PROFLU+ ASSAY

K110968 · Gen-Probe Prodesse, Inc. · OCC · Jun 27, 2011 · Microbiology

Device Facts

Record IDK110968
Device NamePROFLU+ ASSAY
ApplicantGen-Probe Prodesse, Inc.
Product CodeOCC · Microbiology
Decision DateJun 27, 2011
DecisionSESE
Submission TypeTraditional
Regulation21 CFR 866.3980
Device ClassClass 2
AttributesPediatric

Intended Use

The ProFlu™+ Assay is a multiplex Real-Time PCR (RT-PCR) in vitro diagnostic test for the rapid and qualitative detection and discrimination of Influenza A Virus, Influenza B Virus, and Respiratory Syncytial Virus (RSV) nucleic acids isolated and purified from nasopharyngeal (NP) swab specimens obtained from symptomatic patients. This test is intended for use to aid in the differential diagnosis of Influenza A, Influenza B and RSV viral infections in humans and is not intended to detect Influenza C. Negative results do not preclude influenza or RSV virus infection and should not be used as the sole basis for treatment or other management decisions. Conversely, positive results do not ruleout bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease. The use of additional laboratory testing and clinical presentation must be considered in order to obtain the final diagnosis of respiratory viral infection. Performance characteristics for Influenza A Virus were established when Influenza A/H3 and A/H1 were the predominant Influenza A viruses in circulation (2006 - 2007 respiratory season). Performance characteristics for Influenza A were confirmed when Influenza A/H1, 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.

Device Story

The ProFlu+ Assay is a multiplex RT-PCR test for qualitative detection of Influenza A, Influenza B, and RSV (A/B) in nasopharyngeal swabs. The process involves: 1) Nucleic acid isolation/purification using Roche MagNA Pure LC or bioMérieux NucliSENS easyMAG systems; 2) Addition of Internal Control (IC) to monitor for inhibitors; 3) RT-PCR amplification and detection on the Cepheid SmartCycler II instrument. The assay uses Taqman chemistry where target-specific primers and dual-labeled probes (reporter/quencher) are used. Taq polymerase 5'-3' exonuclease activity cleaves the probe during amplification, releasing the reporter dye to generate a fluorescent signal. The SmartCycler Dx software monitors fluorescence in real-time to determine results. The device is used in clinical laboratories by trained personnel. Results aid clinicians in differential diagnosis of respiratory viral infections. The assay includes positive RNA transcript controls and an internal control to ensure procedural integrity and monitor for PCR inhibition.

Clinical Evidence

Performance established via comparison of reformulated assay to original ProFlu+ Assay using 233 prospectively collected archived samples (2008-2009). Concordance confirmed by bidirectional sequencing. Influenza A: 100% PPA, 99.4% NPA. Influenza B: 100% PPA, 100% NPA. RSV: 100% PPA, 99.0% NPA. Analytical specificity (cross-reactivity) tested against 58 respiratory pathogens with 100% specificity. Limit of Detection (LoD) for reformulated assay confirmed identical to original for all strains.

Technological Characteristics

Multiplex RT-PCR assay. Targets: Influenza A (Matrix gene), RSV A/B (Polymerase gene), Influenza B (NS1/NS2 genes). Chemistry: Taqman (5'-3' exonuclease activity). Instrumentation: Cepheid SmartCycler II. Detection: FAM, TET, Texas Red, Cy5 fluorophores. Internal control included for inhibition monitoring. Nucleic acid extraction via MagNA Pure LC or NucliSENS easyMAG.

Indications for Use

Indicated for symptomatic patients (adults and children) requiring differential diagnosis of Influenza A, Influenza B, and RSV viral infections via nasopharyngeal swab specimens.

Regulatory Classification

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.

Special Controls

*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.

Predicate Devices

Related Devices

Submission Summary (Full Text)

