Search Results

The NxTAG® Respiratory Pathogen Panel v2 (NxTAG® RPP v2) is a multiplexed polymerase chain reaction (PCR) test intended for the simultaneous, qualitative detection of multiple respiratory viral and bacterial nucleic acids in nasopharyngeal swab specimens obtained from individuals with signs and symptoms of respiratory tract infection, including COVID-19.

The following organism types and subtypes are identified and differentiated using the NxTAG RPPv2:

Viral Targets: Influenza A, Influenza A H1, Influenza A H1pdm09, Influenza B, Respiratory Syncytial Virus A, Respiratory Syncytial Virus B, SARS-CoV-2, Coronavirus 229E, Coronavirus OC43, Coronavirus NL63, Coronavirus HKU1, Human Metapneumovirus, Rhinovirus, Adenovirus, Parainfluenza 1, Parainfluenza 2, Parainfluenza 3, Parainfluenza 4

Bacterial Targets: Chlamydia pneumoniae, Mycoplasma pneumoniae

Nucleic acids from the viral and bacterial organisms identified by this test are generally detectable in nasopharyngeal specimens during the acute phase of infection. The detection of specific viral and bacterial nucleic acids from individuals exhibiting signs and or symptoms of respiratory infection are indicative of the identified microorganism and aids in diagnosis if used in conjunction with other clinical and epidemiological information, and laboratory findings. The results of this test should not be used as the sole basis for diagnosis, treatment management decisions.

Negative results in the setting of a respiratory illness may be due to infection with pathogens that are not detected by this test, or lower respiratory tract infection that may not be detected by a nasopharyngeal swab specimen. Positive results do not rule out coinfection with other organisms. The agent(s) detected by the NxTAG RPP v2 may not be the definite cause of disease.

Additional laboratory testing (e.g., bacterial and viral culture, immunofluorescence, and radiography) may be necessary when evaluating a patient with possible respiratory tract infection.

The NxTAG® Respiratory Pathogen Panel v2 is indicated for use with the Luminex® MAGPIX® Instrument and xPONENT® and SYNCTTM software.

The NxTAG® Respiratory Pathogen Panel v2 (NxTAG® RPP v2) is designed to simultaneously detect and identify 21 different potential pathogens of respiratory tract infections, including the novel coronavirus SARS-CoV-2, from a single NPS specimen in transport medium. NxTAG® RPP v2 is compatible with Luminex's MAGPIX Instrument, and xPONENT® and SYNCT™ software. It incorporates multiplex Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) with the Luminex® proprietary universal tag sorting system on the Luminex platform to easily detect the 21 respiratory pathogen targets.

Samples are extracted using the IVD-labeled bioMérieux NucliSENS® easyMag® or EMAG® extraction systems. Extracted total nucleic acid is then added to the sealed 96-well micro plate by piercing the seal with pipette tips. Each reaction well is pre-plated with two Lyophilized Bead Reagents (LBRs) that contain all the required reagents including primer mixes, bead mix, and enzyme buffer systems. Once the LBRs are resuspended, the reaction wells are re-sealed using the foils provided in the kit. The sealed plate can be placed inside the thermocycler. The reaction is amplified via RT-PCR and the reaction product undergoes near simultaneous bead hybridization within the sealed reaction wells. The hybridized, tagged beads are then sorted and read on the Luminex® MAGPIX® instrument. The MAGPIX® instrument generates a signal in the form of a median fluorescence intensity (MFI) value for each bead population.

The signals are analyzed using the NxTAG® Respiratory Pathogen Panel v2 Assay File for SYNCT™ Software, providing a reliable, qualitative call for each of the 21 targets and internal controls within each reaction well.

Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided FDA 510(k) summary for the Luminex NxTAG® Respiratory Pathogen Panel v2 (NxTAG® RPP v2):

The NxTAG® Respiratory Pathogen Panel v2 (NxTAG® RPP v2) is a multiplexed polymerase chain reaction (PCR) test intended for the simultaneous, qualitative detection of multiple respiratory viral and bacterial nucleic acids in nasopharyngeal swab specimens from individuals with signs and symptoms of respiratory tract infection, including COVID-19.

Acceptance Criteria and Reported Device Performance

The acceptance criteria for the NxTAG® RPP v2 assay are implied through the robust analytical and clinical performance studies, specifically focusing on sensitivity (Limit of Detection, LoD, and Positive Percent Agreement, PPA) and specificity (Analytical Specificity, Cross-Reactivity, and Negative Percent Agreement, NPA), as well as reproducibility and stability.

Here's a summary of the performance as reported in the document:

Table 1: Acceptance Criteria and Reported Device Performance (Key Metrics)

Study to Prove Device Meets Acceptance Criteria

The device's performance was evaluated through a combination of analytical and clinical studies.

