(88 days)
Not Found
No
The device description and performance studies focus on standard RT-PCR technology and data analysis based on fluorescence thresholds, with no mention of AI or ML algorithms for interpretation or analysis.
No
This device is an in vitro diagnostic test for the qualitative detection and identification of Influenza A and Influenza B virus RNA. It is used as an aid in diagnosis, not for therapy or treatment.
Yes
The "Intended Use / Indications for Use" section explicitly states that the kit is "for the qualitative detection and identification of Influenza A and Influenza B virus RNA... as an aid in the differential diagnosis of Influenza A and Influenza B viral infections." This confirms its role in diagnosing diseases.
No
The device is an in vitro diagnostic test kit that includes reagents and instructions for use with specific hardware instruments (EZ1 Advanced XL instrument, Rotor-Gene Q MDx instrument). While it utilizes software for result interpretation, it is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
The intended use statement explicitly states: "The artus® Infl A/B RG RT-PCR Kit is a multiplex real time PCR in vitro diagnostic test for the qualitative detection and identification of Influenza A and Influenza B virus RNA in nasopharyngeal swab specimens..."
This clearly identifies the device as an in vitro diagnostic test.
N/A
Intended Use / Indications for Use
The artus® Infl A/B RG RT-PCR Kit is a multiplex real time PCR in vitro diagnostic test for the qualitative detection and identification of Influenza A and Influenza B virus RNA in nasopharyngeal swab specimens using the Rotor-Gene® Q MDx instrument. The test is intended for use as an aid in the differential diagnosis of Influenza A and Influenza B viral infections in patients symptomatic for respiratory tract infection in conjunction with clinical and epidemiological risk factors. It is not intended to detect Influenza C virus.
Negative results do not preclude respiratory virus infection and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.
Performance characteristics for Influenza A were established during the 2009/2010 and 2010/2011 flu seasons when Influenza A (H3N2) and Influenza A/2009 (H1N1) were the predominant Influenza A viruses in circulation. When other Influenza A viruses emerge, performance characteristics may vary.
If infection with a novel Influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent influenza viruses and sent to state or local health departments for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
Product codes
OCC, OOI, JJH
Device Description
The artus Infl A/B RG RT-PCR Kit contains reagents and instructions for the detection and differentiation of Influenza A and Influenza B viral RNA in nasopharyngeal swabs of symptomatic patients.
The assay utilizes the EZ1 Advanced XL instrument with the EZ1 Advanced XL DSP Virus Card v. 1.0. and the EZ1 DSP Virus Kit (QIAGEN) for viral nucleic acid extraction. The Rotor-Gene Q MDx instrument with the artus Influenza Assay Software Package (QIAGEN) is used for amplification and detection.
Pathogen detection by the reverse transcription polymerase chain reaction (RT-PCR) is based on the reverse transcription of the RNA into complementary DNA (cDNA) and subsequent amplification of specific regions of the pathogen genome. In real-time PCR the amplified product is detected via fluorescent dyes. These are linked to oligonucleotides that bind specifically to the amplified product. Monitoring the fluorescence intensities during the PCR run (i.e., in real time) allows the detection of the accumulating product without having to re-open the reaction tubes after the PCR run.
The Influenza A/B Master contains primers, probes, enzymes, and other reaction components (except Mg solution) needed for the specific amplification of a 141 bp region of the Influenza A virus genome and a 95 bp region of the influenza virus B genome, and for the direct detection of the specific amplicons in two fluorescence channels of the Rotor-Gene O MDx instrument. The primers are complementary to highly conserved regions of the Matrix gene locus within the influenza B virus genome. The probes are dual-labeled with a reporter dye attached to the 5'-end and a quencher dye attached to the 3'-end. Detection is performed on the Rotor-Gene O MDx instrument at wavelengths listed in Table 5.1.
In addition, the Master contains a second heterologous primer/probe set to detect the Influenza A/B Internal Control (IC). The IC result identifies possible failure of RNA extraction or the presence of PCR inhibition. The Internal Control is detected in a third fluorescence channel.
An Influenza A Control and an Influenza B Control comprised of in vitro transcripts representing the amplified regions of the Influenza A virus genome and the Influenza B virus genome, respectively, are provided. PCR grade water is provided as a negative (notemplate) control.
The procedure consists of four consecutive steps:
- Sample collection: Collect nasopharyngeal swab specimens from symptomatic patients using a polyester, nylon, or rayon swab and place it into virus transport medium.
- Nucleic acid extraction: Add the Influenza IC to the carrier RNA before starting the extraction procedure. Extract viral RNA using the EZ1 DSP Virus Kit in combination with the EZ1 Advanced XL instrument.
- Real-time RT-PCR: Add the extracted RNA and positive and negative control material to Influenza A/B Master mix. Perform real-time RT-PCR using the Rotor-Gene O MDx instrument.
