(221 days)
Not Found
No
The device description details a standard Real Time RT-PCR assay and analysis of fluorescent signals, with no mention of AI or ML algorithms for interpretation or other functions.
No
The device is an in vitro diagnostic test for the qualitative detection and discrimination of Parainfluenza nucleic acids, aiding in diagnosis. It does not provide any therapeutic function.
Yes
The "Intended Use / Indications for Use" section states: "The ProParaflu+ Assay is a multiplex Real Time RT-PCR in vitro diagnostic test for the qualitative detection and discrimination of Parainfluenza 1 Virus, Parainfluenza 2 Virus and Parainfluenza 3 Virus... The detection and discrimination of HPIV-1, HPIV-2 and HPIV-3 nucleic acids from symptomatic patients aid in the diagnosis of human respiratory tract parainfluenza infections..." This explicitly identifies it as an in vitro diagnostic test that aids in diagnosis.
No
The device is an in vitro diagnostic test that involves physical reagents, nucleic acid extraction, and a Real Time RT-PCR instrument (Cepheid SmartCycler® II). While software is used for analysis and interpretation, the core of the device is a hardware-based assay.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states: "The ProParaflu+ Assay is a multiplex Real Time RT-PCR in vitro diagnostic test for the qualitative detection and discrimination of Parainfluenza 1 Virus, Parainfluenza 2 Virus and Parainfluenza 3 Virus (HPIV-1, HPIV-2 and HPIV-3) nucleic acids isolated and purified from nasopharyngeal (NP) swab specimens..."
This statement clearly identifies the device as an in vitro diagnostic test.
N/A
Intended Use / Indications for Use
The ProParaflu+ Assay is a multiplex Real Time RT-PCR in vitro diagnostic test for the qualitative detection and discrimination of Parainfluenza 1 Virus, Parainfluenza 2 Virus and Parainfluenza 3 Virus (HPIV-1, HPIV-2 and HPIV-3) nucleic acids isolated and purified from nasopharyngeal (NP) swab specimens obtained from individuals exhibiting signs and symptoms of respiratory tract infections. This assay targets the conserved regions of the Hemagglutinin-Neuraminidase (HN) gene of HPIV-1, HPIV-2 and HPIV-3. respectively. The detection and discrimination of HPIV-1, HPIV-2 and HPIV-3 nucleic acids from symptomatic patients aid in the diagnosis of human respiratory tract parainfluenza infections if used in conjunction with other clinical and laboratory findings. This test is not intended to detect Parainfluenza 4a or Parainfluenza 4b Viruses.
Negative test results are presumptive and should be confirmed by cell culture. Negative results do not preclude Parainfluenza 1, 2 or 3 virus infections and should not be used as the sole basis for treatment or other management decisions.
Product codes
OQU
Device Description
The ProParaflu+ Assay enables the detection and differentiation of Parainfluenza 1 Virus, Parainfluenza 2 Virus, Parainfluenza 3 Virus and an Internal Control (IC) nucleic acid. Nasopharyngeal swab specimens from symptomatic patients using a polyester, rayon or nylon tipped swab and place into viral transport medium. The IC is added to every sample prior to nucleic acid extraction to monitor for inhibitors present in the specimens.
Isolation and purification of nucleic acids is performed using the bioMérieux NucliSENS easyMAG automated extractor and the Automated Magnetic Extraction Reagents or the Roche MagNA Pure LC Instrument and the MagNA Pure Total Nucleic Acid Isolation Kit.
The purified nucleic acids are added to the ProParaflu+ Supermix along with enzymes included in the ProParaflu+ Detection Kit. The ProParaflu+ Supermix contains oligonucleotide primers that are complementary to highly conserved regions of hemagglutinin neuraminidase gene for each human Parainfluenza type (1, 2 and 3). The probes are dual-labeled with a reporter dye attached to the 5'-end and a quencher dye attached to the 3'-end (see table below).
