(50 days)
No
The description focuses on automated laboratory processes, robotic pipetting, and optical detection with signal analysis based on thresholds. There is no mention of AI or ML algorithms being used for analysis or decision-making.
No
The device is an in vitro diagnostic test used for the detection and identification of viral nucleic acids in patient samples. It aids in diagnosis but does not provide therapy or treatment.
Yes
The device is explicitly described as an "in vitro diagnostic test" intended to be an "aid in the differential diagnosis" of specific viral infections.
No
The device description clearly outlines a system that includes physical instruments (Verigene SP Processor and Verigene Reader) and disposable consumables (Tip Holder Assembly, Extraction Tray, Amplification Tray, RV Test Cartridge) which are essential for the test procedure. While software is involved in controlling the instruments and analyzing results, it is not the sole component of the medical device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Explicitly stated in the Intended Use: The very first sentence of the "Intended Use / Indications for Use" section clearly states: "The Verigene® Respiratory Virus Nucleic Acid Test on the Verigene SP System (RVNATsg) is a qualitative multiplex in vitro diagnostic test..."
- Purpose of the test: The test is designed to detect and identify specific viral nucleic acids from patient specimens (nasopharyngeal swabs) to aid in the diagnosis of infections. This is a core function of an in vitro diagnostic device.
- Testing performed outside the body: The test is performed on specimens collected from the patient, but the analysis and detection of the viral nucleic acids occur in a laboratory setting using the Verigene SP System. This is the definition of "in vitro" (meaning "in glass" or "outside the body").
N/A
Intended Use / Indications for Use
The Verigene® Respiratory Virus Nucleic Acid Test on the Verigene SP System (RVNATsg) is a qualitative multiplex in vitro diagnostic test for the detection and identification of Influenza A Virus, Influenza B Virus, and Respiratory Syncytial Virus (RSV) nucleic acids purified from nasopharyngeal swab specimens obtained from patients symptomatic for viral upper respiratory infection. The test is intended to be used on the Verigene® SP System as an aid in the differential diagnosis of Influenza A, Influenza B, and RSV infections. The test is not intended to detect Influenza C virus.
Negative results do not preclude influenza virus or RSV infection and should not be used as the sole basis for treatment or other management decisions. It is recommended that negative test results be confirmed by culture.
Performance characteristics for Influenza A Virus were established when Influenza A/H3 and A/H1 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 department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
Product codes
OCC, NSU
Device Description
The RVNATSP is designed to identify virus-specific nucleic acids for Influenza A virus, Influenza B virus, and respiratory syncytial virus (RSV). The RVNATSP involves:
- Sample Preparation – magnetic bead-based viral RNA extraction from nasopharyngeal swab specimens obtained from symptomatic patients;
- Target Amplification – Multiplex RT-PCR-based amplification of the eluted viral RNA targets to generate virus-specific amplicons;
- Verigene Hybridization Test and Analysis - detection and identification of virus-specific amplicons by using gold nanoparticle probe-based technology.
The entire RVNATSP is performed on the Verigene® SP System, which is a bench-top molecular diagnostics workstation that consists of two instruments, the Verigene SP Processor and the Verigene Reader. The Verigene SP Processor 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 previous Verigene System with added modules for nucleic acid extraction and RT-PCR target amplification. Key functions of the Verigene SP Processor include:
- Reading of the barcode identification label on inserted Test Consumables to maintain positive identification of patient samples throughout processing.
- Facilitation of nucleic acid extraction, multiplex RT-PCR target amplification, and the Verigene Hybridization Test.
- Real-time communication of test processing status to the Reader.
The Verigene Reader is the same instrument as in the FDA-cleared VRNAT. 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:
- Entry and tracking of specimen identification numbers via manual keyboard input or via barcode-reader wand.
- Test selection for each specimen.
- Automated transfer of specimen processing instructions on Test Cartridge-specific basis to linked Processor unit(s). A single Reader unit can control up to 32 Processor units.
- Automated imaging and analysis of Test Cartridges.
- Results display.
- Results report generation.
RVNATSP 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 SP Processor 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 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 SP Processor 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 subfracted, 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.
Mentions image processing
Yes
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Nasopharyngeal swab specimens
Indicated Patient Age Range
Patients symptomatic for viral upper respiratory infection.
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 sample set representing Influenza B, and RSV was prepared by diluting culture positive nasopharyngeal swab samples with negative samples. Dilutions were aimed to yield viral load levels close to the low positive levels for each virus type. A total of 62 unique samples were diluted, aliquoted, and frozen. The sample set was tested at the internal site (Site 1) using the cleared VRNAT, and at all three sites using the RVNATs for a total of 62x4=248 unique tests.
