(79 days)
The IQuum Liat™ Influenza A/B Assay performed on the Liat™ Analyzer is an automated multiplex real-time RT-PCR assay for the rapid in vitro qualitative detection and discrimination of influenza A virus and influenza B virus 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 and influenza B in humans and is not intended to detect influenza C.
Negative results do not preclude influenza virus 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 when influenza A/H1 and A/H3 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 Liat™ Influenza A/B Assay is a rapid, automated in vitro diagnostic test for the detection and differentiation of Influenza type A and type B viral RNA in nasopharyngeal swab (NPS) specimens in universal transport media (UTM) from patients signs and symptoms of respiratory infection. The assay targets a well-conserved region of the matrix gene of Influenza A viral RNA (Inf A target) and non-structural protein (NS) gene of Influenza B (Inf B target). An Internal Process Control (IPC) is also included. The IPC is present to control for adequate processing of the target viruses and to monitor the presence of inhibitors in the RT-PCR reactions.
The Liat Influenza A/B Assay is performed on the lab-in-a-tube technology platform. The system consists of a disposable Liat Influenza A/B Assay Tube and the Liat™ Analyzer. The Liat™ Tube uses a flexible tube as a sample vessel. It contains all required unit dose reagents prepacked in tube segments, separated by peelable seals, in the order of reagent use. Manipulating a Liat Tube, the Liat Analyzer performs all assay steps from raw sample and report assay result automatically, During the testing process, multiple sample processing actuators of the analyzer compress the Liat Tube to selectively release reagents from tube segments, move the sample from one segment to another, and control reaction volume, temperature and time to conduct sample preparation, nucleic acid extraction, target enrichment, inhibitor removal, nucleic acid elution and real-time RT-PCR. An embedded microprocessor controls and coordinates the actions of these sample processors to perform all required assay processes within the closed Liat Tube. Turnaround time from sample input to result is ~20 minutes.
1. Table of Acceptance Criteria and Reported Device Performance:
The document provided is a 510(k) Summary for the IQuum Liat™ Influenza A/B Assay and Liat™ Analyzer, a diagnostic device. For diagnostic devices like this, "acceptance criteria" are typically defined by performance metrics (e.g., sensitivity, specificity, accuracy) that demonstrate the new device is "substantially equivalent" to a legally marketed predicate device. While explicit numerical acceptance criteria are not always stated directly in the summary, the study's results (performance) serve to demonstrate this equivalence. The key performance indicators presented are clinical agreement (sensitivity and specificity) and analytical performance (limit of detection, reactivity, cross-reactivity, interference, precision, reproducibility).
Here's a table summarizing the reported device performance, which the FDA presumably found acceptable for clearance based on substantial equivalence.
| Performance Metric | Acceptance Criteria (Implied by Predicate Equivalence) | Reported Device Performance (Liat™ Influenza A/B Assay) |
|---|---|---|
| Limit of Detection (LOD) | Must be comparable to relevant predicate or clinical needs. | Influenza A: Ranges from $10^{-1}$ to $10^{-2}$ TCID50/mL for tested strains (A/Brisbane/10/2007, A/Brisbane/59/2007, A/NY/01/2009). |
| Influenza B: Ranges from $10^{-1}$ to $10^{-3}$ TCID50/mL for tested strains (B/Florida/04/06, B/Malaysia/2506/04). | ||
| Reactivity | Must detect a broad range of clinically relevant influenza strains. | Detected all 22 Influenza A strains (8 seasonal H1, 8 seasonal H3, 3 2009 H1N1, 3 swine origin) and all 10 Influenza B strains tested. |
| Cross-Reactivity | No cross-reactivity with common non-influenza respiratory pathogens/microorganisms at specified concentrations. | Showed no cross-reactivity for the panel of 31 human pathogens (bacteria at $10^4-10^6$ CFU/mL, viruses at $10^3-10^5$ TCID50/mL). |
| Interference | No interference from common microorganisms or substances at specified concentrations. | Microorganisms: No interference with detection of Inf A or Inf B by 31 human pathogens (bacteria at $10^4-10^6$ CFU/mL, viruses at $10^3-10^5$ TCID50/mL) when spiked with Inf A or Inf B at 3x LOD. |
| Substances: No interference from 9 common substances (mucin, blood, nasal sprays, corticosteroids, gels, lozenges, antibiotics, antiviral drugs) when tested with Inf A and Inf B strains at 3x LOD. | ||
| Precision (Inter-lot variability) | Low variability between different manufacturing lots. | %CV for Inter-lot imprecision was |
§ 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.