(59 days)
Not Found
No
The device description details a standard Real Time PCR assay for detecting viral DNA. There is no mention of AI or ML in the process, performance studies, or key metrics.
No
This device is an in vitro diagnostic test for the qualitative detection of human Adenovirus (HAdV) DNA to aid in diagnosis, not for therapeutic purposes.
Yes
The "Intended Use / Indications for Use" section explicitly states that "The ProAdeno™+ Assay is a multiplex Real Time PCR in vitro diagnostic test for the qualitative detection of human Adenovirus (HAdV) DNA" and "This test is intended for use to aid in the diagnosis of HAdV infections in humans in conjunction with other clinical and laboratory findings."
No
The device description clearly outlines a multi-component system including reagents (Supermix, primers, probes), a nucleic acid isolation system (MagNA Pure LC System or NucliSENS® easyMAG™ System), and a real-time PCR instrument (Cepheid SmartCycler® II). While software is likely involved in the operation of the instruments and data analysis, the device itself is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states: "The ProAdeno™+ Assay is a multiplex Real Time PCR in vitro diagnostic test for the qualitative detection of human Adenovirus (HAdV) DNA..."
This statement clearly identifies the device as an in vitro diagnostic test.
N/A
Intended Use / Indications for Use
The ProAdeno™+ Assay is a multiplex Real Time PCR in vitro diagnostic test for the qualitative detection of human Adenovirus (HAdV) DNA isolated and purified from nasopharyngeal (NP) swab specimens obtained from individuals exhibiting signs and symptoms of acute respiratory infection. This test is intended for use to aid in the diagnosis of HAdV infections in humans in conjunction with other clinical and laboratory findings. The test detects, but does not differentiate, serotypes 1-51.
Negative results do not preclude HAdV infection and should not be used as the sole basis for treatment or other patient management decisions.
Product codes
OCC
Device Description
The ProAdeno+ Assay enables detection of human adenovirus and an Universal 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 Universal Internal Control (UIC) 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 ProAdeno+ Supermix included in the ProAdeno+ Assay Kit. The ProAdeno+ Mix contains oligonucleotide primers, target-specific oligonucleotide probes, and a Taq DNA polymerase. The primers are complementary to a highly conserved region of human adenovirus. 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). 5. Perform 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 ProAdeno+ Assay is based on Tagman 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 real-time instrument.
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
Performance characteristics of the ProAdeno+ Assay were established during a prospective study at 4 U.S. clinical laboratories from October 2009- August 2010. Samples used for this study were nasopharyngeal (NP) swab specimens that were collected for routine respiratory viral testing by each site.
The reference method was rapid culture (shell vial) followed by direct fluorescent antibody (DFA) screening and identification.
A total of 1167 NP swab samples were tested with the ProAdeno+ Assay and by culture. One sample that initially gave unresolved results remained unresolved upon retesting with the ProAdeno+ Assay and is not included in the analysis below. The sample was culture negative.
Discrepant analysis for samples where ProAdeno+ Assay and culture results were in disagreement was performed using PCR primers obtained from literature followed by sequencing.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Prospective Study:
Sample Size: 1166 NP swab samples
Sensitivity: 97.5% (87.1% - 94.3%) 95% CI
Specificity: 95.6% (94.3% - 96.7%) 95% CI
Results: 39 ProAdeno+ Assay Positive / Reference Method Positive; 49 ProAdeno+ Assay Positive / Reference Method Negative; 1 ProAdeno+ Assay Negative / Reference Method Positive; 1077 ProAdeno+ Assay Negative / Reference Method Negative.
Reproducibility Study:
Study type: Multi-site reproducibility study
Sample Size: 12 simulated clinical samples (adenovirus serotypes at medium and low positive levels, and two high negative samples) tested by 2 operators for 5 days at 3 laboratory sites (total 450 results for samples and controls).
Overall percent agreement for the ProAdeno+ Assay was 99.2%.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Sensitivity 97.5% (87.1% - 94.3%) 95% CI
Specificity 95.6% (94.3% - 96.7%) 95% CI
Overall percent agreement for the ProAdeno+ Assay (reproducibility) was 99.2%.