Each sample set yielded a total of 186 decisions from 62 unique samples as each test provides a decision of 'Detected' or 'Not Detected' for each of the 3 viruses, Influenza B, and RSV. Of the 62 samples, 3 samples had dual infections where 2 viruses were present.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
A. Comparison of Analytical Sensitivity
The analytical sensitivity of the RVNAT was compared to the cleared VRNAT (K083088) by determining the Limit of Detection (LOD) of Influenza B, RSV A, and RSV B viruses. Strains with established titers were used for each virus stock was serially diluted into a sample matrix (Universal Transport Media, Copan), and each concentration was tested in quadruplicate using the RVNAT. The LOD was confirmed by performing an additional 20 replicates for each strain in order to demonstrate that the virus was detected ≥95% of the time. The LOD for each virus was identical to the LOD observed with the same strains on the cleared VRNAT (K083088).
B. Carryover and Crossover Contamination Studies
High positive samples of Influenza A, Influenza B, RSV B were alternated with high negative samples for all four viruses. Based on the collective data, there was no evidence of crosscontamination from any of the test steps including sample extraction, multiplex RT-PCR step, and the Verigene Hybridization Test.
C. Precision/Reproducibility Studies Comparison between the RVNATso and the cleared VRNAT (K083088)
The Precision/Reproducibility Studies were performed at each of three sites. At Site 1, the Reproducibility Study was part of a larger precision/Reproducibility Studies for the RVNAT go were conducted exactly as for the previously cleared VRNAT (K083088) to allow equivalency comparisons. As before, eight unique samples were created by diluting known concentrations of viral particles with Viral Transport Medium. Each strain was represented at 3 distinct concentrations: high negative, low positive, and moderate positive.
The Precision Study (Site 1) tested the sample set over 12 non-consecutive days. On each test day, two operators performed the RVNAT in duplicate for each sample sets per day total). In the reproducibility study performed by sites 2 and 3, the sample set was tested in triplicate daily by 2 operators on each of five non-consecutive days.
Performance characteristics of the RVNAT go in the Precision/Reproducibility Studies were equivalent to those for the cleared VRNAT.
D. Method Comparison Studies for RVNAT sp and the cleared VRNAT (K083088)
A sample set representing Influenza B, and RSV was prepared by diluting culture positive nasopharyngeal swab samples with negative samples (Table 6). Dilutions were aimed to yield viral load levels close to the low positive levels for each virus type. A total of 62 unique samples were diluted, aliquoted, and frozen. The sample set was tested at the internal site (Site 1) using the cleared VRNAT, and at all three sites using the RVNATs for a total of 62x4=248 unique tests.
Each sample set yielded a total of 186 decisions from 62 unique samples as each test provides a decision of 'Detected' or 'Not Detected' for each of the 3 viruses, Influenza B, and RSV. Of the 62 samples, 3 samples had dual infections where 2 viruses were present.
Decisions on the RVNAT of or each site were compared to the cleared VRNAT. The Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) are provided in Tables 7 - 10. The two systems are equivalent based on the collected data.
- Site 1: PPA 100.0% (95%CI=94.4% - 100.0%), NPA 100.0% (95%CI=96.9% - 100.0%)
- Site 2: PPA 98.5% (95%CI=91.8% - 99.7%), NPA 100.0% (95%CI=96.9% - 100.0%)
- Site 3: PPA 95.4% (95%CI=87.3% - 98.4%), NPA 100.0% (95%CI=96.9% - 100.0%)
- Combined across all sites: PPA 97.9% (95%CI=94.8% - 99.0%), NPA 100.0% (95%CI=99.0% - 100.0%)
Overall conclusions:
The analytical sensitivities or Limits of Detection (LOD) of RVNAT were identical to the cleared VRNAT for the Influenza A, Influenza B, RSV A, and RSV B strains tested, demonstrating that the performance characteristics of the two devices were equivalent.
The carryover and cross-contamination studies showed no evidence of contamination in the o RVNATSP.
The Precision/Reproducibility studies performed across three clinical test sites replicated the study that was performed previously for the cleared VRNAT. Comparison of the clinical outcomes and the statistical results for the Precision/Reproducibility studies showed equivalence between the RVNAT sp and the cleared VRNAT.
