K Number
K163628
Device Name
Idylla Respiratory (IFV-RSV) Panel
Date Cleared
2017-08-30

(251 days)

Product Code
Regulation Number
866.3980
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdparty
Intended Use
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.
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. 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.
More Information

Not Found

No
The device description details a fully automated molecular diagnostic test using PCR and fluorescent detection with predetermined criteria for qualitative results. There is no mention of AI or ML in the device description, intended use, or performance studies.

No
The device is an in vitro diagnostic test for detecting viral nucleic acids, which aids in diagnosis rather than providing therapy.

Yes

The device's intended use is 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)" to "aid in the diagnosis of respiratory viral infection when used in conjunction with other clinical and laboratory findings." This clearly indicates its role in disease diagnosis.

No

The device is a molecular diagnostic test that uses a physical cartridge and the Idylla™ System hardware to perform automated sample processing, RT-PCR, and fluorescent detection. 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 device is an "in vitro assay intended for the qualitative detection of nucleic acids... from nasopharyngeal swabs... to aid in the diagnosis of respiratory viral infection". This clearly describes an in vitro diagnostic test.
  • Device Description: The description details how the device performs sample preparation, reverse transcription, and real-time PCR to detect viral RNA. These are all processes performed in vitro (outside the body) on a biological sample.
  • Performance Studies: The document describes clinical performance studies comparing the device's results to a reference method using patient samples. This is a standard requirement for demonstrating the performance of an IVD.
  • Predicate Device: The mention of a "Predicate Device(s)" with a K number (K103209) indicates that this device is being compared to a previously cleared IVD, which is a common regulatory pathway for new IVDs.
  • Reference Device: The use of an "FDA-cleared Nucleic Acid Amplification Test (NAAT)" as a reference method further confirms that this device is intended for diagnostic use and is being evaluated against established diagnostic standards.

N/A

Intended Use / Indications for Use

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.

Product codes (comma separated list FDA assigned to the subject device)

OCC

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.

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.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

nasopharyngeal swabs

Indicated Patient Age Range

adult and pediatric patients

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

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.

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

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 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).

Key results:
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 two-sided 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.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Influenza A (200 µL VTM - Prospective):
Positive Percent Agreement: 92.2% (95% CI: 86.9% - 95.5%)
Negative Percent Agreement: 99.6% (95% CI: 98.9% - 99.9%)

Influenza A (500 µL VTM - Prospective):
Positive Percent Agreement: 93.3% (95% CI: 88.1% - 96.3%)
Negative Percent Agreement: 99.4% (95% CI: 98.5% - 99.7%)

Influenza A H3 (200 µL VTM - Prospective):
Positive Percent Agreement: 93.6% (95% CI: 85.9% - 97.2%)
Negative Percent Agreement: 100% (95% CI: 99.6% - 100%)

Influenza A H3 (500 µL VTM - Prospective):
Positive Percent Agreement: 94.7% (95% CI: 87.1% - 97.9%)
Negative Percent Agreement: Not provided, but 1c was positive by Idylla and negative by comparator, and 4b were negative by Idylla and positive by comparator (sequencing confirmed all AH3 negative)

Influenza A/2009 H1 (200 µL VTM - Prospective):
Positive Percent Agreement: 86.8% (95% CI: 77.4% - 92.7%)
Negative Percent Agreement: 99.8% (95% CI: 99.2% - 99.9%)

Influenza A/2009 H1 (500 µL VTM - Prospective):
Positive Percent Agreement: 89.0% (95% CI: 79.8% - 94.3%)
Negative Percent Agreement: 99.7% (95% CI: 99.1% - 99.9%)

H275Y Mutation of Influenza A Subtype 2009 H1 (200 µL VTM - Prospective):
Positive Percent Agreement: 100% (95% CI: 91.0% - 100%)
Negative Percent Agreement: 100% (95% CI: 99.6% - 100%)

H275Y Mutation of Influenza A Subtype 2009 H1 (500 µL VTM - Prospective):
Positive Percent Agreement: 100% (95% CI: 91.2% - 100%)
Negative Percent Agreement: 100% (95% CI: 99.6% - 100%)

Influenza B (200 µL VTM - Prospective):
Positive Percent Agreement: 85.6% (95% CI: 78.6% - 90.6%)
Negative Percent Agreement: 99.8% (95% CI: 99.1% - 99.9%)

Influenza B (500 µL VTM - Prospective):
Positive Percent Agreement: 85.4% (95% CI: 78.3% - 90.4%)
Negative Percent Agreement: 99.7% (95% CI: 99.1% - 99.9%)