- Result interpretation: The Influenza Assay Package evaluates the results of the positive and negative controls to determine if the run is valid. If the run is valid, the internal control and target-specific results of each specimen are evaluated.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Nasopharyngeal swab specimens
Indicated Patient Age Range
Not specified, but evaluation included patients with age ranges:
§ 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
510(k) SUMMARY
General Information
| Submitted by: | QIAGEN GmbH
Qiagen Strasse 1
Hilden, Germany D-40724 |
|-----------------|-------------------------------------------------------------------------------------------|
| Contact Person: | Volker Riemenschneider
QIAGEN GmbH
Qiagen Strasse 1
Hilden, Germany D-40724 |
| | Phone: +49 2103-29-0
Fax: +49 2103-29-2177
Email: Volker.riemenschneider@qiagen.com |
| Date Prepared: | February 1, 2012 |
| Device Name: | |
| Trade Name: | artus ® Infl A/B RG RT-PCR Kit |
|---|---|
| Common Name: | Influenza A/B Test |
| Classification Name: | Respiratory Viral Panel Multiplex Nucleic Acid Assay, (21 CFR 866.3980, Product Code OCC) |
Predicate Device
| Manufacturer | Product Name | 510(k) No. |
|---|---|---|
| Gen-Probe Prodesse, Inc. | ProFlu+ Assay | K110968 |
Device Description
The artus Infl A/B RG RT-PCR Kit contains reagents and instructions for the detection and differentiation of Influenza A and Influenza B viral RNA in nasopharyngeal swabs of symptomatic patients.
The assay utilizes the EZ1 Advanced XL instrument with the EZ1 Advanced XL DSP Virus Card v. 1.0. and the EZ1 DSP Virus Kit (QIAGEN) for viral nucleic acid extraction. The Rotor-Gene Q MDx instrument with the artus Influenza Assay Software Package (QIAGEN) is used for amplification and detection.
Pathogen detection by the reverse transcription polymerase chain reaction (RT-PCR) is based on the reverse transcription of the RNA into complementary DNA (cDNA) and subsequent amplification of specific regions of the pathogen genome. In real-time PCR the amplified product is detected via fluorescent dyes. These are linked to
1
oligonucleotides that bind specifically to the amplified product. Monitoring the fluorescence intensities during the PCR run (i.e., in real time) allows the detection of the accumulating product without having to re-open the reaction tubes after the PCR run.
The Influenza A/B Master contains primers, probes, enzymes, and other reaction components (except Mg solution) needed for the specific amplification of a 141 bp region of the Influenza A virus genome and a 95 bp region of the influenza virus B genome, and for the direct detection of the specific amplicons in two fluorescence channels of the Rotor-Gene O MDx instrument. The primers are complementary to highly conserved regions of the Matrix gene locus within the influenza B virus genome. The probes are dual-labeled with a reporter dye attached to the 5'-end and a quencher dye attached to the 3'-end. Detection is performed on the Rotor-Gene O MDx instrument at wavelengths listed in Table 5.1.
In addition, the Master contains a second heterologous primer/probe set to detect the Influenza A/B Internal Control (IC). The IC result identifies possible failure of RNA extraction or the presence of PCR inhibition. The Internal Control is detected in a third fluorescence channel.
| Component | Target | Target
Gene | Detection Range
(nm) |
|----------------------|-------------------|-----------------------|-------------------------|
| Influenza A/B Master | Influenza A Virus | Matrix | 510 +/- 5 |
| | Influenza B Virus | Matrix | 710 +/- 5 |
| | Internal Control | Synthetic
sequence | 610 +/- 5 |
Table 5.1. Target genes and detection channels
An Influenza A Control and an Influenza B Control comprised of in vitro transcripts representing the amplified regions of the Influenza A virus genome and the Influenza B virus genome, respectively, are provided. PCR grade water is provided as a negative (notemplate) control.
The procedure consists of four consecutive steps:
-
- Sample collection: Collect nasopharyngeal swab specimens from symptomatic patients using a polyester, nylon, or rayon swab and place it into virus transport medium.
-
- Nucleic acid extraction: Add the Influenza IC to the carrier RNA before starting the extraction procedure. Extract viral RNA using the EZ1 DSP Virus Kit in combination with the EZ1 Advanced XL instrument.
2
-
- Real-time RT-PCR: Add the extracted RNA and positive and negative control material to Influenza A/B Master mix. Perform real-time RT-PCR using the Rotor-Gene O MDx instrument.
-
- Result interpretation: The Influenza Assay Package evaluates the results of the positive and negative controls to determine if the run is valid. If the run is valid, the internal control and target-specific results of each specimen are evaluated.
Intended Use
The artus® Infl A/B RG RT-PCR Kit is a multiplex real time PCR in vitro diagnostic test for the qualitative detection and identification of Influenza B virus RNA in nasopharyngeal swab specimens using the Rotor-Gene® O MDx instrument. The test is intended for use as an aid in the differential diagnosis of Influenza A and Influenza B viral infections in patients symptomatic for respiratory tract infection in conjunction with clinical and epidemiological risk factors. It is not intended to detect Influenza C virus.
Negative results do not preclude respiratory virus infection and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.
Performance characteristics for Influenza A were established during the 2009/2010 and 2010/2011 flu seasons when Influenza A (H3N2) and Influenza A/2009 (H1N1) were the predominant Influenza A viruses in circulation. When other Influenza A viruses emerge, performance characteristics may vary.
