FDA 510(k) Search - By Innolitics (SaMD and AI Experts)

FilmArray Respiratory Panel (RP) is a multiplexed nucleic acid test intended for use with the FilmArray instrument for the simultaneous qualitative detection and identification of multiple respiratory viral and bacterial nucleic acids in nasopharyngeal swabs (NPS) obtained from individuals suspected of respiratory tract infections. The following organism types and subtypes are identified using the FilmArray RP: Adenovirus. Coronavirus 229E, Coronavirus HKU1, Coronavirus NL63, Coronavirus OC43, Human Metapneumovirus, Influenza A, Influenza A subtype H1, Influenza A subtype H3, Influenza A subtype 2009 H1, Influenza B, Parainfluenza Virus 1, Parainfluenza Virus 2, Parainfluenza Virus 3, Parainfluenza Virus 4, Rhinovirus/Enterovirus, Respiratory Syncytial Virus, Bordetella pertussis, Chlamydophila pneumoniae, and Mycoplasma pneumoniae. The detection and identification of specific viral and bacterial nucleic acids from individuals exhibiting signs and symptoms of a respiratory infection aids in the diagnosis of respiratory infection if used in conjunction with other clinical and epidemiological information. The results of this test should not be used as the sole basis for diagnosis, treatment, or other 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 is not detected by a nasopharyngeal swab specimen. Positive results do not rule out co-infection with other organisms; the agent(s) detected by the Film Array RP 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.

Device Description

The FilmArray RP System is a multiplex nucleic acid test system composed of the FilmArray instrument, the FilmArray software (preinstalled on a laptop computer) and the FilmArray RP pouch. The FilmArray RP pouch contains freeze-dried reagents to perform nucleic acid purification, reverse transcription, and nested, multiplex PCR with DNA melt analysis. The Respiratory Panel (RP) pouch identifies 20 common and emerging viral respiratory pathogens (see Table 1). A test is initiated by loading Hydration Solution and an unprocessed patient nasopharyngeal swab (NPS) specimen (i.e., specimen mixed with Sample Buffer) into the FilmArray RP pouch. The pouch contains all of the reagents required for specimen testing and analysis in a freeze-dried format; the addition of Hydration Solution and specimen/Sample Buffer Mix rehydrates the reagents. After the pouch is prepared, the FilmArray software guides the user though the steps of placing the pouch into the instrument, scanning the pouch barcode, entering the sample identification, and initiating the run. The FilmArray instrument contains a coordinated system of inflatable bladders and seal points, which act on the pouch to control the movement of liquid between the pouch blisters. When a bladder is inflated over a reagent blister. it forces liquid from the blister into connecting channels. Alternatively, when a seal is placed over a connecting channel it acts as a valve to open or close a channel. In addition, electronically controlled pneumatic pistons are positioned over multiple plungers in order to deliver the rehydrated reagents into the blisters at the appropriate times. Two Peltier devices control heating and cooling of the pouch to drive the reverse transcription reactions, the PCR reactions, and the melting curve analysis. Nucleic acid extraction occurs within the FilmArray pouch using mechanical lysis and standard magnetic bead technology. After extracting and purifying nucleic acids from the unprocessed sample, the FilmArray performs a nested multiplex PCR that is executed in two stages. During the first stage, the FilmArray performs a single, large volume, highly multiplexed reverse transcription PCR (rt-PCR) reaction. The products from first stage PCR are then diluted and combined with a fresh, primer-free master mix and a fluorescent double stranded DNA binding dye (LC Green®Plus, Idaho Technology). This second master mix solution, is then distributed to each well of the array. Array wells contain sets of primers designed specifically to amplify sequences internal to the PCR products generated during the first stage PCR reaction. The second stage PCR, or nested PCR, is performed in singleplex fashion in each well of the array. At the conclusion of the 200 stage PCR, the array is interrogated by melting curve analysis for the detection of signature amplicons denoting the presence of specific viral or bacterial targets. A digital camera placed in front of the second stage PCR captures fluorescent images of the PCR reactions in real time. The FilmArray software automatically interprets the results of each DNA melting curve analysis and combines the data with the results of the internal pouch controls to provide a test result for each organism on the panel.

