(29 days)
The Focus Diagnostics Simplexa™ HSV 1 & 2 Direct is intended for use on the 3M Integrated Cycler instrument for the qualitative detection and differentiation of HSV-1 and HSV-2 DNA in cerebrospinal fluid (CSF) samples from patients suspected of herpes simplex virus (HSV) infections of the central nervous system (CNS). This test is intended as an aid in the diagnosis of HSV-1 and HSV-2 infections of the CNS.
Negative results do not preclude HSV-1 or HSV-2 infection and should not be used as the sole basis for treatment or other patient management decisions.
The assay is not intended for use as a donor screening test. The assay is for professional use only.
The Simplexa™ HSV 1 & 2 Positive Control Pack is intended to be used as a control with the Simplexa™ HSV 1 & 2 Direct kit. This control is not intended for use with other assays or systems.
The Simplexa™ HSV 1 & 2 Direct assay system is a real-time PCR that enables the direct amplification, detection and differentiation of HSV-1 and/or HSV-2 DNA from unprocessed CSF specimens without nucleic acid extraction. The system consists of the Simplexa™ HSV 1 & 2 Direct assay, the 3M Integrated Cycler (with 3M Integrated Cycler Studio Software), the Direct Amplification Disc and associated accessories.
In the Simplexa™ HSV 1 & 2 Direct assay, bi-functional fluorescent probe-primers are used together with corresponding reverse primers to amplify HSV-1, HSV-2 and internal control targets. Well conserved regions of the HSV-1 and HSV-2 DNA polymerase genes are targeted to identify HSV-1 and HSV-2 DNA respectively in the specimen. An internal control is used to detect PCR failure and/or inhibition.
The provided text describes a 510(k) summary for the Simplexa™ HSV 1 & 2 Direct and Simplexa™ HSV 1 & 2 Positive Control Pack, which is a modification to a previously cleared device (K133621). The changes are specifically related to the Integrated Cycler Studio Software version 6.0.
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:
1. A table of acceptance criteria and the reported device performance
The document mentions that "Verification activities for the Integrated Cycler Studio software version 6.0 included development of verification test plans with defined acceptance criteria (design inputs), conducting and documenting verification testing and review of the verification results as they compared to the verification test plans predetermined acceptance criteria (design outputs)." It also states that "Integrated Cycler Studio software version 6.0 was validated in a similar fashion with the development of validation test plans with defined acceptance criteria (design inputs), conducting validation testing and review of the validation results as they compared to the validation test plans predetermined acceptance criteria (design outputs)."
However, the specific acceptance criteria (e.g., percentage agreement, sensitivity, specificity, or specific values for these metrics) for the software's performance with the assay, and the reported device performance against these criteria, are not explicitly detailed in the provided text. The text only states that "The results of verification and validation of Integrated Cycler Studio software version 6.0 show the results met the predetermined acceptance criteria." and "The results of assays ran with the Integrated Cycler Studio software version 6.0 demonstrate that the results obtained with the previously released versions of Integrated Cycler Studio software were equivalent to the results obtained using Integrated Cycler Studio software version 6.0."
Without the actual defined acceptance criteria and the quantitative or qualitative results against them, a detailed table cannot be created from this document.
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
The document focuses on software changes and comparison to a predicate device. It indicates that "The results of assays ran with the Integrated Cycler Studio software version 6.0 demonstrate that the results obtained with the previously released versions of Integrated Cycler Studio software were equivalent to the results obtained using Integrated Cycler Studio software version 6.0." This suggests that a comparison study was performed, likely using existing assay data or running new assays with the modified software.
However, the sample size for any test set, the specific data provenance (country of origin), and whether the data was retrospective or prospective are not mentioned in the provided text.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
This information is not provided in the text. The device is an in vitro diagnostic for detecting HSV-1 and HSV-2 DNA. The "ground truth" for such devices is typically established through molecular reference methods or clinical diagnosis, not usually expert consensus in the same way as imaging analysis.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
This information is not applicable or provided in the text. Adjudication methods are typically used in studies involving human interpretation (e.g., radiologists reviewing images), where disagreement among experts needs resolution. For a PCR-based diagnostic device, the assessment of results against a ground truth would follow established laboratory protocols for molecular diagnostics, not human adjudication.
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
An MRMC study is not applicable here as the device is a direct molecular diagnostic test, not an AI-assisted human reader interpretation system. The device directly detects viral DNA.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
The device is inherently a "standalone" algorithm (PCR assay interpreted by software) in the sense that it performs the detection and differentiation of HSV DNA without a human interpreting the primary assay signal directly for diagnosis. The software (Integrated Cycler Studio) processes the raw data from the PCR reaction to deliver a qualitative result (presence/absence of HSV-1/HSV-2 DNA). The statement that "The results of assays ran with the Integrated Cycler Studio software version 6.0 demonstrate that the results obtained with the previously released versions of Integrated Cycler Studio software were equivalent to the results obtained using Integrated Cycler Studio software version 6.0" implies an assessment of the software's performance on its own.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
Given that this is a molecular diagnostic for HSV DNA, the ground truth would typically be established by a highly sensitive and specific reference molecular method (e.g., an FDA-cleared or a well-validated in-house laboratory developed test with stringent analytical performance characteristics, or potentially by clinical diagnosis combined with other laboratory findings). The specific method for establishing ground truth is not explicitly stated in the provided text.
8. The sample size for the training set
The document describes software version changes and verification/validation activities. There is no mention of a "training set" in the context of machine learning or AI. The software is designed to interpret PCR assay results.
9. How the ground truth for the training set was established
As there is no mention of a "training set" or AI/machine learning development, this question is not applicable based on the provided text.
§ 866.3307 Herpes simplex virus nucleic acid-based assay for central nervous system infections.
(a)
Identification. A herpes simplex virus nucleic acid-based assay for central nervous system infections is a qualitative in vitro diagnostic device intended for the detection and differentiation of HSV-1 and HSV-2 in cerebrospinal fluid (CSF) samples from patients suspected of Herpes Simplex Virus (HSV) infections of the central nervous system (CNS). This test is intended as an aid in the diagnosis of HSV-1 and HSV-2 infections of the CNS. Negative results do not preclude HSV-1 or HSV-2 infection and should not be used as the sole basis for treatment or other patient management decisions.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Design verification and validation must include:
(i) 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.
(ii) Detailed documentation from the following analytical and clinical performance studies: Analytical sensitivity (limit of detection), reactivity, inclusivity, precision, reproducibility, interference, cross reactivity, carryover, and cross contamination. Documentation must include reagent and sample stability recommendations.
(iii) Detailed documentation from a clinical study. The study, performed on a study population consistent with the intended use population, must compare the device performance to the results of two polymerase chain reaction methods followed by bidirectional sequencing.
(iv) Documentation of 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.
(v) Quality assurance protocols and detailed documentation for device software, including standalone software applications and hardware-based devices that incorporate software.
(2) The labeling required under § 809.10(b) of this chapter must include:
(i) A detailed explanation of the interpretation of results and acceptance criteria.
(ii) A limiting statement indicating that negative results do not preclude HSV-1 or HSV-2 infection and should not be used as the sole basis for treatment or other patient management decisions.