(29 days)
The Influenza A/B Typing Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and 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;
- To provide epidemiologic information for surveillance of circulating influenza viruses.
The Influenza A Subtyping Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and 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 determination of the subtype of seasonal human influenza A viruses as seasonal A(H3), and/or A(H1)pdm09 from 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;
- To provide epidemiologic information for surveillance of circulating influenza viruses.
The Influenza B Lineage Genotyping Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and 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 the determination of the genetic lineage of human influenza B viruses as B/ Victoria or B/Yamagata lineage from 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]) from human patients with signs and symptoms of respiratory infection and/or from viral culture;
- To provide epidemiologic information for surveillance of circulating influenza viruses.
The Influenza A/H5 Subtyping Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (tRT-PCR) assays on an Applied Biosystems (ABI) 7500 Fast Dx Real-Time PCR instrument in conjunction with clinical and epidemiological information:
- 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 Real-Time RT-PCR Diagnostic Panel is used in real-time RT-PCR (rRT-PCR) assays on the Applied Biosystems® (ABI) 7500 Fast Dx Real-time PCR system. The panel is configured in four separate kits. Each kit consists of oligonucleotide primers, fluorescently labeled hydrolysis probes, and controls which are used in rRT-PCR assays for the in vitro qualitative detection and characterization of influenza virus RNA in respiratory specimens from patients presenting with influenza-like illness (ILI). Oligonucleotide primers and probes for detection of influenza A, influenza B, and 2009 influenza A (swine origin) were selected from highly conserved regions of the matrix (M), non-structural (NS), and nucleoprotein (NP) genes, respectively. Oligonucleotide primers and probes for characterization of influenza A(H3) and A(H1)pdm09 viruses and genetic lineages of influenza B were selected from highly conserved regions of their HA genes. Oligonucleotide primers and probes to detect the human RNase P gene (RP) in control samples and clinical specimens is also included in the panel.
This document describes the performance evaluation of a modified CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel, specifically focusing on the addition of new nucleic acid isolation options. The study aims to demonstrate that the modified device is substantially equivalent to its predicate.
Here's an analysis based on your request:
Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly defined by the demonstration of equivalence to a cleared predicate device. This equivalence is shown through specific performance metrics: Limit of Detection (LOD) and Analytical Precision (Reproducibility), and Clinical Performance.
Table of Acceptance Criteria and Reported Device Performance:
| Performance Metric | Acceptance Criteria (Implicit from Equivalence) | Reported Device Performance |
|---|---|---|
| LOD Equivalency | 100% positivity (3 out of 3 replicates) at either the same endpoint concentration or within one 5-fold dilution when compared to the cleared predicate method. | Roche MagNA Pure 96 - DNA and Viral NA Small Volume Kit: Equivalent endpoint concentration (same as predicate, or within one 5-fold dilution), as shown in Table 8-5. Example for 10^1.1^ EID50/mL, both InfA and H3 show 3/3 positivity for both predicate and proposed. |
| QIAGEN EZ1 Advanced XL – DSP Virus Kit: Equivalent endpoint concentration (same as predicate, or within one 5-fold dilution), as shown in Table 8-6. Example for 10^1.1^ EID50/mL, both InfA and H3 show 3/3 positivity for both predicate and proposed. | ||
| QIAGEN EZ1 Advanced XL – RNA Tissue Mini Kit: Equivalent endpoint concentration (same as predicate, or within one 5-fold dilution), as shown in Table 8-7. Example for 10^1.1^ EID50/mL, both InfA and H3 show 3/3 positivity for both predicate and proposed. | ||
| Reproducibility | Good reproducibility (100% agreement across different sites, analysts, and days) compared to the predicate method. | Roche MagNA Pure 96 - DNA and Viral NA Small Volume Kit: 100% agreement (30/30) across all sites, analysts, and days for moderate positive, low positive, and negative samples for InfA, H3, and RP assays (Table 8-10). |
| QIAGEN EZ1 Advanced XL – DSP Virus Kit: 100% agreement (30/30) across all sites, analysts, and days for moderate positive, low positive, and negative samples for InfA, H3, and RP assays (Table 8-8). | ||
| QIAGEN EZ1 Advanced XL – RNA Tissue Mini Kit: 100% agreement (30/30) across all sites, analysts, and days for moderate positive, low positive, and negative samples for InfA, H3, and RP assays (Table 8-9). | ||
| Clinical Performance | 100% agreement with the comparator (predicate method) for both positive and negative clinical specimens. The comparison is based on the qualitative detection of influenza A(H3) virus. | Roche MagNA Pure 96 - DNA and Viral NA Small Volume Kit: 100% agreement (30/30 positive, 30/30 negative) with the predicate (Table 8-11). |
| QIAGEN EZ1 Advanced XL – DSP Virus Kit: 100% agreement (30/30 positive, 30/30 negative) with the predicate (Table 8-12). | ||
| QIAGEN EZ1 Advanced XL – RNA Tissue Mini Kit: 100% agreement (30/30 positive, 30/30 negative) with the predicate (Table 8-13). |
Additional Information:
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Sample sizes used for the test set and the data provenance:
- LOD Equivalency: For each investigational instrument/kit combination, a single characterized influenza A(H3N2) virus (A/Hong Kong/4801/2014) was serially diluted. Triplicate samples of each dilution were tested for both the cleared and investigational methods. The exact number of dilutions is not explicitly stated as a fixed sample size, but the tables show 5 dilution points for each test. This is an analytical study, not directly using human patient samples.