RSV (A or B) (200 µL VTM - Prospective):
Positive Percent Agreement: 90.2% (95% CI: 85.0% - 94.0%)
Negative Percent Agreement: 99.7% (95% CI: 99.1% - 99.9%)

RSV (A or B) (500 µL VTM - Prospective):
Positive Percent Agreement: 87.4% (95% CI: 79.6% - 92.4%)
Negative Percent Agreement: 99.6% (95% CI: 98.9% - 99.9%)

Influenza A (200 µL VTM - Retrospective):
Positive Percent Agreement: 95.2% (95% CI: 88.4% - 98.1%)
Negative Percent Agreement: 100% (95% CI: 98.9% - 100%)

Influenza A (500 µL VTM - Retrospective):
Positive Percent Agreement: 96.5% (95% CI: 90.1% - 98.8%)
Negative Percent Agreement: 100% (95% CI: 98.9% - 100%)

Influenza A H3 (200 µL VTM - Retrospective):
Positive Percent Agreement: 96.4% (95% CI: 82.3% - 99.4%)
Negative Percent Agreement: 100% (95% CI: 99.0% - 100%)

Influenza A H3 (500 µL VTM - Retrospective):
Positive Percent Agreement: 96.6% (95% CI: 82.8% - 99.4%)
Negative Percent Agreement: 100% (95% CI: 99.0% - 100%)

Influenza AH1 (200 µL VTM - Retrospective):
Positive Percent Agreement: 96.2% (95% CI: 81.1% - 99.3%)
Negative Percent Agreement: 100% (95% CI: 99.0% - 100%)

Influenza AH1 (500 µL VTM - Retrospective):
Positive Percent Agreement: 100% (95% CI: 86.7% - 100%)
Negative Percent Agreement: 100% (95% CI: 99.0% - 100%)

Influenza A 2009H1 (200 µL VTM - Retrospective):
Positive Percent Agreement: 96.6% (95% CI: 82.8% - 99.4%)
Negative Percent Agreement: 100% (95% CI: 99.0% - 100%)

Influenza A 2009H1 (500 µL VTM - Retrospective):
Positive Percent Agreement: 96.7% (95% CI: 83.3% - 99.4%)
Negative Percent Agreement: 100% (95% CI: 99.0% - 100%)

Influenza B (200 µL VTM - Retrospective):
Positive Percent Agreement: 95.3% (95% CI: 89.5% - 98.0%)
Negative Percent Agreement: 99.7% (95% CI: 98.1% - 100%)

Influenza B (500 µL VTM - Retrospective):
Positive Percent Agreement: 94.6% (95% CI: 88.8% - 97.5%)
Negative Percent Agreement: Not provided, described 6d which states 6 samples were FluB negative by Idylla @ 500 but positive by the comparator and all were confirmed FluB positive by DNA sequencing.

RSV (A or B) (200 µL VTM - Retrospective):
Positive Percent Agreement: 94.5% (95% CI: 86.7% - 97.9%)
Negative Percent Agreement: 99.7% (95% CI: 98.3% - 100%)

RSV (A or B) (500 µL VTM - Retrospective):
Positive Percent Agreement: 92.1% (95% CI: 84.5% - 96.1%)
Negative Percent Agreement: 99.7% (95% CI: 98.3% - 100%)

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.

K103209

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.

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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.

1

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 nameJanssen Diagnostics NV
Device nameIdylla™ Respiratory (IFV-RSV) Panel
Common nameQualitative nucleic acid amplification based in vitro diagnostic test for
the detection of respiratory viruses
Regulatory Section21 CFR §866.3980 - Respiratory Viral Panel Multiplex Nucleic Acid
Assay
ClassificationII
Product CodeOCC - Respiratory virus panel nucleic acid assay system
Review DivisionMicrobiology (83)
Proposed Intended UseThe 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.

