(251 days)
The Idylla™ Respiratory (IFV-RSV) Panel is an in vitro assay intended for the qualitative detection of nucleic acids for Influenza A, Influenza A subtype H1, Influenza A subtype H3, Influenza A subtype 2009 H1, H275Y mutation of Influenza A subtype 2009 H1, Influenza B and Respiratory Syncytial Virus (A and B) from nasopharyngeal swabs in viral transport media of adult and pediatric patients. The test uses the Idylla™ system to aid in the diagnosis of respiratory viral infection when used in conjunction with other clinical and laboratory findings.
Negative results do not preclude respiratory virus infection or co-infection with other viruses and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.
Performance characteristics for Influenza A were established when influenza A/2009 H1 and 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 BSL3+ facility is available to receive and culture specimens.
The Idylla™ Respiratory (IFV-RSV) Panel is a self-contained molecular diagnostic test designed to work with the IdyllaTM System. The assay is performed using a single-use, disposable, multi-chambered fluidic cartridge. This includes hands-off sample preparation/purification, reverse transcription and real-time, multiplex Polymerase Chain Reaction (PCR) for the detection of viral RNA. All steps in this process are fully automated and completely integrated and results are available in less than 50 minutes.
The Idylla™ Respiratory (IFV-RSV) Panel identifies virus-specific nucleic acids for Influenza (IFV) A virus, Influenza B virus, and Respiratory Syncytial Virus (RSV). The IFV-RSV Panel targets the following genes within the viruses: matrix gene (Influenza A and Influenza B); hemagglutinin gene (Influenza A subtypes H1 and H3, Influenza A subtype 2009 H1); neuraminidase gene (H275Y mutation of 2009 H1); fusion protein gene RSV (A and B). The System amplifies a targeted region of interest generating a change in fluorescent signal, which is measured and applied against predetermined criteria to provide a qualitative result. The automated process steps in the panel are:
Sample processing: Utilizing the automated process of Idylla™ fluidics, sample and Sample Processing Control (SPC) comes in contact with the lysis buffer to release the RNA and solubilize proteins, creating a lysate. Binding buffer is mixed with the lysate to aid in the binding of nucleic acids. Purified RNA is subsequently subject to a RT-PCR reaction within the Cartridge.
RT-PCR: Reverse Transcription, amplification and fluorescent detection of viral targets occur during the RT-PCR cycling. RT-PCR reagents are present in a stable formulation in five PCR chambers located within the Cartridge. The Test contains reagents for the simultaneous detection of a sample processing control and detection of various IFV and RSV targets. Detection of these specific targets is performed using fluorescent labeled probes. All amplification, detection of fluorescence, and the interpretation of the signals are done automatically by the Idylla™ instrument system.
Here's an analysis of the acceptance criteria and study as requested, based on the provided document:
Acceptance Criteria and Device Performance for Idylla™ Respiratory (IFV-RSV) Panel
The acceptance criteria for the Idylla™ Respiratory (IFV-RSV) Panel are stated as "at least 90% positive percent agreement (PPA) with a lower bound of the two-sided 95% CI greater than 80% for all targets."
For negative results, the criterion is "negative percent agreement (NPA) exceeding 99% with a lower bound of 95% (two-sided) confidence interval exceeding 90% for all targets."
1. Table of Acceptance Criteria and Reported Device Performance
The device performance is reported across two clinical studies: a multi-site prospective study and an additional retrospective study. The tables below summarize the initial reported performance and the re-evaluated performance after sequencing of discordant samples, comparing them to the acceptance criteria.
Table 1.1: Prospective Study Performance vs. Acceptance Criteria (excluding H275Y mutation due to specific sample handling)
| Target | Performance Measure | Acceptance Criteria (PPA > 90%, CI-LB > 80%; NPA > 99%, CI-LB > 90%) | Reported Device Performance (200 µL VTM) | Reported Device Performance (500 µL VTM) | Met Acceptance Criteria (before re-evaluation) |
|---|---|---|---|---|---|
| Influenza A | PPA | > 90% (CI-LB > 80%) | 92.2% (86.9% - 95.5%) | 93.3% (88.1% - 96.3%) | Yes |
| NPA | > 99% (CI-LB > 90%) | 99.6% (98.9% - 99.9%) | 99.4% (98.5% - 99.7%) | Yes | |
| Influenza A H3 | PPA | > 90% (CI-LB > 80%) | 93.6% (85.9% - 97.2%) | 94.7% (87.1% - 97.9%) | Yes |
| NPA | > 99% (CI-LB > 90%) | 100% (99.6% - 100%) | Not explicitly stated (implied 100%) | Yes | |
| Influenza A/2009 H1 | PPA | > 90% (CI-LB > 80%) | 86.8% (77.4% - 92.7%) | 89.0% (79.8% - 94.3%) | No |
| NPA | > 99% (CI-LB > 90%) | 99.8% (99.2% - 99.9%) | 99.8% (implied) (99.2% - 99.9%) | Yes | |
| Influenza B | PPA | > 90% (CI-LB > 80%) | 85.6% (78.6% - 90.6%) | 85.4% (78.3% - 90.4%) | No |
| NPA | > 99% (CI-LB > 90%) | 99.8% (99.1% - 99.9%) | 99.7% (99.1% - 99.9%) | Yes | |
| RSV (A or B) | PPA | > 90% (CI-LB > 80%) | 90.2% (85.0% - 94.0%) | 87.4% (79.6% - 92.4%) | Yes (200µL), No (500µL close) |
| NPA | > 99% (CI-LB > 90%) | 99.7% (99.1% - 99.9%) | 99.6% (98.9% - 99.9%) | Yes | |
| H275Y mutation of Influenza A subtype 2009 H1 | PPA | > 90% (CI-LB > 80%) | 100% (91.0% - 100%) | 100% (91.2% - 100%) | Yes (Note: Contrived samples) |
| NPA | > 99% (CI-LB > 90%) | 100% (99.6% - 100%) | 100% (99.6% - 100%) | Yes |
Table 1.2: Combined Prospective and Retrospective Study Performance vs. Acceptance Criteria (after re-evaluation of discordant results by sequencing)
The conclusion states that after re-evaluation of discordant results by bidirectional sequencing, ALL targets demonstrated at least 90% PPA with a lower bound of the two-sided 95% CI greater than 80%. For NPA, the combined study results also met and exceeded acceptance criteria.
