(70 days)
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 tract infection. The following virus types and subtypes are identified using the RV+: Influenza A, Influenza A subtype H1, Influenza A subtype H3, 2009 H1N1, 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.
Negative results for Influenza A, Influenza B, or RSV do not preclude influenza virus or RSV infection and should not be used as the sole basis for diagnosis, treatment, or patient management decisions. Conversely, positive results do not rule-out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease. The use of additional laboratory testing and clinical presentation must be considered in order to obtain the final diagnosis of respiratory viral infection.
Performance characteristics for Influenza A Virus were established when Influenza A/H3, A/H1, and 2009 H1N1 were the predominant Influenza A viruses circulating. These characteristics may vary when other Influenza A viruses are emerging.
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 used specifically for novel virulent influenza viruses and sent to state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
The entire RV+ test is performed on the Verigene® System, which is a bench-top molecular diagnostics workstation that consists of two instruments, the Verigene Processor SP and the Verigene Reader. The Verigene Processor SP performs the assay steps on each sample by using a robotic pipettor to transfer and mix reagents within and between separate testing modules designed for nucleic acid extraction, target amplification, and the Verigene Hybridization Test. The Verigene Hybridization Test module is the same as in the original Verigene System with added modules for nucleic acid extraction and RT-PCR target amplification. Key functions of the Verigene Processor SP include: 1) Reading of the barcode identification label on inserted Test Consumables to maintain positive identification of patient samples throughout processing. 2) Facilitation of nucleic acid extraction, multiplex RT-PCR target amplification, and the Verigene Hybridization Test. 3) Real-time communication of test processing status to the Reader.
The Verigene Reader is the same instrument as in the FDA-cleared RVNATSP. It is a free-standing instrument with a touch screen control panel and a wand-based barcode scanner. It utilizes a graphical user interface to guide the user through the process of ordering tests and reporting results. There are no serviceable parts and no user calibration is required. Interaction with the touch screen is minimized through barcode use. This instrument also serves as the reader of the Test Cartridges using advanced optics. The key functions of the Verigene Reader include: 1) Entry and tracking of specimen identification numbers via manual keyboard input or via barcode-reader wand. 2) Test selection for each specimen. 3) Automated transfer of specimen processing instructions on Test Cartridge-specific basis to linked Processor SP unit(s). A single Reader unit can control up to 32 Processor units. 4) Automated imaging and analysis of Test Cartridges. 5) Results display. 6) Results report generation.
RV+ consumables within each single-use disposable test kit include: (i) Tip Holder Assembly; (ii) Extraction Tray; (iii) Amplification Tray; and (iv) RV+ Test Cartridge. The kit components are inserted into the corresponding module of the Verigene Processor SP prior to each test, and the sample is added to the Extraction Tray. Patient information is entered into the Reader to initiate the test procedure.
- Tip Holder Assembly - The robotic pipettor picks up pipettes from the Tip Holder Assembly. The pipettes are used for mixing and transferring reagents within the test procedure.
- Extraction Tray – Nucleic acids are extracted from the sample by using magnetic bead-based methods within the Extraction Tray. Each Tray contains reagents for a single extraction procedure. A robotic pipette transfers reagents to designated wells within the Extraction Tray to affect the steps of lysis, capture of nucleic acids onto the magnetic beads, washing, and eluting the isolated nucleic acids from the magnetic beads.
- Amplification Tray – The isolated nucleic acids are amplified by using multiplex RT-PCR within the Amplification Tray. Each Tray contains reagents for a single multiplex RT-PCR procedure. A robotic pipette transfers the reagents to a specific well within the Amplification Tray. A set thermal profile is then initiated to perform all of the amplification related steps including UDG-based decontamination, reverse transcription, and multiplex PCR in a single tube. Upon completion, an aliquot of the amplified sample is mixed with hybridization buffer containing the virus specific mediator probes. The sample is then transferred to the Test Cartridge.
- RV+ Test Cartridge for Verigene Hybridization Test – The virus-specific and subtype-specific amplicons are detected and identified within a Test Cartridge by using specific nucleic acid probes in conjunction with gold nanoparticle probe-based detection technology. Each Test Cartridge is a self-contained, laboratory consumable that consists of two parts. The upper housing of each cartridge is called the "reagent pack" and contains reservoirs filled with the detection reagents. When in place with the 'substrate holder', the reagent pack creates an air-tight hybridization chamber surrounding the region of the substrate containing a target-specific capture array. As each step of the test is completed, old reagents are moved out of the hybridization chamber and new reagents are added from the reagent pack via microfluidic channels and pumps. Once the test is complete, the Test Cartridge is removed from the Verigene Processor SP unit and the reagent pack is snapped off and discarded. The remaining slide is now ready for imaging and analysis in the Verigene Reader.
- End-point detection on the Verigene Reader: The test slide is inserted into the Verigene Reader wherein it is illuminated along its side. The gold-silver aggregates at the test sites scatter the light, which is in turn captured by a photosensor. The relative intensity arising from each arrayed test site is tabulated. Net signals, defined as the absolute signal intensities with background signals subtracted, are compared with thresholds determined by negative controls within the slide in order to arrive at a decision regarding the presence or absence of target. These results are linked to the test and patient information entered at the beginning of each test session to provide a comprehensive results file.