If infection with a novel Influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent influenza viruses and sent to state or local health departments for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
Comparison of the artus® Infl A/B RG RT-PCR Kit and the Predicate Device
The artus® Infl A/B RG RT-PCR Kit is substantially equivalent to the predicate device:
- · K110968; ProFlu+ Assay, Gen-Probe Prodesse, Inc.
Similarities and differences between the artus® Infl A/B RG RT-PCR Kit and the predicate device are shown in Table 5.2.
3
| Table 5.2. Comparison of the artus® Infl A/B RG RT-PCR Kit with the predicate | |||||||
|---|---|---|---|---|---|---|---|
| device. |
| Characteristic | Device | Predicate | ||||
|---|---|---|---|---|---|---|
| Name | artus® Infl A/B RG RT-PCR Kit | ProFlu+TM Assay | ||||
| 510(k) No. | K113323 | K110968 | ||||
| Regulation | 866.3980 | 866.3980 | ||||
| Product Code | OCC | OCC | ||||
| Device Class | II | II | ||||
| Similarities | ||||||
| Intended Use | The artus® Infl A/B RG RT-PCR | The ProFlu" + Assay is a | ||||
| Kit is a multiplex real time PCR in | multiplex Real-Time PCR (RT- | |||||
| vitro diagnostic test for the | PCR) in vitro diagnostic test for | |||||
| qualitative detection and | the rapid and qualitative detection | |||||
| identification of influenza A and | and discrimination of Influenza A | |||||
| influenza B virus RNA in | Virus, Influenza B Virus, and | |||||
| nasopharyngeal swab specimens | Respiratory Syncytial Virus | |||||
| using the Rotor-Gene® Q MDx | (RSV) nucleic acids isolated and | |||||
| instrument. The test is intended for | purified from nasopharyngeal | |||||
| use as an aid in the differential | (NP) swab specimens obtained | |||||
| diagnosis of influenza A and | from symptomatic patients. This | |||||
| influenza B virus infections in | test is intended for use to aid in | |||||
| patients symptomatic for | the differential diagnosis of | |||||
| respiratory tract infection in | Influenza A, Influenza B and | |||||
| conjunction with clinical and | RSV viral infections in humans | |||||
| epidemiological risk factors. It is | and is not intended to detect | |||||
| not intended to detect influenza C | Influenza C. | |||||
| virus. | Negative results do not preclude | |||||
| influenza or RSV virus infection | ||||||
| Negative results do not preclude | and should not be used as the sole | |||||
| respiratory virus infection and | basis for treatment or other | |||||
| should not be used as the sole | management decisions. | |||||
| basis for diagnosis, treatment or | Conversely, positive results do | |||||
| other patient management | not rule out bacterial infection or | |||||
| decisions. | co-infection with other viruses. | |||||
| The agent detected may not be the | ||||||
| Performance characteristics for | definite cause of disease. The use | |||||
| influenza A were established | of additional laboratory testing | |||||
| during the 2009/2010 and | and clinical presentation must be | |||||
| 2010/2011 flu seasons when | considered in order to obtain the | |||||
| influenza A (H3N2) and influenza | final diagnosis of respiratory viral | |||||
| A/2009 (HIN1) were the | infection. | |||||
| predominant influenza A viruses | Performance characteristics for | |||||
| circulation. When other | ||||||
| in | Influenza A Virus were | |||||
| Influenza A viruses emerge, | established when Influenza A/H3 | |||||
| performance characteristics may | and A/H1 were the predominant |
4
| Characteristic | Device | Predicate |
|---|---|---|
| vary. | ||
| If infection with a novel influenza | ||
| A virus is suspected based on | ||
| current clinical and | ||
| epidemiological screening criteria | ||
| recommended by public health | ||
| authorities, specimens should be | ||
| collected with appropriate | ||
| infection control precautions for | ||
| novel virulent influenza viruses | ||
| and sent to state or local health | ||
| departments for testing. Viral | ||
| culture should not be attempted in | ||
| these cases unless a BSL 3+ | ||
| facility is available to receive and | ||
| culture specimens. | Influenza A viruses in circulation | |
| (2006 - 2007 respiratory season). | ||
| Performance characteristics for | ||
| Influenza A were confirmed when | ||
| Influenza A/Hl, Influenza A/H3, | ||
| and Influenza A/2009 H1N1 were | ||
| the predominant Influenza A | ||
| viruses in circulation (2008 and | ||
| 2009). 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. | ||
| Specimen Type | Nasopharyngeal swab | Nasopharyngeal swab |
| Assay Targets | Influenza A, Influenza B | Influenza A, Influenza B, RSV |
| Amplification | ||
| and Detection | ||
| Technology | Multiplex real-time PCR | Multiplex real-time PCR |
| Assay Controls | Influenza A Control, Influenza B | |
| Control, Influenza A/B Internal | ||
| Control, each prepared from in | ||
| vitro transcripts. | Influenza A RNA Control, | |
| Influenza B RNA Control, RSV A | ||
| RNA Control, RSV B RNA | ||
| Control and Internal RNA | ||
| Control, each prepared from in | ||
| vitro transcripts. | ||
| Influenza A | ||
| Virus Target | Matrix gene | Matrix gene |
| Differences | ||
| Influenza B | ||
| Virus Target | Matrix | Non-structural NS1 and NS2 |
| Characteristic | Device | Predicate |
| Nucleic Acid | ||
| Extraction | Automated extraction using the | |
| EZ1 DSP Virus Kit with the EZ1 | ||
| Advanced XL instrument | Automated extraction using the | |
| Roche MagNA Pure LC System | ||
| with the MagNA Pure Total | ||
| Nucleic Acid Isolation Kit or the | ||
| bioMerieux NucliSENS | ||
| easyMAG System with the | ||
| Automated Magnetic Extraction | ||
| Reagents. | ||
| Amplification | ||
| and Detection | ||
| Instrument | ||
| System | Rotor-Gene® Q MDx | Cepheid SmartCycler® II |
5
Clinical Studies
Prospective clinical evaluation
The performance of the artus Infl A/B RG RT-PCR test was established during a prospective study at 3 clinical laboratories in the United States during the 2010-11 respiratory virus season. Nasopharyngeal (NP) swab specimens were collected for routine influenza testing by each site. In this prospective study the reference method was standard viral culture (shell vial) followed by direct fluorescent antibody (DFA) screening and identification. Demographic details for this patient population are summarized in Table .