In a comparison study conducted across three sites, the same set of samples was compared between the RVNAT op and the cleared VRNAT. The collective lower bound 95% Cl for the positive and negative percent agreements was greater than 90%. Moreover, comparisons of signal intensities between the two devices showed equivalent performance across sites and across the individual tests. Collectively, the data showed that the RVNATsp and the cleared VRNAT performance were equivalent.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Precision/Reproducibility:
Agreement of 'Observed Results' to 'Expected Results' for RVNATSP compared to cleared VRNAT across three sites for Influenza A, Influenza B, RSV A, and RSV B at high negative, low positive, and moderate positive concentrations. Agreements were generally high, often 100% or very close.
Method Comparison (Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA)):
- Site 1: PPA 100.0 % (95%CI=94.4% - 100.0%), NPA 100.0% (95%CI=96.9% - 100.0%)
- Site 2: PPA 98.5 % (95%CI=91.8% - 99.7%), NPA 100.0% (95%CI=96.9% - 100.0%)
- Site 3: PPA 95.4 % (95%CI=87.3% - 98.4%), NPA 100.0% (95%CI=96.9% - 100.0%)
- All Sites Combined: PPA 97.9 % (95%CI=94.8% - 99.0%), NPA 100.0% (95%CI=99.0% - 100.0%)
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 866.3980 Respiratory viral panel multiplex nucleic acid assay.
(a)
Identification. A respiratory viral panel multiplex nucleic acid assay is a qualitative in vitro diagnostic device intended to simultaneously detect and identify multiple viral nucleic acids extracted from human respiratory specimens or viral culture. The detection and identification of a specific viral nucleic acid from individuals exhibiting signs and symptoms of respiratory infection aids in the diagnosis of respiratory viral infection when used in conjunction with other clinical and laboratory findings. The device is intended for detection and identification of a combination of the following viruses:(1) Influenza A and Influenza B;
(2) Influenza A subtype H1 and Influenza A subtype H3;
(3) Respiratory Syncytial Virus subtype A and Respiratory Syncytial Virus subtype B;
(4) Parainfluenza 1, Parainfluenza 2, and Parainfluenza 3 virus;
(5) Human Metapneumovirus;
(6) Rhinovirus; and
(7) Adenovirus.
(b)
Classification. Class II (special controls). The special controls are:(1) FDA's guidance document entitled “Class II Special Controls Guidance Document: Respiratory Viral Panel Multiplex Nucleic Acid Assay;”
(2) For a device that detects and identifies Human Metapneumovirus, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Human Metapneumovirus (hMPV) Using Nucleic Acid Assays;” and
(3) For a device that detects and differentiates Influenza A subtype H1 and subtype H3, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Detection and Differentiation of Influenza A Virus Subtypes Using Multiplex Nucleic Acid Assays.” See § 866.1(e) for the availability of these guidance documents.
0
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Image /page/0/Picture/1 description: The image shows the word "Nanosphere" in a sans-serif font. To the left of the word is a circular logo that is divided into two halves. The left half of the logo is filled with a pattern of small dots, while the right half is filled with a pattern of horizontal lines.
OCT - 9 2009
Summary of 510(k)
| 510(k)
| numbers: | K092566: Verigene® Respiratory Virus Nucleic Acid Test on the Verigene® SP System (RVNATSP) |
|---|---|
| Summary | |
| preparation | |
| date: | October 7, 2009 |
| Submitted | |
| by: | Nanosphere, Inc. |
| 4088 Commercial Avenue | |
| Northbrook, IL 60062 | |
| Phone: 847-400-9000 Fax: 847-400-9199 | |
| Contact: | Gregory W. Shipp, M.D. |
| Chief Medical Officer | |
| VP, Medical and Regulatory Affairs and Quality Assurance | |
| Proprietary | |
| names: | For instrument: |
| Verigene® SP System | |
| For the assay: | |
| Verigene® Respiratory Virus Nucleic Acid Test on the Verigene® SP System (RVNATSP) | |
| Common | |
| names: | For the instrument: |
| Bench-top molecular diagnostics workstation | |
| For the assays: | |
| Respiratory panel | |
| Respiratory virus panel | |
| Respiratory viruses | |
| Influenza A assay | |
| Influenza B assay | |
| RSV assay | |
| Influenza A/B and RSV assay | |
| Comparison | |
| VRNAT and | |
| RVNATSP: | Additional claim to the 510(k) application, K083088 is described. The Verigene Respiratory Virus Nucleic |
| Acid Test (VRNAT) will add the Verigene SP System to the labeling as a cleared system. The safety and | |
| effectiveness of the Verigene® Respiratory Virus Nucleic Acid Test on the Verigene SP System | |
