(29 days)
The Prodesse® Pro hMPV®+ Assay is a Real-Time PCR (RT-PCR) in vitro diagnostic test for the qualitative detection of human Metapneumovirus (hMPV) nucleic acid isolated and purified from nasopharyngeal swab (NP) specimens obtained from individuals exhibiting signs and symptoms of acute respiratory infection. This Assay targets a highly conserved region of the Nucleocapsid gene of hMPV. The detection of hMPV nucleic acid from symptomatic patients aids in the diagnosis of human respiratory hMPV infection if used in conjunction with other clinical and laboratory findings. This test is not intended to differentiate the four genetic sub-lineages of hMPV.
Negative results do not preclude hMPV infection and should not be used as the sole basis for diagnosis, treatment or other management decisions.
The Pro hMPV+ Assay enables detection of human Metapneumovirus and internal control nucleic acid. Nasopharyngeal swab specimens are collected from patients with signs and symptoms of a respiratory infection 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 Pro hMPV+ Supermix along with enzymes included in the Pro hMPV+ Assay Kit. The Pro hMPV+ Supermix contains oligonucleotide primers complementary to a highly conserved region of the Nucleocapsid gene of hMPV and a targetspecific oligonucleotide probe dual-labeled with a reporter dye attached to the 5'-end and a quencher dve attached to nucleotide #7 from the 5 end.
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 Pro hMPV+ 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 SmartCyclerII instrument.
Here's a breakdown of the acceptance criteria and study information for the Prodesse® Pro hMPV®+ Assay, based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state numerical acceptance criteria in terms of sensitivity, specificity, or predictive values. Instead, the "Verification/Validation Result" column of the "SUBSTANTIAL EQUIVALENCE" table functions as the reported performance, indicating that the modified device continues to meet the performance claims of the predicate device.
| Acceptance Criteria (Implied) | Reported (Modified) Device Performance |
|---|---|
| Ability to detect target organisms at the limit of detection (LOD) | The UIC (Universal Internal Control) did not affect the ability of the Pro hMPV+ Assay to detect target organisms at the limit of detection, as evinced by the results of Analytical Sensitivity, IC Interference, Extractor Equivalency, and Sample Stability studies. |
| Clinical performance of the Pro hMPV+ Assay | A retrospective clinical comparison study demonstrated the modified Pro hMPV+ Assay with UIC continues to meet the performance claims for the current Pro hMPV+ Assay. |
| All clinical and analytical performance/functionality remains unchanged from the previous device | Verification and validation studies performed demonstrated that all clinical and analytical performance/functionality remains unchanged from the previous device. |
2. Sample Size Used for the Test Set and Data Provenance
The document mentions a "retrospective clinical comparison study" (page 2), but does not specify the sample size used for this study. It also does not explicitly state the country of origin. The term "retrospective" indicates that the data was collected prior to the study being designed.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not provide information on the number of experts used or their qualifications for establishing ground truth in the clinical comparison study.
4. Adjudication Method for the Test Set
The document does not specify any adjudication method for the test set used in the clinical comparison study.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and the Effect Size of Human Readers Improve with AI vs. Without AI Assistance
This question is not applicable to this device. The Prodesse® Pro hMPV®+ Assay is an in vitro diagnostic test (Real-Time PCR) for qualitative detection of nucleic acid, not an AI-powered diagnostic imaging or interpretation device that would involve human readers or MRMC studies.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the studies described (analytical sensitivity, IC interference, extractor equivalency, and sample stability) and the clinical comparison study effectively demonstrate the standalone performance of the assay as an in vitro diagnostic test. The "algorithm" here is the assay's chemical and enzymatic process, and its performance is evaluated in isolation.
7. The Type of Ground Truth Used
Based on the nature of the device (a diagnostic test for a pathogen), the ground truth for human Metapneumovirus (hMPV) infection would likely be based on clinical diagnosis in conjunction with other laboratory findings, as suggested by the intended use statement: "The detection of hMPV nucleic acid from symptomatic patients aids in the diagnosis of human respiratory hMPV infection if used in conjunction with other clinical and laboratory findings."
For the analytical studies (LOD, interference, etc.), the ground truth would be established by controlled experiments with known concentrations of the target analyte (hMPV nucleic acid) and known interfering substances.
8. The Sample Size for the Training Set
The document does not mention a training set sample size. This is common for predicate-based 510(k) submissions where the device "continues to meet the performance claims" of an already approved device, rather than being a de novo artificial intelligence or machine learning device that requires explicit training data. The development of the original predicate device would have involved internal optimization and validation, but these details are not provided for this submission.
9. How the Ground Truth for the Training Set Was Established
As no explicit "training set" is mentioned in the context of this 510(k) submission (due to it being a modification of an existing device), the method for establishing ground truth for a training set (if one were used in the original development) is not described. For the development and optimization of the original assay, ground truth would have been established through methods similar to those described in point 7, involving known positive and negative controls, spiked samples, and potentially clinical samples with confirmed hMPV status.
§ 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.