| Sex | Number of Subjects |
|---|---|
| Male | 138 (54%) |
| Female | 116 (46%) |
| Age (years) | |
| artus Infl A/B RG | + |
| RT-PCR test | - |
| Total |
Table 5.6 Influenza A results from retrospective clinical evaluation 1
a The artus Infl A/B RG RT-PCR test also identified an additional 2 specimens as positive for influenza A that were called negative or "No Call" by the molecular test.
| Reference method | ||||
|---|---|---|---|---|
| + | - | Total | ||
| artus Infl A/B RG | + | 33 | 2a | 35 |
| RT-PCR test | - | 0 | 177 | 177 |
| Total | 33 | 179 | 212 | |
| Positive agreement = 100% (95% confidence interval: 90-100%) | ||||
| Negative agreement = 98.9% (95% confidence interval: 96-100%) |
4 An additional 2 specimens were identified as positive for influenza B that were called negative by the molecular test .
Prospectively collected and archived clinical evaluation
A total of 462 well-characterized, de-identified, residual specimens were collected from August 2009 to May 2011 respiratory virus season. All specimens had been previously tested with FDA cleared molecular tests for routine patient management. These clinical results were used as the reference method. Demographic details for this patient population are summarized in Table 5.8
| Sex | Number of Subjects |
|---|---|
| Male | 190 (41%) |
| Female | 272 (59%) |
| Age (years) | |
| artus Infl A/B RG + | 94 |
| RT-PCR test - | 2 |
| Total | 96 |
| Positive agreement = 97.9% (95% confidence interval: 93-99%) | |
| Negative agreement = 94.8% (95% confidence interval: 92-97%) |
Table 5.9 Influenza A results from retrospective clinical evaluation 2
a The artus Infl A/B RG RT-PCR test also identified an additional 19 specimens as positive for influenza A that were reported as negative during routine clinical testing.
Table 5.10 Influenza B results from retrospective clinical evaluation 2
| Reference method | ||||
|---|---|---|---|---|
| + | - | Total | ||
| artus Infl A/B RG | + | 14 | 2a | 16 |
| RT-PCR test | - | 0 | 446 | 446 |
| Total | 14 | 448 | 462 | |
| Positive agreement = 100% (95% confidence interval: 79–100%) | ||||
| Negative agreement = 99.6% (95% confidence interval: 98-100%) |
4 An additional 2 specimens were identified as positive for influenza B that were called negative during routine clinical testing.
Non-clinical Studies
Reproducibility
The reproducibility of the artus Infl A/B RG RT-PCR test was evaluated using 3 investigational sites. A panel of 10 simulated specimens was provided for testing. Five of the specimens contained influenza A and the other 5 specimens contained influenza B. Each half of the panel included duplicate low-positive specimens at approximately 2 times the limit of detection (Low Pos #1 and #2), duplicate moderately positive specimens at approximately 10 times the limit of detection (Mod Pos #1 and #2), and one specimen well below the limit of detection for each analyte (Neg). The 10-member panel plus 3 controls were tested by 2 different technologists each day for 6 days. Therefore, 10 samples plus 3 controls, times 2 technologists, for 6 days, at 3 sites equals 468. The overall percent agreement for the artus Infl A/B RG RT-PCR test was 99.4% (Table 5. , Table 5., Table 5. , Table 5.).