| (RVNATSP) is demonstrated with analytical and method comparison studies. | |
| The FDA-cleared VRNAT (K083088) is a qualitative test based on identifying virus-specific nucleic acids | |
| for Influenza A virus, Influenza B virus, and respiratory syncytial virus (RSV). Within this test, the steps of | |
| sample preparation (or nucleic acid extraction), target amplification, and hybridization test and analysis | |
| take place on three separate instruments (Table 1). The RVNATSP is the same assay with additional | |
| system claims for the Verigene SP System, a modified Verigene® System that allows sample preparation, | |
| target amplification, and hybridization test and analysis using a single system (Table 1). |
1
| Table 1. | ||||
|---|---|---|---|---|
| Sample Preparation | Target Amplification | Hybridization Test and Analysis | ||
| VRNAT | ||||
| (cleared, K083088) | NucliSENS EasyMAG | |||
| (bioMerieux) | Thermocycler | Verigene System | ||
| RVNATSP | Verigene SP System | Verigene SP System | Verigene SP System | |
| The RVNATSP is designed to identify virus-specific nucleic acids for Influenza A virus, Influenza B virus, and respiratory syncytial virus (RSV). The RVNATSP involves: | ||||
| 1) | Sample Preparation – magnetic bead-based viral RNA extraction from nasopharyngeal swab specimens obtained from symptomatic patients; | |||
| 2) | Target Amplification – Multiplex RT-PCR-based amplification of the eluted viral RNA targets to generate virus-specific amplicons; | |||
| 3) | Verigene Hybridization Test and Analysis - detection and identification of virus-specific amplicons by using gold nanoparticle probe-based technology. | |||
| The entire RVNATSP is performed on the Verigene® SP System, which is a bench-top molecular diagnostics workstation that consists of two instruments, the Verigene SP Processor and the Verigene Reader. The Verigene SP Processor 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 previous Verigene System with added modules for nucleic acid extraction and RT-PCR target amplification. Key functions of the Verigene SP Processor 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. | |||
| Device description: | 3) | Real-time communication of test processing status to the Reader. | ||
| The Verigene Reader is the same instrument as in the FDA-cleared VRNAT. 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 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. | |||
| RVNATSP 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 SP Processor 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. | ||||
| 1) | 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. |
.
2
- 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. 3) 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. 4) RV Test Cartridge for Verigene Hybridization Test - The virus-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 SP Processor unit and the reagent pack is snapped off and discarded. The remaining slide is now ready for imaging and analysis in the Verigene Reader. 5) 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 subfracted, 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. The RVNAT so is a qualitative multiplex in vitro diagnostic test for the detection and identification of Influenza A Virus, Influenza B Virus, and Respiratory Syncytial Virus (RSV) nucleic acids purified from nasopharyngeal swab specimens obtained from patients symptomatic for viral upper respiratory infection. The test is intended to be used on the Verigene® SP System as an aid in the differential diagnosis of Influenza A, Influenza B, and RSV infections. The test is not intended to detect Influenza C virus. Neqative results do not preclude influenza virus or RSV infection and should not be used as the sole basis for treatment or other management decisions. It is recommended that negative test results be confirmed by culture. Intended uses: Performance characteristics for Influenza A Virus were established when Influenza A/H3 and A/H1 were the predominant Influenza A viruses in circulation. When other Influenza A viruses are emerging, performance characteristics may vary. If infections 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 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 cleared Verigene® Respiratory Virus Nucleic Acid Test (VRNAT), K083088 is claimed as the predicate Predicate device (Table 2). It is a multiplex in vitro diagnostic test for the rapid and qualifative detection and device: discrimination of Influenza A Virus, Influenza B Virus, and Respiratory Syncytial Virus (RSV).
