(83 days)
The CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel is intended for use in real-time RT-PCR (rRT-PCR) assays on an Applied Biosystems (ABI) 7500 Fast Dx Real-Time PCR Instrument in conjunction with clinical and epidemiological information:
- For qualitative detection of influenza virus type A or B viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], nasal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture.
- For determination of the subtype of seasonal human influenza A virus as seasonal A/H1, A/H3, and/or A/H1pdm09 from viral RNA in upper respiratory tract clinical specimens (including NPS, NS, TS, NA, NW and NPS/TS) and lower respiratory tract specimens (including BAL, BW, TA, sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture.
- For the presumptive identification of virus in patients who may be infected with influenza A subtype A/H5 (Asian Lineage) from viral RNA in human respiratory specimens and viral culture in conjunction with clinical and epidemiological risk factors.
- To provide epidemiologic information for surveillance of circulating influenza viruses.
The CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel is used in real-time RT-PCR assays (rRT-PCR) on the ABI 7500 Fast Dx Real-Time PCR Instrument. The CDC Human Influenza Virus Real-time RT-PCR Diagnostic Panel is a panel of oligonucleotide primers and dual-labeled hydrolysis (TaqMan®) probes to be used in rRT-PCR for the in vitro qualitative detection and characterization of human influenza viruses from viral RNA in respiratory specimens from patients presenting with influenza-like illness (ILI). Detection of viral RNA not only aids in the diagnosis of illness caused by seasonal and novel influenza viruses in patients with ILI, but also provides epidemiological information on influenza and aids in the presumptive laboratory identification of specific novel influenza A viruses. The CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel is based on technology which is used in many molecular diagnostic assays. rRT-PCR assays are one-tube assays that first reverse-transcribe specific regions of RNA into cDNA copies. The cDNA then serves as a template for a polymerase chain reaction that utilizes a thermocyclic heating and cooling of the reaction to logarithmically amplify a specific region of DNA. The probe anneals to a specific internal target sequence located between the target loci of the forward and reverse primers. During the extension phase of the PCR cycle, the 5' nuclease activity of Tag polymerase degrades any probe molecules hybridized to amplified target sequence, causing the reporter dye to separate from the quencher dye, and generating a fluorescent signal. With each cycle, additional reporter dye molecules are cleaved from their respective probes, increasing the fluorescence intensity. Fluorescence intensity is monitored at each PCR cycle. Amplification of targets is reflected by logarithmic increase in fluorescence over time in comparison to background signal.
The provided text does not contain specific acceptance criteria with numerical thresholds that the device must meet, nor does it detail a dedicated pivotal study with a defined sample size and ground truth establishment methodology for this specific device (K111507) to demonstrate its performance against those criteria.
Instead, the submission for K111507 relies on the "substantial equivalence comparison" to two previously FDA-cleared predicate devices (K080570 and K101564). The performance data cited for K111507 directs the reader to the performance characteristics established for these predicate devices. The document also includes additional performance data collected during the 2010-2011 influenza season to show that recent circulating strains can be detected.
Therefore, the following information is extracted and presented based on the available text:
1. Table of Acceptance Criteria and Reported Device Performance
As specific, quantified acceptance criteria for K111507 are not explicitly stated in the provided text, a direct comparison table cannot be created in the traditional sense. The submission for K111507 primarily relies on the equivalency to predicate devices and additional data showing detection of recent circulating strains.
Reported Device Performance (for K111507, based on additional data for recent circulating strains):
| Performance Aspect | Reported Device Performance (K111507) |
|---|---|
| Detection of recent seasonal influenza A/H3 and Influenza B strains | The device demonstrated detection of recent circulating seasonal influenza virus strains. |
| - Influenza A/H3: Detected in 24 of 49 (49%) original specimens received from US public health laboratories. | |
| - Influenza B: Detected in 25 of 49 (51%) original specimens received from US public health laboratories. | |
| Detection in Lower Respiratory Tract Specimens | The device detected influenza A/H3, A/H1pdm09, and influenza B in various lower respiratory tract specimens (bronchoalveolar lavage, bronchial washes, tracheal aspirates, sputum, and lung tissue) from 18 original lower respiratory specimens received from US public health laboratories. |
2. Sample Size and Data Provenance for Test Set
- Sample Size for Test Set:
- For detection of recent seasonal influenza A/H3 and B: 49 original specimens.