| Target | Performance Measure | Acceptance Criteria (PPA > 90%, CI-LB > 80%; NPA > 99%, CI-LB > 90%) | Reported Device Performance (200 µL VTM) - Re-evaluated | Reported Device Performance (500 µL VTM) - Re-evaluated | Met Acceptance Criteria (after re-evaluation) |
|---|---|---|---|---|---|
| All targets (general statement) | PPA | > 90% (CI-LB > 80%) | At least 90% (CI-LB > 80%) | At least 90% (CI-LB > 80%) | Yes |
| NPA | > 99% (CI-LB > 90%) | Exceeding 99% (CI-LB > 90%) | Exceeding 99% (CI-LB > 90%) | Yes | |
| Influenza A 2009 H1 | PPA | > 90% (CI-LB > 80%) | Met acceptance with rounding | Met acceptance | Yes |
| Influenza B | PPA | > 90% (CI-LB > 80%) | Met acceptance | Met acceptance (500µL) | Yes |
| RSV (A or B) | PPA | > 90% (CI-LB > 80%) | Met acceptance | Met acceptance (500µL) | Yes |
2. Sample Size Used for the Test Set and Data Provenance
-
Total Test Set Sample Size:
- Prospective Samples: 1014 subjects were collected. After exclusions, 960 samples were usable for the 200 µL VTM testing and 929 for the 500 µL VTM testing. This included 214 fresh samples and 800 archived samples.
- Retrospective Samples: 419 patient samples tested at 200 µL (408 reported results) and 449 patient samples tested at 500 µL (418 reported results).
- Contrived H275Y Mutation Samples: 40 samples (processed, blinded, and tested). These were excluded from the agreement measures of other targets.
-
Data Provenance:
- Prospective Samples:
- Collected during the 2015-2016 IFV-RSV season (fresh samples).
- Stored samples from the 2012-2013 and 2013-2014 IFV and RSV seasons (archived samples), collected under a separate protocol.
- Multi-site study: Samples were distributed across four external sites for testing.
- Retrospective Samples:
- Archived banked retrospective clinical collections.
- Tested at an in-house facility.
- Prospective Samples:
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not explicitly state the number of experts used to establish the ground truth. However, it indicates:
- The "comparator" methods were an FDA-cleared Nucleic Acid Amplification Test (NAAT), and for retrospective samples, Culture/NAAT/Sequencing.
- Bi-directional sequencing at an independent reference laboratory was used to confirm and/or analyze discordant results between the Idylla™ Panel and the reference method.
- The qualifications of the individuals interpreting the sequencing results are not provided (e.g., "radiologist with 10 years of experience").
4. Adjudication Method for the Test Set
The primary ground truth appears to be based on an FDA-cleared Nucleic Acid Amplification Test (NAAT). Discrepancies between the Idylla™ device and this comparator were adjudicated using bi-directional sequencing performed at an independent reference laboratory. This suggests a form of resolution by a higher-tier method for discordant results, rather than a strict 2+1 or 3+1 consensus process among human readers.
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 study focuses on the performance of a diagnostic device against a comparator method, not on the improvement of human reader performance with AI assistance. The device is an in vitro diagnostic assay, an automated molecular test, not an AI-assisted diagnostic tool for human interpretation.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, this was a standalone performance study. The Idylla™ Respiratory (IFV-RSV) Panel is described as a "self-contained molecular diagnostic test designed to work with the Idylla™ System." The assay is "fully automated and completely integrated," and "all amplification, detection of fluorescence, and the interpretation of the signals are done automatically by the Idylla™ instrument system." This confirms it's an algorithm-only (automated system) performance evaluation without human-in-the-loop for result interpretation.
7. The Type of Ground Truth Used
The ground truth used was a combination of:
- FDA-cleared Nucleic Acid Amplification Test (NAAT) results (for prospective samples).
- Culture, NAAT, and Sequencing (for retrospective samples).
- Bi-directional sequencing at an independent reference laboratory for the adjudication of discordant results.
This represents a form of reference standard comparison, relying on established molecular and culture methods, with sequencing as the ultimate arbiter for discrepancies.
8. The Sample Size for the Training Set
The document does not specify the sample size for a training set. The descriptions provided are for the clinical performance evaluation (i.e., test set) of the device, which is typically conducted after the device's development and internal validation (training) phases are complete. Since this is an IVD assay, it's likely proprietary internal development data, not typically disclosed in 510(k) summaries unless specifically required or relevant to the clinical study design.
9. How the Ground Truth for the Training Set Was Established
Given that the document does not mention a training set or its size, it also does not describe how the ground truth for a training set was established. The entire document focuses on the validation against clinical samples (test set) using established comparator methods and sequencing as ground truth reference.