3
| Feature | VRNAT (Predicate, K083088) | Verigene RVNATSP |
|---|---|---|
| Intended use | The Verigene® Respiratory Virus Nucleic Acid Test | |
| on Verigene SP System (RVNAT gp) is a qualitative | ||
| multiplex in vitro diagnostic test for the detection and | ||
| identification of Influenza A Virus, Influenza B Virus, | ||
| and Respiratory Syncytial Virus (RSV) nucleic acids | ||
| purified from nasopharyngeal swab specimens | ||
| obtained from patients symptomatic for viral upper | ||
| respiratory infection. The test is intended to be used | ||
| on the Verigene® SP System as an aid in the | ||
| differential diagnosis of Influenza A, Influenza B, and | ||
| RSV infections. The test is not intended to detect | ||
| Influenza C virus. | ||
| Negative results do not preclude influenza virus or | ||
| RSV infection and should not be used as the sole | ||
| basis for treatment or other management decisions. It | ||
| is recommended that negative results be confirmed by | ||
| culture. | ||
| Performance characteristics for Influenza A Virus were | ||
| established when Influenza A/H3 and A/H1 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 department for testing. Viral culture should not | ||
| be attempted in these cases unless a BSL 3+ facility is | ||
| available to receive and culture specimens. | Same test on Verigene SP System | |
| l argets | Intluenza A, Influenza B, RSV | ldentical |
| Specimen | Nasopharyngeal swabs in sample matrix | Identical |
| Sample | ||
| preparation | Automated extraction of nucleic acids performed | |
| externally on the NucliSENS EasyMAG (bioMerieux) | ||
| using silica coated magnetic beads and chaotropic | ||
| salts using chemistry based on U.S. Patent 5,234,809. | Automated extraction of nucleic acids | |
| performed on the Verigene SP Processor | ||
| using silica coated magnetic beads and | ||
| chaotropic salts licensing the identical | ||
| patent chemistry. | ||
| Sample size | 200 µL | Identical |
| Quality | ||
| control | Internal procedural quality control, external quality | |
| control solutions | Identical | |
| Amplification | ||
| method | Multiplex RT-PCR: Target Amplification by RT-PCR is | |
| performed on an external thermocycler | Multiplex RT-PCR: Identical reagents; | |
| performed within the added Amplification | ||
| Module on the Verigene SP Processor | ||
| M-MLV Reverse Transcriptase | Identical | |
| Pipetting | ||
| Pipetting | Pipetting between the three steps is performed by the user. | Robotic pipettor added to automate fluid transfer steps. |
| Detection | ||
| Method | Verigene Hybridization Test is performed in the hybridization module housed in the Processor of the Verigene® System by using single-use Test Cartridges | Identical |
| Decision | ||
| algorithm | Target-specific signal intensities are compared to a signal threshold and ratioed against positive and negative controls for a decision. | Identical |
| Results | Positive or negative qualitative results | Identical |
| Reader | Provides the user interface, controls the Processor, performs image analysis, and provides results. | Identical |
| Software | A custom embedded software application running under the Micro-C/OS real-time operating system. | Architecture is the same. Additional software programming to control the Extraction and Amplification Modules. |
| Reagent | ||
| storage | Test Cartridge: 2 - 8 °C | |
| Amplification Kit: -20 °C | Test Cartridge and Extraction Tray: 2 - 8 °C. | |
| Amplification Tray: -20 °C | ||
| Assay | ||
| Performance | As in the cleared VRNAT (K083088). | Identical Limits of Detection as the cleared VRNAT. |
| Precision/Reproducibility - Clinically and statistically equivalent. | ||
| Method Comparison - Clinically and statistically equivalent |
Table 2. Similarities and Differences between the Cleared and the New System.
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4
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5
Performance Characteristics of the RVNATse
Analytical and method comparison studies to establish the performance of the test on the Verigene SP System are described.
- A. Comparison of Analytical Sensitivity
The analytical sensitivity of the RVNAT o was compared to the cleared VRNAT (K083088) by determining the Limit of Detection (LOD) of Influenza B, RSV A, and RSV B viruses. Strains with established titers were used for each virus stock was serially diluted into a sample matrix (Universal Transport Media, Copan), and each concentration was tested in quadruplicate using the RVNAT ge. The LOD was confirmed by performing an additional 20 replicates for each strain in order to demonstrate that the virus was detected ≥95% of the time. The LOD for each virus was identical to the LOD observed with the same strains on the cleared VRNAT (K083088) (Table 3).
| Limits of Detection | Concentration |
|---|---|
| Influenza A (A/Wisconsin/67/05) | 2 TCID50/mL |
| Influenza B (B/Florida/04/2006) | 50 TCID50/mL |
| RSV A (Strain Long) | 10 TCID50/mL |
| RSV B (B-1 Wild Type (B WV/14617/85)) | 2 TCID50/mL |
| Table 3. Limit of Detection | ||
|---|---|---|
-
B. Carryover and Crossover Contamination Studies
High positive samples of Influenza A, Influenza B, RSV B were alternated with high neqative samples for all four viruses. Based on the collective data, there was no evidence of crosscontamination from any of the test steps including sample extraction, multiplex RT-PCR step, and the Verigene Hybridization Test. -
C. Precision/Reproducibility Studies Comparison between the RVNATso and the cleared VRNAT (K083088)
The Precision/Reproducibility Studies were performed at each of three sites. At Site 1, the Reproducibility Study was part of a larger precision/Reproducibility Studies for the RVNAT go were conducted exactly as for the previously cleared VRNAT (K083088) to allow equivalency comparisons. As before, eight unique samples were created by diluting known concentrations of viral particles with Viral Transport Medium (Table 4). Since the Analytical Sensitivity of the RVNATs was identical to the cleared VRNAT, the same strains and levels were used in the studies. Each strain was represented at 3 distinct concentrations: high negative, low positive, and moderate positive.