{0}------------------------------------------------ Gen-Probe Prodesse, Inc. ProFlu+ Assay 510(k) Submission K110968 Page 1 of 4 Date: June 20, 2011 ### Attachment D 510(k) SUMMARY ## CONTACT JUN 27 2011 Karen Harrington Gen-Probe Prodesse, Inc. W229 N1870 Westwood Dr. Waukesha, WI 53186 #### NAME OF DEVICE | Trade Name: | ProFlu+ <sup>TM</sup> Assay | |----------------------|------------------------------------------------------| | Regulation Number: | 21 CFR 866.3980 | | Classification Name: | Respiratory viral panel multiplex nucleic acid assay | #### PREDICATE DEVICE - K063765, K081483, K091677 ID Tag Respiratory Virus Panel, Luminex Molecular ● Diagnostics - . K073029, K081030, K092500 - ProFlu+ Assay, Gen-Probe Prodesse, Inc. #### INTENDED USE The ProFlu™+ Assay is a multiplex Real-Time PCR (RT-PCR) in vitro diagnostic test for the rapid and qualitative detection and discrimination of Influenza A Virus, Influenza B Virus, and Respiratory Syncytial Virus (RSV) nucleic acids isolated and purified from nasopharyngeal (NP) swab specimens obtained from symptomatic patients. This test is intended for use to aid in the differential diagnosis of Influenza A, Influenza B and RSV viral infections in humans and is not intended to detect Influenza C. Negative results do not preclude influenza or RSV virus infection and should not be used as the sole basis for treatment or other management decisions. Conversely, positive results do not ruleout bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease. The use of additional laboratory testing and clinical presentation must be considered in order to obtain the final diagnosis of respiratory viral infection. Performance characteristics for Influenza A Virus were established when Influenza A/H3 and A/H1 were the predominant Influenza A viruses in circulation (2006 - 2007 respiratory season). Performance characteristics for Influenza A were confirmed when Influenza A/H1, 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 {1}------------------------------------------------ Gen-Probe Prodesse, Inc. ProFlu+ Assay 510(k) Submission K110968 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 DESCRIPTION The ProFlu+ Assay enables detection and differentiation of Influenza A Virus. Influenza B Virus, Respiratory Syncytial Virus (Types A and B), and Internal Control. An overview of the procedure is as follows: - 1. Collect nasopharyngeal swab specimens from symptomatic patients using a polyester, rayon or nylon tipped swab and place into viral transport medium. - 2. Add an Internal Control (IC) to every sample to monitor for inhibitors present in the specimens. - 3. Perform isolation and purification of nucleic acids using a MagNA Pure LC System (Roche) and the MagNA Pure Total Nucleic Acid Isolation Kit (Roche) or a NucliSENS easyMAG System (bioMérieux) and the Automated Magnetic Extraction Reagents (bioMérieux). - 4. Add purified nucleic acids to Influenza A/Influenza B/RSV Mix along with enzymes included in the ProFlu+ Detection Kit. The Influenza A/Influenza B/RSV Mix contains oligonucleotide primers and target-specific oligonucleotide probes. The primers are complementary to highly conserved regions of genetic sequences for these respiratory viruses. The probes are dual-labeled with a reporter dye and a quencher (see table below). - 5. Perform reverse transcription of RNA into complementary DNA (cDNA) and subsequent amplification of DNA in a Cepheid SmartCycler II instrument. In this process, the probe anneals specifically to the template followed by primer extension and amplification. The ProFlu+ Assay is based on Taqman reagent chemistry, which utilizes the 5' - 3' exonuclease activity of the Taq polymerase to cleave the probe thus separating the reporter dye from the quencher. This generates an increase in fluorescent signal upon excitation from a light source. With each cycle, additional reporter dye molecules are cleaved from their respective probes, further increasing fluorescent signal. The amount of fluorescence at any given cycle is dependent on the amount of amplification products present at that time. Fluorescent intensity is monitored during each PCR cycle by the realtime instrument. | Analyte | Gene Targeted | Probe Fluorophore | Absorbance<br>Peak | Emission<br>Peak | Instrument<br>Channel | |----------------------------------|-------------------------------|-------------------------|--------------------|------------------|-----------------------| | Influenza A Virus | Matrix | FAM | 495 nm | 520 nm | FAM | | Respiratory Syncytial<br>Virus A | Polymerase | CAL Fluor<br>Orange 560 | 540 nm | 561 nm | TET | | Respiratory Syncytial<br>Virus B | Polymerase | CAL Fluor<br>Orange 560 | 540 nm | 561 nm | TET | | Influenza B Virus | Non-structural<br>NS1 and NS2 | CAL Fluor Red<br>610 | 595 nm | 615 nm | Texas Red | | Internal Control | NA | Quasar 670 | 647 nm | 667 nm | Cy5 | {2}------------------------------------------------ ## SUBSTANTIAL EQUIVALENCE ## Clinical Comparison Study The ProFlu+ Assay's supermix was reformulated and performance characteristics were established by comparing the reformulated assay to the original ProFlu+ Assay. All samples positive for IA, IB or RSV using either the current ProFlu+ Assay and/or the reformulated "New" ProFlu+ Assay were confirmed using