(40 days)
Not Found
No
The summary describes a multiplex nucleic acid test system that uses standard molecular biology techniques (PCR, melt curve analysis) and software for automated interpretation of results based on predefined criteria (melting curve analysis and internal controls). There is no mention of AI or ML algorithms being used for data analysis or interpretation.
No.
The FilmArray Residential Panel (RP) is a diagnostic device that detects and identifies respiratory viral nucleic acids. It does not provide treatment or therapy.
Yes
The "Intended Use / Indications for Use" section explicitly states that the detection and identification of viral nucleic acids "aids in the diagnosis of respiratory viral infection". Although it notes that results should be used "in conjunction with other clinical and epidemiological information" and "should not be used as the sole basis for diagnosis," its primary function is to assist in the diagnostic process.
No
The device is a system that includes hardware (FilmArray instrument), software, and a disposable pouch with reagents. It is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the 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 nucleic acids in nasopharyngeal swabs (NPS) obtained from individuals suspected of respiratory tract infections." This describes a test performed in vitro (outside the body) on a biological specimen (nasopharyngeal swab) to aid in the diagnosis of a disease (respiratory viral infection).
- Device Description: The description details a system that processes a biological sample (NPS specimen) using reagents within a pouch to perform nucleic acid purification, reverse transcription, and PCR. This entire process is conducted in vitro.
- Purpose: The test is designed to detect and identify specific viral nucleic acids to aid in the diagnosis of respiratory viral infection, which is a core function of an in vitro diagnostic device.
- Comparison to Predicate Devices: The mention of predicate devices like the Luminex® xTAG™ Respiratory Viral Panel (RVP), which are also IVDs, further supports the classification of the FilmArray RP as an IVD.
N/A
Intended Use / Indications for Use
The 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 nucleic acids in nasopharyngeal swabs (NPS) obtained from individuals suspected of respiratory tract infections. The following virus types and subtypes are identified using the FilmArray RP: Adenovirus, Coronavirus HKU1, Coronavirus NL63, 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, and Respiratory Syncytial Virus. The detection and identification of specific viral 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. Negative results do not preclude respiratory infection and should not be used as the sole basis for diagnosis, treatment or other management decisions. Positive results do not rule out bacterial infection or coinfection with other organisms. The agent detected may not be the definite cause of disease. The use of additional laboratory testing (e.g. bacterial and viral culture, immunofluorescence, and radiography) and clinical presentation must be taken into consideration in order to obtain the final diagnosis of respiratory infection.
Due to seasonal prevalence, performance characteristics for Influenza A/H1, Influenza A/H3, Influenza A/2009 H1, Influenza B, Parainfluenza Virus 1, Parainfluenza Virus 2, and Parainfluenza Virus 4 were established primarily with retrospective clinical specimens.
Due to the genetic similarity between human Rhinovirus and Enterovirus, the FilmArray RP cannot reliably differentiate them. A positive FilmArray RP Rhinovirus/Enterovirus result should be followed-up using an alternate method (e.g. cell culture or sequence analysis).
The FilmArray RP detects Adenovirus species C serotype 2 and serotype 6 with reduced sensitivity. It is recommended that specimens found to be negative for Adenovirus after examination using FilmArray RP be confirmed by an alternate method (e.g. FDA-cleared molecular test or cell culture).
Performance characteristics for influenza A were established when influenza A/2009 H1N1, A/H1, and A/H3 were the predominant influenza A viruses in circulation. 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 departments for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
Product codes (comma separated list FDA assigned to the subject device)
OCC, OEM, OOU, OEP, OTG, NXD, OOI
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 15 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 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 dve (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.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Nasopharyngeal swabs (NPS)
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Clinical Performance Study:
- Sample Size: 1117 subjects (initially 1144 enrolled, 4 withdrawn, 20 omitted due to improper storage, 3 omitted due to lack of valid external control mix results).
- Data Source: Nasopharyngeal swabs (NPS) obtained from individuals suspected of respiratory tract infections. Collected from 3 U.S. clinical sites during December 2009 - May 2010 and September 2010 - January 2011.