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| Unique Samples | Viral Strains and Levels |
|---|---|
| 1 | Influenza A - High Negative; Influenza B - High Negative |
| 2 | RSV A - High Negative; RSV B - High Negative |
| 3 | Influenza A - Low Positive |
| 4 | Influenza B - Low Positive |
| 5 | RSV A - Low Positive |
| 6 | RSV B - Low Positive |
| 7 | Influenza A - Moderate Positive; RSV A - Moderate Positive |
| 8 | Influenza B - Moderate Positive; RSV B - Moderate Positive |
| Table 4. Sample panel for the Precision/Reproducibility Studies. | |||||
|---|---|---|---|---|---|
| -- | -- | -- | -- | ------------------------------------------------------------------ | -- |
The Precision Study (Site 1) tested the sample set over 12 non-consecutive days. On each test day, two operators performed the RVNAT و in duplicate for each sample sets per day total). In the reproducibility study performed by sites 2 and 3, the sample set was tested in triplicate daily by 2 operators on each of five non-consecutive days.
Performance characteristics of the RVNAT go in the Precision/Reproducibility Studies were equivalent to those for the cleared VRNAT (Table 5).
| Agreement of 'Observed Results' to 'Expected Results' | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| New RVNATSP | Cleared VRNAT | ||||||||||||
| Panel Member | Site 1 | Site 2 | Site 3 | All | |||||||||
| Sites | % | ||||||||||||
| Agreement | 95% Score | ||||||||||||
| CI | Site 1 | Site 2 | Site 3 | All | |||||||||
| Sites | % | ||||||||||||
| Agreement | 95% Score | ||||||||||||
| CI | |||||||||||||
| Influenza A | High | ||||||||||||
| Negative | 48/48 | 15/15 | 15/15 | 78/78 | 100% | 95.3 - 100% | 46/48 | 14/15 | 15/15 | 75/78 | 96% | 89.3 - 98.7% | |
| Low | |||||||||||||
| Positive | 48/48 | 15/15 | 15/15 | 78/78 | 100% | 95.3 - 100% | 48/48 | 14/15 | 15/15 | 77/78 | 98.7% | 93.1 - 99.8% | |
| Moderate | |||||||||||||
| Positive | 48/48 | 15/15 | 15/15 | 78/78 | 100% | 95.3 - 100% | 48/48 | 15/15 | 15/15 | 78/78 | 100.0% | 95.3 - 100% | |
| Influenza B | High | ||||||||||||
| Negative | 48/48 | 15/15 | 15/15 | 78/78 | 100% | 95.3 - 100% | 48/48 | 15/15 | 15/15 | 78/78 | 100% | 95.3 - 100% | |
| Low | |||||||||||||
| Positive | 47/48 | 15/15 | 15/15 | 77/78 | 98.7% | 93.1 - 99.8% | 47/48 | 15/15 | 15/15 | 77/78 | 98.7% | 93.1 - 99.8% | |
| Moderate | |||||||||||||
| Positive | 48/48 | 15/15 | 15/15 | 78/78 | 100% | 95.3 - 100% | 48/48 | 15/15 | 15/15 | 78/78 | 100% | 95.3 - 100% | |
| RSV A | High | ||||||||||||
| Negative | 48/48 | 15/15 | 14/15 | 77/78 | 99% | 93.1 - 99.8% | 48/48 | 13/15 | 15/15 | 76/78 | 97% | 91.1 - 99.3% | |
| Low | |||||||||||||
| Positive | 47/48 | 15/15 | 15/15 | 77/78 | 98.7% | 93.1 - 99.8% | 47/48 | 15/15 | 15/15 | 77/78 | 98.7% | 93.1 - 99.8% | |
| Moderate | |||||||||||||
| Positive | 48/48 | 15/15 | 15/15 | 78/78 | 100.0% | 95.3 - 100% | 48/48 | 15/15 | 15/15 | 78/78 | 100.0% | 95.3 - 100% | |
| RSV B | High | ||||||||||||
| Negative | 48/48 | 15/15 | 15/15 | 78/78 | 100% | 95.3 - 100% | 46/48 | 14/15 | 14/15 | 74/78 | 95% | 87.5 - 98.0% | |
| Low | |||||||||||||
| Positive | 48/48 | 15/15 | 15/15 | 78/78 | 100% | 95.3 - 100% | 48/48 | 15/15 | 15/15 | 78/78 | 100% | 95.3 - 100% | |
| Moderate | |||||||||||||
| Positive | 48/48 | 15/15 | 15/15 | 78/78 | 100% | 95.3 - 100% | 48/48 | 15/15 | 15/15 | 78/78 | 100.0% | 95.3 - 100% |
Table 5. Comparison of Precision/Reproducibility data from the new RVNAT م to the cleared VRNAT
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D. Method Comparison Studies for RVNAT sp and the cleared VRNAT (K083088)
A sample set representing Influenza B, and RSV was prepared by diluting culture positive nasopharyngeal swab samples with negative samples (Table 6). Dilutions were aimed to yield viral load levels close to the low positive levels for each virus type. A total of 62 unique samples were diluted, aliquoted, and frozen. The sample set was tested at the internal site (Site 1) using the cleared VRNAT, and at all three sites using the RVNATs for a total of 62x4=248 unique tests.
