(82 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 from nasopharyngeal swab (NPS) and nasopharyngeal 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 laboratory (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 non-structural 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 (RNAseP target) will be used as an inhibition and extraction control.
Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
For the JBAIDS Influenza A & B Detection Kit, the primary performance metrics are Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) compared to a reference method. The document does not explicitly state pre-defined acceptance criteria (e.g., "PPA must be >90%"). However, the reported performance is presented to demonstrate substantial equivalence, implying that these agreement percentages were considered acceptable for clearance.
| Metric | Sample Type | Purification Kit | Reported Device Performance |
|---|---|---|---|
| Influenza A - PPA | NPW | Platinum Path | 100.0% (65/65) |
| NPW | MagNA Pure | 100.0% (39/39) | |
| NPW | Combined | 100.0% (104/104) | |
| NPS | Platinum Path | 100.0% (42/42) | |
| NPS | MagNA Pure | 100.0% (20/20) | |
| NPS | Combined | 100.0% (62/62) | |
| Influenza A - NPA | NPW | Platinum Path | 99.5% (213/214) |
| NPW | MagNA Pure | 98.8% (170/172) | |
| NPW | Combined | 99.2% (383/386) | |
| NPS | Platinum Path | 100.0% (91/91) | |
| NPS | MagNA Pure | 99.4% (160/161) | |
| NPS | Combined | 99.6% (251/252) | |
| Influenza B - PPA | NPW | Platinum Path | 95.1% (39/41) |
| NPW | MagNA Pure | 93.5% (29/31) | |
| NPW | Combined | 94.4% (68/72) | |
| NPS | Platinum Path | 94.7% (18/19) | |
| NPS | MagNA Pure | 100.0% (6/6) | |
| NPS | Combined | 96.0% (24/25) | |
| Influenza B - NPA | NPW | Platinum Path | 99.6% (237/238) |
| NPW | MagNA Pure | 98.3% (177/180) | |
| NPW | Combined | 99.0% (414/418) | |
| NPS | Platinum Path | 100.0% (114/114) | |
| NPS | MagNA Pure | 100.0% (175/175) | |
| NPS | Combined | 100.0% (289/289) | |
| Influenza A/H1 (Archived) - PPA | NPS | Combined | 100% (30/30) |
| Influenza A/H1 (Archived) - NPA | NPS | Combined | 100% (21/21) |
| Influenza A (Surrogate) - PPA | NPW | Not Specified | 98.1% (53/54) |
| Influenza A (Surrogate) - NPA | NPW | Not Specified | 100.0% (8/8) |
| Influenza A (Surrogate) - PPA | NPS | Not Specified | 100.0% (59/59) |
| Influenza A (Surrogate) - NPA | NPS | Not Specified | 100.0% (7/7) |
| Influenza B (Surrogate) - NPA | NPW | Not Specified | 98.5% (66/67) |
| Influenza B (Surrogate) - NPA | NPS | Not Specified | 100.0% (65/65) |
| Reproducibility (Flu A, ≥ LoD) | NPS | Both Kits | 99% (179/180) |
| NPW | Both Kits | 99% (179/180) | |
| Reproducibility (Flu B, ≥ LoD) | sNPS | Both Kits | 100% (180/180) |
| sNPW | Both Kits | 100% (180/180) |
2. Sample Sizes and Data Provenance
- Clinical Performance (Prospective Study):
- Test Set Sample Size: 804 valid specimens (314 NPS, 490 NPW).
- Data Provenance: Prospective study conducted at 5 geographically separated military clinical sites in the U.S. during the 2010-2011 influenza season (December 2010 to April 2011).
- Testing of Preselected Archived Specimens:
- Test Set Sample Size: 51 NPS specimens (30 known positive seasonal Influenza A/H1, 21 influenza-negative).
- Data Provenance: Retrospective, pre-selected archived clinical NPS specimens. Country of origin not explicitly stated but implied to be US-based given the context of US military sites.
- Testing of Surrogate Clinical Specimens:
- Test Set Sample Size: 136 individual influenza-negative clinical specimens (68 NPS, 68 NPW) that were spiked. 128 produced valid test results for analysis.
- Data Provenance: Contrived clinical samples created by spiking residual influenza-negative NPS and NPW samples. Origin of the original negative specimens is clinical, likely from the US military sites or similar sources.
- Analytic Studies (LoD, Inclusivity, Exclusivity, Reproducibility):
- These studies used distinct sample sizes, generally involving multiple replicates (e.g., 20 replicates for LoD, 30-90 results per spike level for reproducibility). The samples were either live, quantified virus strains or simulated NPS/NPW matrices spiked with specific organisms.
3. Number of Experts and Qualifications for Ground Truth
The document does not mention the use of human experts to establish ground truth for the test sets in the clinical performance study.
- Clinical Performance (Prospective, Archived, and Surrogate Studies): The ground truth was established by a comparator method, the CDC rRT-PCR Flu Panel influenza A and influenza B assays. This is a laboratory-based reference standard, not a human expert consensus.
- Analytic Studies: The ground truth for these (e.g., LoD, inclusivity, exclusivity) was based on the known presence and concentration of specific viruses or bacteria in the spiked samples.
4. Adjudication Method
There is no mention of an adjudication method in the studies described, as the comparator method (CDC rRT-PCR Flu Panel) served as the direct reference standard. The results of the JBAIDS kit were compared to this objective method.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC comparative effectiveness study was performed or described. This device is an in-vitro diagnostic (IVD) assay designed for laboratory use, not for direct interpretation by human readers in the same way an image-based diagnostic AI might be. Therefore, the concept of human readers improving with AI assistance is not applicable in this context. The device's results are intended to be interpreted by trained laboratory personnel.
6. Standalone Performance
Yes, a standalone performance study was done. The entire set of clinical and analytical performance evaluations (PPA, NPA, LoD, inclusivity, exclusivity, reproducibility) directly measures the performance of the JBAIDS Influenza A & B Detection Kit algorithm and associated testing procedure in isolation (without human-in-the-loop performance influencing the assay's output). The device's software automatically analyzes fluorescence amplification curves and reports results (positive, negative, or uncertain).
7. Type of Ground Truth Used
- Clinical Performance (Prospective, Archived, Surrogate): The ground truth was based on the results from a legally marketed comparator device: the CDC rRT-PCR Flu Panel influenza A and influenza B assays. This is a highly sensitive and specific laboratory-based molecular diagnostic method, often considered a "gold standard" for viral nucleic acid detection.
- Analytical Studies (LoD, Inclusivity, Exclusivity, Reproducibility): The ground truth was based on known concentrations of specific viral or bacterial strains in the spiked samples.
8. Sample Size for the Training Set
The document does not specify a separate training set for the JBAIDS Influenza A & B Detection Kit. As an IVD based on rRT-PCR, the "training" analogous to machine learning models is typically inherent in the assay design and optimization process (e.g., primer and probe design, reaction condition optimization), rather than a distinct data-driven training phase on labeled samples as seen in AI/ML products. The mentioned studies focus on the validation of the optimized kit.
9. How the Ground Truth for the Training Set was Established
As no explicit training set is described in the context of an AI/ML model, this question is not directly applicable. If one considers the development and optimization of the rRT-PCR assays as an analogous process, the "ground truth" during this phase would involve using well-characterized viral isolates and clinical samples with confirmed presence/absence of influenza to optimize the assay's sensitivity and specificity parameters.
§ 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.