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August 30, 2017
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
Janssen Pharmaceutica NV Sarah Parsons Director, Global Regulatory Affairs 920 US Highway 202 Raritan, NJ 08869
Re: K163628
Trade/Device Name: Idvlla Respiratory (IFV-RSV) Panel Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory viral panel multiplex nucleic acid assay Regulatory Class: II Product Code: OCC Dated: July 26, 2017 Received: July 28, 2017
Dear Ms. Parsons:
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 premarket approval application (PMA). 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, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21. Parts 800 to 898. 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); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. 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 Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Steven R. Gitterman -S
for
Uwe Scherf Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K163628
Device Name Idylla Respiratory (IFV-RSV) Panel
Indications for Use (Describe)
The Idylla Respiratory (IFV-RSV) Panel is an in vitro assay intended for the qualitative detection of nucleic acids for Influenza A, Influenza A subtype H1, Influenza A subtype H3, Influenza A subtype 2009 H1, H275Y mutation of Influenza A subtype 2009 H1, Influenza B and Respiratory Syncytial Virus (A and B) from nasopharyngeal swabs in viral transport media of adult and pediatric patients. The test uses the Idylla system to aid in the diagnosis of respiratory viral infection when used in conjunction with other clinical and laboratory findings.
Neqative results do not preclude respiratory virus infection with other viruses and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.
Performance characteristics for Influenza A were established when influenza A/2009 H1 and 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 BSL3+ facility is available to receive and culture specimens.
| Type of Use ( Select one or both, as applicable ) |
|---|
| Prescription Use (Part 21 CFR 801 Subpart D) Over-The-Counter Use (21 CFR 801 Subpart C) |
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The 510(k) summary is being provided per condition of 21CFR807.92.
Image /page/3/Picture/1 description: The image shows the Janssen Pharmaceutical Companies logo. The logo consists of the word "Janssen" in blue, followed by a stylized blue symbol that resembles a stylized letter "J". To the right of the Janssen logo, there is the text "PHARMACEUTICAL COMPANIES" in a smaller font, followed by "of Johnson & Johnson" in red script. The logo is clean and professional, and it is likely used on the company's website, marketing materials, and products.
- -– Submitter: Janssen Diagnostics, a division of Janssen Pharmaceutica NV
- Turnhoutseweg 30
- 2340 Beerse
- Belgium
-
- US Contact: Sarah Parsons, Director Regulatory Affairs, Janssen R&D
- Address: 920 US Highway 202 South, Raritan NJ 08869
- Phone: 585-455-4925
- Date Summary was prepared: July 10, 2017
| Company name | Janssen Diagnostics NV |
|---|---|
| Device name | Idylla™ Respiratory (IFV-RSV) Panel |
| Common name | Qualitative nucleic acid amplification based in vitro diagnostic test forthe detection of respiratory viruses |
| Regulatory Section | 21 CFR §866.3980 - Respiratory Viral Panel Multiplex Nucleic AcidAssay |
| Classification | II |
| Product Code | OCC - Respiratory virus panel nucleic acid assay system |
| Review Division | Microbiology (83) |
| Proposed Intended Use | The Idylla™ Respiratory (IFV-RSV) Panel is an in vitro assayintended for the qualitative detection of nucleic acids for InfluenzaA, Influenza A subtype H1, Influenza A subtype H3, Influenza Asubtype 2009 H1, H275Y mutation of Influenza A subtype 2009H1, Influenza B and Respiratory Syncytial Virus (A and B) fromnasopharyngeal swabs in viral transport media of adult andpediatric patients. The test uses the Idylla™ system to aid in thediagnosis of respiratory viral infection when used in conjunctionwith other clinical and laboratory findings.Negative results do not preclude respiratory virus infection or co-infection with other viruses and should not be used as the solebasis for diagnosis, treatment or other patient managementdecisions. |
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| Performance characteristics for Influenza A were established wheninfluenza A/2009 H1 and H3 were the predominant influenza Aviruses in circulation. When other Influenza A viruses areemerging, performance characteristics may vary. | |
|---|---|
| If infection with a novel Influenza A virus is suspected based oncurrent clinical and epidemiological screening criteriarecommended by public health authorities, specimens should becollected with appropriate infection control precautions for novelvirulent influenza viruses and sent to state or local healthdepartments for testing. Viral culture should not be attempted inthese cases unless a BSL3+ facility is available to receive andculture specimens. | |
| Indications for Use | Same as intended use. |
| Special Instrument | Idylla™ System manufactured by Biocartis, NV |
| Requirements | |
| Proposed Predicate Device | Nanosphere Verigene® Respiratory Virus Plus Nucleic Acid Test |
| (RV+) on the Nanosphere Verigene® System (K103209) |
Device Description
The Idylla™ Respiratory (IFV-RSV) Panel is a self-contained molecular diagnostic test designed to work with the IdyllaTM System. The assay is performed using a single-use, disposable, multi-chambered fluidic cartridge. This includes hands-off sample preparation/purification, reverse transcription and real-time, multiplex Polymerase Chain Reaction (PCR) for the detection of viral RNA. All steps in this process are fully automated and completely integrated and results are available in less than 50 minutes.
The Idylla™ Respiratory (IFV-RSV) Panel identifies virus-specific nucleic acids for Influenza (IFV) A virus, Influenza B virus, and Respiratory Syncytial Virus (RSV). The IFV-RSV Panel targets the following genes within the viruses: matrix gene (Influenza A and Influenza B); hemagglutinin gene (Influenza A subtypes H1 and H3, Influenza A subtype 2009 H1); neuraminidase gene (H275Y mutation of 2009 H1); fusion protein gene RSV (A and B). The System amplifies a targeted region of interest generating a change in fluorescent signal, which is measured and applied against predetermined criteria to provide a qualitative result. The automated process steps in the panel are:
Sample processing: Utilizing the automated process of Idylla™ fluidics, sample and Sample Processing Control (SPC) comes in contact with the lysis buffer to release the RNA and solubilize proteins, creating a lysate. Binding buffer is mixed with the lysate to aid in the binding of nucleic acids. Purified RNA is subsequently subject to a RT-PCR reaction within the Cartridge.