Each sample set yielded a total of 186 decisions from 62 unique samples as each test provides a decision of 'Detected' or 'Not Detected' for each of the 3 viruses, Influenza B, and RSV. Of the 62 samples, 3 samples had dual infections where 2 viruses were present.
| Sample Set | Positives | Negatives | Totals |
|---|---|---|---|
| Influenza A | 15 | 47 | 62 |
| Influenza B | 16 | 46 | 62 |
| RSV A/B | 34 | 28 | 62 |
| Total | 65* | 121 | 186 |
Table 6. Method Comparison Study Sample Set.
*3 samples had 2 viruses raising the total number of positives from 62 to 65
Decisions on the RVNAT of or each site were compared to the cleared VRNAT. The Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) are provided in Tables 7 - 10. The two systems are equivalent based on the collected data.
| All Viruses | VRNAT (Old System) | ||||
|---|---|---|---|---|---|
| Positive | Negative | Total | |||
| RVNATSP | |||||
| (New System) | Positive | 65 | 0 | 65 | PPA 100.0 % |
| (95%CI=94.4% - 100.0%) | |||||
| Negative | 0 | 121 | 121 | NPA 100.0% | |
| (95%CI=96.9% - 100.0%) | |||||
| Total | 65 | 121 | 186 |
Table 8. RVNAT se Method Comparison Data collected at Site 2
| All Viruses | VRNAT (Old System) | ||||
|---|---|---|---|---|---|
| Positive | Negative | Total | |||
| RVNATSP | |||||
| (New System) | Positive | 64 | 0 | 64 | PPA 98.5 % |
| (95%CI=91.8% - 99.7%) | |||||
| Negative | 1a | 121 | 122 | NPA 100.0% | |
| (95%CI=96.9% - 100.0%) | |||||
| Total | 65 | 121 | 186 |
3Low positive discordant Influenza A. Repeat tests were positive and gave the expected result.
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| All Viruses | VRNAT (Old System) | ||||
|---|---|---|---|---|---|
| Positive | Negative | Total | |||
| RVNATSP | |||||
| (New System) | Positive | 62 | 0 | 62 | PPA 95.4 % |
| (95%CI=87.3% - 98.4%) | |||||
| Negative | 3a | 121 | 124 | NPA 100.0% | |
| (95%CI=96.9% - 100.0%) | |||||
| Total | 65 | 121 | 186 |
Table 9. RVNAT sp Method Comparison Data collected at Site 3
All discordant samples were Influenza A low positive Repeat tests were positive and gave the expected result.
| Table 10. RVNAT و Method Comparison Data - Combined data from all 3 sites | ||
|---|---|---|
| All Viruses/All Sites | VRNAT (Old System) | ||||
|---|---|---|---|---|---|
| Positive | Negative | Total | |||
| RVNATSP | |||||
| (New System) | Positive | 191 | 0 | 191 | PPA 97.9 % |
| (95%CI=94.8% - 99.0%) | |||||
| Negative | 4a | 363 | 367 | NPA 100.0% | |
| (95%CI=99.0% - 100.0%) | |||||
| Total | 195 | 363 | 558 |
8 All discordant samples were Influenza A low positive. Repeat tests were positive and gave the expected result.
Conclusions Concerning Claim of Substantial Equivalence
The FDA-cleared VRNAT (K083088) is a multiplexed, qualitative test, based on identifying virus-specific nucleic acids for Influenza A virus. Influenza B virus, and Respiratory Syncytial Virus (RSV). Nucleic acids are externally extracted and amplified from viruses and then detected within the Verigene® System by using single-use disposable Test Cartridges.