4

| | 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. |
| 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 panel
nucleic acid assay system | OCC |
| Device Class | Class II | Class II |
| Intended Use | 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
infoction or co-infection | The Verigene® Respiratory Virus
Plus Nucleic Acid Test (RV+) on
the Verigene system is a qualitative
nucleic acid multiplex test intended
to simultaneously detect and
identify multiple respiratory virus
nucleic acids in nasopharyngeal
(NP) swab specimens from
individuals with signs and
symptoms of respiratory infection.
The following virus types and
subtypes are identified using the
RV+: Influenza A, Influenza A
subtype H1, Influenza A subtype
H3, 2009H1N1, Influenza B,
Respiratory Syncytial Virus (RSV)
subtype A and RSV subtype B. The
test is not intended to detect
Influenza C virus. Detecting and
identifying specific viral nucleic
acids from individuals exhibiting
signs and symptoms of respiratory
infection aids in the diagnosis of
respiratory viral infection, if used in
conjunction with other clinical and
laboratory findings. The use of this
test aids in the diagnosis of
respiratory viral infection when used
in conjunction with other clinical
and laboratory findings. |
| Feature | Subject Device:Idylla™
Respiratory (IFV-RSV) Panel | Predicate: Verigene® RV+
(K103209) |
| | 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. | 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
management decisions. Positive
results do not rule out bacterial
infection, and the agent detected
may not be the definite cause of
disease.
Performance characteristics for
Influenza A were established when
Influenza A/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 criterial recommended by
public health authorities, specimens
should be collected with
appropriated 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. |
| Targets | Influenza A
Influenza A/H1
Influenza A/H3
Influenza A/2009 H1
Influenza B
RSV (A and B) | Influenza A
Influenza A/H1
Influenza A/H3
Influenza A/2009 H1N1
Influenza B
RSV A
RSV B |
| Feature | Subject Device:Idylla™
Respiratory (IFV-RSV) Panel | Predicate: Verigene® RV+
(K103209) |
| Specimen | Nasopharyngeal Swabs in Viral
Transport Media | Nasopharyngeal swabs in sample
matrix |
| Detection Method | PCR amplification | same |
| Nucleic Acid Isolation | Automated internal extraction of
nucleic acids isolated onto silica
membrane. | Automated internal extraction of
nucleic acids performed on the
Processor SP using silica coated
magnetic 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 strains
within analyte parameters | Same |
| Specificity | Test does not give false results in
the presence of non-influenza and
RSV viruses, interferents or
bacterial cultures tested in the
analytical studies | Same |
| | Differences | |
| Targets | Influenza A H275Y mutation in
2009 H1
RSV A and B combined as RSV | No Influenza A H275Y mutation
determination
Differentiation of RSV A and RSV
B |
| Detection Method | The Idylla™ Respiratory (IFV-
RSV) Panel: Amplified nucleic
acid target sequences are
identified by a unique type of
fluorophore attached to their
respective probe that is cleaved
by the exonuclease activity of the
Taq polymerase enzyme and
allows for the identification and
differentiation of the target
viruses and subtypes. Each gene
marker is detected using
fluorescent molecules with
different excitation and emission
wavelengths. | Verigene Test amplicons are
hybridized to gold nanoparticles
probes through a mediator
oligonucleotide and target specific
capture oligonucleotides on a
microarray-based chip in a
disposable test cartridge. |
| Quality control | Each cartridge contains a single
Sample Process Control (SPC) in
the sample chamber for
monitoring adequate sample
processing and downstream
amplification. The SPC is co- | Multiple internal procedural quality
controls: PC1 (IC1) – inhibition
control; PC2 (IC2) - process
control; internal positive and
negative controls; external positive |
| Feature | Subject Device:Idylla™
Respiratory (IFV-RSV) Panel | Predicate: Verigene® RV+
(K103209) |
| amplified in each chamber to
monitor that proper detection has
occurred and that no PCR
inhibitors were present in the
sample. | controls | |