1. Sample sizes used for the test set and data provenance:

   • Analytical Studies (Reproducibility):
     • Site-to-Site: 9-member reproducibility panel tested in 4 replicates on 5 non-consecutive days by 2 operators at 3 sites (30 runs x 4 replicates = 120 data points per panel member). Total of 22,560 data points.
     • Lot-to-Lot: 17-member reproducibility panel tested in 10 replicates on each of 3 assay kit lots by 1 operator at 1 site (30 data points per panel member). Total of 10,680 data points.
     • LoD: 20 replicates for each target.
     • Analytical Reactivity/Specificity/Interference: Generally, 3 replicates per strain/substance.
   • Clinical Studies (Test Set):
     • Prospective (Arm 1): 1820 prospectively collected de-identified specimens (after retest resolving invalid results). Data provenance: Five geographically diverse clinical sites within the United States. Type: Prospective.
     • Pre-selected (Arm 2): 308 pre-selected, de-identified leftover specimens (after retest resolving invalid results). Data provenance: Six sites in the United States. Type: Retrospective (leftover specimens).
     • Contrived (Arm 3): 199 contrived specimens (spiked into negative human nasopharyngeal specimens). Type: Laboratory-generated.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

   • The document does not explicitly state the number or qualifications of experts involved in establishing the ground truth.
   • For the clinical study, the ground truth was established by:
     • An FDA-cleared molecular assay (predicate device or other cleared assays).
     • PCR followed by bi-directional sequencing (BDS) for specific targets (Influenza A subtyping, and to confirm pre-selected specimens and indeterminate results from the molecular comparator).
   • The implication is that these are either validated laboratory methods or the expertise is inherent in the design and validation of the comparator FDA-cleared molecular assay. For PCR/BDS, it would typically be performed by trained molecular diagnosticians or laboratory personnel.

3. Adjudication method for the test set:

   • The document describes a comparator method algorithm: The NxTAG® RPP v2 results were compared to an FDA-cleared molecular assay. For influenza A subtyping, and potentially for other targets where initial molecular testing was insufficient, PCR/bi-directional sequencing (BDS) was used.
   • Composite reference method: For cases where the initial FDA-cleared molecular assay provided certain results (e.g., in some cases of false positives/negatives for Adenovirus, Human Metapneumovirus, Influenza A, RSV A, and SARS-CoV-2 in the prospective cohort, as noted in the footnotes to Table 19), further investigation with molecular SoC assay or BDS was conducted to determine the final truth. This represents a form of adjudication, where a "truth" panel (FDA-cleared assay + PCR/BDS) is used to establish the final ground truth.

4. 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:

   • This question is not applicable to this device. The NxTAG® RPP v2 is an in vitro diagnostic (IVD) PCR test kit for detecting nucleic acids, not an AI-assisted diagnostic imaging or human-in-the-loop (HITL) system. The output is qualitative (positive/negative for each pathogen), and does not involve human "readers" in the context of image interpretation that would be augmented by AI.

5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

   • This question is not entirely applicable in the AI sense, as it’s a molecular diagnostic test. However, the analytical performance studies (e.g., LoD, inclusivity, exclusivity, precision) can be considered "standalone" performance of the assay itself, demonstrating its inherent accuracy in detecting specific pathogens under controlled conditions, without the variability of actual clinical human samples that might contain inhibitors or mixed infections. The outputs are generated by the Luminex® MAGPIX® Instrument and xPONENT® and SYNCT™ software, which provides a "reliable, qualitative call for each of the 21 targets and internal controls." This part of the system operates without continuous human "in-the-loop" interpretation of the raw data for diagnosis on a case-by-case basis.

6. The type of ground truth used:

   • Clinical Study:
     • Reference molecular methods: An FDA-cleared molecular assay was the primary comparator.
     • Confirmatory sequencing: PCR followed by bi-directional sequencing (BDS) was used for specific targets (e.g., influenza A subtyping) and to confirm pre-selected specimens prior to enrollment, and potentially to adjudicate discrepancies.
   • Analytical Studies:
     • Known concentrations: For LoD and analytical reactivity/specificity, samples were prepared with known concentrations of highly characterized viral or bacterial strains (cultured material, clinical specimens of known titer, or WHO standards).
     • In silico analysis: For inclusivity and exclusivity, genetic sequences from public databases (GISAID EpiCoV, GISAID EpiFlu, GenBank) were analyzed, assuming complete detection if probe binding matched certain criteria.

7. The sample size for the training set:

   • The document describes a marketing submission (510(k)) for a medical device that has completed its development and validation. Therefore, it focuses on the test set (clinical validation and analytical verification) rather than a "training set" which is typically associated with machine learning model development. For an IVD such as this, the "training" (i.e., development and optimization) of the assay's reagents and parameters would have occurred internally during product development, using various internal samples and iterative refinement. The document does not specify the sample size of any development/training set.

8. How the ground truth for the training set was established:

   • As noted above, a "training set" in the context of this 510(k) submission would refer to the internal development and optimization work, not typically disclosed in detail for regulatory submissions like this. The ground truth during that phase would have been established through a combination of purified nucleic acid standards, well-characterized clinical samples, and comparison to established reference methods or culture, depending on the stage of development.

Ask a specific question about this device