RT-PCR amplification is performed in a Cepheid SmartCycler® II instrument. During this process, the primers and probes anneal specifically to the template (if present) followed by primer extension and amplification. The ProParaflu+ Assay is based on Taqman 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 the fluorescent signal. The amount of fluorescence at any given cycle is dependent on the amount of amplification product present at that time. Fluorescent intensity is monitored during each PCR cycle by the real-time instrument. Results are analyzed and interpreted as presented by the software.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
nasopharyngeal (NP) swab specimens
Indicated Patient Age Range
Not Found
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
Prospective Study:
Study type: Clinical performance study.
Sample size: 857 eligible NP swab samples.
Data source: Specimens represented excess nasopharyngeal (NP) swab specimens that were prospectively collected from symptomatic individuals suspected of respiratory infection, and were submitted for routine analysis at 4 U.S. clinical laboratories during May 2008 - September 2009.
Annotation protocol: Performance of the ProParaflu+ Assay was compared to the reference method of cell culture (rapid or traditional) followed by direct fluorescent antibody (DFA) screening and HPIV type identification. Discrepant analysis for samples where ProParaflu+ Assay and culture results were in disagreement was performed using RT-PCR with virus specific primers obtained from literature® 9 (and different from those used in ProParaflu+) followed by bi-directional sequencing.
Retrospective Study:
Study type: Retrospective study.
Sample size: 91 frozen NP swab samples.
Data source: Samples that had been previously tested by direct DFA.
Annotation protocol: Not explicitly detailed beyond prior DFA testing.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Clinical Performance - Prospective Study:
Study type: Clinical performance, prospective study.
Sample size: 857 NP swab samples.
Key results:
- ProParaflu+ performed successfully on 99.2% (852/857) of samples on the first attempt.
- Parainfluenza 1 Comparison Results:
- Sensitivity 88.9% (67.2% - 96.9%) 95% CI
- Specificity 99.9% (99.3% - 100.0%) 95% CI
- Parainfluenza 2 Comparison Results:
- Sensitivity 96.3% (81.7% - 99.3%) 95% CI
- Specificity 99.8% (99.1% - 99.9%) 95% CI
- Parainfluenza 3 Comparison Results:
- Sensitivity 97.3% (86.2% - 99.5%) 95% CI
- Specificity 99.2% (98.1% - 99.5%) 95% CI
Clinical Performance - Retrospective Study:
Study type: Retrospective study (conducted due to minimal HPIV-1 positive samples in prospective study).
Sample size: 91 frozen NP swab samples.
Key results:
- Parainfluenza 1 Comparison Results:
- Sensitivity 82.8% (65.4% - 92.4%) 95% CI
- Specificity 100% (94.2% - 100%) 95% CI
Reproducibility Study:
Study type: Reproducibility study.
Sample size: Panel of 12 simulated samples tested at 3 laboratory sites by 2 operators for 5 days.
Key results: The overall percent agreement with the expected result for the ProParaflu+ Assay was 97.8%.
Additional Reproducibility Study:
Study type: Reproducibility study for intermediate concentration samples.
Key results:
- Percent positive for intermediate member across all sites: 56.7% for HPIV-1, 86.7% for HPIV-2, and 30.0% for HPIV-3. These results were expected as samples were lower concentration than the LoD.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Prospective Study:
- Parainfluenza 1: Sensitivity 88.9% (95% CI: 67.2% - 96.9%), Specificity 99.9% (95% CI: 99.3% - 100.0%)
- Parainfluenza 2: Sensitivity 96.3% (95% CI: 81.7% - 99.3%), Specificity 99.8% (95% CI: 99.1% - 99.9%)
- Parainfluenza 3: Sensitivity 97.3% (95% CI: 86.2% - 99.5%), Specificity 99.2% (95% CI: 98.1% - 99.5%)
Retrospective Study (HPIV-1 only):
- Parainfluenza 1: Sensitivity 82.8% (95% CI: 65.4% - 92.4%), Specificity 100% (95% CI: 94.2% - 100%)
Reproducibility:
- Overall percent agreement with expected result: 97.8%
Additional Reproducibility Study for intermediate concentration:
- HPIV-1: Total Agreement with Positive Result 56.7% (95% CI: 39.2% - 72.6%)
- HPIV-2: Total Agreement with Positive Result 86.7% (95% CI: 70.3% - 94.7%)
- HPIV-3: Total Agreement with Positive Result 30.0% (95% CI: 16.7% - 47.9%)
- Control samples: Total Agreement with Positive Result 100% (95% CI: 88.7 - 100%)
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.