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RT-PCR: Reverse Transcription, amplification and fluorescent detection of viral targets occur during the RT-PCR cycling. RT-PCR reagents are present in a stable formulation in five PCR chambers located within the Cartridge. The Test contains reagents for the simultaneous detection of a sample processing control and detection of various IFV and RSV targets. Detection of these specific targets is performed using fluorescent labeled probes. All amplification, detection of fluorescence, and the interpretation of the signals are done automatically by the Idylla™ instrument system.
Comparison to Predicate Device
| Feature | Subject Device:Idylla™Respiratory (IFV-RSV) Panel | Predicate: Verigene® RV+(K103209) |
|---|---|---|
| Similarities | ||
| Regulation | 866.3980 | 866.3980 |
| Product Codes | OCC -Respiratory virus panelnucleic acid assay system | OCC |
| Device Class | Class II | Class II |
| Intended Use | The Idylla Respiratory(IFV-RSV) Panel is an invitro assay intended for thequalitative detection ofnucleic acids for InfluenzaA, Influenza A subtype H1,Influenza A subtype H3,Influenza A subtype 2009H1, H275Y mutation ofInfluenza A subtype 2009H1, Influenza B andRespiratory Syncytial Virus(A and B) fromnasopharyngeal swabs inviral transport media ofadult and pediatric patients.The test uses the Idyllasystem to aid in thediagnosis of respiratoryviral infection when used inconjunction with otherclinical and laboratoryfindings.Negative results do notpreclude respiratory virusinfoction or co-infection | The Verigene® Respiratory VirusPlus Nucleic Acid Test (RV+) onthe Verigene system is a qualitativenucleic acid multiplex test intendedto simultaneously detect andidentify multiple respiratory virusnucleic acids in nasopharyngeal(NP) swab specimens fromindividuals with signs andsymptoms of respiratory infection.The following virus types andsubtypes are identified using theRV+: Influenza A, Influenza Asubtype H1, Influenza A subtypeH3, 2009H1N1, Influenza B,Respiratory Syncytial Virus (RSV)subtype A and RSV subtype B. Thetest is not intended to detectInfluenza C virus. Detecting andidentifying specific viral nucleicacids from individuals exhibitingsigns and symptoms of respiratoryinfection aids in the diagnosis ofrespiratory viral infection, if used inconjunction with other clinical andlaboratory findings. The use of thistest aids in the diagnosis ofrespiratory viral infection when usedin conjunction with other clinicaland laboratory findings. |
| Feature | Subject Device:Idylla™Respiratory (IFV-RSV) Panel | Predicate: Verigene® RV+(K103209) |
| with other viruses andshould not be used as thesole basis for diagnosis,treatment or other patientmanagement decisions.Performance characteristicsfor Influenza A wereestablished when influenzaA/2009 H1 and H3 were thepredominant influenza Aviruses in circulation. Whenother Influenza A virusesare emerging, performancecharacteristics may vary. Ifinfection with a novelInfluenza A virus issuspected based on currentclinical and epidemiologicalscreening criteriarecommended by publichealth authorities,specimens should becollected with appropriateinfection controlprecautions for novelvirulent influenza virusesand sent to state or localhealth departments fortesting. Viral culture shouldnot be attempted in thesecases unless a BSL3+facility is available toreceive and culturespecimens. | Negative results do not precluderespiratory virus infection or co-infection with other viruses andshould not be used as the sole basisfor diagnosis, treatment or othermanagement decisions. Positiveresults do not rule out bacterialinfection, and the agent detectedmay not be the definite cause ofdisease.Performance characteristics forInfluenza A were established whenInfluenza A/H1 and H3 were thepredominant influenza A viruses incirculation. When other Influenza Aviruses are emerging, performancecharacteristics may vary.If infection with a novel Influenza Avirus is suspected based on currentclinical and epidemiologicalscreening criterial recommended bypublic health authorities, specimensshould be collected withappropriated infection controlprecautions for novel virulentinfluenza viruses and sent to state orlocal health departments for testing.Viral culture should not beattempted in these cases unless aBSL 3+ facility is available toreceive and culture specimens. | |
| Targets | Influenza AInfluenza A/H1Influenza A/H3Influenza A/2009 H1Influenza BRSV (A and B) | Influenza AInfluenza A/H1Influenza A/H3Influenza A/2009 H1N1Influenza BRSV ARSV B |
| Feature | Subject Device:Idylla™Respiratory (IFV-RSV) Panel | Predicate: Verigene® RV+(K103209) |
| Specimen | Nasopharyngeal Swabs in ViralTransport Media | Nasopharyngeal swabs in samplematrix |
| Detection Method | PCR amplification | same |
| Nucleic Acid Isolation | Automated internal extraction ofnucleic acids isolated onto silicamembrane. | Automated internal extraction ofnucleic acids performed on theProcessor SP using silica coatedmagnetic beads and chaotropic salts. |
| Results | Positive or negative results | Same |
| LoD for target analytes (200 µL) | 0.09-5 TCID50/mL | 0.1 - 10 TCID50/mL |
| Reactivity across viral strains | Test reacts to multiple strainswithin analyte parameters | Same |
| Specificity | Test does not give false results inthe presence of non-influenza andRSV viruses, interferents orbacterial cultures tested in theanalytical studies | Same |
| Differences | ||
| Targets | Influenza A H275Y mutation in2009 H1RSV A and B combined as RSV | No Influenza A H275Y mutationdeterminationDifferentiation of RSV A and RSVB |
| Detection Method | The Idylla™ Respiratory (IFV-RSV) Panel: Amplified nucleicacid target sequences areidentified by a unique type offluorophore attached to theirrespective probe that is cleavedby the exonuclease activity of theTaq polymerase enzyme andallows for the identification anddifferentiation of the targetviruses and subtypes. Each genemarker is detected usingfluorescent molecules withdifferent excitation and emissionwavelengths. | Verigene Test amplicons arehybridized to gold nanoparticlesprobes through a mediatoroligonucleotide and target specificcapture oligonucleotides on amicroarray-based chip in adisposable test cartridge. |
| Quality control | Each cartridge contains a singleSample Process Control (SPC) inthe sample chamber formonitoring adequate sampleprocessing and downstreamamplification. The SPC is co- | Multiple internal procedural qualitycontrols: PC1 (IC1) – inhibitioncontrol; PC2 (IC2) - processcontrol; internal positive andnegative controls; external positive |
| Feature | Subject Device:Idylla™Respiratory (IFV-RSV) Panel | Predicate: Verigene® RV+(K103209) |
| amplified in each chamber tomonitor that proper detection hasoccurred and that no PCRinhibitors were present in thesample. | controls |
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Performance Data
Analytical Performance
The analytical performance of the Idylla™ Respiratory (IFV-RSV) Panel was established following the recommendation found in FDA guidance document class II special controls specific for respiratory viral panels and nucleic acids (Guidance for Industry and FDA Staff-Class II Special Controls Guidance Document: Respiratory Viral Panel Multiplex Nucleic Acid Assay, October 9, 2009 and Class II Special Controls Guidance Document: Testing for Detection and Differentiation of Influenza A Virus Subtypes Using Multiplex Assays, October 9, 2009). These studies included analytical sensitivity, specificity (exclusivity), reactivity), interfering substances, competitive inhibition, and freeze/thaw studies. The results from these studies support claims that the product is substantially equivalent to the predicate device.
