(28 days)
The Joint Biological Agent Identification and Diagnostic System (JBAIDS) Influenza A & B Detection Kit is intended for use on the JBAIDS instruments, for the in vitro qualitative detection of influenza A and influenza B viral nucleic acids isolated and purified nasopharygeal swab (NPS) and nasopharygeal wash (NPW) specimens from human patients with signs and symptoms of respiratory infection.
The JBAIDS Influenza A & B Detection Kit contains reverse transcriptase real-time polymerase chain reaction (rRT-PCR) assays that target the Matrix protein gene of influenza A viruses, and the Non-structural protein gene of influenza B viruses. This kit is not intended to detect influenza C viruses.
Test results are to be used in conjunction with other clinical and epidemiological information. Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions.
Performance characteristics for detection of influenza A were established when 2009 H1N1 Influenza, Influenza A H1N1, and Influenza A H3N2 were the predominant influenza A viruses in circulation. Due to low seasonal prevalence, performance characteristics for detection of seasonal Influenza A/H1 were established primarily with retrospective and surrogate clinical specimens. When other influenza A viruses are present, performance characteristics may vary.
All users, analysts, and any person reporting diagnostic results from use of this device should be trained to perform and interpret the results from this procedure by JBAIDS instructors or designees prior to use. Use of this device is limited to designated Department of Defense (DoD) laboratories equipped with the JBAIDS instruments.
If infection with a novel influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent influenza viruses and sent to state or local health departments for testing. Viral culture should not be attempted in these cases unless a biosafety (BSL) 3+ facility is available to receive and culture specimens.
The JBAIDS Influenza A & B Detection Kit is a rRT-PCR test kit, which, when used with the JBAIDS instrument and software, allows the qualitative in vitro detection of influenza A and B viral RNA. These two assays have been optimized as freeze-dried assays with primer and fluorescent-probe sets for the detection of influenza A and B viral RNA. In particular, the influenza A assay targets a region of the matrix gene specific to the influenza A virus genera, and the influenza B assay targets a region of the nonstructural gene specific to the influenza B virus genera. The tests are performed using the previously FDA-cleared JBAIDS instrument and software. A human gene target assay (RNAse P target) will be used as an inhibition and extraction control.
The provided text describes the JBAIDS Influenza A & B Detection Kit, a real-time PCR assay for the qualitative in vitro detection of influenza A and B viral nucleic acids. The information primarily focuses on the technical aspects of the device and its substantial equivalence to a previously cleared predicate device, especially regarding the detection of specific influenza strains.
However, the document does not contain the kind of information typically found in a study proving a new device meets acceptance criteria, specifically not for an AI/ML-based diagnostic or imaging device. The document is a 510(k) summary for a premarket notification, which focuses on demonstrating substantial equivalence to a legally marketed predicate device rather than presenting a performance study against acceptance criteria in the way one would for a novel device, especially one involving AI.
Therefore, many of the requested items (e.g., sample size for training set, number of experts for ground truth, MRMC study, effect size of AI assistance) are not applicable or cannot be extracted from this document, as it describes a PCR-based diagnostic kit, not an AI/ML device.
Given the constraints of the provided document, I will extract the available relevant information and note where information is not present or non-applicable given the nature of the device described.
Acceptance Criteria and Device Performance (Limited to Analytical Sensitivity/LoD)
The document describes selected analytical studies to determine the Limit of Detection (LoD) for certain influenza A strains, specifically H3N2 and H7N9, which were additions to the device's labeling. This can be interpreted as demonstrating the device's performance against an implicit analytical sensitivity acceptance criterion.
Table 1: Acceptance Criteria (Implied Analytical Sensitivity) and Reported Device Performance
| Criterion/Performance Metric | Acceptance Criterion (Implicit) | Reported Device Performance |
|---|---|---|
| Analytical Sensitivity (LoD) | Detection of target influenza strains at low concentrations (standard method for establishing LoD, typically requiring ≥95% positivity at LoD). | H7N9 (A/Anhui/1/2013): |
- Estimated LoD: 4 x 10^4^ EID50/mL (confirmed)
- 3/3 replicates positive at 4 x 10^4^ EID50/mL
- 2/3 replicates positive at 8.0 x 10^3^ EID50/mL
Influenza A H3N2 (seasonal): - A/Victoria/361/2011: LoD = 63.0 TCID50/mL
- A/Perth/16/2009: LoD = 6.3 TCID50/mL
Influenza A swine variant H3N2v: - A/West/Virginia/06/2011: LoD = 31.6 TCID50/mL
- A/Minnesota/11/2010: LoD = 2.0 TCID50/mL |
Note: The document explicitly states: "Serial dilutions were run in triplicate, with all three replicates required to read positive in order for that dilution to be called positive." This stringent requirement for calling a dilution positive influences the reported LoD values.