9
Table 5. 11 Reproducibility - site 1
| Panel member | Agreement with
expected result | Average CT | CV% |
|------------------------|-----------------------------------|------------|-----|
| Influenza A Neg | 12/12 | 29.54 | 2.2 |
| Influenza A Low Pos #1 | 12/12 | 31.38 | 0.9 |
| Influenza A Low Pos #2 | 12/12 | 31.47 | 1.5 |
| Influenza A Mod Pos #1 | 12/12 | 29.20 | 0.9 |
| Influenza A Mod Pos #2 | 12/12 | 29.17 | 1.2 |
| Influenza B Neg | 12/12 | 29.55 | 2.2 |
| Influenza B Low Pos #1 | 12/12 | 30.35 | 1.2 |
| Influenza B Low Pos #2 | 12/12 | 30.42 | 1.1 |
| Influenza B Mod Pos #1 | 12/12 | 28.21 | 1.1 |
| Influenza B Mod Pos #2 | 12/12 | 28.27 | 1.1 |
| Influenza A Control | 12/12 | 34.35 | 2.2 |
| Influenza B Control | 12/12 | 30.85 | 1.9 |
| Negative control | 12/12 | 27.19 | 1.4 |
.
10
| Table 5.3 Reproducibility - site 2 | |||
|---|---|---|---|
| Agreement with | |||
|---|---|---|---|
| Panel member | expected result | Average Ст | CV% |
| Influenza A Neg | 11/12 | 29.89 | 2.5 |
| Influenza A Low Pos #1 | 12/12 | 31.24 | 1.5 |
| Influenza A Low Pos #2 | 12/12 | 31.35 | 1.2 |
| Influenza A Mod Pos #1 | 12/12 | 29.17 | 1.4 |
| Influenza A Mod Pos #2 | 12/12 | 29.16 | 1.4 |
| Influenza B Neg | 12/12 | 29.77 | 2.5 |
| Influenza B Low Pos #1 | 12/12 | 30.39 | 1.2 |
| Influenza B Low Pos #2 | 12/12 | 30.31 | 1.1 |
| Influenza B Mod Pos #1 | 12/12 | 28.29 | 1.0 |
| Influenza B Mod Pos #2 | 12/12 | 28.28 | 1.1 |
| Influenza A Control | 12/12 | 33.83 | 0.9 |
| Influenza B Control | 12/12 | 31.06 | 2.1 |
| Negative control | 12/12 | 27.48 | 2.1 |
Table 5. 4 Reproducibility – site 3
| Agreement with | |||
|---|---|---|---|
| Panel member | expected result | Average Ст | CV% |
| Influenza A Neg | 10/12 | 29.89 | 1.7 |
| Influenza A Low Pos #I | 12/12 | 31.45 | 0.8 |
| Influenza A Low Pos #2 | 12/12 | 31.35 | 0.6 |
| Influenza A Mod Pos #1 | 12/12 | 29.26 | 1.1 |
| Influenza A Mod Pos #2 | 12/12 | 29.45 | 2.4 |
| Influenza B Neg | 12/12 | 30.02 | 1.4 |
| Influenza B Low Pos #1 | 12/12 | 30.54 | 1.3 |
| Influenza B Low Pos #2 | 12/12 | 30.52 | 1.3 |
| Influenza B Mod Pos #1 | 12/12 | 28.46 | 1.8 |
| Influenza B Mod Pos #2 | 12/12 | 28.40 | 1.3 |
| Influenza A Control | 12/12 | 34.58 | 2.6 |
| Influenza B Control | 12/12 | 31.53 | 2.4 |
| Negative control | 12/12 | 27.61 | 1.4 |
Table 5.5 Reproducibility - combined (sites 1 - 3)
11
| Panel member | Agreement
with expected
result | Average
CT | CV% | 95%
confidence
interval |
|------------------------|--------------------------------------|---------------|-----|-------------------------------|
| Influenza A Neg | 33/36 | 29.76 | 2.2 | 78–97% |
| Influenza A Low Pos #1 | 72/72 | 31.37 | 1.1 | 95–100% |
| Influenza A Mod Pos #1 | 72/72 | 29.23 | 1.5 | 95–100% |
| Influenza B Neg | 36/36 | 29.78 | 2.1 | 90–100% |
| Influenza B Low Pos #1 | 72/72 | 30.42 | 1.2 | 95–100% |
| Influenza B Mod Pos #1 | 72/72 | 28.32 | 1.2 | 95–100% |
| Influenza A Control | 36/36 | 34.25 | 2.2 | 90–100% |
| Influenza B Control | 36/36 | 31.14 | 2.3 | 90–100% |
| Negative control | 36/36 | 27.42 | 1.8 | 90–100% |
Limit of Detection (LoD)
The limit of detection (LoD) of the artus Infl A/B RG RT-PCR Kit was determined and confirmed for six influenza A strains (two strains representing each of the influenza A subtypes of H1N1, H3N2, and 2009 H1N1) and two influenza B strains. Samples were prepared from cultured virus diluted in nasopharyngeal clinical matrix. The LoD of each strain was initially determined by limiting dilution testing of three replicates per dilution level. The result was confirmed by testing an additional 20 replicates at the LoD concentration. The LoD, defined as the level of virus that yields at least a 95% (19/20) detection rate with the artus Infl A/B RG RT-PCR Kit, ranged from 10e1.1 to 10e-0.1 TCID50/ml (Table 5.).