Clinical Performance
The clinical performance was measured in a multi-site prospective study using samples collected during the 2015-2016 IFV-RSV season plus stored samples from the 2012-2013 and 2013-2014 IFV and RSV seasons prospectively collected under a separate protocol. The samples were distributed across four external sites and tested with the Idylla™ Respiratory (IFV-RSV) Panel at the site or sent to a reference lab for testing with an FDA cleared molecular respiratory test. A total of 1014 subjects (214 fresh and 800 archived samples) were collected with nasopharyngeal swabs in viral transport media and were available for testing during this study. An additional 40 contrived H275Y mutation samples were processed, sent blinded to the sites and tested due to a low incidence of this mutational variant circulating in the last Flu seasons. The 40 samples were not included in the agreement measures of the other targets that were evaluated using prospectively collected clinical samples. Fifteen subjects were excluded due to protocol deviation, eligibility criteria, or missing comparator data. Eighty-eight samples were excluded due to failure to pass daily quality control (QC). The daily QC was an inadvertent error in the lab protocol that continued to run patient samples after 5 instances where the daily QC did not pass but was not repeated. A study performed in-house of Nasopharyngeal swab specimens from archived banked retrospective clinical collections were tested on the Idylla™ Respiratory (IFV-RSV) Panel and comparator Assays (Culture/NAAT/Sequencing). Testing of the Idylla™ IFV-RSV Panel was conducted by three operators on three Idylla™ Systems at both 200 uL and 500 uL. A total of 419 patient samples were tested at 200 uL with 408 reported results, and a total of 449 patient samples were tested at 500 µL with 418 reported results. The results of the
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prospectively collected samples testing for each target, including Positive and Negative Agreement, are presented in Table 1 through Table 6. The retrospective collected samples testing for each target, including Positive and Negative Agreement, are presented in Table 7 through Table 12. The IFV-RSV Panel performance was compared to a FDA-cleared Nucleic Acid Amplification Test (NAAT). H275Y genotype determination and discordant results between the IFV-RSV Panel and the reference method were confirmed and/or analyzed respectively by using bi-directional sequencing at an independent reference laboratory (described in the table footnotes).
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| 200 µL VTM | |||
|---|---|---|---|
| IFV-RSV Panel Result | ComparatorPositive | ComparatorNegative | Total |
| Positive | 142 | 3a | 145 |
| Negative | 12b | 803 | 815 |
| Total | 154 | 806 | 960 |
| Point Estimate | 95% CI | ||
| Positive Percent Agreement | 92.2% | 86.9% - 95.5% | |
| Negative Percent Agreement | 99.6% | 98.9% - 99.9% | |
| 500 µL VTM | |||
| IFV-RSV Panel Result | ComparatorPositive | ComparatorNegative | Total |
| Positive | 139 | 5c | 144 |
| Negative | 10d | 775 | 785 |
| Total | 149 | 780 | 929 |
| Point Estimate | 95% CI | ||
| Positive Percent Agreement | 93.3% | 88.1% - 96.3% | |
| Negative Percent Agreement | 99.4% | 98.5% - 99.7% |
Prospective Sample Positive Percent, Negative Percent, and Sanger Sequencing for Table 1: INFLUENZA A
4: Three samples were FluA positive by Idylla™ @ 200 µl but negative by the comparator. Sequencing result confirmed one of three samples as FluA positive and the two samples were FluA negative.
b: 12 samples were FluA negative by Idylla™ @ 200 ul but FluA positive by the comparator. Sequencing result confirmed ten samples as FluA negative and two samples as FluA positive..
« Five samples were FluA positive by Idylla™ @ 500 µl but negative by the comparator. Sequencing result confirmed four samples as FluA negative and one sample as FluA positive.
d: 10 samples were FluA negative by Idylla™ @ 500 µl but positive by the comparator. Sequencing result confirmed nine samples as FluA negative and one sample as FluA positive.