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
Page 1 of 5 Date: December 3, 2010
510(k) SUMMARY
CONTACT
Emily Ziegler Gen-Probe Prodesse, Inc. W229 N1870 Westwood Dr. Waukesha. WI 53186
DEL - : 2010
NAME OF DEVICE
Trade Name: Regulation Number: Classification Name: · ProAdeno™+ Assay 21 CFR 866.3980 Respiratory viral panel multiplex nucleic acid assay
PREDICATE DEVICE
INTENDED USE
The ProAdeno™+ Assay is a multiplex Real Time PCR in vitro diagnostic test for the qualitative detection of human Adenovirus (HAdV) DNA isolated and purified from nasopharyngeal (NP) swab specimens obtained from individuals exhibiting signs and symptoms of acute respiratory infection. This test is intended for use to aid in the diagnosis of HAdV infections in humans in conjunction with other clinical and laboratory findings. The test detects, but does not differentiate, serotypes 1-51.
Negative results do not preclude HAdV infection and should not be used as the sole basis for treatment or other patient management decisions.
1
PRODUCT DESCRIPTION .
The ProAdeno+ Assay enables detection of human adenovirus and an Universal Internal Control.
An overview of the procedure is as follows:
-
- Collect nasopharyngeal swab specimens from symptomatic patients using a polyester, rayon or nylon tipped swab and place into viral transport medium.
-
- Add Universal Internal Control (UIC) to every sample to monitor for inhibitors present in the specimens.
-
- 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).
-
- Add purified nucleic acids to ProAdeno+ Supermix included in the ProAdeno+ Assay Kit. The ProAdeno+ Mix contains oligonucleotide primers, target-specific oligonucleotide probes, and a Taq DNA polymerase. The primers are complementary to a highly conserved region of human adenovirus. 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).
-
- Perform 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 ProAdeno+ Assay is based on Tagman 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 real-time instrument.
| Analyte | Gene Targeted | Probe Fluorophore | Absorbance Peak | Emission Peak | Instrument Channel |
|---|---|---|---|---|---|
| Adenovirus | hexon | FAM | 495 nm | 520 nm | FAM |
| Universal Internal Control | NA | Quasar 670 | 647 nm | 667 nm | Cy5 |
2
SUBSTANTIAL EQUIVALENCE
Clinical Performance
Performance characteristics of the ProAdeno+ Assay were established during a prospective study at 4 U.S. clinical laboratories from October 2009- August 2010. Samples used for this study were nasopharyngeal (NP) swab specimens that were collected for routine respiratory viral testing by each site.
The reference method was rapid culture (shell vial) followed by direct fluorescent antibody (DFA) screening and identification.
A total of 1167 NP swab samples were tested with the ProAdeno+ Assay and by culture. One sample that initially gave unresolved results remained unresolved upon retesting with the ProAdeno+ Assay and is not included in the analysis below. The sample was culture negative.
Discrepant analysis for samples where ProAdeno+ Assay and culture results were in disagreement was performed using PCR primers obtained from literature followed by sequencing.
Results from Prospective Study
Adenovirus Comparison Results
| Reference Method | ||||
|---|---|---|---|---|
| Positive | Negative | Total | Comments | |
| ProAdeno |
- Assay
Positive | 39 | 49a | 88 | Sensitivity 97.5% (87.1% - 94.3%)
95% CI |
| ProAdeno - Assay
Negative | 1b | 1077 | 1078 | Specificity 95.6% (94.3% - 96.7%)
95% CI |
| Total | 40 | 1126 | 1166 | |
435 samples positive for HAdV by bi-directional sequence analysis, 14 samples negative for HAdV by bi-directional sequence analysis.
b1 sample negative for HAdV by bi-directional sequence analysis
3
.