12
Table 5.6 Limit of detection
| Influenza strain | LoD concentration (TCID50/ml*) |
|---|---|
| A/New Caledonia/20/1999 (H1N1) | 10e0.5 |
| A/Brisbane59/2007-like virus (H1N1) | 10e1.1 |
| A/Hong Kong/8/68 (TC-adapted) (H3N2) | 10e0.2 |
| A/Wisconsin/67/2005 (H3N2) | 10e0.4 |
| A/California/7/09-like virus (2009 H1N1) | 10e0.9 |
| A/Hamburg/05/09 (2009 H1N1) | 10e0.4 |
| B/Brisbane/60/2008-like virus | 10e-0.1 |
| B/Florida/4/2006-like virus | 10e0.9 |
- Based on re-titered virus stock concentrations.
Reactivity
The analytical reactivity of the artus Infl A/B RG RT-PCR Kit was demonstrated by testing 18 strains of influenza A (including four strains originally identified in non-human species) and six strains of influenza B at concentrations near the limit of detection (LoD) of the test. Samples were prepared from cultured virus diluted in nasopharyngeal clinical matrix. Each viral strain was extracted and tested in triplicate. A "+" results indicates the concentration was detected positive in three of three replicates; a "-" result indicates a negative response in each of the replicates (Table 5.).
Table 5.7 Analytical reactivity
| Influenza strain | Concentration | Influenza A | Influenza B |
|---|---|---|---|
| A/Virginia/ATCC2/2009 | |||
| (2009 H1N1) | 1 x 102 TCID50/ml | + | - |
| A/PR/8/34 (H1N1) | 1 x 101 TCID50/ml | + | - |
| A/FM/1/47 (H1N1) | 1 x 101 CEID50/ml | + | - |
| A/Solomon Islands/3/2006 | |||
| like virus (H1N1) | 1 x 101 TCID50/ml | + | - |
| A/Mal/302/54 (H1N1) | 1 x 101 CEID50/ml | + | - |
| A/New Jersey/8/76 (H1N1) | 1 x 101 CEID50/ml | + | - |
| A/NWS/33 (H1N1) | 1 x 102 CEID50/ml | + | - |
| A1/Denver/1/57 (H1N1) | 1 x 103 CEID50/ml | + | - |
| A/Weiss/43 (H1N1) | 1 x 104 CEID50/ml | + | - |
| A/Victoria x187 (H3N2) | 1 x 101 TCID50/ml | + | - |
| A2/Aichi2/68 (H3N2) | 1 x 101 CEID50/ml | + | - |
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| Influenza strain | Concentration | Influenza A | Influenza B |
|---|---|---|---|
| A/Victoria/3/75 (H3N2) | 1 x 10¹ CEID50/ml | + | - |
| A/Alice (H3N2) | 1 x 10² EID50/ml | + | - |
| A/MRC2 (H3N2) | 1 x 10² CEID50/ml | + | - |
| A/Turkey/Germany 176/95 - | |||
| like (H9N2) | 1 x 10⁰ TCID50/ml | + | - |
| A/Duck/Potsdam 2243/84- | |||
| like (H5N6) | 1 x 10⁰ TCID50/ml | + | - |
| A/Swine/Iowa/15/30 (H1N1) | 1 x 10² CEID50/ml | + | - |
| A/Equine/2/Miami/63-like | |||
| (H3N8) | 1 x 10⁴ CEID50/ml | + | - |
| B/Lee/40 | 1 x 10¹ TCID50/ml | - | + |
| B/Allen/45 | 1 x 10¹ CEID50/ml | - | + |
| B/Taiwan/2/62 | 1 x 10¹ CEID50/ml | - | + |
| B/Hong Kong/5/72 | 1 x 10¹ CEID50/ml | - | + |
| B/Maryland/1/59 | 1 x 10¹ CEID50/ml | - | + |
| B/Malaysia/2506/2004 | 1 x 10¹ TCID50/ml | - | + |
Interfering Substances
The potential for blood or medications that might be present in a nasopharyngeal swab specimen to interfere with the detection of low levels of influenza A or influenza B by the artus Infl A/B RG RT-PCR test was evaluated. Human blood and substances representing the active ingredient in over-the-counter or prescription medications were tested. Each potentially interfering substance was evaluated in triplicate with each of two reference influenza strains, one influenza A strain and one influenza B strain. The reference influenza strains were successfully detected in all samples except for one aliquot containing the reference influenza B strain and Mupirocin at 10 mg/ml. The reference influenza B strain was successfully detected in three of three aliquots with Mupirocin at 2 mg/ml. (Mupirocin is an antibiotic ointment used to treat skin infections. The product tested contains Mupirocin at 20mg/g.). Substances tested are shown in Table 5..
| Source | Description /
Active Ingredient | Concentration |
|---------------|------------------------------------|------------------------|
| Blood (human) | Blood (human)† | 5% v/v |
| Visadron | Phenylephrine | 10% v/v
(125 µg/ml) |
| Table 5.8 Potentially interfering substances | ||
|---|---|---|
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| Source | Description /
Active Ingredient | Concentration | |
|--------------------------------------|------------------------------------|---------------------|--|
| Beclomet Nasal
Aqua (nasal spray) | Beclomethasone
dipropionate | 61.73 µg/ml | |
| Luffa opperculata | Luffa opperculata | 4.5 mg/ml | |
| Galphimia glauca | Galphimia glauca | 4.5 mg/ml | |
| Menthol | Menthol | 5 mg/ml | |
| Relenza | Zanamivir | 3 mg/ml | |
| Infectopyoderm
(ointment) | Mupirocin | 10 mg/ml,
2mg/ml | |
| Tobramaxin | Tobramycin | 0.3 mg/ml | |
- The human blood sample was stored frozen before testing.