- For detection in lower respiratory tract specimens: 18 original specimens.
- Data Provenance: Retrospective, from US public health laboratories (identified as "original specimens received from US public health laboratories").
3. Number of Experts and Qualifications for Ground Truth
The document does not specify the number or qualifications of experts used to establish the ground truth for the test set. Given the nature of a PCR diagnostic panel, the ground truth would typically be established through a reference method, often a combination of viral culture and/or additional molecular testing performed by qualified laboratory personnel, rather than expert interpretation of images or clinical assessments.
4. Adjudication Method for Test Set
The document does not describe any adjudication method (e.g., 2+1, 3+1) for establishing the ground truth of the test set.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No MRMC study was done. This device is a real-time RT-PCR diagnostic panel, not an AI-assisted diagnostic tool for human readers. Therefore, the concept of human readers improving with AI vs. without AI assistance is not applicable.
6. Standalone Performance Study (Algorithm Only)
- Yes, a standalone study was implicitly done. The performance data presented (detection of influenza A/H3 and B in specimens) represents the algorithm's (the PCR panel's) performance independent of human-in-the-loop diagnostic interpretation beyond standard laboratory procedures. The detection is based on the fluorescent signal generated by the rRT-PCR assay.
7. Type of Ground Truth Used
- The ground truth type is implied to be a reference method for influenza detection and characterization, likely viral culture and/or a validated molecular method accepted as the standard for influenza diagnosis. The text states "Performance characteristics for influenza were established...as demonstrated by analytical testing of the 49 original specimens...". For the lower respiratory specimens, it states the panel "detected influenza A/H3, A/H1pdm09, and influenza B," implying comparison to an established truth.
8. Sample Size for Training Set
- The document does not explicitly mention a "training set" in the context of this diagnostic panel. As a PCR diagnostic kit, its development involves designing primers and probes that target specific viral genetic sequences. This process typically involves bioinformatics analysis and wet-lab analytical validation using known positive and negative controls, rather than a machine learning "training set" in the conventional sense. The "performance characteristics" data mentioned (from predicate devices and the additional 2010-2011 season data) serve as validation or evaluation data.
9. How Ground Truth for Training Set Was Established
- Not applicable, as a discrete "training set" with established ground truth in the context of machine learning is not described or relevant for this type of PCR diagnostic device. The design and analytical validation of PCR primers and probes rely on known viral sequences and synthetic or cultured viral samples with confirmed identities, not a "ground truth" derived from human experts interpreting a diagnostic outcome.
§ 866.3332 Reagents for detection of specific novel influenza A viruses.
(a)
Identification. Reagents for detection of specific novel influenza A viruses are devices that are intended for use in a nucleic acid amplification test to directly detect specific virus RNA in human respiratory specimens or viral cultures. Detection of specific virus RNA aids in the diagnosis of influenza caused by specific novel influenza A viruses in patients with clinical risk of infection with these viruses, and also aids in the presumptive laboratory identification of specific novel influenza A viruses to provide epidemiological information on influenza. These reagents include primers, probes, and specific influenza A virus controls.(b)
Classification. Class II (special controls). The special controls are:(1) FDA's guidance document entitled “Class II Special Controls Guidance Document: Reagents for Detection of Specific Novel Influenza A Viruses.” See § 866.1(e) for information on obtaining this document.
(2) The distribution of these devices is limited to laboratories with experienced personnel who have training in standardized molecular testing procedures and expertise in viral diagnosis, and appropriate biosafety equipment and containment.