Here's an analysis of the acceptance criteria and the study proving the device meets those criteria, based on the provided text:
Acceptance Criteria and Device Performance for Verigene® Respiratory Virus Plus Nucleic Acid Test (RV+)
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria in terms of specific sensitivity and specificity thresholds. Instead, it presents the "Performance Characteristics" from a methods comparison study, and the acceptance is implied by the FDA's clearance of the device (K103209). Therefore, the "acceptance criteria" here are interpreted as the observed performance deemed acceptable for FDA clearance, and the "reported device performance" refers to the results from the clinical methods comparison study.
| Target Virus/Subtype | Implied Acceptance Criterion (Observed Sensitivity Percentage) | Reported Device Performance (Sensitivity) | Implied Acceptance Criterion (Observed Specificity Percentage) | Reported Device Performance (Specificity) |
|---|---|---|---|---|
| Influenza A (Overall) | 98.7% (96.8%-99.5% CI) | 98.7% | 93.2% (91.1%-94.8% CI) | 93.2% |
| Influenza A Subtype H3 | 100% (96.6%-100% CI) | 100% | 100% (99.6%-100% CI) | 100% |
| Influenza A Subtype H1 | 100% (91.0%-100% CI) | 100% | 99.9% (99.4%-100% CI) | 99.9% |
| Influenza A Subtype 2009 H1N1 | 99.5% (97.3%-99.9% CI) | 99.5% | 100% (99.5%-100% CI) | 100% |
| Influenza B | 100% (91.8%-100% CI) | 100% | 99.7% (99.1%-99.9% CI) | 99.7% |
| RSV (Overall) | 97.2% (92.1%-99.0% CI) | 97.2% | 99.5% (98.7%-99.8% CI) | 99.5% |
| RSV Subtype A | 100% (93.7%-100% CI) | 100% | 100% (99.6%-100% CI) | 100% |
| RSV Subtype B | 100% (93.2%-100% CI) | 100% | 99.9% (99.6%-100% CI) | 99.9% |
Reproducibility/Precision Study:
The document also presents reproducibility data, interpreted as another form of acceptance criteria for device performance stability.
- Total Agreement for all panel members across all 3 sites: 97.2% - 100% (95% CI range from 90.3% - 99.7% to 95.0% - 100.0%).
- "No Call" rate: 1.6% (14/864)
- "Pre-analytical error" failure rate: 0.2% (2/864)
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: 1022 prospectively-collected specimens were used for the methods comparison study.
- Data Provenance:
- Country of Origin: Not explicitly stated, but the study was conducted at "three collection hospital sites" and shipped to "Nanosphere" (located in Northbrook, IL, USA) for processing and then to "testing sites." Given the FDA submission from a US-based company, it is highly probable the data is from the USA.
- Retrospective or Prospective: The samples were collected prospectively during the 2008-2009 and 2009-2010 respiratory seasons. Residual specimens were then de-identified, frozen, and shipped to Nanosphere, then shipped to testing sites.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- Number of Experts: Not explicitly stated as "experts." The ground truth was established using a combination of methods:
- Culture-based methods confirmed with an FDA-cleared Direct Fluorescent Antibody (DFA) test for Influenza A, Influenza B, and RSV.
- Bidirectional sequencing for Influenza A subtyping (H3, H1, 2009 H1N1) and RSV subtyping (RSV A, RSV B).
- For discordant results between RV+ and culture/DFA, bidirectional sequencing and/or NAAT (Nucleic Acid Amplification Test) was used for resolution.
- Qualifications of Experts: Not specified. The reference methods mentioned are laboratory-based standard tests, implying qualified laboratory personnel perform these tests, but no specific "expert" role or qualifications (e.g., years of experience) are detailed.
4. Adjudication Method for the Test Set
The adjudication method for the test set involved a multi-step process for resolving discrepancies:
- Initial comparison of RV+ results against culture-based methods confirmed with FDA-cleared DFA.
- For Influenza A subtyping and RSV subtyping, bidirectional sequencing was used as the primary comparative method.
- For discordant results between RV+ and culture/DFA, further clarification was sought using bi-directional sequencing and/or NAAT.
- Specific notes for individual discrepancies (e.g., footnote comments below the tables) illustrate this process, where sequencing or repeat testing with NAAT/culture informed the final ground truth. This resembles a tie-breaker adjudication approach for discordant results.
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 mentioned. This study focuses on the standalone performance of the RV+ device against established laboratory methods, not on comparing human reader performance with and without AI assistance. The device itself is a molecular diagnostic test, not an AI-powered image analysis tool for human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
- Yes, a standalone performance study was conducted. The methods comparison study evaluated the RV+ system (which includes sample preparation, target amplification, and a Verigene Hybridization Test with automated imaging and analysis, generating results automatically) as a direct comparison against standard laboratory ground truth methods. The Verigene System is described as a "bench-top molecular diagnostics workstation" that automates various steps and provides "results display" and "results report generation." This indicates a standalone performance evaluation of the device as a diagnostic tool without continuous human-in-the-loop adjustments to the test outcome.
7. The Type of Ground Truth Used
The ground truth used was a composite gold standard primarily consisting of:
- Culture-based methods confirmed with an FDA-cleared DFA test: For general detection of Influenza A, Influenza B, and RSV.
- Bidirectional sequencing: For subtyping of Influenza A (H3, H1, 2009 H1N1) and RSV (RSV A, RSV B), and for resolution of discordant results.
- NAAT (Nucleic Acid Amplification Test): Used for further clarification in cases of culture/DFA discordance.
This approach uses a combination of established laboratory diagnostic techniques.
8. The Sample Size for the Training Set
The document does not report a separate training set or its sample size for the Verigene® Respiratory Virus Plus Nucleic Acid Test (RV+). The provided information focuses on the validation studies (analytical and methods comparison) for the final trained/developed device. Molecular diagnostic tests like this one are typically developed through iterative optimization and then validated, rather than having a distinct "training set" in the machine learning sense for the final product evaluation.