Analytical Specificity
The analytical specificity of the artus Infl A/B RG RT-PCR Kit was evaluated by testing a panel of respiratory pathogens consisting of 21 non-target respiratory viruses and 18 bacterial strains. The pathogens were tested at medically relevant levels. Samples were prepared by diluting the cultured virus or bacteria in Universal Transport Medium. Each strain was extracted once and tested in triplicate. There were no false positive or invalid results among the 21 non-target respiratory viruses tested. Of the 18 bacterial strains evaluated, 16 were negative for influenza A and influenza B; two strains, Bordetella pertussis (at 104 cfu/ml) and Streptococcus pneumoniae (at 2 x 10° cfu/ml), were invalid in three of three replicates. Each strain was prepared at a one-log lower concentration, extracted once, and tested in triplicate. At the lower concentration each strain generated valid negative results for influenza A and influenza B in three of three replicates (Table 5.).
| Strain | Concentration | Influenza A | Influenza B |
|---|---|---|---|
| RSVA VR-26 | 10e5.0 TCID50/ml | - | - |
| RSVB VR-1400 | 10e4.45 TCID50/ml | - | - |
| PIV1 VR-94 | 10e3.45 TCID50/ml | - | - |
| PIV2 VR-92 | 10e5.0 TCID50/ml | - | - |
| PIV3 VR-93 | 10e5.0 TCID50/ml | - | - |
| PIV4a VR-1378 | 10e3.95 TCID50/ml | - | - |
| ADVE 4 VR-1572 | 10e5.0 TCID50/ml | - | - |
| Strain | Concentration | Influenza A | Influenza B |
| ADVB 3 VR-3 | 10e5.0 TCID50/ml | - | - |
| ADVC 5 VR-5 | 10e5.0 TCID50/ml | - | - |
| Echovirus 11 VR-41 | 10e5.0 TCID50/ml | - | - |
| Rhinovirus 1a VR-1559 | 10e5.0 TCID50/ml | - | - |
| Rhinovirus 39 VR-340 | 10e5.0 TCID50/ml | - | - |
| Coxsackie B1 VR-28 | 10e5.0 TCID50/ml | - | - |
| 229E VR-740 | 10e4.2 TCID50/ml | - | - |
| OC43 VR-1558 | 10e4.45 TCID50/ml | - | - |
| CMV VR-538 | 10e4.95 TCID50/ml | - | - |
| HSV VR-260 | 10e5.0 TCID50/ml | - | - |
| Varicella-zoster virus | |||
| VR-1367 | 10e3.95 TCID50/ml | - | - |
| EBV VR-603 | 10e3.0 cfu/ml | - | - |
| Measels VR-24 | 10e3.2 TCID50/ml | - | - |
| Mumps virus VR-106 | 10e5.0 TCID50/ml | - | - |
| Bordetella pertussis | 10e3.0 cfu/ml | Invalid* | Invalid* |
| Bordetella pertussis | 10e2.0 cfu/ml | - | - |
| Chlamydophila | |||
| pneumoniae | 10e5.0 TCID50/ml | - | - |
| Corynebacterium sp. | 10e3.0 cfu/ml | - | - |
| Escherichia coli | 10e6.0 cfu/ml | - | - |
| Hemophilus influenzae | 10e6.0 cfu/ml | - | - |
| Lactobacillus sp. | 10e3.0 cfu/ml | - | - |
| Legionella spp. | 9 x 10e5.0 bacteria/ml | - | - |
| Moraxella catarrhalis | 10e3.0 cfu/ml | - | - |
| Mycobacterium | |||
| tuberculosis avirulent | 10e2.0 cfu/ml | - | - |
| Mycoplasma | |||
| pneumoniae | 10e3.0 cfu/ml | - | - |
| Neisseria ssp. #14685 | 10e2.0 cfu/ml | - | - |
| Strain | Concentration | Influenza A | Influenza B |
| Neisseria meningitis | 10e6.0 bacteria/ml | - | - |
| Pseudomonas | |||
| aeruginosa | 10e6.0 cfu/ml | - | - |
| Staphylococcus aureus | |||
| Protein A producer | 10e6.0 bacteria/ml | - | - |
| Staphylococcus | |||
| epidermidis | 10e6.0 bacteria/ml | - | - |
| Streptococcus | |||
| pneumoniae | 2 x 10e5.0 cfu/ml | Invalid* | Invalid* |
| Streptococcus | |||
| pneumoniae | 2 x 10e4 cfu/ml | - | - |
| Streptococcus pyogenes | 10e3.0 cfu/ml | - | - |
| Streptococcus salivarius | 10e6.0 cfu/ml | - | - |
Table 5.9 Analytical specificity
15
ー
16
- Samples were invalid because influenza A and influenza B results were negative and the Cr of the IC was outside of the acceptance range for specimen validity. A second concentration was tested successfully and is presented below the "invalid" sample.