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Prospective Sample Positive Percent, Negative Percent Agreement, and Sanger Sequencing for Table 2: INFLUENZA A H3
| 200 µL VTM | |||
|---|---|---|---|
| IFV-RSV Panel Result | ComparatorPositive | ComparatorNegative | Total |
| Positive | 73 | 0 | 73 |
| Negative | 5a | 882 | 887 |
| Total | 78 | 882 | 960 |
| Point Estimate | 95% CI | ||
| Positive Percent Agreement | 93.6% | 85.9 - 97.2% | |
| Negative Percent Agreement | 100% | 99.6% - 100% | |
| 500 µL VTM | |||
| IFV-RSV Panel Result | ComparatorPositive | ComparatorNegative | Total |
| Positive | 71 | 1c | 72 |
| Negative | 4b | 853 | 857 |
| Total | 75 | 854 | 929 |
| Point Estimate | 95% CI | ||
| Positive Percent Agreement | 94.7% | 87.1% - 97.9% |
ª Five samples were AH3 negative by Idylla™ 200 µL but positive by the comparator. Sequencing confirmed all samples AH3 negative.
b Four samples were AH3 negative by Idylla™ 500 µL but positive by the comparator. Sequencing result confirmed all samples as AH3 negative.
& One sample was AH3 positive by Idylla™ but negative by the comparator. Sequencing result confirmed AH3 positive.
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| 200 µL VTM | |||
|---|---|---|---|
| IFV-RSV Panel Result | ComparatorPositive | ComparatorNegative | Total |
| Positive | 66 | 2a | 68 |
| Negative | 10b | 882 | 892 |
| Total | 76 | 884 | 960 |
| Point Estimate | 95% CI | ||
| Positive Percent Agreement | 86.8% | 77.4% - 92.7% | |
| Negative Percent Agreement | 99.8% | 99.2% - 99.9% | |
| 500 µL VTM | |||
| IFV-RSV Panel Result | ComparatorPositive | ComparatorNegative | Total |
| Positive | 65 | 2c | 67 |
| Negative | 8d | 854 | 862 |
| Total | 73 | 856 | 929 |
| Point Estimate | 95% CI | ||
| Positive Percent Agreement | 89.0% | 79.8% - 94.3% |
Prospective Sample Positive Percent, Negative Percent, and Sanger Sequencing for Table 3: INFLUENZA A/2009 H1
4: Two samples were 2009H1 positive by Idylla™ and negative by the comparator. Sequencing results confirmed one sample as 2009H1 positive and one as negative.
b: 10 samples were 2009H1 negative by Idylla™ @ 200 µl and positive by the comparator. Nine samples were confirmed negative and one sample was confirmed positive by sequencing.
« Two samples were 2009H1 positive by Idylla™ @ 500 µl and negative by the comparator. Sequencing results confirmed one sample as 2009H1 positive and one sample as negative.
4: Eight samples were 2009H1 negative by Idylla™ @ 500 ul but positive by the comparator. Sequencing results confirmed seven samples as 2009H1 negative and one sample positive.
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| 200 µL VTM | |||
|---|---|---|---|
| IFV-RSV Panel Result | ComparatorPositive1 | ComparatorNegative | Total |
| Positive | 39 | 0 | 39 |
| Negative | 0 | 960 | 960 |
| Total | 39 | 960 | 999 |
| Point Estimate | 95% CI | ||
| Positive Percent Agreement | 100% | 91.0% - 100% | |
| Negative Percent Agreement | 100% | 99.6% - 100% | |
| 500 µL VTM | |||
| IFV-RSV Panel Result | ComparatorPositive | ComparatorNegative | Total |
| Positive | 40 | 0 | 40 |
| Negative | 0 | 929 | 929 |
| Total | 40 | 929 | 969 |
| Point Estimate | 95% CI | ||
| Positive Percent Agreement | 100% | 91.2% - 100% | |
| Negative Percent Agreement | 100% | 99.6% - 100% |
Table 4: Prospective Sample Positive Percent, Negative Percent Agreement, and Sanger Sequencing for
H275Y Mutation of Influenza A Subtype 2009 H1
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| 200 µL VTM | |||
|---|---|---|---|
| IFV-RSV Panel Result | Comparator Positive | ComparatorNegative | Total |
| Positive | 113 | 2a | 115 |
| Negative | 19b | 826 | 845 |
| Total | 132 | 828 | 960 |
| Point Estimate | 95% CI | ||
| Positive Percent Agreement | 85.6% | 78.6% - 90.6% | |
| Negative Percent Agreement | 99.8% | 99.1% - 99.9% | |
| 500 µL VTM | |||
| IFV-RSV Panel Result | Comparator Positive | ComparatorNegative | Total |
| Positive | 111 | 2c | 113 |
| Negative | 19d | 797 | 816 |
| Total | 130 | 799 | 929 |
| Point Estimate | 95% CI | ||
| Positive Percent Agreement | 85.4% | 78.3% - 90.4% | |
| Negative Percent Agreement | 99.7% | 99.1% - 99.9% |
Table 5: Prospective Sample Positive Percent, Negative Percent, and Sanger Sequencing for INFLUENZA B
a: Two samples were FluB positive by Idylla but negative by the comparator @ 200 µl. Sequencing result confrired two samples FluB negative.
b: 19 samples were FluB negative by Idylla but positive by the comparator @ 200 µl. Two samples were confirmed positive by sequencing and 17 samples were confirmed negative by sequencing.
c: Two samples were FluB positive by Idylla but negative by the comparator @ 500 µl. DNA sequencing confirmed both samples as FluB negative.
d: 19 samples were FluB negative by Idylla but positive by the comparator @ 200 µl. DNA sequencing confirmed three samples as FluB positive and 16 samples as FluB negative.
