(15 days)
The Prodesse® ProFluTM+ Assay is a multiplex Real-Time PCR (RT-PCR) in vitro diagnostic test for the rapid and qualitative detection and discrimination of Influenza B Virus, and Respiratory Syncytial Virus (RSV) nucleic acids isolated and purified from nasopharyngeal (NP) swab specimens obtained from symptomatic patients. This test is intended for use to aid in the differential diagnosis of Influenza B and RSV viral infections in humans and is not intended to detect Influenza C.
Negative results do not preclude influenza or RSV virus infection and should not be used as the sole basis for treatment or other 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. The use of additional laboratory testing and clinical presentation must be considered in order to obtain the final diagnosis of respiratory viral infection.
Performance characteristics for Influenza A Virus were established when Influenza A/H3 and A/H1 were the predominant Influenza A viruses in circulation (2006 - 2007 respiratory season). Performance characteristics for Influenza A were confirmed when Influenza A/H1, Influenza A/H3, and Influenza A/2009 H1N1 were the predominant Influenza A viruses in circulation (2008 and 2009). 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 ProFlu+ Assay enables detection and differentiation of Influenza A Virus, Influenza B Virus, Respiratory Syncytial Virus (RSV) (Types A and B), and Universal Internal Control nucleic acids. Nasopharyngeal swab specimens are collected from symptomatic patients using a polyester, rayon or nylon tipped swab and place into viral transport medium.
A Universal Internal Control (UIC) is added to each sample prior to nucleic acid isolation to monitor for inhibitors present in the specimens. The isolation and purification of the nucleic acids is performed using either a MagNA Pure LC Instrument (Roche) and the MagNA Pure Total Nucleic Acid Isolation Kit (Roche) or a NucliSENS® easyMAG™ System (bioMérieux) and the Automated Magnetic Extraction Reagents (bioMérieux).
The purified nucleic acids are added to Influenza B/RSV Mix along with enzymes included in the ProFlu+ Assay Kit. The Influenza B/RSV mix contains oligonucleotide primers and target-specific oligonucleotide probes. The primers are complementary to highly conserved regions of genetic sequences for these respiratory viruses. The probes are dual-labeled with a reporter dye and a quencher.
Reverse transcription of the RNA in the sample into complementary DNA (cDNA) and subsequent amplification of DNA is performed in a Cepheid SmartCycler® II instrument. In this process, the probe anneals specifically to the template followed by primer extension and amplification. The ProFlu+ Assay is based on Taqman chemistry, which utilizes the 5 - 3' exonuclease activity of the Taq polymerase to cleave the probe thus separating the reporter dye from the quencher. This generates an increase in fluorescent signal upon excitation from a light source. With each cycle, additional reporter dye molecules are cleaved from their respective probes, further increasing fluorescent signal. The amount of fluorescence at any given cycle is dependent on the amount of amplification products present at that time. Fluorescent intensity is monitored during each PCR cycle by the SmartCycler II instrument.
The provided text is related to a 510(k) premarket notification for a medical device called Prodesse® ProFlu™+ Assay. This assay is an in vitro diagnostic test for the rapid and qualitative detection and discrimination of certain influenza and respiratory syncytial viruses. The document describes the device, its intended use, and substantial equivalence to predicate devices. It also mentions a study performed to test the reactivity of the assay to an emerging strain of Influenza A.
However, the provided document does not contain a table of acceptance criteria and reported device performance in the typical format requested for clinical studies (e.g., sensitivity, specificity, accuracy with confidence intervals). It also does not detail the study design elements such as sample size for the test set, data provenance, number and qualifications of experts, adjudication methods, MRMC studies, standalone performance, ground truth type, training set details, or how training ground truth was established, as these are typically found in more comprehensive clinical study reports or summaries, not a 510(k) clearance letter and its associated summary.
The document mainly focuses on the regulatory aspects of the device, its components, and a specific study conducted to address the reactivity of the assay to a new strain of influenza A to update the product's instructions for use. It outlines the analytical performance regarding the detection of this new strain.
Therefore, many of the requested points cannot be extracted directly from the given text.
Here's an attempt to answer based only on the provided information, noting what isn't available:
Acceptance Criteria and Study for Prodesse® ProFlu™+ Assay
The document provided details a 510(k) premarket notification for the Prodesse® ProFlu™+ Assay. While it references a study for a modified device, it does not explicitly state "acceptance criteria" in the format of numerical thresholds for clinical performance metrics (e.g., sensitivity, specificity) for the overall device. Instead, it describes a reactivity study for a specific emerging strain of Influenza A, aimed at updating the Instructions for Use.
The implied acceptance criterion for this specific reactivity study appears to be the ability of the assay to detect the new strain.
1. Table of Acceptance Criteria and Reported Device Performance
| Parameter | Acceptance Criteria (Implied) | Reported Device Performance (for the specific strain) |
|---|---|---|
| Detection of Influenza A/New York/1/2015 (H3N2) strain | Assay should be able to detect the new strain. | The Assay was able to detect the nucleic acids of the cultured virus at a concentration of 2x10¹ TCID50/mL. |
2. Sample size used for the test set and the data provenance
- Sample Size: Not explicitly stated for this particular reactivity study. The phrase "a study was performed to test the reactivity... to an emerging strain" suggests a focused analytical study rather than a large clinical test set. The concentration mentioned (2x10¹ TCID50/mL) implies testing was done on dilutions of a cultured virus.
- Data Provenance: Not specified (e.g., country of origin, retrospective/prospective). This was an analytical study performed on cultured virus.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
- Not applicable/Not provided. For an analytical reactivity study, the "ground truth" would be the known presence and concentration of the cultured virus, not expert interpretation of clinical samples.
4. Adjudication method for the test set
- Not applicable/Not provided. This was an analytical reactivity study, not a clinical study requiring adjudication of expert readings.
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 device is an in vitro diagnostic assay (a lab test), not an AI-assisted diagnostic tool that involves human readers for interpretation of images or other complex data.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- The information provided refers to an in vitro diagnostic (IVD) assay. IVDs inherently operate in a "standalone" manner in the sense that the assay itself generates a result (e.g., positive/negative, concentration). The results are then interpreted by laboratory personnel and clinicians. The study described is an analytical test of the assay's capability to detect a specific viral strain.
7. The type of ground truth used
- For the specific reactivity study mentioned, the ground truth was the known presence and concentration of a cultured viral strain (Influenza A, A/New York/1/2015 H3N2), quantified by TCID50/mL.
8. The sample size for the training set
- Not applicable/Not provided. This document describes a modification to an existing device and a reactivity study, not the development or training of a machine learning model.
9. How the ground truth for the training set was established
- Not applicable/Not provided. As above, this is not a machine learning model; thus, a "training set" in that context is not relevant. The device's underlying chemistry and primer/probe design (described in the "Product Description") would have been developed based on known viral genetic sequences, but this is a different concept from a "training set" for an algorithm.
§ 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.