9. How the Ground Truth for the Training Set Was Established
Since a distinct "training set" is not reported in the context of device development as per the provided text, the method for establishing its ground truth is also not applicable or reported. The focus is on the performance evaluation of the already developed device using the methods comparison and reproducibility studies.
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Image /page/0/Picture/1 description: The image contains the word "Nanosphere" in a bold, sans-serif font. To the left of the word is a circular logo that is partially filled with diagonal lines. The logo is black and white, and the text is black.
JAN 1 0 2011
510(k) Summary
This 510(k) Summary is being submitted in accordance with the requirements of SMDA 1900 and CFR 807.92.
"
| 510(k)numbers: | K103209: Verigene® Respiratory Virus Plus Nucleic Acid Test on the Verigene® System (RV+) |
|---|---|
| Summarypreparationdate: | December 28, 2010 |
| Submittedby: | Nanosphere, Inc.4088 Commercial AvenueNorthbrook, IL 60062Phone: 847-400-9000 Fax: 847-400-9199 |
| Contact: | Gregory W. Shipp, M.D.Chief Medical OfficerVP, Medical and Regulatory Affairs |
| Proprietarynames: | For instrument:Verigene® SystemFor the assay:Verigene® Respiratory Virus Plus Nucleic Acid Test on the Verigene® System (RV+) |
| Commonnames: | For the instrument:Bench-top molecular diagnostics workstationFor the assay:Respiratory viral panel multiplex nucleic acid assayRespiratory panel assay with sub-typing:- Flu A (H3, H1, 2009H1N1)- Flu B- RSV (RSV A, RSV B) |
| Regulatoryinformation: | Regulation section:866.3980 Respiratory viral panel multiplex nucleic acid assayClass IIPanel:Microbiology (83)Product Code:OCC (Respiratory viral panel multiplex nucleic acid assay) |
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| Comparisonof RVNATSPand RV+: | The instrumentation used with the RVNATSP (K092566) and the RV+ is identical. The Verigene® Systemutilized for both assays allows sample preparation, target amplification, and hybridization test and analysisusing a single system. The RVNATSP and the RV+ reagents and substrate have been modified to allowsubtyping of Influenza A (H3, H1, 2009H1N1) and RSV (RSV A, RSV B). The safety and effectiveness of theVerigene® Respiratory Virus Plus Nucleic Acid Test on the Verigene System (RV+) are demonstrated with theanalytical and methods comparison studies described below. | |
|---|---|---|
| The RV+ is designed to identify virus-specific nucleic acids for Influenza A virus, Influenza A virus subtype H1,Influenza A virus subtype H3, Influenza A virus subtype 2009 H1N1, Influenza B virus, and respiratory syncytialvirus (RSV A. RSV B). The RVNATSP involves: | ||
| 1) Sample Preparation - magnetic bead-based viral RNA extraction from nasopharyngeal swab specimensobtained from symptomatic patients; | ||
| 2) Target Amplification - multiplex RT-PCR-based amplification of the eluted viral RNA targets to generatevirus-specific amplicons; | ||
| 3) Verigene Hybridization Test and Analysis - detection and identification of virus-specific amplicons by usinggold nanoparticle probe-based technology. | ||
| The entire RV+ test is performed on the Verigene® System, which is a bench-top molecular diagnosticsworkstation that consists of two instruments, the Verigene Processor SP and the Verigene Reader. TheVerigene Processor SP performs the assay steps on each sample by using a robotic pipettor to transfer andmix reagents within and between separate testing modules designed for nucleic acid extraction, targetamplification, and the Verigene Hybridization Test. The Verigene Hybridization Test module is the same as inthe original Verigene System with added modules for nucleic acid extraction and RT-PCR target amplification.Key functions of the Verigene Processor SP include: | ||
| 1) Reading of the barcode identification label on inserted Test Consumables to maintain positive identificationof patient samples throughout processing. | ||
| 2) Facilitation of nucleic acid extraction, multiplex RT-PCR target amplification, and the VerigeneHybridization Test. | ||
| Devicedescription: | 3) Real-time communication of test processing status to the Reader. | |
| The Verigene Reader is the same instrument as in the FDA-cleared RVNATSP. It is a free-standing instrumentwith a touch screen control panel and a wand-based barcode scanner. It utilizes a graphical user interface toguide the user through the process of ordering tests and reporting results. There are no serviceable parts andno user calibration is required. Interaction with the touch screen is minimized through barcode use. Thisinstrument also serves as the reader of the Test Cartridges using advanced optics. The key functions of theVerigene Reader include: | ||
| 1) Entry and tracking of specimen identification numbers via manual keyboard input or via barcode-readerwand. | ||
| 2) Test selection for each specimen. | ||
| 3) Automated transfer of specimen processing instructions on Test Cartridge-specific basis to linkedProcessor SP unit(s). A single Reader unit can control up to 32 Processor units. | ||
| 4) Automated imaging and analysis of Test Cartridges. | ||
| 5) Results display. | ||
| 6) Results report generation. | ||
| RV+ consumables within each single-use disposable test kit include: (i) Tip Holder Assembly; (ii) ExtractionTray; (iii) Amplification Tray; and (iv) RV+ Test Cartridge. The kit components are inserted into thecorresponding module of the Verigene Processor SP prior to each test, and the sample is added to theExtraction Tray. Patient information is entered into the Reader to initiate the test procedure. | ||
| 1) Tip Holder Assembly - The robotic pipettor picks up pipettes from the Tip Holder Assembly. The pipettesare used for mixing and transferring reagents within the test procedure. | ||
| Intendeduse: | 2) Extraction Tray – Nucleic acids are extracted from the sample by using magnetic bead-based methodswithin the Extraction Tray. Each Tray contains reagents for a single extraction procedure. A robotic pipettetransfers reagents to designated wells within the Extraction Tray to affect the steps of lysis, capture ofnucleic acids onto the magnetic beads, washing, and eluting the isolated nucleic acids from the magneticbeads. | |