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K09/053
Page 1 of 7 Date: November 5, 2009
Attachment D 510(k) SUMMARY
CONTACT
NOV 2 0 2009
Karen Harrington Gen-Probe Prodesse, Inc. W229 N1870 Westwood Dr. Waukesha, WI 53186
NAME OF DEVICE
Trade Name: Regulation Number: Classification Name:
ProParaflu+TM Assay 21 CFR 866.3980 Respiratory viral panel multiplex nucleic acid assay
PREDICATE DEVICE
K063765 - ID Tag Respiratory Virus Panel, Luminex Molecular Diagnostics
INTENDED USE
The ProParaflu+ Assay is a multiplex Real Time RT-PCR in vitro diagnostic test for the qualitative detection and discrimination of Parainfluenza 1 Virus, Parainfluenza 2 Virus and Parainfluenza 3 Virus (HPIV-1, HPIV-2 and HPIV-3) nucleic acids isolated and purified from nasopharyngeal (NP) swab specimens obtained from individuals exhibiting signs and symptoms of respiratory tract infections. This assay targets the conserved regions of the Hemagglutinin-Neuraminidase (HN) gene of HPIV-1, HPIV-2 and HPIV-3, respectively. The detection and discrimination of HPIV-1, HPIV-2 and HPIV-3 nucleic acids from symptomatic patients aid in the diagnosis of human respiratory tract parainfluenza infections if used in conjunction with other clinical and laboratory findings. This test is not intended to detect Parainfluenza 4a or Parainfluenza 4b Viruses.
Negative test results are presumptive and should be confirmed by cell culture. Negative results do not preclude Parainfluenza 1, 2 or 3 virus infections and should not be used as the sole basis for treatment or other management decisions.
PRODUCT DESCRIPTION
The ProParaflu+ Assay enables the detection and differentiation of Parainfluenza 1 Virus, Parainfluenza 2 Virus, Parainfluenza 3 Virus and an Internal Control (IC) nucleic acid. Nasopharyngeal swab specimens from symptomatic patients using a polyester, rayon or nylon tipped swab and place into viral transport medium. The IC is added to every sample prior to nucleic acid extraction to monitor for inhibitors present in the specimens.
Isolation and purification of nucleic acids is performed using the bioMérieux NucliSENS
1
easyMAG automated extractor and the Automated Magnetic Extraction Reagents or the Roche MagNA Pure LC Instrument and the MagNA Pure Total Nucleic Acid Isolation Kit.
The purified nucleic acids are added to the ProParaflu+ Supermix along with enzymes included in the ProParaflu+ Detection Kit. The ProParaflu+ Supermix contains oligonucleotide primers that are complementary to highly conserved regions of hemagglutinin neuraminidase gene for each human Parainfluenza type (1, 2 and 3). The probes are dual-labeled with a reporter dye attached to the 5'-end and a quencher dye attached to the 3'-end (see table below).