AI/ML Overview

Acceptance Criteria and Device Performance Study for FilmArray® Respiratory Panel (RP)

This document describes the acceptance criteria and supporting studies for the FilmArray® Respiratory Panel (RP) device with added assays for Coronavirus OC43, Coronavirus 229E, Bordetella pertussis, Mycoplasma pneumoniae, and Chlamydophila pneumoniae.

1. Table of Acceptance Criteria and Reported Device Performance

The provided document does not explicitly state pre-defined acceptance criteria (e.g., "sensitivity must be >90%"). Instead, the clinical performance is presented as observed Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) with 95% confidence intervals. The reproducibility study shows percent agreement with expected results at various concentrations. For clarity, we will present the key performance metrics observed in the clinical and archived specimen studies as "reported device performance."

Category	Metric	Acceptance Criteria (Implicit)	Reported Device Performance (Clinical Study - Prospective) (95% CI)	Reported Device Performance (Archived Specimens) (95% CI)	Reported Device Performance (Contrived Specimens for C. pneumoniae) (95% CI)	Reported Device Performance (Reproducibility - All Sites, LoD) (95% CI)
Coronavirus 229E	Positive Percent Agreement (PPA)	High agreement with comparator	100% (73.5-100%) (N=12)	100% (75.3-100%) (N=13)	Not applicable	100% (94.0-100%) (N=60)
	Negative Percent Agreement (NPA)	High agreement with comparator	99.8% (99.4-100%) (N=1103)	95.7% (85.5-99.5%) (N=45)	Not applicable	Not applicable
Coronavirus OC43	Positive Percent Agreement (PPA)	High agreement with comparator	100% (76.8-100%) (N=14)	100% (85.8-100%) (N=24)	Not applicable	100% (94.0-100%) (N=60)
	Negative Percent Agreement (NPA)	High agreement with comparator	99.6% (99.0-99.9%) (N=1098)	91.7% (77.5-98.2%) (N=33)	Not applicable	Not applicable
Bordetella pertussis	Positive Percent Agreement (PPA)	High agreement with comparator	100% (54.1-100%) (N=6)	94.6% (85.1-98.9%) (N=53)	Not applicable	100% (94.0-100%) (N=60)
	Negative Percent Agreement (NPA)	High agreement with comparator	99.9% (99.5-100%) (N=1110)	96.5% (88.1-99.6%) (N=56)	Not applicable	Not applicable
Chlamydophila pneumoniae	Positive Percent Agreement (PPA)	High agreement with comparator	100% (N/A) (N=1)	Not applicable	100% (92.9-100%) (N=50)	98.3% (91.1-100%) (N=59)
	Negative Percent Agreement (NPA)	High agreement with comparator	100% (99.7-100%) (N=1116)	Not applicable	100% (92.9-100%) (N=50)	Not applicable
Mycoplasma pneumoniae	Positive Percent Agreement (PPA)	High agreement with comparator	100% (39.8-100%) (N=4)	84.4% (73.1-92.2%) (N=54)	Not applicable	93.3% (83.8-98.2%) (N=56)
	Negative Percent Agreement (NPA)	High agreement with comparator	100% (99.7-100%) (N=1113)	89.2% (79.1-95.6%) (N=58)	Not applicable	Not applicable
Reproducibility	Agreement with Expected Result	Consistent results across sites and runs (e.g., >80% at LoD)	Not applicable	Not applicable	Not applicable	Coronavirus OC43: 100% (3x LoD, 1x LoD), 80.0% (LoD/10)
Coronavirus 229E: 100% (3x LoD, 1x LoD), 53.3% (LoD/10)
B. pertussis: 100% (3x LoD, 1x LoD), 66.7% (LoD/10)
C. pneumoniae: 98.3% (1x LoD), 58.3% (LoD/10)
M. pneumoniae: 93.3% (1x LoD), 33.3% (LoD/10)

(N/A - Not Applicable, LoD - Limit of Detection)

2. Sample Sizes Used for the Test Set and Data Provenance

The evaluation for the newly added assays was conducted through a combination of prospective clinical studies, retrospective testing of archived clinical specimens, and contrived specimens.