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| Table 6: Prospective Sample Positive Percent, Negative Percent Agreement, and Sanger Sequencing for |
|---|
| RSV (A or B) |
| 200 µL VTM | |||
|---|---|---|---|
| IFV-RSV Panel Result | ComparatorPositive | ComparatorNegative | Total |
| Positive | 96 | 3a | 99 |
| Negative | 14b | 847 | 861 |
| Total | 110 | 850 | 960 |
| Point Estimate | 95% CI | ||
| Positive Percent Agreement | 90.2% | 85.0% - 94.0% | |
| Negative Percent Agreement | 99.7% | 99.1% - 99.9% | |
| 500 µL VTM | |||
| IFV-RSV Panel Result | ComparatorPositive | ComparatorNegative | Total |
| Positive | 90 | 3c | 93 |
| Negative | 13d | 823 | 836 |
| Total | 103 | 826 | 929 |
| Point Estimate | 95% CI | ||
| Positive Percent Agreement | 87.4% | 79.6% - 92.4% | |
| Negative Percent Agreement | 99.6% | 98.9% - 99.9% |
a: Three samples were RSV positive by Idylla @ 200 µl but RSV negative by the comparator. Two samples were confirmed negative and one sample was confirmed positive by sequencing.
b: 14 samples were RSV negative by Idylla @ 200 µl but RSV positive by the comparator. Four samples were confirmed RSV negative by sequencing. 10 samples were confirmed RSV positive by sequencing.
c: Three samples were RSV positive by Idylla but negative by the comparator @ 500 µl. Sequencing results confirmed one RSV positive and two RSV negative samples.
d: 13 samples were RSV negative @ 500 µl by Idylla and RSV positive by the comparator. Sequencing results confirmed four samples as RSV negative and nine samples as RSV positive.
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| 200 µL VTM | |||
|---|---|---|---|
| IFV-RSV Panel Result | ComparatorPositive | ComparatorNegative | Total |
| Positive | 80 | 0 | 80 |
| Negative | 4b | 324 | 328 |
| Total | 84 | 324 | 408 |
| Point Estimate | 95% CI | ||
| Positive Percent Agreement | 95.2% | 88.4% - 98.1% | |
| Negative Percent Agreement | 100% | 98.9% - 100% | |
| 500 µL VTM | |||
| IFV-RSV Panel Result | ComparatorPositive | ComparatorNegative | Total |
| Positive | 82 | 0 | 82 |
| Negative | 3a | 333 | 336 |
| Total | 85 | 333 | 418 |
| Point Estimate | 95% CI | ||
| Positive Percent Agreement | 96.5% | 90.1% - 98.8% | |
| Negative Percent Agreement | 100% | 98.9% - 100% |
Table 7: Retrospective Sample Positive Percent and Negative Percent Agreement for INFLUENZA A
b: four samples were FluA negative by Idylla @ 200ul but positive by the sample was negative at 200ul by ldylla but detected at 500ul by Idylla, therefore sample was not tested in sequencing. Two samples were confirmed Flux neguencing. one of the sample had insufficient volume remained to complete sequencing.
a: Three samples were FluA negative by Idyla @ 500ul but positive by the three samples were confirmed FluA negative by sequencing. One sample had insufficient volume to complete DNA sequencing.
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Table 8: Retrospective Sample Positive Percent and Negative Percent Agreement for INFLUENZA A H3
| 200 µL VTM | |||
|---|---|---|---|
| IFV-RSV Panel Result | ComparatorPositive | ComparatorNegative | Total |
| Positive | 27 | 0 | 27 |
| Negative | 1 a | 380 | 381 |
| Total | 28 | 380 | 408 |
| Point Estimate | 95% CI | ||
| Positive Percent Agreement | 96.4% | 82.3% - 99.4% | |
| Negative Percent Agreement | 100% | 99.0% - 100% | |
| 500 µL VTM | |||
| IFV-RSV Panel Result | ComparatorPositive | ComparatorNegative | Total |
| Positive | 28 | 0 | 28 |
| Negative | 1 a | 389 | 390 |
| Total | 29 | 389 | 418 |
| Point Estimate | 95% CI | ||
| Positive Percent Agreement | 96.6% | 82.8% - 99.4% | |
| Negative Percent Agreement | 100% | 99.0% - 100% |
a: One sample was negative for AH3 by ldylla @ 200ul and 500ul but the comparator result was AH3 positive. Insufficient material remained for DNA Sequencing
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| 200 µL VTM | |||
|---|---|---|---|
| IFV-RSV Panel Result | ComparatorPositive | ComparatorNegative | Total |
| Positive | 25 | 0 | 25 |
| Negative | 1a | 382 | 383 |
| Total | 26 | 382 | 408 |
| Point Estimate | 95% CI | ||
| Positive Percent Agreement | 96.2% | 81.1% - 99.3% | |
| Negative Percent Agreement | 100% | 99.0% - 100% | |
| 500 µL VTM | |||
| IFV-RSV Panel Result | ComparatorPositive | ComparatorNegative | Total |
| Positive | 25 | 0 | 25 |
| Negative | 0 | 393 | 393 |
| Total | 25 | 393 | 418 |
| Point Estimate | 95% CI | ||
| Positive Percent Agreement | 100% | 86.7% - 100% | |
| Negative Percent Agreement | 100% | 99.0% - 100% |
Table 9: Retrospective Sample Positive Percent and Negative Percent Agreement for INFLUENZA AH1
a: one sample was Idylla negative for AH1 at 200uL but detected by Idylla at 500uL, therefore not tested in sequencing.