bidirectional sequencing. The sequencing assays targeted either a different gene than the ProFlu+ Assay or targeted a different region of the same gene as the ProFlu+ Assay. Prospectively collected archived samples from respiratory season years 2008 and 2009 that were collected at two clinical study sites (Columbus, OH and Albuquerque, NM) were used for this study. "True" influenza A. influenza B or RSV positives were considered as any sample that tested positive for the respective analyte by the original ProFlu+ Assay. "True" Influenza A, Influenza B or RSV negatives were considered as any sample that tested negative by the original ProFlu+ Assay. ## Influenza A Comparison Results | | Current ProFlu+ Assay | | | | |----------------------------------|-----------------------|----------|-------|------------------------------------------------------------| | | Positive | Negative | Total | Comments | | New ProFlu+<br>Assay<br>Positive | 60 | 1* | 61 | Percent Positive Agreement 100%<br>(93.98%-100%) 95% CI | | New ProFlu+<br>Assay<br>Negative | 0 | 172 | 172 | Percent Negative Agreement 99.4%<br>(96.80%-99.90%) 95% CI | | Total | 60 | 173 | 233 | | * Sample was positive for Influenza A using bi-directional sequencing. ## Influenza B Comparison Results | | | Current ProFlu+ Assay | | | | |----------------------|----------|-----------------------|----------|-------|-----------------------------------------------------------| | | | Positive | Negative | Total | Comments | | New ProFlu+<br>Assay | Positive | 14 | 0 | 14 | Percent Positive Agreement 100%<br>(78.47% - 100%) 95% CI | | | Negative | 0 | 219 | 219 | Percent Negative Agreement 100%<br>(98.28% - 100%) 95% CI | | | Total | 14 | 219 | 233 | | {3}------------------------------------------------ ## Gen-Probe Prodesse, Inc. ProFlu+ Assay 510(k) Submission K110968 . . ## RSV Comparison Results | | Current ProFlu+ Assay | | | | |----------------------------------|-----------------------|----------|-------|------------------------------------------------------------| | | Positive | Negative | Total | Comments | | New ProFlu+<br>Assay<br>Positive | 35 | 2* | 37 | Percent Positive Agreement 100%<br>(90.11% - 100%) 95% CI | | New ProFlu+<br>Assay<br>Negative | 0 | .196 | 196 | Percent Negative Agreement 99.0%<br>(96.39%-99.72%) 95% CI | | Total | 35 | 198 | 233 | | * Two samples positive for RSV using bi-directional sequencing. {4}------------------------------------------------ #### DEPARTMENT OF HEALTH & HUMAN SERVICES Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular border with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" arranged around the top half of the circle. Inside the circle is a stylized image of an abstract human figure, with three faces overlapping and merging together, resembling a bird in flight. #### Public Health Service Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993 Gen-Probe Prodesse, Inc. c/o Karen Harrington, Ph.D. Manager, Clinical Affairs W229 N1870 Westwood Drive Waukesha, Wisconsin 53186 Re: K110968 JUN 2 7 2011 Trade/Device Name: ProFlu+"M assay Regulation Number: 21 CFR§ 866.3980 Regulation Name: Respiratory viral panel multiplex nucleic acid assay Regulatory Class: Class II Product Code: OCC, OOI . Dated: April 4, 2011 Received: April 6, 2011 Dear Dr. Harrington: 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 {5}------------------------------------------------ Page 2 - Karen Harrington 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/ReportalProblem/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, Huyatagmas Sally A. Hojvat, 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 {6}------------------------------------------------ # Indication for Use 510(k) Number (if known): K110968 Device Name: ProFlu+TM Assay #### Indication For Use: The ProFlu™+ Assay is a multiplex Real-Time PCR (RT-PCR) in vitro diagnostic test for the rapid and qualitative detection and discrimination of Influenza A Virus. Influenza B Virus, and Respiratory Syncytial Virus (RSV) nucleic acids isolated and purified from nasopharyngeal (NP) swab specimens obtained from symptomatic patients. This test is intended for use to aid in the differential diagnosis of Influenza A. Influenza B and RSV viral infections in humans and is not intended to detect Influenza C. Negative results do not preclude influenza or RSV virus infection and should not be used as the sole basis for treatment or other management decisions. Conversely, positive results do not rule-out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease. The use of additional laboratory testing and clinical presentation must be considered in order to obtain the final diagnosis of respiratory viral infection. Performance characteristics for Influenza A Virus were established when Influenza A/H3 and A/H1 were the predominant Influenza A viruses in circulation (2006 - 2007 respiratory season). Performance characteristics for Influenza A were confirmed when Influenza A/H1, 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. Prescription Use X (21 CFR Part 801 Subpart D) And/Or Over the Counter Use (21 CFR Part 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) Uwe Schlf Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety 510(k) k110968 .
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