(19 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 with clinical and epidemiological risk factors. The test is intended for use as an aid in the differential diagnosis of 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 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/H/N1 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 BSL 3+ facility is available to receive and culture specimens.
The cobas® 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 cobas® Liat® Analyzer which automates and integrates sample purification, nucleic acid amplification, and detection of the target sequence in biological samples using real-time 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 cobas® Liat® 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).
Here's a breakdown of the acceptance criteria and study information for the cobas® Influenza A/B & RSV Nucleic acid test, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document primarily focuses on demonstrating that the modified device (cobas® Influenza A/B & RSV Assay Script v1.16) has equivalent performance to the predicate device (cobas® Influenza A/B & RSV Assay Script v1.15). Therefore, the acceptance criteria are largely implicitly tied to matching or maintaining the performance characteristics of the predicate device.
| Performance Characteristic | Acceptance Criteria (from Predicate Device) | Reported Device Performance (Modified Device) |
|---|---|---|
| Intended Use | Same as predicate | Same as predicate |
| Regulation | Same as predicate | Same as predicate |
| Product Code | Same as predicate | Same as predicate |
| Assay Target | Same as predicate | Same as predicate |
| Sample Type | Same as predicate | Same as predicate |
| Internal Control | Yes, for sample prep and RT-PCR performance | Same as predicate |
| Influenza A Viral Target | Well-conserved region of matrix gene | Same as predicate |
| Influenza B Viral Target | Well-conserved region of non-structural protein (NSP) gene | Same as predicate |
| RSV Viral Target | Well-conserved region of matrix (M) gene | Same as predicate |
| Assay Instrument | cobas® Liat® Analyzer | Same as predicate |
| CORE Software | cobas® Liat® Analyzer Core Software 3.3 (K200065) | Same as predicate |
| Assay Script (FRTA) | 1.15 | 1.16 (Modified) |
| Self-contained System | Yes | Same as predicate |
| All Assay Reagents Contained in Disposable | Yes | Same as predicate |
| Sample Volume Detection | Yes, automatic check | Same as predicate |
| Automated Assay | Yes, sample prep, amplification, interpretation | Same as predicate |
| Error Diagnostic System | Yes, monitors and records system parameters | Same as predicate |
| Extraction Method | Silica-magnetic bead-based nucleic acid extraction | Same as predicate |
| Assay Method | RT-PCR | Same as predicate |
| Detection Technique | Multiplex assay using different reporter dyes | Same as predicate |
| Result Interpretation | Automated | Same as predicate |
| PCR Curve Pattern Recognition | Yes | Same as predicate |
| Assay Result | Qualitative | Same as predicate |
| User | CLIA Waived (CW150018) | Same as predicate |
| Test Availability | Random access, on-demand test | Same as predicate |
| Time-to-result | ~20 minutes | Same as predicate |
| Limit of Detection | 10⁻³ - 10⁻¹ TCID50/mL | Same as predicate |
| Reactivity | Reactive against 28 Flu A, 15 Flu B, and 7 RSV strains | Same as predicate |
| Cross-Reactivity | No cross-reactivity with 35 microorganisms and human genomic DNA | Same as predicate |
| Interfering Microorganisms | No effect on detection due to 35 microorganisms and human genomic DNA | Same as predicate |
| Interfering Substances | No effect on detection due to 10 substances | Same as predicate |
| Reproducibility | ≥99.8% total percent agreement | Same as predicate |
| Overall Assay Performance | Not Impacted by changes in v1.16 compared to v1.15 | Not Impacted by changes in v1.16 compared to v1.15 |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: The test set included "multiple sample types" for each configuration of the assay script (v1.15 and v1.16). Specifically, these included negative controls, positive controls, negative specimens, and positive specimens containing co-formulated Influenza A, Influenza B, and RSV target material at a concentration of 3X the Limit of Detection (LoD). For the 3X LoD samples, mean Ct values were assessed.
- Data Provenance: The document does not explicitly state the country of origin. It indicates the study was conducted internally by Roche Molecular Diagnostics (RMD), Pleasanton, CA. It is a retrospective study in the sense that it compares a modified version of the software (v1.16) against a previously cleared version (v1.15) using defined sample types, rather than collecting new clinical samples from patients.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
Not applicable. This study is an analytical performance assessment comparing a software version against a previous version, not a clinical study involving diagnosis by experts. The "ground truth" for the test set specimens (e.g., negative controls, positive controls, 3X LoD samples) would have been established by the manufacturer's internal quality control and characterization processes.
4. Adjudication Method for the Test Set
Not applicable, as this was an analytical comparison study of software versions, not a clinical trial requiring adjudication of diagnostic outcomes.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No. This was not a multi-reader, multi-case comparative effectiveness study. It was a technical comparison of an updated software algorithm (Assay Script v1.16) against a previous version (v1.15) for an existing in vitro diagnostic device. Therefore, there's no mention of human readers or improved performance with AI assistance.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, this study is inherently a standalone performance assessment of the updated algorithm. The cobas® Liat® System is an automated system that outputs an interpreted result directly (qualitative detection of viral RNA). The study assessed the impact of the algorithm change on these automated results.
7. The Type of Ground Truth Used
The ground truth for the test set samples used in this study was based on:
- Defined characteristics of controls: Negative controls and positive controls have known compositions.
- Spiked samples: Positive specimens containing co-formulated target material at a known concentration (3X LoD) were used, allowing for a quantitative ground truth for viral load.
8. The Sample Size for the Training Set
The document does not provide information about a training set. The changes implemented were to an "Algorithm parameter" and "Correction of defects (bug fixes)" in the assay script. This suggests the changes were based on identifying and addressing specific performance characteristics or issues with the original algorithm, rather than a re-training of a machine learning model.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as a discrete "training set" in the context of machine learning model development is not mentioned or implied by the description of the software changes. The algorithm modifications were likely based on internal engineering analysis and optimization to address specific performance aspects (like tolerating early Cts) or bug fixes within the existing RT-PCR assay interpretation.
§ 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.