Study Details:
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Sample sizes used for the test set and the data provenance:
- Test set sample size: Not specified as a distinct "test set" in the context of clinical validation data for a new device. The data presented is for analytical sensitivity (LoD) testing.
- For LoD, serial dilutions of viral strains were tested. The number of replicates per dilution is specified: "Serial dilutions were run in triplicate." It is implied that multiple concentrations were tested for each strain.
- Data provenance: Not explicitly stated for all strains, but the H3N2v and H7N9 strains suggest a focus on variant strains that would have emerged more recently (e.g., A/Anhui/1/2013 for H7N9). The samples were "simulated nasopharyngeal swab samples" meaning they were laboratory-prepared samples rather than clinical patient specimens. The study is described as "Selected Analytical Studies", indicating a laboratory-based evaluation of the assay itself. This falls under retrospective data generated in a controlled lab setting, not real-world clinical samples. No country of origin for test data is specified beyond the DoD context.
- Test set sample size: Not specified as a distinct "test set" in the context of clinical validation data for a new device. The data presented is for analytical sensitivity (LoD) testing.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not applicable. For an analytical sensitivity study of a PCR-based diagnostic kit, the "ground truth" is typically defined by the known concentration of the purified viral standard used to prepare the simulated samples. This does not involve human expert interpretation of results, as the device provides a qualitative "positive, negative, or uncertain" result based on fluorescence thresholds.
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Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Not applicable. As the "ground truth" is based on known viral concentrations in simulated samples and the device provides an automated qualitative result, there is no human adjudication process involved in interpreting the device's output or establishing the true state of the samples. The requirement for positivity was "all three replicates required to read positive".
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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 device is a molecular diagnostic (PCR-based) kit, not an AI-assisted imaging device or a diagnostic requiring human reader interpretation in the context of an MRMC study design. It delivers an objective "positive/negative" result based on molecular detection.
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If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, this is a standalone device. The JBAIDS kit itself, when used with the JBAIDS instrument and software, performs the detection and provides a result (positive, negative, or uncertain) without requiring human diagnostic interpretation of complex outputs like images. The document states: "JBAIDS Software analyzes the fluorescence amplification curves and reports results as positive, negative, or uncertain."
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The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- For the analytical studies described, the ground truth was based on known concentrations of purified viral strains (e.g., EID50/mL or TCID50/mL) in simulated samples. This is a highly controlled laboratory ground truth, not clinical ground truth from patients (like pathology or outcomes data).
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The sample size for the training set:
- Not applicable/Not specified. This document describes a traditional real-time PCR diagnostic kit, not an AI/ML device that requires a training set in the machine learning sense. The "training" of such a device involves optimizing primer/probe sets and reaction conditions during its development, not training on a large dataset like an AI model.
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How the ground truth for the training set was established:
- Not applicable. (See point 7). The "ground truth" during the development of such a PCR kit would involve characterizing the specificity and sensitivity of the molecular components against known viral targets and non-targets, rather than establishing ground truth for a training set in an AI/ML context.
§ 866.3980 Respiratory viral panel multiplex nucleic acid assay.
(a)
Identification. A respiratory viral panel multiplex nucleic acid assay is a qualitative in vitro diagnostic device intended to simultaneously detect and identify multiple viral nucleic acids extracted from human respiratory specimens or viral culture. The detection and identification of a specific viral nucleic acid from individuals exhibiting signs and symptoms of respiratory infection aids in the diagnosis of respiratory viral infection when used in conjunction with other clinical and laboratory findings. The device is intended for detection and identification of a combination of the following viruses:(1) Influenza A and Influenza B;
(2) Influenza A subtype H1 and Influenza A subtype H3;
(3) Respiratory Syncytial Virus subtype A and Respiratory Syncytial Virus subtype B;
(4) Parainfluenza 1, Parainfluenza 2, and Parainfluenza 3 virus;
(5) Human Metapneumovirus;
(6) Rhinovirus; and
(7) Adenovirus.
(b)
Classification. Class II (special controls). The special controls are:(1) FDA's guidance document entitled “Class II Special Controls Guidance Document: Respiratory Viral Panel Multiplex Nucleic Acid Assay;”
(2) For a device that detects and identifies Human Metapneumovirus, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Human Metapneumovirus (hMPV) Using Nucleic Acid Assays;” and
(3) For a device that detects and differentiates Influenza A subtype H1 and subtype H3, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Detection and Differentiation of Influenza A Virus Subtypes Using Multiplex Nucleic Acid Assays.” See § 866.1(e) for the availability of these guidance documents.