| 3) | Amplification Tray – The isolated nucleic acids are amplified by using multiplex RT-PCR within theAmplification Tray. Each Tray contains reagents for a single multiplex RT-PCR procedure. A roboticpipette transfers the reagents to a specific well within the Amplification Tray. A set thermal profile is theninitiated to perform all of the amplification related steps including UDG-based decontamination, reversetranscription, and multiplex PCR in a single tube. Upon completion, an aliquot of the amplified sample ismixed with hybridization buffer containing the virus specific mediator probes. The sample is thentransferred to the Test Cartridge. | |
| 4) | RV+ Test Cartridge for Verigene Hybridization Test – The virus-specific and subtype-specific amplicons aredetected and identified within a Test Cartridge by using specific nucleic acid probes in conjunction with goldnanoparticle probe-based detection technology. Each Test Cartridge is a self-contained, laboratoryconsumable that consists of two parts. The upper housing of each cartridge is called the "reagent pack"and contains reservoirs filled with the detection reagents. When in place with the 'substrate holder', thereagent pack creates an air-tight hybridization chamber surrounding the region of the substrate containinga target-specific capture array. As each step of the test is completed, old reagents are moved out of thehybridization chamber and new reagents are added from the reagent pack via microfluidic channels andpumps. Once the test is complete, the Test Cartridge is removed from the Verigene Processor SP unit andthe reagent pack is snapped off and discarded. The remaining slide is now ready for imaging and analysisin the Verigene Reader. | |
| 5) | End-point detection on the Verigene Reader: The test slide is inserted into the Verigene Reader wherein itis illuminated along its side. The gold-silver aggregates at the test sites scatter the light, which is in turncaptured by a photosensor. The relative intensity arising from each arrayed test site is tabulated. Netsignals, defined as the absolute signal intensities with background signals subtracted, are compared withthresholds determined by negative controls within the slide in order to arrive at a decision regarding thepresence or absence of target. These results are linked to the test and patient information entered at thebeginning of each test session to provide a comprehensive results file. | |
| The Verigene® Respiratory Virus Plus Nucleic Acid Test on the Verigene® System (RV+) is a qualitative nucleic acidmultiplex 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 tract infection. The following virus types andsubtypes are identified using the RV+: Influenza A, Influenza A subtype H1, Influenza A subtype H3, 2009 H1N1, InfluenzaB, 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 infectionaids in the diagnosis of respiratory viral infection, if used in conjunction with other clinical and laboratory findings. | ||
| Negative results for Influenza A, Influenza B, or RSV do not preclude influenza virus or RSV infection and should not beused as the sole basis for diagnosis, treatment, or patient management decisions. Conversely, positive results do not rule-out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease. Theuse of additional laboratory testing and clinical presentation must be considered in order to obtain the final diagnosis ofrespiratory viral infection. | ||
| Performance characteristics for Influenza A Virus were established when Influenza A/H3, A/H1, and 2009 H1N1 were thepredominant Influenza A viruses circulating. These characteristics may vary when other Influenza A viruses are emerging. | ||
| If infection with a novel Influenza A virus is suspected based on current clinical and epidemiological screening criteriarecommended by public health authorities, specimens should be collected with appropriate infection control precautionsused specifically for novel virulent influenza viruses and sent to state or local health department for testing. Viral cultureshould not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens. |
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Comparison between the Cleared and the New Systems
| Feature | Verigene RV+ | Verigene RVNAT SP | Prodesse ProFAST+ | Specimen | Nasopharyngeal swabs in sample matrix | Nasopharyngeal swabs in sample matrix | Nasopharyngeal swabs in sample matrix |
|---|---|---|---|---|---|---|---|
| Subject Device | Predicate 1 | Predicate 2 | Nucleic Acid Isolation | Automated internal extraction of nucleic acids performed on the Processor SP using silica coated magnetic beads and chaotropic salts. | Automated internal extraction of nucleic acids performed on the Processor SP using silica coated magnetic beads and chaotropic salts. | External isolation of nucleic acids on the Roche MagNA Pure LC System and bioMerieux NucliSENS easyMAG. | |
| 510(k) # | K103209 | K092566 | K101855 | Quality control | Internal procedural quality controls: IC1 – inhibition control; IC2 – process control; internal positive and negative controls; external positive controls | Internal procedural quality controls: PC1 (IC1) – inhibition control; PC2 (IC2) – process control; internal positive and negative controls; external positive controls | Influenza positive RNA transcript control and an internal RNA control provided |
| Regulation | 866.3980 | 866.3980 | 866.3332 | Amplification method | Internal multiplexed RT-PCR performed within the Amplification Module on the Processor SP | Internal multiplexed RT-PCR performed within the Amplification Module on the Processor SP | Real Time RT-PCR detection |
| Product Codes | OCC | OCC; NSU | OQW | M-MLV Reverse Transcriptase | M-MLV Reverse Transcriptase | M-MLV Reverse Transcriptase | |
| Device Class | Class II | Class II | Class II | Pipetting | Pipetting module to automate fluid transfer steps | Pipetting module to automate fluid transfer steps | Mostly manual |