Competitive Inhibition
Competitive inhibition of the artus Infl A/B RG RT-PCR test was evaluated by testing samples containing reference strains A/California/7/09-like virus or B/Florida/4/2006like virus at the limit of detection (LoD) concentration of 10e1 TCIDsoml. Samples containing the influenza A reference strain also contained high levels of one of three competing influenza B strains while samples containing the influenza B reference strain also contained high levels of one of seven competing influenza A strains. Samples were extracted once and tested in triplicate with the artus Infl A/B RG RT-PCR Kit.
Detection of the reference influenza A strain was inhibited when the competing influenza B strains B/Florida/4/2006-like virus or B/Brisbane/60/2008-like virus was present at 10e5 TCIDso/ml; no inhibition was observed when the same competing virus strains were present at 10e4 TCID50ml. No inhibition was observed with the competing influenza B strain B/Malaysia/2506/2004. The reference influenza B strain was successfully detected in the presence of each of the seven competing Influenza A strains present at 10e5 TCID50/ml (Table 5.).
17
| Positive replicates/total replicates | |||
|---|---|---|---|
| Competing virus strain | Concentration | ||
| (TCID50/ml) | Influenza A | ||
| reference | |||
| strain | Influenza B | ||
| reference | |||
| strain | |||
| A/California/7/09-like virus | 10e5 | n/a* | 3/3 |
| A/Hong Kong/8/68 (TC | |||
| adapted) | 10e5 | n/a | 3/3 |
| A/PR/8/34 | 10e5 | n/a | 3/3 |
| A2/Wisconsin/67/2005 | 10e5 | n/a | 3/3 |
| A/Solomon Islands/3/2006 | |||
| (H1N1)-like virus | 10e5 | n/a | 3/3 |
| A/Duck/Potsdam 2243/84 | 10e5 | n/a | 3/3 |
| A/Brisbane/59/2007 | |||
| (H1N1)-like virus | 10e5 | n/a | 3/3 |
| B/Florida/4/2006-like virus | 10e5 | 1/3 | n/a |
| B/Florida/4/2006-like virus | 10e4 | 3/3 | n/a |
| B/Brisbane/60/2008-like | |||
| virus | 10e5 | 2/3 | n/a |
| B/Brisbane/60/2008-like | |||
| virus | 10e4 | 3/3 | n/a |
| B/Malaysia/2506/2004 | 10e5 | 3/3 | n/a |
Table 5.10 Competitive inhibition
Carryover / Cross Contamination
The artus Infl A/B RG RT-PCR test (including extraction using the EZ1 DSP Virus Kit with the EZ1 Advanced XL) showed no evidence of carryover or cross-contamination when 5 runs of a panel of 6 members of mock samples containing influenza A at a concentration just below the limit of detection of the assay were extracted and tested in alternating order with a panel of 6 members of mock samples of the same strain present at a high concentration.
18
Image /page/18/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS). The seal features a stylized eagle with three overlapping wings, representing the department's commitment to health, human services, and science. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" are arranged in a circular pattern around the eagle.
10903 New Hampshire Avenue Silver Spring, MD 20993
FEB - 6 2012
Oiagen GmbH c/o Hina Patel Associate Director, Regulatory and Clinical Affairs 1201 Clopper Road Gaithersburg, MD 20878
Re: K113323
Trade/Device Name: artus® Infl A/B RG RT-PCR Kit Regulation Number: 21 CFR§ 866.3980 Regulation Name: Respiratory viral panel multiplex nucleic acid assay Regulatory Class: Class II Product Code: OCC, OOI, JJH Dated: October 24, 2011 Received: November 10, 2011
Dear Ms. Patel:
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 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
19
Page 2 - Hina Patel
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,
Salla Agnis
Sally A. Hojvat, M.Sc., I Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
20
Indications for Use
510(k) Number (if known): K113323
Device Name: artus® Infl A/B RG RT-PCR Kit
Indications for Use:
The artus® Infl A/B RG RT-PCR Kit is a multiplex real time PCR in vitro diagnostic test for the qualitative detection and identification of Influenza A and Influenza B virus RNA in nasopharyngeal swab specimens using the Rotor-Gene® Q MDx instrument. The test is intended for use as an aid in the differential diagnosis of Influenza A and Influenza B viral infections in patients symptomatic for respiratory tract infection in conjunction with clinical and epidemiological risk factors. It is not intended to detect Influenza C virus.
Negative results do not preclude respiratory virus infection and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.
Performance characteristics for Influenza A were established during the 2009/2010 and 2010/2011 flu seasons when Influenza A (H3N2) and Influenza A/2009 (H1N1) were the predominant Influenza A viruses in circulation. When other Influenza A viruses emerge, performance characteristics may vary.
If infection with a novel Influenza A virus is suspected based on current clinical and evidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent influenza viruses and sent to state or local health departments for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
Prescription Use X (21 CFR 801 Subpart D)
And/Or
Over-The-Counter Use | | (21 CFR 807 Subpart C)
(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)
Tauran V. Feldberg
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K 113323
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10/24/2011