(117 days)
The Cepheid Xpert Flu/RSV XC Assay is an automated, multiplex real-time, reverse transcriptase polymerase chain reaction (RT-PCR) assay intended for the in vitro qualitative detection and differentiation of influenza B, and respiratory syncytial virus (RSV) viral RNA. The Xpert Flu/RSV XC Assay uses nasopharyngeal swab and nasal aspirate/wash specimens collected from patients with signs and symptoms of respiratory infection. The Xpert Flu/RSV XC Assay is intended as an aid in the diagnosis of influenza and respiratory syncytial virus infections in conjunction with clinical and epidemiological risk factors.
Negative results do not preclude influenza virus or respiratory syncytial virus infection and should not be used as the sole basis for treatment or other patient management decisions.
Performance characteristics for influenza A were established during the 2013-2014 influenza season. When other novel 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 Xpert Flu/RSV XC Assay is a rapid, automated in vitro diagnostic test for qualitative detection and differentiation of influenza A. influenza B, and respiratory syncytial virus (RSV). The assay is performed on the Cepheid GeneXpert Instrument Systems (GeneXpert Dx systems and GeneXpert Infinity Systems). The GeneXpert Instrument System platform automates and integrates sample purification, nucleic acid amplification, and detection of the target sequence in simple or complex samples using real-time PCR and reverse transcriptase PCR (RT-PCR) assays. The systems require the use of singleuse disposable cartridges (the Xpert Flu/RSV XC cartridges) that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained and specimens never come into contact with working parts of the instrument modules, cross-contamination between samples is minimized.
The Xpert Flu/RSV XC Assay includes reagents for the detection and differentiation of influenza A, influenza B, and RSV viral RNA directly from nasopharyngeal (NP) swab and nasal aspirate/wash (NA/W) specimens collected from patients with signs and symptoms of respiratory infection. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are also included in the cartridge. The SPC is present to control for adequate processing of the target viruses and to monitor the presence of inhibitors in the PCR reaction. The Probe Check Control (PCC) verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity and dye stability.
The single-use, multi-chambered fluidic cartridges are designed to complete sample preparation and real-time RT-PCR for detection and differentiation of influenza A, influenza B and RSV viral RNA in approximately 60 minutes or less. The GeneXpert Instrument Systems, comprised of the GeneXpert Dx Systems and the GeneXpert Infinity Systems, have 1 to 80 randomly accessible modules, depending upon the instrument, that are each capable of performing separate sample preparation and real-time PCR and RT-PCR tests. Each module contains a syringe drive for dispensing fluids (i.e., the syringe drive activates the plunger that works in concert with the rotary valve in the cartridge to move fluids between chambers), an ultrasonic horn for lysing cells or spores, and a proprietary I-CORE® thermocycler for performing real-time PCR and RT-PCR and detection.
Specimens are collected following the user's institution standard procedures for collecting NA/W specimens and NP swab specimens for influenza and RSV testing. The ancillary Cepheid Xpert Nasopharyngeal Sample Collection Kit (Cepheid catalog #SWAB/B-100) or Cepheid's Sample Collection Kit (Cepheid catalog #NASL-100N-100) are required but not provided for use with the assay. Both kits contain the identical viral transport medium and sterile nylon flocked swab. The NA/W specimen or the NP swab specimen is placed into the Xpert viral transport medium and sent to the GeneXpert® testing area for processing. When stored in the transport medium, the NA/W specimen or NP swab specimen is stable for up to 24 hours at 2-30 ℃ or up to seven days at 2-8 ℃. When ready to test the specimen, the user briefly mixes the specimen by inverting the tube five times, transfers the eluted material to the sample chamber in the top of the disposable fluidic cartridge. The user initiates a test from the system user interface and places the cartridge into the GeneXpert instrument platform, which performs hands-off real-time, multiplex polymerase chain reaction (PCR) for detection of RNA. The results are automatically generated at the end of the process in a report that can be viewed and printed.