RT-PCR amplification is performed in a Cepheid SmartCycler® II instrument. During this process, the primers and probes anneal specifically to the template (if present) followed by primer extension and amplification. The ProParaflu+ Assay is based on Taqman 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 the fluorescent signal. The amount of fluorescence at any given cycle is dependent on the amount of amplification product present at that time. Fluorescent intensity is monitored during each PCR cycle by the real-time instrument. Results are analyzed and interpreted as presented by the software.
| Analyte | Gene Targeted | Probe
Fluorophore | Absorbance
Peak | Emission
Peak | Instrument
Channel |
|--------------------------|--------------------------------|----------------------|--------------------|------------------|-----------------------|
| Parainfluenza 1
Virus | Hemagglutinin
neuraminidase | FAM | 495 nm | 520 nm | FAM |
| Parainfluenza 3
Virus | Hemagglutinin
neuraminidase | Cal Orange 560 | 540 nm | 561 nm | TET |
| Parainfluenza 2
Virus | Hemagglutinin
neuraminidase | Cal Red 610 | 595 nm | 615 nm | Texas Red |
| Internal Control | NA | Quasar 670 | 647 nm | 667 nm | Cy5 |
2
SUBSTANTIAL EQUIVALENCE
Clinical Performance
The clinical performance of the ProParaflu+ Assay was established during a prospective study at 4 U.S. clinical laboratories during May 2008 - September 2009. Specimens used in the study represented excess nasopharyngeal (NP) swab specimens that were prospectively collected from symptomatic individuals suspected of respiratory infection, and were submitted for routine analysis. Demographic details for this patient population are summarized in the following table.
| Sex | Number of Subjects |
|---|---|
| Female | 407 (47.5%) |
| Male | 450 (52.5%) |
| Age (yrs) | |
| ≤ 5 years | 580 (67.7%) |
| 6 - 21 years | 168 (19.6%) |
| 22 - 59 years | 67 (7.8%) |
| ≥ 60 years | 42 (4.9%) |
Gender and Age Demographic Detail for ProParaflu+ Prospective Study
Performance of the ProParaflu+ Assay was compared to the reference method of cell culture (rapid or traditional) followed by direct fluorescent antibody (DFA) screening and HPIV type identification.
A total of 857 eligible NP swab samples were tested with the ProParaflu+ Assay and by culture across four clinical sites. Of the ProParaflu+ Assay run on all eligible specimens, 99.2% (852/857) of these specimens were successful on the first attempt. The remaining 5 gave "Unresolved" results on the first attempt. Unresolved results occur when the sample is negative for all three HPIVs and the Internal Control, indicating potentially PCR-inhibiting samples. Of the 5 "Unresolved" specimens on the first attempt, 60.0% (3/5) gave a valid result on the second attempt. The remaining 2 were "Unresolved" on the second attempt and are not included in the analysis below. Both samples were culture negative.
Discrepant analysis for samples where ProParaflu+ Assay and culture results were in disagreement was performed using RT-PCR with virus specific primers obtained from literature® 9 (and different from those used in ProParaflu+) followed by bi-directional sequencing.
3
Prospective Study
| Culture/DFA | |||||
|---|---|---|---|---|---|
| Positive | Negative | Total | |||
| ProParaflu+ | |||||
| Assay | Positive | 16 | 1a | 17 | Sensitivity 88.9% (67.2% - 96.9%) 95% CI |
| Negative | 2b | 838 | 840 | Specificity 99.9% (99.3% - 100.0%) 95% CI | |
| Total | 18 | 839 | 857 |
Parainfluenza 1 Comparison Results
4One (1) sample positive for HPIV-1 by bi-directional sequence analysis.
bTwo (2) samples negative for HPIV-1 by bi-directional sequence analysis. One sample positive for HPIV-3 by ProParaflu+ and bi-directional sequence analysis.
Parainfluenza 2 Comparison Results
| Culture/DFA | |||||
|---|---|---|---|---|---|
| Positive | Negative | Total | |||
| ProParaflu+ | |||||
| Assay | Positive | 26 | 2a | 28 | Sensitivity 96.3% (81.7% - 99.3%) |
| 95% CI | |||||
| Negative | 1b | 828 | 829 | Specificity 99.8% (99.1% - 99.9%) | |
| 95% CI | |||||
| Total | 27 | 830 | 857 |
4Two (2) samples positive for HPIV-2 by bi-directional sequence analysis.
bOne (1) sample negative for HPIV-2 by bi-directional sequence analysis.