- Annotation Protocol (Reference/Comparator Methods):
- Parainfluenza Virus 1: Viral culture followed by DFA (Fluorescent Antibody) identification. "True" positives were samples positive by viral culture/DFA. "True" negatives were samples negative by viral culture/DFA.
- Parainfluenza Virus 2: Viral culture followed by DFA (Fluorescent Antibody) identification. "True" positives were samples positive by viral culture/DFA. "True" negatives were samples negative by viral culture/DFA.
- Parainfluenza Virus 4: Viral culture followed by one analytically validated PCR assay with bi-directional sequence confirmation. The comparator assay amplified a different sequence from the FilmArray assay. "True" positives had bi-directional sequencing data meeting pre-defined quality acceptance criteria that matched PIV4 sequences in NCBI GenBank (from viral culture material). "True" negatives were samples for which viral culture material tested negative by the specific comparator PCR assay.
Preselected Archived Specimens Study:
- Sample Size: 147 confirmed specimens out of 168.
- Data Source: Archived clinical NPS specimens. Selected based on previously testing positive or negative for Parainfluenza Virus 1, 2, or 4.
- Annotation Protocol: Prior to FilmArray RP testing, the presence or absence of the analyte of interest was confirmed in each specimen using analyte specific PCR and bi-directional sequencing. Specimens were organized into "test panels" and randomized for blinded testing.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Clinical Performance Study (Prospective Clinical Study):
- Study Type: Prospective, multi-center clinical study.
- Sample Size: 1117 subjects.
- Standalone Performance:
- Parainfluenza Virus 1: Sensitivity: 100% (1/1), Specificity: 99.9% (1115/1116).
- Parainfluenza Virus 2: Sensitivity: 87.4% (7/8), Specificity: 99.8% (1107/1109).
- Parainfluenza Virus 4: Sensitivity: 100% (9/9), Specificity: 99.9% (1107/1108).
- Key Results: Low prevalence of Parainfluenza Viruses 1, 2, and 4 (0.2% - 0.9%) was observed in this study. The majority of detections were in children 5 years and younger (90%; 19/21). Analysis found 103 co-infections (9% of all analyzed specimens), with 6 co-infections involving PIV1, PIV2, or PIV4.
Testing of Preselected Archived Specimens:
- Study Type: Evaluation of preselected archived samples.
- Sample Size: 147 confirmed specimens.
- Standalone Performance:
- Parainfluenza Virus 1: Positive Percent Agreement (PPA): 97.1% (34/35), Negative Percent Agreement (NPA): 100.0% (94/94).
- Parainfluenza Virus 2: PPA: 100.0% (28/28), NPA: 100.0% (101/101).
- Parainfluenza Virus 4: PPA: 100.0% (11/11), NPA: 100.0% (6/6).
Precision (Reproducibility) Study:
- Study Type: Multicenter reproducibility study.
- Sample Size: Each specimen was tested 4 times a day on five days at three testing sites, for a total of 60 tests per analyte per concentration. Two operators at each site, two aliquots per specimen, two different FilmArray instruments.
- Key Results:
- Parainfluenza Virus 1 (Medium Positive): All Sites: 98.3% agreement (59/60).
- Parainfluenza Virus 1 (Low Positive): All Sites: 100% agreement (60/60).
- Parainfluenza Virus 1 (High Negative): All Sites: 71.7% agreement (43/60).
- Parainfluenza Virus 1 (Negative): All Sites: 100% agreement (540/540).
- Parainfluenza Virus 2 (Medium Positive): All Sites: 100% agreement (60/60).
- Parainfluenza Virus 2 (Low Positive): All Sites: 100% agreement (60/60).
- Parainfluenza Virus 2 (High Negative): All Sites: 58.3% agreement (35/60).
- Parainfluenza Virus 2 (Negative): All Sites: 100% agreement (540/540).
- Parainfluenza Virus 4 (Medium Positive): All Sites: 100% agreement (60/60).
- Parainfluenza Virus 4 (Low Positive): All Sites: 100% agreement (60/60).
- Parainfluenza Virus 4 (High Negative): All Sites: 33.3% agreement (20/60).