| Intended Use | The Verigene® Respiratory VirusPlus Nucleic Acid Test (RV+) onthe Verigene® System is aqualitative nucleic acid multiplextest intended to simultaneouslydetect and identify multiplerespiratory virus nucleic acids innasopharyngeal (NP) swabspecimens from individuals withsigns and symptoms ofrespiratory tract infection. Thefollowing virus types andsubtypes are identified using theRV+: Influenza A, Influenza Asubtype H1, influenza A subtypeH3, 2009 H1N1, Influenza B,Respiratory Syncytial Virus (RSV)subtype A, and RSV subtype B.The test is not intended to detectInfluenza C virus. Detecting andidentifying specific viral nucleicacids from individuals exhibitingsigns and symptoms ofrespiratory infection aids in thediagnosis of respiratory viralinfection, if used in conjunctionwith other clinical and laboratoryfindings. | The Verigene® RespiratoryVirus Nucleic Acid Test(RVNATSP) is a qualitativemultiplex in vitro diagnostic testfor the detection andidentification of Influenza AVirus, Influenza B Virus, andRespiratory Syncytial Virus(RSV) nucleic acids purifiedfrom nasopharyngeal swabspecimens obtained frompatients symptomatic for viralupper respiratory infection. | The Prodesse ProFAST+ Assay is amultiplex Real Time RT-PCR in vitrodiagnostic test for the qualitative detectionand discrimination of seasonal InfluenzaA/H1, seasonal Influenza A/H3 andInfluenza A/2009 H1N1 Influenza viralnucleic acids isolated and purified fromnasopharyngeal (NP) swab specimensfrom human patients with signs andsymptoms of respiratory infection inconjunction with clinical andepidemiological risk factors. | Detection Method | Verigene Test (hybridization) is performed in the hybridization module housed in the Processor SP of the Verigene® System by using single-use Test Cartridges | Verigene Test (hybridization) is performed in the hybridization module housed in the Processor SP of the Verigene® System by using single-use Test Cartridges | In the Cepheid Smartcycler II instrument, the amount of fluorescence at a given cycle is dependent on the amount of amplification products present at the time |
| Targets | Influenza AInfluenza A/H1Influenza A/H3Influenza A/2009 H1N1Influenza BRSV ARSV B | Influenza AInfluenza BRSV | Influenza A/H1Influenza A/H3Influenza A/2009 H1N1 | Decision algorithm | Target-specific signal intensities are compared to a signal threshold and ratioed against positive and negative controls for a decision. | Target-specific signal intensities are compared to a signal threshold and ratioed against positive and negative controls for a decision. | Fluorescent intensity is monitored during each PCR cycle by the real-time instrument. A specific number of cycles are defined as a threshold for presence or absence of a target. |
| Results | Positive or negative qualitative results | Positive or negative qualitative results | Positive or negative qualitative results | ||||
| Reader | Provides the user interface, controls the Processor SP, performs image analysis, and provides results. | Provides the user interface, controls the Processor SP, performs image analysis, and provides results. | Not applicable | ||||
| Software | A custom embedded software application running under the Micro-C/OS real-time operating system. Additional software programming to control the Extraction and Amplification Modules | A custom embedded software application running under the Micro-C/OS real-time operating system. Additional software programming to control the Extraction and Amplification Modules | Not applicable |
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Performance Characteristics of the RV+ Test
Analytical and methods comparison studies to establish the performance of the test on the Verigene System were performed.
-
A. Analytical Studies for the RV+ Test Overview
In order to establish analytical performance characteristics of the RV+, various analytical studies were conducted by following recommendations delineated in FDA Guidance Documents. The studies included Analytical Sensitivity Determination, Analytical Reactivity Studies, Analytical Specificity Studies, Interference Studies, Competitive Inhibition Studies, Carry-Over/Cross-Contamination Studies, Fresh-vs-Frozen Comparison Studies, and Assay Design and Cut-Off Determination. The results from these studies supported a claim of safety and effectiveness and support the proposed labeling of the RV+. -
B. Methods Comparison Studies for the RV+ Test
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A Methods Comparison study was conducted at three sites. The study was conducted under IRB supervision.
The Verigene System, including the Verigene Processor SP, the Verigene Reader, the Verigene Respiratory Virus Plus Nucleic Acid Test Cartridges (RV+), Amplification Trays and Extraction Trays used in the methods comparison studies were identical to the devices intended for market with respect to their functional features and reagent composition.
Clinical samples for methods comparison study were collected prospectively at three collection hospital sites during the 2008-2009 and 2009-2010 respiratory seasons. Each site saved prospectively-collected residual specimens that were then de-identified on-site, frozen at -70°C, and shipped on dry ice to Nanosphere. Nanosphere stored the specimens at -70°C, labeled the specimens with a random number generated unique identifier while removing the collection site identifier, and shipped the specimens to the testing sites overnight on dry ice. The sites stored the specimens at -70°C before and after testing.
One thousand and twenty-two (1022) prospectively-collected specimens were tested at the three external study sites. All tests were performed by laboratory personnel using the RV+ on the Verigene System. The Influenza A, Influenza B and RSV results in the methods comparison study were compared to results obtained for the samples using culture-based methods confirmed with a FDA-cleared DFA test. Influenza A subtyping and RSV subtyping results were compared to results obtained for the specimens utilizing bidirectional sequencing. Discordant results were resolved utilizing bi-directional sequencing and/or the NAAT. Seven (7) samples that were deemed discrepant for the RV+ test compared to culture/DFA were tested on the NAAT for further clarification of results.
