostic (IVD) assay, which is an algorithm-only (standalone) test. It does not involve human readers in the primary diagnostic decision-making process that would warrant an MRMC study comparing human performance with and without AI assistance.
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If a Standalone Performance Study Was Done:
- Yes. The entire clinical performance section (Section 11.b) is a standalone performance study where the HSV 1&2 ELITe MGB Assay's performance is compared directly against a composite reference method. The assay operates without human intervention in the interpretation of results.
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The Type of Ground Truth Used:
- Composite Reference Method: This ground truth combined an FDA-cleared PCR assay and a validated HSV 1&2 PCR followed by bi-directional sequencing. This type of ground truth integrates highly sensitive and specific molecular methods, reflecting a robust laboratory-based gold standard.
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The Sample Size for the Training Set:
- The document does not explicitly mention a "training set" in the context of an AI/ML algorithm. This device is a real-time PCR assay, which is a chemical and enzymatic reaction rather than a machine learning model that would typically require a separate training set. The various analytical performance studies (Limit of Detection, Analytical Reactivity, Specificity, etc.) serve to characterize the assay's performance across different conditions, which is analogous to how a system is "trained" or refined during development, but not in the sense of a distinct machine learning training set. The "assay cut-off" was established using a separate set of 141 clinical samples, which could be considered a form of calibration/training for the threshold of positivity.
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How the Ground Truth for the Training Set Was Established:
- As noted above, a traditional "training set" for an AI model is not applicable here. For the establishment of the assay cut-off (using 141 clinical samples), the ground truth was established using the same "composite reference method" (FDA-cleared real-time PCR assay combined with PCR amplification and bidirectional sequencing). For other analytical studies (like LoD, inclusivity, cross-reactivity), quantitated viral strains or characterized organisms were used as the reference.
§ 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.