- Parainfluenza Virus 4 (Negative): All Sites: 100% agreement (540/540).
Precision (Repeatability) Study:
- Study Type: In-house repeatability testing.
- Sample Size: 48 test results per specimen over 12 testing days. Each of 12 specimens tested 4 times by two operators on two FilmArray instruments daily.
- Key Results:
- Parainfluenza Virus 1 (Moderate Positive): 97.9% (47/48).
- Parainfluenza Virus 1 (Low Positive): 100.0% (48/48).
- Parainfluenza Virus 1 (High Negative): 66.7% (32/48).
- Parainfluenza Virus 2 (Moderate Positive): 100.0% (48/48).
- Parainfluenza Virus 2 (Low Positive): 97.9% (47/48).
- Parainfluenza Virus 2 (High Negative): 56.3% (27/48).
- Parainfluenza Virus 4 (Moderate Positive): 100.0% (48/48).
- Parainfluenza Virus 4 (Low Positive): 100.0% (48/48).
- Parainfluenza Virus 4 (High Negative): 54.2% (26/48).
Limit of Detection (LoD) Study:
- Study Type: Analytical sensitivity study.
- Key Results:
- Parainfluenza Virus 1: 500 TCID50/mL
- Parainfluenza Virus 2: 10 TCID50/mL
- Parainfluenza Virus 4: 5000 TCID50/mL
Analytical Reactivity (Inclusivity) Study:
- Study Type: Evaluation with an inclusivity panel.
- Key Results: All tested strains of Parainfluenza Viruses 1, 2, and 4 were detected at or near their respective LoD.
Analytical Specificity (Cross-reactivity and Exclusivity) Study:
- Study Type: Evaluation of potential cross-reactivity with FilmArray RP analytes and exclusivity with non-FilmArray RP organisms.
- Key Results: No cross-reactivity was observed with high concentrations of other FilmArray RP analytes. The FilmArray RP system did not cross-react with the exclusivity panel organisms (45 bacteria, 10 viruses, 1 fungus) with one exception: One measles virus strain was found to contain Adenovirus, which was detected by the FilmArray RP, but this was due to contamination, not cross-reactivity. Additional exclusivity testing for avian influenza A strains also showed no cross-reactivity, except for expected detection of Influenza A for H5N1 and H7N2 strains which contain Influenza A.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Clinical Performance:
- Parainfluenza Virus 1:
- Sensitivity: 100%
- Specificity: 99.9%
- Parainfluenza Virus 2:
- Sensitivity: 87.4%
- Specificity: 99.8%
- Parainfluenza Virus 4:
- Sensitivity: 100%
- Specificity: 99.9%
Archived Specimen Performance Data Summary:
- Parainfluenza Virus 1:
- Positive Percent Agreement (PPA): 97.1%
- Negative Percent Agreement (NPA): 100.0%
- Parainfluenza Virus 2:
- Positive Percent Agreement (PPA): 100.0%
- Negative Percent Agreement (NPA): 100.0%
- Parainfluenza Virus 4:
- Positive Percent Agreement (PPA): 100.0%
- Negative Percent Agreement (NPA): 100.0%
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
K063765, K081483, K091677 - Luminex® xTAG™ Respiratory Viral Panel (RVP).
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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.
0
APR 2 7 2011
10 510(k) Summary
510(k) Summary Idaho Technology Inc.
Modification of FilmArray RP Test System To unmask results for PIV1, PIV2 and PIV4 assays in the FilmArray RP
Introduction: According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.
Submitted by:
Idaho Technology Inc 390 Wakara Way Salt Lake City, UT 84108
Telephone: 801-736-6354 Facsimile: 801-588-0507
Contact: Beth Lingenfelter, ext. 407
Date Submitted: March 17, 2011
Device Name and Classification:
Trade Name: FilmArray RP System
Regulation Number: 21 CFR 866.3980
Classification Name: Respiratory Viral Panel Multiplex Nucleic Acid Assay
Predicate Device:
K063765, K081483, K091677 - Luminex® xTAG™ Respiratory Viral Panel (RVP).