The age distribution of the 1022 samples tested during the methods comparison study is presented below.
| Age Categorization (yrs) | Number of Subjects | Proportion (%) |
|---|---|---|
| 0-2 | 269 | 26.3% |
| 3-5 | 118 | 11.5% |
| 6-11 | 147 | 14.4% |
| 12-18 | 124 | 12.1% |
| 19-64 | 297 | 29.1% |
| ≥ 65 | 67 | 6.6% |
| All Ages | 1022 | 100% |
Age Distribution in the RV+ Methods Comparison Study
During the methods comparison study, across all three sites, there were a total of 25 processing errors (2.4%=25/1022) ("pre-analysis error" [pre-ae] results). There were 34 initial "no call" results (3.3%=34/1022). Both the "no call" and "pre-ae" specimens were repeated and only 2 resulted in a final "no call" result (0.2%=2/1022).
Combined results for the method comparison study across the three sites are presented below. They reflect the results after all "no call" results were repeated per the proposed package insert quidance. Results from the RV+ were initially compared to results from culture-based - DFA methods and the NAAT test. Bi-directional sequencing was used to subtype Influenza A, differentiate RSV A and RSV B, and for discordant testing. The tables show results for Influenza B, and RSV both compared to culture-based methods and the NAAT and after resolution using sequencing. RSV A and RSV B results are shown after resolution by sequencing.
Percent positive and negative agreement for each table are provided as well as the lower and upper twosided 95% confidence limits that were calculated using the exact binomial method.
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Influenza A and subtyping results for all three sites combined:
| INFA | Culture/DFA | ||||
|---|---|---|---|---|---|
| Positive | Negative | Total | Total | ||
| Positive | 311a, c | 48b | 359 | Sensitivity = 98.7% (96.8%-99.5%) 95% CI | |
| RV+ | Negative | 4d, e, f | 659 | 663 | Specificity = 93.2% (91.1%-94.8%) 95% CI |
| Total | 315 | 707 | 1022g |
Influenza A Results: RV+ vs. Culture/DFA
8 1 specimen was positive for Influenza A by both culture and RV+. No sub-typing was observed on the RV+ result. Also, the speciment failed subtype sequencing for H1, H3 and 2009 H1N1. 84 specimens were Influenza A positive by RV+. No sub-typing was observed on the RV+, All 4 specimens were culture negative and failed sequencing. §1 specimen was Influenza A/H1 by RV+ and positive for Influenza A by culture. Sequencing resulted in a positive result for Influenza A/2009H1N1. 9 1 specimen was negative by RV+ for Flu B. Initial culture/DFA of the specimen was Flu A positive. By sequencing, the specimen was positive for Flu A. By NAAT and upon repeat culture/DFA, the specimen was positive for Flu B and negative for Flu A and RSV. 8 1 specimen was negative for Flu A and positive for RSV B by RV+. By initial culture/DFA, the specimen was Flu A positive. By sequencing the specimen was positive for RSV B and negative for Flu A. By NAAT and upon repeat culture/DFA the specimen was positive for RSV and negative for Flu A and Flu B. 2 specimens were negative by RV+ but Flu A positive by culture. By sequencing both specimens were negative for Flu A. Both specimens were negative for Flu A (and negative for Flu B and RSV B) by NAAT. 85 specimens failed sequencing or were not subtyped by the RV+ assay and are not included in the Sublyping Tables.
Influenza A Subtype H3 Results: RV+ vs. Culture/DFA/Sequencing
| INFA/H3 | Culture/DFA/Sequencing | ||||
|---|---|---|---|---|---|
| Positive | Negative | Total | Total | ||
| RV+ | Positive | 108 | 0 | 108 | Sensitivity = 100% (96.6%-100%) 95% CI |
| Negative | 0 | 909 | 909 | Specificity = 100% (99.6%-100%) 95% CI | |
| Total | 108 | 909 | 1017 |
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| INFA/H1 | Culture/DFA/Sequencing | ||||
|---|---|---|---|---|---|
| Positive | Negative | Total | Total | ||
| Positive | 39 | 1c | 40 | Sensitivity = 100% (91.0%-100%) 95% CI | |
| RV+ | Negative | 0 | 977 | 977 | Specificity = 99.9% (99.4%-100%) 95% CI |
| Total | 39 | 978 | 1017 |
Influenza A Subtype H1 Results: RV+ vs. Culture/DFA/Sequencing
Influenza A Subtype 2009 H1N1 Results: RV+ vs. Culture/DFA/Sequencing
| INFA/2009 H1N1 | Culture/DFA/Sequencing | ||||
|---|---|---|---|---|---|
| Positive | Negative | Total | Total | ||
| Positive | 206 | 0 | 206 | Sensitivity = 99.5% (97.3%-99.9%) 95% CI | |
| RV+ | Negative | 1c | 810 | 811 | Specificity = 100% (99.5%-100%) 95% CI |
| Total | 207 | 810 | 1017 |
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Influenza B results for all three sites combined:
| INFB | Culture/DFA | |||
|---|---|---|---|---|
| Positive | Negative | Total | Total | |
| Positive | 43 | 3 a, b | 46 | Sensitivity = 100% (91.8%-100%) 95% CI |
| RV+Negative | 0 | 976 | 976 | Specificity = 99.7% (99.1%-99.9%) 95% CI |
| Total | 43 | 979 | 1022 |
Influenza B Results: RV+ vs. Culture/DFA
ª 1 specimen was positive for Influenza B by RV+ and negative for Influenza B by culture/DFA. This specimen was tested by NAAT assay and found to be positive for Influenza B. Specimen was positive for Influenza B by sequencing and upon repeat culture/DFA. °2 specimens were positive for Influenza B by RV+ and negative for Influenza B by culture. Both specimens were positive for Influenza B by sequencing.