Parainfluenza 3 Comparison Results
| Culture/DFA | |||||
|---|---|---|---|---|---|
| Positive | Negative | Total | |||
| ProParaflu+ | |||||
| Assay | Positive | 36 | 8a | 44 | Sensitivity 97.3% (86.2% - 99.5%) |
| 95% CI | |||||
| Negative | 1b | 812 | 813 | Specificity 99.2% (98.1% - 99.5%) | |
| 95% CI | |||||
| Total | 37 | 820 | 857 |
4Seven (7) samples positive for HPIV-3 and one (1) sample negative for HPIV-3 by bidirectional sequence analysis.
bone (1) sample negative for HPIV-3 by bi-directional sequence analysis.
4
Retrospective Study
Due to a minimal number of HPIV-1 positive samples, a retrospective study was also conducted using a total of 91 frozen NP swab samples that had been previously tested by direct DFA. Demographic details for this patient population are summarized in the following table.
Gender and Age Demographic Detail for ProParaflu+ Retrospective Study
| Sex | Number of Subjects |
|---|---|
| Female | 40 (44.4%) |
| Male | 50 (55.6%) |
| Age (yrs) | |
| ≤ 5 years | 81 (90.0%) |
| 6 - 21 years | 5 (5.6%) |
| 22 – 59 years | 2 (2.2%) |
| ≥ 60 years | 2 (2.2%) |
Parainfluenza 1 Comparison Results
| DFA | |||||
|---|---|---|---|---|---|
| Positive | Negative | Total | |||
| ProParaflu+ | |||||
| Assay | Positive | 24 | 0 | 24 | Sensitivity 82.8% (65.4% - 92.4%) |
| 95% CI | |||||
| Negative | 5a | 62 | 67 | Specificity 100% (94.2% - 100%) | |
| 95% CI | |||||
| Total | 29 | 62 | 91 |
4Five (5) samples negative for HPIV-1 by bi-directional sequence analysis.
5
ProParaflu Assay 510(k) Submission
Reproducibility
The reproducibility of the ProParaflu+ Assay was evaluated at 3 laboratory sites. Reproducibility was assessed using a panel of 12 simulated samples that included medium positive, low positive (near the assay limit of detection, ≥95% positive), intermediate (1 log below the assay limit of detection), and high negative (below the assay limit of detection, Trade/Device Name: ProParaflu+ "M Assay Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory viral panel multiplex nucleic acid assay Regulatory Class: Class II Product Code: OQU Dated: October 14, 2009 Received: October 15, 2009
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 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.
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
8
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,
Fally weArb
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
9
Indication for Use
510(k) Number (if known): K091053
Device Name: ProParaflu+TM Assay
Indication For Use:
The ProParaflu+ Assay is a multiplex Real Time RT-PCR in vitro diagnostic test for the qualitative detection and discrimination of Parainfluenza 1 Virus, Parainfluenza 2 Virus and Parainfluenza 3 Virus (HPIV-1, HPIV-2 and HPIV-3) nucleic acids isolated and purified from nasopharyngeal (NP) swab specimens obtained from individuals exhibiting signs and symptoms of respiratory tract infections. This assay targets the conserved regions of the Hemagglutinin-Neuraminidase (HN) gene of HPIV-1, HPIV-2 and HPIV-3. respectively. The detection and discrimination of HPIV-1, HPIV-2 and HPIV-3 nucleic acids from symptomatic patients aid in the diagnosis of human respiratory tract parainfluenza infections if used in conjunction with other clinical and laboratory findings. This test is not intended to detect Parainfluenza 4a or Parainfluenza 4b Viruses.
Negative test results are presumptive and should be confirmed by cell culture. Negative results do not preclude Parainfluenza 1, 2 or 3 virus infections and should not be used as the sole basis for treatment or other management decisions.
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)
the Schuf
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K091053