The RVNAT go is the identical test as the cleared VRNAT with regard to sample extraction chemistry, RT-PCR amplification reagents, and assay detection methods, but it is performed on the Verigene SP System, a fully automated 'sample-to-result' device. As with the Verigene System, the Verigene SP System comprises two units: Reader and SP Processor. The SP Processor has the same hybridization module as the Verigene Processor plus additional modules for sample extraction and multiplex RT-PCR - steps that are performed externally on two separate instruments in the cleared VRNAT.
Assay comparison studies were performed for the RVNAT sp. The studies included:
-
- Analytical Sensitivity (Limits of Detection) determination of the RVNAT sp
- The analytical sensitivities or Limits of Detection (LOD) of RVNAT p were identical to the o cleared VRNAT for the Influenza A, Influenza B, RSV A, and RSV B strains tested, demonstrating that the performance characteristics of the two devices were equivalent.
-
- Carryover and Cross-contamination Studies on the RVNAT se
- The carryover and cross-contamination studies showed no evidence of contamination in the o RVNATSP.
-
- Precision/Reproducibility studies on the RVNATsp and comparison to the corresponding VRNAT studies
- The Precision/Reproducibility studies performed across three clinical test sites replicated the o study that was performed previously for the cleared VRNAT. Comparison of the clinical outcomes and the statistical results for the Precision/Reproducibility studies showed equivalence between the RVNAT sp and the cleared VRNAT.
9
-
- Method Comparison Studies on the RVNAT (New) and VRNAT (Cleared).
- In a comparison study conducted across three sites, the same set of samples was compared o between the RVNAT op and the cleared VRNAT. The collective lower bound 95% Cl for the positive and neqative percent agreements was greater than 90%. Moreover, comparisons of signal intensities between the two devices showed equivalent performance across sites and across the individual tests. Collectively, the data showed that the RVNATsp and the cleared VRNAT performance were equivalent.
The performance data support the claims of equivalence between the RVNAT ۾ and the cleared VRNAT. Thus, the performance characteristics in the package insert for the cleared VRNAT with respect to accuracy, sensitivity, specificity, and additional attributes are applicable to the RVNAT sp.
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Image /page/10/Picture/0 description: The image shows the seal of the Department of Health & Human Services (HHS). The seal is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. In the center of the seal is an abstract image of a bird-like figure.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Building 66 Silver Spring, MD 20993
Gregory W. Shipp, M.D. Vice President, Medical and Regulatory Affairs Nanosphere, Inc. 4088 Commercial Avenue Northbrook, IL 60062
OCT - 9 2009
Re: K092566 Trade/Device Name: Verigene® Respiratory Virus Nucleic Acid Test on the Verigene® SP System Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory Viral Panel Multiplex Nucleic Acid Assay Regulatory Class: Class II Product Code: OCC, NSU Dated: September 29, 2009 Received: September 30, 2009
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 either class II (Special Controls) or class III (PMA), 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.
11
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); 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.
Sincerely yours.
Sally A. Hoivat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indication for Use
510(k) Number (if known): K092566
Device Name: Verigene® Respiratory Virus Nucleic Acid Test on the Verigene® SP System (RVNATsp)
Indication for Use:
The Verigene® Respiratory Virus Nucleic Acid Test on the Verigene SP System (RVNATsg) is a qualitative multiplex in vitro diagnostic test for the detection and identification of Influenza A Virus, Influenza B Virus, and Respiratory Syncytial Virus (RSV) nucleic acids purified from nasopharyngeal swab specimens obtained from patients symptomatic for viral upper respiratory infection. The test is intended to be used on the Verigene® SP System as an aid in the differential diagnosis of Influenza A, Influenza B, and RSV infections. The test is not intended to detect Influenza C virus.
Negative results do not preclude influenza virus or RSV infection and should not be used as the sole basis for treatment or other management decisions. It is recommended that negative test results be confirmed by culture.
Performance characteristics for Influenza A Virus were established when Influenza A/H3 and A/H1 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 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 X (Part 21 CFR 801 Subpart D) And/Or
Over-The-Counter Use (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)
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510(k) K092566