(210 days)
The cobas® Influenza A/B & RSV Nucleic acid test for use on the cobas® Liat® System (cobas® Influenza A/B & RSV) is an automated multiplex real-time RT-PCR assay for the rapid in vitro qualitative detection and discrimination of Influenza A virus, Influenza B virus and respiratory syncytial virus (RSV) RNA in nasopharyngeal swab specimens from patients with signs and symptoms of respiratory infection in conjunction with clinical and epidemiological risk factors. The test is intended for use as an aid in the differential diagnosis of Influenza A, Influenza B, and RSV in humans and is not intended to detect Influenza C.
Negative results do not preclude Influenza virus or RSV infection and should not be used as the sole basis for treatment or other patient management decisions. Conversely, positive results do not rule out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease.
Performance characteristics for Influenza A were established during the 2013-2014 and the 2014-2015 influenza seasons when Influenza A/H3 and A/H1N1 pandemic were the predominant Influenza A viruses in circulation. When other Influenza A viruses are emerging, performance characteristics may vary.
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 department for testing. Viral culture should not be attempted in these cases unless a BSL3+ facility is available to receive and culture specimens.
The cobas® Liat® Influenza A/B & RSV Nucleic Acid Test for use on the cobas® Liat® System (cobas® Influenza A/B & RSV) is an automated in vitro diagnostic test for the qualitative detection of Influenza A, Influenza B, and RSV RNA in nasopharyngeal swab (NPS) specimens. The sample-to-result time is ~20 minutes.
The assay is performed on the Analyzer which automates and integrates sample purification, nucleic acid amplification, and detection of the target sequence in biological samples using realtime RT-PCR assays. The assay targets a well-conserved region of the matrix gene of Influenza A (Inf A target), the non-structure protein gene of Influenza B (Inf B target), and the matrix gene of RSV (RSV target). An Internal Process Control (IPC) is also included. The IPC is present to control for adequate processing of the target virus through all steps of the assay process and to monitor the presence of inhibitors in the RT-PCR reactions.
The System consists of an instrument and preloaded software for running tests and viewing the results. The system requires the use of a single-use disposable cobas® Influenza A/B & RSV assay tube that holds the nucleic acid purification and RT-PCR reagents, and hosts the sample preparation and RT-PCR processes.
The detection module monitors the reaction in real-time, while an on-board computer analyzes the collected data and outputs an interpreted result. The latter is displayed in the assay report on the integrated LCD touch screen of the cobas® Liat® Analyzer and in an electronic file. The report can be printed directly through a USB or network-connected printer. The results can also be exported to an external server, middleware or data management system, or to a Laboratory Information System (LIS).
The provided text describes a 510(k) premarket notification for a medical device: "cobas Influenza A/B & RSV nucleic acid test for use on the cobas Liat System." This document is focused on demonstrating the substantial equivalence of a modified device to a previously cleared predicate device, specifically regarding a change in the negative control buffer and positive control diluent. It does not contain detailed information about initial acceptance criteria, a comprehensive study proving the device met those criteria, sample sizes for test sets, data provenance, expert adjudication, MRMC studies, standalone performance, or training set details that would be typical for a de novo device clearance or a more extensive clinical validation study.
Therefore, many of the requested details cannot be extracted from this document. The document primarily states that the performance claims were not impacted by the change, implying that the performance previously demonstrated for the predicate device still holds true.
Here's what can be extracted and what cannot:
1. Table of acceptance criteria and reported device performance:
The document doesn't explicitly lay out "acceptance criteria" for a new device but rather compares the performance aspects of the submitted device (with the changed control materials) to the predicate device. It asserts that performance claims were not impacted. The relevant performance aspects of the predicate device (which the current device is deemed equivalent to) are listed, essentially serving as the implied performance to be met.
| Performance Aspect | Implied Acceptance Criteria (from Predicate Device) | Reported Device Performance (with modified controls) |
|---|---|---|
| Limit of Detection | 10^-3 – 10^-1 TCID50/mL | Same (performance claims not impacted) |
| Reactivity | Reactive against 28 Flu A, 15 Flu B, and 7 RSV strains tested | Same (performance claims not impacted) |
| Cross Reactivity | No cross reactivity found with 35 microorganisms and human genomic DNA | Same (performance claims not impacted) |
| Interfering Microorganisms | No effect on detection found with 35 microorganisms and human genomic DNA | Same (performance claims not impacted) |
| Interfering Substances | No effect on detection found with 10 substances | Same (performance claims not impacted) |
| Reproducibility | ≥99.8% total percent agreement | Same (performance claims not impacted) |
2. Sample sized used for the test set and the data provenance:
- The document states: "Performance of the cobas® Influenza A/B & RSV assay when used with NEG BUF as a negative control and positive control diluent was assessed."
- Sample size and data provenance are NOT explicitly stated. This document focuses on demonstrating that a change to control materials did not impact performance, rather than providing the full details of a new clinical study. The original predicate device's performance characteristics for Influenza A were established during the 2013-2014 and 2014-2015 influenza seasons, implying retrospective data from those periods for the predicate. However, details of the assessment of the impact of the control material change (which is the focus of this 510(k)) are not provided.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- NOT explicitly stated. This type of detail is typically found in clinical study reports for initial device approvals, not usually in a 510(k) for a minor modification like a control reagent change. The ground truth for real-time PCR assays like this is usually established by highly sensitive and specific laboratory methods (e.g., cell culture, sequencing, or a gold-standard PCR).
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- NOT applicable/explicitly stated. This refers to human reader adjudication for image-based AI devices. This document describes an in vitro diagnostic (IVD) PCR assay, which ideally has a definitive laboratory-based ground truth rather than subjective human interpretation needing 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:
- NOT applicable. This is a PCR assay, not an AI-assisted diagnostic imaging device that involves human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Partially Applicable. The cobas Liat System is an automated assay that processes samples and outputs results. The "performance" described (Limit of Detection, Reactivity, etc.) inherently represents its standalone (algorithm/instrument only) performance. There is no human interpretation component that would require a human-in-the-loop study.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- For molecular diagnostic tests like this, the ground truth is typically established by:
- Clinically confirmed cases: Samples from patients with confirmed infections by other validated methods (e.g., viral culture, sequencing, or a highly sensitive and specific reference PCR method).
- Characterized challenge panels: Samples with known concentrations of the target analytes and related organisms.
- The document implies that the ground truth for the predicate's performance was based on the presence/absence of viral RNA and likely confirmed by other laboratory methods. It references "established during the 2013-2014 and the 2014-2015 Influenza seasons," which suggests clinical samples with confirmed infection statuses.
8. The sample size for the training set:
- NOT applicable/explicitly stated. This is not an AI/machine learning device that typically has a "training set" in the common sense. It's a PCR assay with defined reagents and a fixed algorithm. The development would involve analytical verification and validation, but not machine learning "training."
9. How the ground truth for the training set was established:
- NOT applicable. See point 8.
§ 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.