Here's an analysis of the provided text, focusing on acceptance criteria and study details:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state formal "acceptance criteria" for the clinical performance in terms of specific PPA/NPA thresholds that had to be met for clearance. It presents the performance of the device and claims substantial equivalence to predicate devices. However, we can infer the desired performance from the presented data and the implicit expectation for a diagnostic assay to perform well. The analytical studies (LoD, specificity, inclusivity) demonstrate performance against well-defined criteria.
Inferred Clinical Acceptance Criteria (Based on Comparator Performance and FDA Clearance): The device's performance (PPA and NPA) should be demonstrably similar to or better than previously cleared predicate devices, with high positive and negative agreement. While no explicit thresholds like "PPA > X%" are stated for clinical studies, the demonstration of high agreement values and the claim of "substantially equivalent" implies these levels were considered acceptable by the FDA.
| Category | Acceptance Criteria (Inferred from Predicate Equivalence and High Performance) | Reported Device Performance (Xpert Flu/RSV XC Assay) |
|---|---|---|
| Analytical Studies | ||
| Limit of Detection (LoD) | Lowest concentration with 95% confidence (19/20 positive replicates) | Flu A 2009 H1N1: 0.3-16 TCID50/mL |
| Flu A H3N2: 0.3-0.8 TCID50/mL | ||
| Flu B: 0.5-0.6 TCID50/mL | ||
| RSV A: 1.0-1.2 TCID50/mL | ||
| RSV B: 1.8-2.0 TCID50/mL | ||
| Flu A H7N9: 21.0 TCID50/mL | ||
| Analytical Specificity | 100% negative results for common respiratory pathogens or encountered microbes | 100% (negative for 44 viral, bacterial, and yeast strains) |
| Analytical Reactivity | Positive detection for multiple strains of target viruses | 100% (positive for 64 strains including various Influenza A, B, and RSV A/B) |
| Non-Interference | No assay interference from potentially interfering substances | No assay interference observed for 14 tested substances at specified concentrations |
| Carry-Over Contamination | No carry-over contamination from high positive to subsequent negative samples | 100% (40 positive, 42 negative samples all correctly reported) |
| Fresh vs. Frozen Sample Equivalency | Statistically equivalent performance between fresh and freeze-thaw cycles | No statistically significant effect observed |
| Clinical Performance (NA/W Specimens) | High PPA and NPA relative to comparator assay | Flu A (Fresh): PPA 100%, NPA 100% |
| Flu B (Fresh): PPA 99.2%, NPA 100% | ||
| RSV (Fresh): PPA 98.5%, NPA 99.6% | ||
| Flu A (Frozen): PPA 97.1%, NPA 100% | ||
| Flu B (Frozen): PPA 100%, NPA 100% | ||
| RSV (Frozen): PPA 84.6%, NPA 100% | ||
| Clinical Performance (NP Swab Specimens) | High PPA and NPA relative to comparator assay | Flu A (Fresh): PPA 85.7%, NPA 98.9% |
| Flu B (Fresh): PPA 100%, NPA 100% | ||
| RSV (Fresh): PPA 100%, NPA 100% | ||
| Flu A (Frozen): PPA 99.0%, NPA 92.8% | ||
| Flu B (Frozen): PPA 98.8%, NPA 100% | ||
| RSV (Frozen): PPA 90.4%, NPA 99.1% | ||
| Acceptable Indeterminate Rate | Low rate of indeterminate results during initial testing and upon retest | 1.4% initial indeterminate rate (17/18 retested, 14 yielded valid results, 4 still indeterminate) |
| Reproducibility | High agreement across sites, operators, and days (qualitative) | |
| Low variability in Ct values (quantitative) | Qualitative agreement mostly >90% for positive samples; 80%; >90% for higher positive samples | |
| Total CVs for Ct values generally |
§ 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.