Influenza RSV and subtyping results for all three sites combined:
| RSV | Culture/DFA | ||||
|---|---|---|---|---|---|
| Positive | Negative | Total | Total | ||
| RV+ | Positive | 104 | 5 a, d | 109 | Sensitivity = 97.2% (92.1%-99.0%) 95% CI |
| Negative | 3 b, c | 910 | 913 | Specificity = 99.5% (98.7%-99.8%) 95% CI | |
| Total | 107 | 915 | 1022e |
RSV Results: RV+ vs. Culture/DFA
² 1 specimen was positive for RSV B by RV+ and by sequency br RSV by culture/DFA. Specimen
was positive for RSV by NAAT and upon repeat culture/DFA. ° 1 specimen were nega positive for RSV by culture. The specimens were negative for RSV by NAAT assay and failed sequencing. 84 specimens were positive for RSV B by RV+ but negative by culture . 1 was positive for RSV A and 3 were
positive for RSV B by RV+ and by sequencing. 3 specimens failed subt Subtyping Tables.
RSV Subtype A Results: RV+ vs. Culture/DFA/Sequencing
| RSV A | Culture/DFA/Sequencing | ||||
|---|---|---|---|---|---|
| Positive | Negative | Total | Total | ||
| RV+ | Positive | 57f | 0 | 57 | Sensitivity = 100% (93.7%-100%) 95% CI |
| Negative | 0 | 962 | 962 | Specificity = 100% (99.6%-100%) 95% CI | |
| Total | 57 | 962 | 1019 |
1 specimen was positive for both RSV A and RSV B (dual infection) by RV+ and was culture positive for RSV. By sequencing specimen was positive for both RSV A and RSV B.
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| RSV B | Culture/DFA/Sequencing | ||||
|---|---|---|---|---|---|
| Positive | Negative | Total | Total | ||
| RV+ | Positive | 53 f | 0 | 53 | Sensitivity = 100% (93.2%-100%) 95% CI |
| Negative | 0 | 966 | 966 | Specificity = 99.9% (99.6%-100%) 95% CI | |
| Total | 53 | 966 | 1019 |
RSV Subtype B Results: RV+ vs. Culture/DFA/Sequencing
1 specimen was positive for both RSV A and RSV B (dual infection) by RV+ and was culture positive for RSV. By sequencing specimen was positive for both RSV A and RSV B.
C. Reproducibility/Precision Studies for the RV+ Test
The Reproducibility/Precision study was conducted at three sites (two external and one internal) to investigate the inter-laboratory reproducibility of the RV+. The reproducibility panels (see Table below) were developed by using 6 unique virus strains that together represented all of the RV+. The 6 virus strains were combinations such that each virus strain was represented at 3 levels: HN- High Negative, LP - Low Positive, and MP - Moderate Positive. For two of the unique samples, virus strains were combined as in the case of INFA/H3 and RSVA and Influenza B and RSV B. For the Reproducibility/Precision study, the Test Panel comprised the 12 unique samples in duplicate for a total of 24 samples. The Test Panel samples were then divided equally into Panel A (12 samples) and Panel B (12 samples).
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| Viral Panel | Virus Strain | Level | Samples |
|---|---|---|---|
| A | INFB + RSVB | High Negative | 1 |
| 2 | |||
| Low Positive | 3 | ||
| 4 | |||
| Moderate Positive | 5 | ||
| 6 | |||
| INFA/2009H1N1-MT | High Negative | 7 | |
| 8 | |||
| Low Positive | 9 | ||
| B | 10 | ||
| Moderate Positive | 11 | ||
| 12 | |||
| INFA/H1-MT | High Negative | 1 | |
| 2 | |||
| Low Positive | 3 | ||
| 4 | |||
| Moderate Positive | 5 | ||
| 6 | |||
| INFA/H3 + RSVA | High Negative | 7 | |
| 8 | |||
| Low Positive | 9 | ||
| 10 | |||
| Moderate Positive | 11 | ||
| 12 |
At the two external study sites, Test Panel A and Test Panel B were tested on separate days. Testing each day involved 2 operators testing the same Test Panel in two replicate runs. Both Test Panels A and B were tested for a total testing period of six non-consecutive days.
The internal site ran a 12-day precision study and utilized the same four unique samples at the three levels. The complete Test Panel (Test Panel A and B) was tested separately by two operators each day. The precision study was run for a total testing period of 12 non-consecutive days. The cumulative results from the Reproducibility/Precision Studies are summarized. Data is presented for each individual site and then combined to provide collective results. The Table contains the agreement between the expected results and the obtained results for each virus strain in the Test Panel. These are grouped further based on their concentration levels (MP, LP, and HN). NOTE: Though some samples in the Test Panels contained combinations of viruses, results are stratified by individual virus strains.