Intended Use:
The 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 nucleic acids in nasopharyngeal swabs (NPS) obtained from individuals suspected of respiratory tract infections. The following virus types and subtypes are identified using the FilmArray RP: Adenovirus, Coronavirus
1
HKU1, Coronavirus NL63. 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, and Respiratory Syncytial Virus. The detection and identification of specific viral 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. Negative results do not preclude respiratory infection and should not be used as the sole basis for diagnosis, treatment or other management decisions. Positive results do not rule out bacterial infection or coinfection with other organisms. The agent detected may not be the definite cause of disease. The use of additional laboratory testing (e.g. bacterial and viral culture, immunofluorescence, and radiography) and clinical presentation must be taken into consideration in order to obtain the final diagnosis of respiratory infection.
Due to seasonal prevalence, performance characteristics for Influenza A/H1, Influenza A/H3, Influenza A/2009 H1, Influenza B, Parainfluenza Virus 1, Parainfluenza Virus 2, and Parainfluenza Virus 4 were established primarily with retrospective clinical specimens.
Due to the genetic similarity between human Rhinovirus and Enterovirus, the FilmArray RP cannot reliably differentiate them. A positive FilmArray RP Rhinovirus/Enterovirus result should be followed-up using an alternate method (e.g. cell culture or sequence analysis).
The FilmArray RP detects Adenovirus species C serotype 2 and serotype 6 with reduced sensitivity. It is recommended that specimens found to be negative for Adenovirus after examination using FilmArray RP be confirmed by an alternate method (e.g. FDA-cleared molecular test or cell culture).
Performance characteristics for influenza A were established when influenza A/2009 H1N1, A/H1, and A/H3 were the predominant influenza A viruses in circulation. 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 departments for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
2
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 15 common and emerging viral respiratory pathogens (see Table 1).
| Table 1. Viruses Detected by the Film Array Respiratory Panel | |||||||
|---|---|---|---|---|---|---|---|
| --------------------------------------------------------------- | -- | -- | -- | -- | -- | -- | -- |
| Viral Respiratory Pathogens |
|---|
| Influenza A |
| H1 subtype |
| H3 subtype |
| 2009 H1 subtype |
| Influenza B |
| Adenovirus |
| Coronavirus HKU1 |
| Coronavirus NL63 |
| Human Metapneumovirus |
| Parainfluenza Virus 1 |
| Parainfluenza Virus 2 |
| Parainfluenza Virus 3 |
| Parainfluenza Virus 4 |
| Respiratory Syncytial Virus |
| Rhinovirus and Enterovirus |
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 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
3
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 dve (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.
Substantial Equivalence:
The Luminex® xTAG™ RVP is a PCR-based system for detecting the presence of viral nucleic acid in nasopharyngeal swabs collected from individuals with signs and symptoms of respiratory illness. The similarities and differences between the xTAG RVP and the FilmArrav RP are outlined below.
| Element | FilmArray Respiratory Panel Test
System | Luminex® xTAG™ RVP |
|-----------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------|
| Organisms
Detected | Influenza A, Influenza A subtype H1,
Influenza A subtype H3, Influenza B,
Respiratory Syncytial Virus, human
Metapneumovirus, Adenovirus,
Parainfluenza 1, Parainfluenza 2,
Parainfluenza 3, and
Rhinovirus/Enterovirus | Same except the differences listed below |
| Analyte | RNA/DNA | Same |
| Technological
Principles | multiplex nucleic acid | Same except the differences listed
below |
| Specimen
Types | Nasopharyngeal swabs | Same |
Table 2. Similarities between the xTAG RVP and the FilmArray RP
4
| Element | FilmArray Respiratory Panel Test
System | Luminex® xTAG™ RVP |
|---------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Organisms
Detected | Can distinguish Influenza A subtype 2009
H1 from Influenza A subtype H1.