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| Table 10: Retrospective Sample Positive Percent and Negative Percent Agreement for INFLUENZA |
|---|
| A 2009H1 |
| 200 µL VTM | |||
|---|---|---|---|
| IFV-RSV Panel Result | Comparator Positive | Comparator Negative | Total |
| Positive | 28 | 0 | 28 |
| Negative | 1 a | 379 | 380 |
| Total | 29 | 379 | 408 |
| Point Estimate | 95% CI | ||
| Positive Percent Agreement | 96.6% | 82.8% - 99.4% | |
| Negative Percent Agreement | 100% | 99.0% – 100% | |
| 500 µL VTM | |||
| IFV-RSV Panel Result | Comparator Positive | Comparator Negative | Total |
| Positive | 29 | 0 | 29 |
| Negative | 1 a | 388 | 389 |
| Total | 30 | 388 | 418 |
| Point Estimate | 95% CI | ||
| Positive Percent Agreement | 96.7% | 83.3% - 99.4% | |
| Negative Percent Agreement | 100% | 99.0% – 100% |
a: One sample was 2009H negative at 200aL by Idylla, but detected by the comparator. DNA sequencing confirmed the
absence of HINI 2009 and Influenza A.
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| 200 µL VTM | |||
|---|---|---|---|
| IFV-RSV Panel Result | Comparator Positive | Comparator Negative | Total |
| Positive | 102 | 1a | 103 |
| Negative | 5b | 300 | 305 |
| Total | 107 | 301 | 408 |
| Point Estimate | 95% CI | ||
| Positive Percent Agreement | 95.3% | 89.5% - 98.0% | |
| Negative Percent Agreement | 99.7% | 98.1% - 100% | |
| 500 µL VTM | |||
| IFV-RSV Panel Result | Comparator Positive | Comparator Negative | Total |
| Positive | 106 | 1c | 107 |
| Negative | 6d | 305 | 311 |
| Total | 112 | 306 | 418 |
| Point Estimate | 95% CI | ||
| Positive Percent Agreement | 94.6% | 88.8% - 97.5% |
Table 11: Retrospective Sample Positive Percent and Negative Percent Agreement for INFLUENZA B
a: One sample was FluB positive by Idylla @ 200ul but negative by the comparator. This sample was confirmed FluB positive by DNA sequencing.
b: Five samples were FluB negative by ldylla @ 200ul and positive by the comparator. All five samples were confirmed FluB positive by sequencing.
c: One sample was FluB positive by Idylla but negative by the comparator @ 500ul. DNA sequencing confirmed this sample as FluB positive.
d: Six samples were FluB negative by Idylla @ 500 but positive by the comples were confirmed FluB positive by DNA sequencing.
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| 200 µL VTM | |||
|---|---|---|---|
| IFV-RSV Panel Result | ComparatorPositive | ComparatorNegative | Total |
| Positive | 69 | 1 a | 70 |
| Negative | 4b | 334 | 338 |
| Total | 73 | 335 | 408 |
| Point Estimate | 95% CI | ||
| Positive Percent Agreement | 94.5% | 86.7% – 97.9% | |
| Negative Percent Agreement | 99.7% | 98.3% – 100% | |
| 500 µL VTM | |||
| IFV-RSV Panel Result | ComparatorPositive | ComparatorNegative | Total |
| Positive | 81 | 1c | 82 |
| Negative | 7d | 329 | 336 |
| Total | 88 | 330 | 418 |
| Point Estimate | 95% CI | ||
| Positive Percent Agreement | 92.1% | 84.5% – 96.1% | |
| Negative Percent Agreement | 99.7% | 98.3% – 100% |
Table 12: Retrospective Sample Positive Percent and Negative Percent Agreement for RSV (A or B)
a: One sample was RSV positive by Idylla @ 200ul but negative by the comparator. Insufficient sample remained for DNA sequencing.
b: Four samples were RSV negative by Idylla @ 200ul but positive by the comparator. All four samples were confirmed negative by sequencing.
c: One RSV sample was positive by Idylla but negative by the comparator.@500ul. Sequencing result confirmed this sample as RSV positive.
d: Seven samples were RSV negative by Idylla @ 500ul but the comparator. Six samples were confirmed RSV negative and one sample confirmed RSV positive by sequencing.
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Conclusion:
In the multisite clinical study, nasopharyngeal swabs in VTM tested at 200 uL or 500 uL demonstrated at least 90% positive percent agreement (PPA) with a lower bound of the twosided 95% CI greater than 80% for Influenza A, Influenza A H3. Influenza A H275Y 2009 H1. From the multisite study, results for Influenza A 2009/H1N1, for influenza B, and for RSV in nasopharyngeal swabs did not meet acceptance criteria in this study. However, the RSV call came very close to meeting the acceptance criteria with a point estimate of 87.4 and CI of 79.6-92.5% for nasopharyngeal swabs. Bidirectional sequencing results agreed most often with the Idylla™ results. When the discordant results were re-evaluated following sequencing of the samples, ALL targets (including the combined RSV call) demonstrated at least 90% PPA with a lower bound of the two-sided 95% CI greater than 80%.
When the results of the multisite prospective clinical study are combined with the retrospective testing, nasopharyngeal swabs tested in 200 uL or 500 uL VTM demonstrated at least 90% positive percent agreement (PPA) with a lower bound of the two-sided 95% CI greater than 80% for Influenza A, Influenza A H1, Influenza A H275Y 2009/H1 and Influenza A H3. From the combined testing, results for Influenza A 2009 H1 (200 µL), Influenza B (500µL), and RSV (500µL) in nasopharyngeal swabs met acceptance criteria when rounding of the PPA is applied. Bidirectional sequencing results agreed most often with the Idylla™ results. When the discordant results were re-evaluated following sequencing of the samples, ALL targets (including the RSV call) demonstrated at least 90% PPA with a lower bound of the two-sided 95% CI greater than 80%.
In the multisite clinical study, nasopharyngeal swab specimens in 200 uL or 500 uL VTM demonstrated negative percent agreement (NPA) exceeding 99% with a lower bound of 95% (two-sided) confidence interval exceeding 90% for all targets meeting and exceeding acceptance criteria.
A comparison of the Intended Use, device features, non-clinical and clinical data support the Idylla™ Respiratory (IFV-RSV) Panel is substantially equivalent to the predicate device.
§ 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.