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| Site | Site 1 | Site 2 | Site 3 | All 3 Sites | |||
|---|---|---|---|---|---|---|---|
| Specific PanelMember | Level | Agreement | Agreement | Agreement | TotalAgreement | %Agreement | 95% CI |
| INFA/H1-MT | MP | 12/12 | 12/12 | 46/481,2 | 70/72 | 97.2% | 90.4% - 99.2% |
| INFA/H1-MT | LP | 12/12 | 12/12 | 48/48 | 72/72 | 100% | 94.9% - 100% |
| INFA/H1-MT | HN | 11/123 | 12/12 | 48/48 | 71/72 | 98.6% | 92.5% - 99.8% |
| INFA/H3 | MP | 12/12 | 12/12 | 48/48 | 72/72 | 100% | 94.9% - 100% |
| INFA/H3 | LP | 12/12 | 12/12 | 47/484 | 71/72 | 98.6% | 92.5% - 99.8% |
| INFA/H3 | HN | 12/12 | 12/12 | 48/48 | 72/72 | 100% | 94.9% - 100% |
| INFA/2009H1N1-MT | MP | 12/12 | 12/12 | 48/48 | 72/72 | 100% | 94.9% - 100% |
| INFA/2009H1N1-MT | LP | 12/12 | 12/12 | 48/48 | 72/72 | 100% | 94.9% - 100% |
| INFA/2009H1N1-MT | HN | 12/12 | 12/12 | 47/485 | 71/72 | 98.6% | 92.5% - 99.8% |
| INFB | MP | 12/12 | 12/12 | 48/48 | 72/72 | 100% | 94.9% - 100% |
| INFB | LP | 12/12 | 12/12 | 48/48 | 72/72 | 100% | 94.9% - 100% |
| INFB | HN | 12/12 | 11/12a | 48/48 | 71/72 | 98.6% | 92.5% - 99.8% |
| RSVA | MP | 12/12 | 12/12 | 48/48 | 72/72 | 100% | 94.9% - 100% |
| RSVA | LP | 12/12 | 12/12 | 46/48b,4 | 70/72 | 97.2% | 90.4% - 99.2% |
| RSVA | HN | 12/12 | 12/12 | 48/48 | 72/72 | 100% | 94.9% - 100% |
| RSVB | MP | 12/12 | 12/12 | 48/48 | 72/72 | 100% | 94.9% - 100% |
| RSVB | LP | 11/12c | 12/12 | 47/48d | 70/72 | 97.2% | 90.4% - 99.4% |
| RSVB | HN | 11/12e | 12/12 | 48/48 | 71/72 | 98.60% | 92.5% - 99.8% |
Reproducibility Study Results - Agreement to Specific Panel Member
Expected Calls: *One (1) INFR + RSVB HN detected Influenza B. "One (1) INFAH3 + RSVA LP Sander Influenza A and H3 but did not detect RSV A. ^One (1) INFB + RSVB LP sample detect Influenza B but did not detect RSVB LP sample detected Influenza B but did not detect RSV B. °One INFB + RSVB HN sample detected RSV B but did not defect Influenza B. Additional Positive Calls: One (1) INFA/H1-MT MP sample detected both Influenza A and H1 as expected H3 which was unexpected. 30ne (1) INFA/H1-MT MP sample detected both Influenza A and H1 as expected, but also delected H3, Flu B and RSV A which was unexpected. 30ne (1) INFA/H1-MT HN sample detected Influenza A, but did not detect H1 which was expected as this is a high negative sample. However, RSV A was also detected which was unexpected. *One INFA/H3 + RSVA LP sample detected both Influerza A, H3 and RSV A as expected for a low positive sample, but also detected 2009H1N1 which was not expected. Cone NFA/2009H1N1-MT HN sample did not detect Influenza A and 2009H1N1 which was expected as this is a high negalive sample. Showever, Influenza B and RSV B were also detected which was not expected. NOTE: All the samples with additional positive calls gave the expected results for the intended virus; there were no mis-calls. The source of the additional positives is likely cross-contamination artifacts during the Test Panel preparation.
{12}------------------------------------------------
There were 14 "No Calls" and 2 "pre-analytical errors" in the study. These 16 samples were repeat tested successfully. In this study the "No Call" rate was 1.6% (14/864) and the "pre-analysis error" failure rate was 0.2% (2/864). Out of the 864 samples tested, the percent agreement for all panel members for the combined sites ranged from 97.2%-100% (95% Cl range from 90.3% - 99.7% to 95.0% - 100.0%, respectively).
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/13/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized depiction of an eagle or bird in flight, positioned to the right of a circular inscription. The inscription reads "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in capital letters, arranged around the circumference of the circle.
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993
NANOSPHERE, INC. c/o Gregory W. Shipp, M.D. Chief Medical Officer VP, Medical and Regulatory Affairs 4088 Commercial Avenue Northbrook, ILLINOIS 60062
JAN 1 0 201
Re: K103209
Trade/Device Name: Verigene Respiratory Virus Plus Nucleic Acid Test (RV+) Regulation Number: 21 CFR§ 866.3980 Regulation Name: Respiratory viral panel multiplex nucleic acid assay Regulatory Class: Class II Product Code: OCC; NSU Dated: December 23, 2010 Received: December 27, 2010
Dear Dr. Shipp:
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.
If your device is classified (see above) into class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of
{14}------------------------------------------------
Page 2 - Gregory W. Shipp
medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours.
Saly attaynes
Sally A. Hojvat, M.Sc., Ph. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
{15}------------------------------------------------
Indications for Use
JAN 1 0 2011
510(k) Number (if known):
Device Name: Verigene® Respiratory Virus Plus Nucleic Acid Test (RV+)
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 tract infection. The following virus types and subtypes are identified using the RV+: Influenza A subtype H1, Influenza A subtype H3, 2009 H1N1, Influenza B, Respiratory Syncytial Virus (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.
Negative results for Influenza B, or RSV do not preclude influenza virus or RSV infection and should not be used as the sole basis for diagnosis, treatment decisions. Conversely, positive results do not rule-out bacterial infection with other viruses. The agent detected may not be the definite cause of disease. The use of additional laboratory testing and clinical presentation must be considered in order to obtain the final diagnosis of respiratory viral infection.
Performance characteristics for Influenza A Virus were established when Influenza A/H3, A/H1, and 2009 H1N1 were the predominant Influenza A viruses circulating. These characteristics may vary when other Influenza A viruses are emerging.
If infection with a novel Influenza A virus is suspected based on current clinical and epidemiological screening citieria recommended by public health authorities, specimens should be collected with appropriate infection control precautions used specifically for novel viruses and sent to state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
Prescription Use × (Part 21 CFR 801 Subpart D)
and/or
Over-The-Counter Use (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Uhe Self
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
§ 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.