Also detects Coronavirus NL63,
Coronavirus HKU1, and Parainfluenza 4. | Can distinguish Respiratory Syncytial Virus
Type A from Respiratory Syncytial Virus
Type B. |
| Technological
Principles | Nested multiplex RT-PCR followed by high
resolution melting analysis to confirm
identity of amplified product. | Multiplex RT-PCR and multiplex TSPE
followed by Fluorescence-activated sorting
of labeled beads coupled to streptavidin-
conjugated biotinylated products |
| Instrumentation | FilmArray Instrument | PCR Thermocycler
Luminex® 100 IS or 200 system |
| Time to result | Less than 1 hour | Approximately 8 hours |
| Test
Interpretation | Automated test interpretation and report
generation. User cannot access raw data. | Semi-automated test interpretation. User
must review all "no call" results to
determine cause and retesting strategy. |
| Sample
Preparation
Method | Sample Processing is automated in the
FilmArray instrument. | Up front sample processing is required to
extract nucleic acid. |
| Reagent
Storage | Reagents are stored at room temperature. | Reagents stored at 4°C and -20°C. |
| Controls | Two controls are included in each reagent
pouch to control for sample processing and
both stages of PCR and melt analysis. | Internal control added to each sample.
External control processed with each batch
of samples. |
| User
Complexity | Moderate/Low | High |
Table 3. Differences between the xTAG RVP and the FilmArray RP
Summary of Performance Data for Parainfluenza Viruses 1, 2 and 4
The purpose of this 510(k) is to support unmasking of test results for the Parainfluenza Virus 1, 2 and 4 assays that are part of the FilmArray RP. Refer to the 510k summary for K103175 for performance data of the previously cleared assays (Adenovirus, Coronavirus HKU1, Coronavirus NL63, Human Metapneumovirus, Influenza A, Influenza A subtype H1, Influenza A subtype H3, Influenza A subtype 2009 H1, Influenza B, Parainfluenza Virus 3, Rhinovirus/Enterovirus, and Respiratory Syncytial).
Clinical Performance
The clinical performance of the FilmArray RP system for Parainfluenza Viruses 1, 2, and 4 was established during a prospective study at 3 U.S. clinical sites where enrollment spanned an 11 month time period encompassing two respiratory seasons (December 2009 - May 2010 and September 2010 - January 2011). Subjects with signs and/or symptoms of respiratory infection were invited to participate. Upon obtaining informed consent, NPS samples were collected for FilmArray and comparator testing; a second respiratory
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sample was collected from each subject for viral culture reference testing. A total of 1144 subjects were initially enrolled in the study (857, at 3 sites, between December 2009 and May 2010; 287, at 2 sites, between September 2010 and January 2011) and four were withdrawn. Specimens from 20 subjects were omitted from analysis due to improper storage prior to testing: and 3 specimens were omitted due to the lack of valid external control mix results on the day of testing. Table 4, provides a summary of demographic information for the remaining 1117 subjects that participated in the prospective study.
| Sex | Number of Subjects |
|---|---|
| Male | 600 (54%) |
| Female | 517 (46%) |
| Age | |
| ≤5 | 724 (65%) |
| 6-21 | 119 (11%) |
| 22-49 | 190 (17%) |
| ≥50 | 84 (8%) |
Table 4. Demographic Summary for FilmArray RP Prospective Study (All Specimens Analyzed for PIV1, PIV2, and PIV4)
Each NPS specimen was tested with the FilmArray RP. The performance of the FilmArray RP for Parainfluenza Viruses 1, 2, and 4 was evaluated by comparing the FilmArray RP test result for each virus with the appropriate comparator/reference methods shown in Table 5.
Table 5. Reference/Comparator Methods Used to Assess FilmArray RP Performance
| Organism/Virus | Reference/Comparator Method(s) |
|---|---|
| Parainfluenza Virus 1 | Viral culture followed by DFA identification1 |
| Parainfluenza Virus 2 | |
| Parainfluenza Virus 4 | 1 PCR test of viral culture with bi-directional sequence confirmation2 |
1 Performance of the FilmArray RP system detecting Parainfluenza Virus 1 and Parainfluenza Virus 2 was compared to viral culture followed by fluorescent antibody identification. "True" Parainfluenza Virus 2, positives, were considered as any sample that tested positive for Parainfluenza Virus I or Parainfluenza virus 2 by viral culture followed by DFA testing. "True" Parainfluenza Virus 1 or Parainfluenza Virus 2 negatives were considered as any sample that tested negative for Parainfluenza Virus 1 or Parainfluenza Virus 2, by viral culture followed by DF A testing.