6

7

8

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 ResultComparator
PositiveComparator
NegativeTotal
Positive1423a145
Negative12b803815
Total154806960
Point Estimate95% CI
Positive Percent Agreement92.2%86.9% - 95.5%
Negative Percent Agreement99.6%98.9% - 99.9%
500 µL VTM
IFV-RSV Panel ResultComparator
PositiveComparator
NegativeTotal
Positive1395c144
Negative10d775785
Total149780929
Point Estimate95% CI
Positive Percent Agreement93.3%88.1% - 96.3%
Negative Percent Agreement99.4%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 ResultComparator
PositiveComparator
NegativeTotal
Positive73073
Negative5a882887
Total78882960
Point Estimate95% CI
Positive Percent Agreement93.6%85.9 - 97.2%
Negative Percent Agreement100%99.6% - 100%
500 µL VTM
IFV-RSV Panel ResultComparator
PositiveComparator
NegativeTotal
Positive711c72
Negative4b853857
Total75854929
Point Estimate95% CI
Positive Percent Agreement94.7%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 ResultComparator
PositiveComparator
NegativeTotal
Positive662a68
Negative10b882892
Total76884960
Point Estimate95% CI
Positive Percent Agreement86.8%77.4% - 92.7%
Negative Percent Agreement99.8%99.2% - 99.9%
500 µL VTM
IFV-RSV Panel ResultComparator
PositiveComparator
NegativeTotal
Positive652c67
Negative8d854862
Total73856929
Point Estimate95% CI
Positive Percent Agreement89.0%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 ResultComparator
Positive1Comparator
NegativeTotal
Positive39039
Negative0960960
Total39960999
Point Estimate95% CI
Positive Percent Agreement100%91.0% - 100%
Negative Percent Agreement100%99.6% - 100%
500 µL VTM
IFV-RSV Panel ResultComparator
PositiveComparator
NegativeTotal
Positive40040
Negative0929929
Total40929969
Point Estimate95% CI
Positive Percent Agreement100%91.2% - 100%
Negative Percent Agreement100%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 ResultComparator PositiveComparator
NegativeTotal
Positive1132a115
Negative19b826845
Total132828960
Point Estimate95% CI
Positive Percent Agreement85.6%78.6% - 90.6%
Negative Percent Agreement99.8%99.1% - 99.9%
500 µL VTM
IFV-RSV Panel ResultComparator PositiveComparator
NegativeTotal
Positive1112c113
Negative19d797816
Total130799929
Point Estimate95% CI
Positive Percent Agreement85.4%78.3% - 90.4%
Negative Percent Agreement99.7%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 ResultComparator
PositiveComparator
NegativeTotal
Positive963a99
Negative14b847861
Total110850960
Point Estimate95% CI
Positive Percent Agreement90.2%85.0% - 94.0%
Negative Percent Agreement99.7%99.1% - 99.9%
500 µL VTM
IFV-RSV Panel ResultComparator
PositiveComparator
NegativeTotal
Positive903c93
Negative13d823836
Total103826929
Point Estimate95% CI
Positive Percent Agreement87.4%79.6% - 92.4%
Negative Percent Agreement99.6%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 ResultComparator
PositiveComparator
NegativeTotal
Positive80080
Negative4b324328
Total84324408
Point Estimate95% CI
Positive Percent Agreement95.2%88.4% - 98.1%
Negative Percent Agreement100%98.9% - 100%
500 µL VTM
IFV-RSV Panel ResultComparator
PositiveComparator
NegativeTotal
Positive82082
Negative3a333336
Total85333418
Point Estimate95% CI
Positive Percent Agreement96.5%90.1% - 98.8%
Negative Percent Agreement100%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 ResultComparator
PositiveComparator
NegativeTotal
Positive27027
Negative1 a380381
Total28380408
Point Estimate95% CI
Positive Percent Agreement96.4%82.3% - 99.4%
Negative Percent Agreement100%99.0% - 100%
500 µL VTM
IFV-RSV Panel ResultComparator
PositiveComparator
NegativeTotal
Positive28028
Negative1 a389390
Total29389418
Point Estimate95% CI
Positive Percent Agreement96.6%82.8% - 99.4%
Negative Percent Agreement100%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 ResultComparator
PositiveComparator
NegativeTotal
Positive25025
Negative1a382383
Total26382408
Point Estimate95% CI
Positive Percent Agreement96.2%81.1% - 99.3%
Negative Percent Agreement100%99.0% - 100%
500 µL VTM
IFV-RSV Panel ResultComparator
PositiveComparator
NegativeTotal
Positive25025
Negative0393393
Total25393418
Point Estimate95% CI
Positive Percent Agreement100%86.7% - 100%
Negative Percent Agreement100%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 ResultComparator PositiveComparator NegativeTotal
Positive28028
Negative1 a379380
Total29379408
Point Estimate95% CI
Positive Percent Agreement96.6%82.8% - 99.4%
Negative Percent Agreement100%99.0% – 100%
500 µL VTM
IFV-RSV Panel ResultComparator PositiveComparator NegativeTotal
Positive29029
Negative1 a388389
Total30388418
Point Estimate95% CI
Positive Percent Agreement96.7%83.3% - 99.4%
Negative Percent Agreement100%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 ResultComparator PositiveComparator NegativeTotal
Positive1021a103
Negative5b300305
Total107301408
Point Estimate95% CI
Positive Percent Agreement95.3%89.5% - 98.0%
Negative Percent Agreement99.7%98.1% - 100%
500 µL VTM
IFV-RSV Panel ResultComparator PositiveComparator NegativeTotal
Positive1061c107
Negative6d305311
Total112306418
Point Estimate95% CI
Positive Percent Agreement94.6%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 ResultComparator
PositiveComparator
NegativeTotal
Positive691 a70
Negative4b334338
Total73335408
Point Estimate95% CI
Positive Percent Agreement94.5%86.7% – 97.9%
Negative Percent Agreement99.7%98.3% – 100%
500 µL VTM
IFV-RSV Panel ResultComparator
PositiveComparator
NegativeTotal
Positive811c82
Negative7d329336
Total88330418
Point Estimate95% CI
Positive Percent Agreement92.1%84.5% – 96.1%
Negative Percent Agreement99.7%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.