- Reproducibility: A blinded panel (contrived samples) containing a moderate positive, a low positive (near LOD), and a negative sample was used. For each of the three instrument/method combinations, the sample panel was tested 5 times by two different analysts at three separate sites over 5 different days. This means 5 samples (3 test specimens, plus internal controls likely) x 5 days x 2 analysts x 3 sites = 150 test events for each instrument/method. The specific agreement percentages shown in the tables are for 30 samples (presumably 10 runs per site over 5 days by 2 analysts, combined for totals of 30 for each category, e.g., A(H3) Moderate). Data provenance is not explicitly stated as country of origin, but it is an internal study of the CDC's diagnostic panel. The samples for reproducibility were contrived.
- Clinical Performance: A total of 60 retrospective clinical specimens were used for each investigational instrument/kit combination: 30 positive for influenza A(H3) and 30 negative. The specimens were collected during the 2011-2012 and 2013-2014 influenza seasons. Data provenance is internal ("study was performed internally") using retrospective specimens, likely from the U.S. (given CDC's location).
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Analytical studies (LOD and Reproducibility): Ground truth was established by precise laboratory preparation of known viral concentrations and by a reference method (the cleared predicate method and the CDC's established influenza real-time RT-PCR diagnostic panel). Human experts were involved in performing the tests and interpreting results (e.g., "All users, analysts, and any person reporting results from use of this device should be trained to perform and interpret the results from this procedure by a competent instructor prior to use"). However, the ground truth itself is based on the inherent properties of the prepared samples and the established performance of the predicate device, not on expert consensus of clinical cases.
- Clinical Performance: The ground truth for the retrospective clinical specimens was their prior determination as positive or negative for influenza A(H3) virus. The document does not specify how this prior determination was made (e.g., by culture, another PCR, or an expert committee). It implies that the "comparator" (Roche MagNA Pure Compact instrument using the RNA Isolation Kit) served as the reference standard for this equivalency study.
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Adjudication method (e.g. 2+1, 3+1, none) for the test set:
Not applicable (N/A). This study evaluates a laboratory diagnostic test (RT-PCR) with objective results (positive/negative based on PCR signal) and quantitative metrics (Ct values, EID50/mL). It does not involve human interpretation of images or clinical assessments requiring adjudication. -
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:
N/A. This is a study of an in vitro diagnostic (IVD) device (RT-PCR), not an AI-based imaging or interpretation tool. It does not involve human readers interpreting cases or AI assistance. -
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
This is an IVD device. Its performance is inherent in the device itself (reagents, instrumentation, assay design). The tests performed (LOD, reproducibility, clinical equivalency) are standalone evaluations of the analytical and clinical performance of the new nucleic acid extraction methods in conjunction with the existing PCR panel. While human analysts operate the device, the "performance" refers to the device's output, not human interpretation. -
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Analytical Studies (LOD & Reproducibility): "Spiked" or "contrived" samples with known concentrations of influenza virus.
- Clinical Performance: Previously determined positivity/negativity of retrospective clinical specimens, with the results from the predicate device serving as the comparator/reference.
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The sample size for the training set:
N/A. This is a 510(k) submission for a device modification, focusing on testing the performance of added components (nucleic acid extraction systems) within an already established diagnostic panel. There is no mention of a "training set" in the context of machine learning or algorithm development. The "training" described in the document refers to human analysts being trained to use the device. -
How the ground truth for the training set was established:
N/A, as there is no machine learning training set in this 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.