2 Performance of the FilmArray RP system detecting Parainfluenza Virus 4 was compared to viral culture followed by one analytically validated PCR assay with bi-directional sequence confirmation. The comparator assay was designed to amplify a different sequence from that amplified by the FilmArray assay. "True" Parainfluenza Virus 4 positives were considered as any sample that had bi-directional sequencing data meeting pre-defined quality acceptance criteria that matched Parainfluenza Virus 4 sequences deposited in the National Center for Biotechnology Information (NCBI) GenBank database (www.ncbi.nlm.nih.gov) with acceptable E-values, when tested from viral culture material. "True" Parainfluenza Virus 4 negatives were considered as any sample for which viral culture material tested negative for Parainfluenza Virus 4 by the specific comparator PCR assay.
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A total of 1117 specimens were evaluated for Parainfluenza Viruses 1, 2, and 4 in this study. Clinical sensitivity or positive percent agreement (PPA) was calculated as 100% x (TP / TP + FN). True positive (TP) indicates that both the FilmArray RP and comparator method had a positive result for this specific analyte and false negative (FN) indicates that the FilmArray result was negative while the comparator result was positive. Specificity was calculated as 100% x (TN / TN + FP). True negative (TN) indicates that both the FilmArray RP and the comparator method had negative results and a false positive (FP) indicates that the FilmArray RP result was positive but the comparator results was negative. The exact binomial two-sided 95% confidence interval was calculated. The results are summarized in Table 6.
| Sensitivity | 95% CI | Specificity | 95% CI | |||
|---|---|---|---|---|---|---|
| Parainfluenza Virus 1 | 1/1 | 100% | n/a | 1115/1116a | 99.9% | 99.5 – 100% |
| Parainfluenza Virus 2 | 7/8b,d | 87.4% | 47.4 – 99.7% | 1107/1109c,d | 99.8% | 99.4 – 100% |
| Parainfluenza Virus 4 | 9/9 | 100% | 66.4 -100% | 1107/1108e | 99.9% | 99.5 – 100% |
Table 6. Clinical Sensitivity and Specificity for the FilmArray RP Prospective Clinical Study
a. PIV1 was identified in this specimen using bi-directional sequence analysis.
b. PIV2 Virus was not detected in the single false negative specimen using PCR analysis.
& PIV2 Virus was detected in both false positive specimens using bi-directional sequencing analysis.
Two adjacent specimens (one false negative) may have been switched during the viral culture reference method testing as is evidenced by bi-directional sequence analysis of these specimens.
- A PIV4 Virus was detected in this false positive NPS specimen by bi-directional sequence analysis although it was not detected from viral culture.
A total of 103 co-infections (9% of all analyzed specimens; 103/1117) were detected by FilmArray during this study. The FilmArray detected 6 co-infections involving PIV1, 2, or 4 (Table 7), representing approximately 6% of all co-infections detected (6/103).
| Distinct Co-infection Combinations Detected by FilmArray RP | Total Co-infections | Number of Discrepant Co-infectionsa | Discrepant Analyte(s)a | |
|---|---|---|---|---|
| Analyte 1 | Analyte 2 | |||
| hMPV | PIV 4 | 1 | 1 | hMPV (1) |
| HRV/Entero | PIV 1 | 1 | 1 | PIV 1 (1)b |
| HRV/Enteroa | PIV 2 | 1 | 0 | - |
| HRV/Enteroa | PIV 4 | 3 | 0 | - |
| Total Co-infections | 6 | Total Analytes in 6 Co-infections = 12 |
Table 7. Co-infections Involving Parainfluenza Viruses 1, 2, or 4 as Detected by FilmArray RP.
a. HRV/Entero was not analyzed by a comparator method for the single HRV/Entero + PV2 of the HRV/Entero + PIV4 co-infections due to the HRV/Entero analyte being cleared (K103175) prior to testing of these specimens.
b. PIV1 virus was detected in this specimen using bi-directional sequence analysis.
