(33 days)
The Prodesse® ProParaflu®+ Assay is a multiplex Real-Time PCR (RT-PCR) in vitro diagnostic test for the qualitative detection and discrimination of Parainfluenza 1 Virus, Parainfluenza 2 Virus and Parainfluenza 3 Virus (HPIV-1. HPIV-2 and HPIV-3) nucleic acids isolated and purified from nasopharyngeal (NP) swab specimens obtained from individuals exhibiting signs and symptoms of respiratory tract infections. This Assay targets the conserved regions of the Hemagglutinin-Neuraminidase (HN) gene of HPIV-1, HPIV-2 and HPIV-3, respectively. The detection and discrimination of HPIV-1, HPIV-2 and HPIV-3 nucleic acids from symptomatic patients aid in the diagnosis of human respiratory tract parainfluenza infections if used in conjunction with other clinical and laboratory findings. This test is not intended to detect Parainfluenza 4a or Parainfluenza 4b Viruses.
Negative test results are presumptive and should be confirmed by cell culture. Negative results do not preclude Parainfluenza 1, 2 or 3 virus infections and should not be used as the sole basis for treatment or other management decisions.
The ProParaflu+ assay enables detection and differentiation of Parainfluenza 1 Virus, Parainfluenza 2 Virus, Parainfluenza 3 Virus and Universal Internal Control nucleic acids. Nasopharyngeal swab specimens are collected from symptomatic patients using a polyester, rayon or nylon tipped swab and placed 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 ProParaflu+ Supermix along with enzymes included in the ProParaFlu+ Assay Kit. The ProParaflu+ Supermix 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 ProParaFlu+ Assay is based on Tagman 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.
This document describes the Prodesse® ProParaflu®+ Assay, a multiplex Real-Time PCR (RT-PCR) in vitro diagnostic test for the qualitative detection and discrimination of Parainfluenza 1, 2, and 3 Viruses.
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Acceptance Criteria and Device Performance
The provided document is a 510(k) summary, which focuses on demonstrating substantial equivalence to a predicate device. It highlights similarities and differences, and mentions limitations related to specific CAP samples. Crucially, this document does not explicitly state acceptance criteria in terms of performance metrics (e.g., sensitivity, specificity, accuracy) nor does it present detailed study results proving the device meets said acceptance criteria.
The "Substantial Equivalence" section primarily states that the Intended Use, Warnings and Precautions, Organisms Detected, Analyte, Technological Principles, Specimen Types, User Complexity, Sample Preparation Method, Instrumentation, Time to Result, and Controls are the same as the predicate device (K091053). This implies that the device is expected to perform at a similar level to the predicate, but specific performance criteria for the new device are not enumerated here.
The key difference noted is a "Limited reactivity with the 2014 CAP sample ID2-08 and the 2015 CAP sample ID2-02," attributed to a viral mutation in the probe binding region of HPIV3. This limitation implies a potential issue with sensitivity for specific HPIV3 variants, which could be considered a deviation from an implied acceptance criterion of detecting all clinically relevant HPIV3 strains.
Given the information, a table of implied acceptance criteria and reported "performance" (which is more a statement of similarity or a recognized limitation) would be:
| Acceptance Criterion (Implied) | Reported Device Performance / Status |
|---|---|
| Detection and discrimination of HPIV-1, HPIV-2, and HPIV-3 | Same as predicate device (K091053). The device targets conserved regions of the HN gene for each virus. However, there is Limited reactivity with the 2014 CAP sample ID2-08 and 2015 CAP sample ID2-02 (HPIV3 variants due to viral mutation). |
| Use with nasopharyngeal (NP) swab specimens | Same as predicate device. |
| Qualitative detection assay | Same as predicate device. |
| Performance with specific isolation methods (MagNA Pure LC, NucliSENS easyMAG) and instrumentation (Cepheid SmartCycler II) | Same as predicate device. The assay uses a Universal Internal Control (UIC) for inhibition monitoring and external controls with each batch. |
| Aid in the diagnosis of human respiratory tract parainfluenza infections in conjunction with other clinical and laboratory findings | Same as predicate device. |
| Not intended to detect Parainfluenza 4a or 4b Viruses | Same as predicate device. |
| Negative results are presumptive and may require confirmation | Same as predicate device. (Negative test results are presumptive and should be confirmed by cell culture. Negative results do not preclude Parainfluenza 1, 2 or 3 virus infections and should not be used as the sole basis for treatment or other management decisions.) |
The document does not provide the following information:
- Sample sizes used for the test set and the data provenance: There is no specific data presented from a test set. The document refers to "the 2014 CAP sample ID2-08 and the 2015 CAP sample ID2-02" which indicates external proficiency testing samples, but not a full clinical test set used for performance validation in this submission.
- Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not applicable, as detailed performance data from a test set is not provided.
- Adjudication method for the test set: Not applicable.
- If a multi-reader multi-case (MRMC) comparative effectiveness study was done, and the effect size of how much human readers improve with AI vs without AI assistance: Not applicable. This is an in vitro diagnostic (IVD) assay, not an AI/imaging device requiring human reader analysis.
- If a standalone (i.e. algorithm only without human-in-the-loop performance) was done: The device is a "standalone" in the sense that it's an assay. Performance is measured by its output based on the sample, not by an algorithm's interpretation for a human-in-the-loop. However, specific standalone performance study results (e.g., sensitivity, specificity clinical studies) are not provided in this 510(k) summary. The summary focuses on substantial equivalence based on the technological similarity to a predicate.
- The type of ground truth used: Not explicitly stated for performance verification studies, as such studies are not detailed here. For the CAP samples mentioned, "sequencing analysis" was used to establish the genetic makeup of the viral strain, which served as a form of ground truth for assessing reactivity.
- The sample size for the training set: Not applicable for this type of IVD assay. The assay utilizes PCR primers and probes designed based on conserved genetic regions, not a machine learning model trained on a dataset.
- How the ground truth for the training set was established: Not applicable.
In summary, this 510(k) notification primarily argues for substantial equivalence based on the device's technical and analytical similarity to a previously cleared predicate and its intended use. It discloses a specific limitation identified through external proficiency samples but does not provide comprehensive clinical performance data or details of a validation study with defined acceptance criteria and corresponding results. Such data would typically be part of the full 510(k) submission, but not always summarized in this manner in the publicly available summary.
§ 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.