Prospective Clinical Study:
- Sample Size: 1117 subjects (initially 1144 enrolled, 27 withdrawn or omitted).
- Data Provenance: 3 U.S. clinical sites.
- Retrospective or Prospective: Prospective. The study spanned two respiratory seasons (December 2009 - May 2010 and September 2010 - January 2011).
Archived Specimens Study (for B. pertussis, Coronavirus 229E, Coronavirus OC43, or M. pneumoniae):
- Sample Size: 305 total specimens.
- Data Provenance: Not explicitly stated but implied to be from various sources, likely within the U.S., as they were "preselected archived samples."
- Retrospective or Prospective: Retrospective.
Contrived C. pneumoniae Specimens Study:
- Sample Size: 100 specimens (50 spiked, 50 unspiked).
- Data Provenance: Residual specimens from the prospective clinical study, spiked with C. pneumoniae.
- Retrospective or Prospective: Contrived/Spiked.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

The document describes the reference/comparator methods used to establish the ground truth, rather than directly mentioning "experts" in the context of adjudication for individual test results.

Method: For Coronavirus 229E, Coronavirus OC43, B. pertussis, C. pneumoniae, and M. pneumoniae, the ground truth was established by composite comparator methods consisting of two analytically validated PCR assays followed by bi-directional sequencing.
- "True" positives were defined as samples with bi-directional sequencing data meeting pre-defined quality acceptance criteria and matching NCBI GenBank database sequences.
- "True" negatives were defined as samples negative by both comparator PCR assays.
Number of Experts: Not explicitly stated as a number of human experts adjudicating each case. The "experts" implied are the skilled laboratory personnel performing and interpreting the bi-directional sequencing, which is a highly technical molecular biology method. Their qualifications would implicitly be in molecular diagnostics and sequence analysis.

4. Adjudication Method for the Test Set

The adjudication method relies on the described composite comparator methods:

Method: Two independent PCR assays targeting different sequences, followed by bi-directional sequencing for confirmation.
Rule: "True" positives were confirmed by sequencing matching GenBank. "True" negatives were confirmed by negativity in both PCR assays. Discrepant results between the FilmArray RP and the initial comparator PCRs were further investigated using bi-directional sequencing (as seen in the footnotes for discrepancy investigations in Table 4).

This is a form of adjudicated ground truth based on a robust laboratory method rather than human consensus interpretation of device output.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done.

This device is an automated multiplex nucleic acid test. Its performance is evaluated against reference laboratory methods, not by comparing human reader performance with and without AI assistance. The readout is qualitative (presence/absence of target nucleic acid), and interpretation is automated by the device's software.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, a standalone performance study was done.

The clinical performance data (PPA, NPA) presented in Tables 4, 8, and 9 reflects the performance of the FilmArray RP system (including the algorithm responsible for interpreting the raw data and providing a result) operating independently without human modification or interpretation of the final result. The system's software automatically interprets results based on melting curve analysis and internal controls.

7. The Type of Ground Truth Used

The primary type of ground truth used was expert-defined laboratory gold standard:

Clinical and Archived Specimen Studies: Ground truth was established using composite comparator methods comprising two analytically validated PCR assays followed by bi-directional sequencing. This is a highly robust and specific laboratory reference method.
Contrived C. pneumoniae Specimens: Ground truth was established by spiking known concentrations of the pathogen into clinical matrix, and also by using unspiked controls.

8. The Sample Size for the Training Set

The document does not explicitly state the sample size for the training set used to develop the FilmArray RP algorithms for the newly added assays. Regulatory submissions typically focus on the performance of the final, locked algorithm on independent test sets (as described in this document), rather than detailing the internal development and training processes.

9. How the Ground Truth for the Training Set Was Established

As the document does not provide details on a specific "training set," it also does not describe how the ground truth for any training set was established. It's common for diagnostic device development to use well-characterized positive and negative specimens, often confirmed by highly sensitive and specific laboratory methods (similar to the comparator methods described for the test set), for initial algorithm development and optimization.

Summary

Regulation Number and Section

§ 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.