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Table 8 provides a summary of the FilmArray RP test results for PIV1, PIV2, and PIV4 obtained during this study, including the prevalence of each organism detected by the FilmArray RP System and distribution among the age groups. The majority of Parainfluenza 1, 2, and 4 Viruses were detected in children five years and younger (90%; 19/21). A single PIV1 and a single PIV4 were also detected in older children.
| Analyte | Total (Prevalence) | ≤ 5 years | 6-21 years | 22-49 years | ≥ 50 years |
|---|---|---|---|---|---|
| Parainfluenza Virus 1 | 2 (0.2%) | 1 | 1 | 0 | 0 |
| Parainfluenza Virus 2 | 9 (0.8%) | 9 | 0 | 0 | 0 |
| Parainfluenza Virus 4 | 10 (0.9%) | 9 | 1 | 0 | 0 |
Table 8. Prevalence and Age Distribution of Analytes in the Clinical Study
All three viruses were of low prevalence during the clinical study (0.2 - 0.9%). To supplement the results of the prospective clinical study, an evaluation of preselected archived samples was performed.
Testing of Preselected Archived Specimens
In addition to the prospective clinical study, archived clinical NPS specimens were also tested using the FilmArray RP. The specimens were selected because they had previously tested positive for Parainfluenza Virus 1, 2, or 4, or had been negative for these viruses by previous testing methods. Prior to testing with the FilmArray RP, the presence or absence of the analyte of interest was confirmed in each specimen using analyte specific PCR and bi-directional sequencing. Of 168 specimens, 147 were confirmed to contain the analyte of interest (or lack thereof for negative specimens). The specimens were organized into "test panels" and randomized such that the users testing the samples with the FilmArray RP were blinded as to the expected test result. Each panel contained specimens known to be positive and negative for the specific analyte being evaluated allowing the calculation of a positive percent agreement (PPA) and a negative percent agreement (NPA). A summary of the available demographic information of the tested samples is provided in Table 9 and the results of the FilmArray testing are presented in Table 10.
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| Total Specimens | 147 | |
|---|---|---|
| Sex | Female (%) | 46 (31.3%) |
| Male (%) | 49 (33.3%) | |
| Unknown | 52 (35.4%) | |
| Age | Avg | 10.6 |
| Median | 1.0 | |
| Min | 0.5 | |
| Max | 81.0 | |
| Age Range | ≤5 | 75 (51%) |
| 6-21 | 5 (3.4%) | |
| 22-49 | 5 (3.4%) | |
| ≥50 | 10 (6.8%) | |
| Unknowna | 52 (35.4%) |
Table 9. Demographic Summary of FilmArray RP Archived Specimen Study
4 Demographic information was not provided for specimens from one source. Because the specimens were provided by a pediatric hospital, it is understood that the age range of specimens was from Staphylococcus aureus $1.0 x 10^6$ CFU/mL |
| 20 ng/µL | Neisseria meningitides $1.0 x 10^6$ CFU/mL |
| | Corynebacterium diptheriae $1.0 x 10^6$ CFU/mL |
| Exogenous Substances | |
| Saline Nasal Spray with Preservatives (1% v/v) | Analgesic ointment (1% w/v) |
| Nasal Decongestant Spray (Oxymetazoline HCl) (1%v/v) | Petroleum Jelly (1% w/v) |
| Tobramycin (0.6 mg/mL) | Smokeless Tobacco (1% w/v) |
| Mupirocin (2% w/v) | |
| Technique Specific Substances | |
| Laboratory Reagents: | Viral Transport Media: Swabs: |
| Bleach (1%, 2%, 5% v/v) | Remel M4
Copan 168C (rayon / twisted aluminum shaft) |
| Disinfecting wipes | Remel M4-RT
Copan FloQ (flocked nylon / plastic shaft) |
| Ethanol (7% v/v) | Remel M5
Copan 175KS01 (polyester / aluminum shaft) |
| DNAzap (1% v/v) | Remel M6
Millipore 519CS01M (flocked nylon / plastic shaft) |
| RNaseOut (1% v/v) | Copan UTM |
| Table 20. List of Potentially Interfering Substances Evaluated | ||||
|---|---|---|---|---|
| -- | ---------------------------------------------------------------- | -- | -- | -- |
Evaluation of the FilmArray RP system was not performed using clinical NPS specimens obtained from individuals who had recently received the FluMist® nasal influenza vaccine (MedImmune). However, analytical testing was performed with simulated samples containing various concentrations of the 2009-2010 formulation of the vaccine material. The FilmArray RP assays react with the Influenza A H1, Influenza A H3 and Influenza B viral material contained in the vaccine. No cross-reactivity was observed with other, non-influenza FilmArray RP assays.
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Image /page/18/Picture/0 description: The image shows the seal of the Department of Health & Human Services (HHS) of the United States. The seal features the department's name arranged in a circular pattern around a central emblem. The emblem consists of a stylized caduceus, a symbol often associated with medicine and healthcare, with a modern and abstract design.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993
Idaho Technology Inc. c/o Beth Lingenfelter 390 Wakara Way Salt Lake City, UT 84108
Re: K110764
Trade/Device Name: FilmArray Respiratory Panel (RP) System Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory Viral Panel Multiplex Nucleic Acid Assay Regulatory Class: Class II Product Code: OCC, OEM, OOU, OEP, OTG, NXD, OOI Dated: March 17, 2011 Received: March 18, 2011
Dear Ms. Lingenfelter:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a provisions of the Pederal Food, Drug,
You may, therefore, market the del You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeline . quilibitions against misbranding and adulteration.
If your device is classified (see above) into class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed
APR 27 2011
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Page 2 – Beth Lingenfelter
predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its tolli the (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours.
Veils. Hyr
Sally A. Hojvat, M.Sc., Ph.D. Director, Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number: K110764 Device Name: FilmArray Respiratory Panel (RP) System
Indications for Use:
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 nucleic acids in nasopharyngeal swabs (NPS) obtained from individuals suspected of respiratory tract infections. The following virus types and subtypes are identified using the FilmArray RP: Adenovirus, Coronavirus HKU1, Coronavirus NL63, 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, and Respiratory Syncytial Virus. The detection and identification of specific viral nucleic acids from individuals exhibiting signs and symptoms of a respiratory infection aids in the diagnosis of respiratory viral infection if used in conjunction with other clinical and epidemiological information. Negative results do not preclude respiratory viral infection and should not be used as the sole basis for diagnosis, treatment or other management decisions. Positive results do not rule out bacterial infection or co-infection with other organisms. The agent detected may not be the definite cause of disease. The use of additional laboratory testing (e.g. bacterial and viral culture, immunofluorescence, and radiography) and clinical presentation must be taken into consideration in order to obtain the final diagnosis of respiratory infection.
Due to seasonal prevalence, performance characteristics for Influenza A/H1, Influenza A/H3, Influenza A/2009 H1, Influenza B, Parainfluenza Virus 1, Parainfluenza Virus 2, and Parainfluenza Virus 4 were established primarily with retrospective clinical specimens.
Due to the genetic similarity between human Rhinovirus and Enterovirus, the FilmArray RP cannot reliably differentiate them. A positive FilmArray RP Rhinovirus/Enterovirus result should be followed-up using an alternate method (e.g. cell culture or sequence analysis).
The FilmArray RP detects Adenovirus species C serotype 2 and serotype 6 with reduced sensitivity. It is recommended that specimens found to be negative for Adenovirus after examination using FilmArray RP be confirmed by an alternate method (e.g. FDA cleared molecular test or cell culture).
Performance characteristics for influenza A were established when influenza A/2009 H1N1, A/H1, and A/H3 were the predominant influenza A viruses in circulation. 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
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departments for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
Prescription Use X (Part 21 CFR 801 Subpart D)
AND/OR
Over-the-Counter Use (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE—CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)
Vali Am
Division Sian-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K110764