| Age Group | Total (N) | Prospective
Total # Positive by
ProAdeno+ Assay | Observed Prevalence |
|-------------|-----------|-------------------------------------------------------|---------------------|
| 65 years | 89 | 0 | 0% |
| Total | 1166 | 88 | 7.5% |
4
Reproducibility
The reproducibility of the ProAdeno+ Assay was evaluated at 3 laboratory sites. Reproducibility was assessed using a panel of 12 simulated clinical samples that included two adenovirus serotypes at medium and low positive levels (near the assay limit of detection, > 95% positive) and two high negative samples (high negative-1 at 0.1xLoD; high negative-2 at 0.001xLoD). Panels and controls were tested at each site by 2 operators for 5 days (12 samples and 3 controls X 2 operators X 5 days X 3 sites = 450). The overall percent agreement for the ProAdeno+ Assay was 99.2%.
| | Panel
Member ID
Concentration | HAdV-3 high
negative-2"
0.001
X LoD | HAdV-3 high
negative-1
0.1X
LoD | HAdV-3 low positive
2X
LoD | HAdV-3 medium
positive
10X
LoD | HAdV-31 high
negative-2"
0.001
X LoD | HAdV-31 high
negative-1
0.1X
LoD | HAdV-31 low
positive
2X
LoD | HAdV-31 medium
positive
10X
LoD | Extraction
Control
N/A | Adenovirus DNA
Control
N/A | Negative Control"
N/A | Total % Agreement |
|---------|-----------------------------------------------|----------------------------------------------|------------------------------------------|----------------------------------|-----------------------------------------|-----------------------------------------------|-------------------------------------------|--------------------------------------|------------------------------------------|------------------------------|----------------------------------|--------------------------|-------------------|
| Site 1° | Agreement
with Expected
Result | 15/15 | 5/15b | 15/15 | 15/15 | 15/15 | 10/15b | 15/15 | 15/15 | 10/10 | 10/10 | 10/10 | 120/120d (100%) |
| | Mean CT
Value | 36.9 | 40.4c | 35.8 | 33.9 | 37.2 | 38.6c | 33.8 | 29.3 | 31.8 | 32.5 | 36.7 | |
| | % CV | 2.5 | 2.8c | 1.2 | 1.0 | 2.2 | 6.2c | 1.7 | 1.4 | 0.5 | 0.8 | 1.0 | |
| Site 2r | Agreement
with Expected
Result | 14/14 | 3/16b | 16/16 | 14/14 | 15/16 | 6/14b | 14/14 | 16/16 | 11/11 | 11/11 | 11/11 | 122/123d (99.2%) |
| | Mean CT
Value | 36.5 | 39.8c | 36.9 | 34.9 | 36.9 | 39.6c | 35.1 | 30.9 | 34.9 | 33.3 | 36.5 | |
| | % CV | 1.0 | 3.5c | 1.3 | 0.9 | 2.0 | 6.6c | 2.8 | 3.4 | 2.2 | 1.2 | 1.1 | |
| Site 3r | Agreement
with Expected
Result | 15/15 | 2/15b | 15/15 | 15/15 | 13/15 | 3/15b | 15/15 | 15/15 | 10/10 | 10/10 | 10/10 | 118/120d (98.3%) |
| | Mean CT
Value | 36.5 | 40.1c | 36.7 | 34.6 | 36.3 | 39.2c | 34.9 | 30.8 | 32.3 | 32.5 | 36.5 | |
| | % CV | 1.1 | 5.3c | 2.6 | 1.1 | 1.3 | 6.1c | 1.3 | 1.1 | 1.0 | 1.5 | 1.1 | |
| | Total
Agreement
with Expected
Result | 44/44 | 10/46b | 46/46 | 44/44 | 43/46 | 19/44b | 44/44 | 46/46 | 31/31 | 31/31 | 31/31 | 360/363d (99.2%) |
| | 95% CI | 92.0-
100% | N/A | 92.3-
100 | 92.0-
100% | 82.1-
98.6% | N/A | 92.0-
100% | 92.3-
100 | 88.8-
100% | 88.8-
100% | 88.8-
100% | 98.0-99.9% |
| | Overall Mean
CT Value | 36.6 | 40.2c | 36.5 | 34.4 | 36.8 | 39.0c | 34.6 | 30.3 | 33.1 | 32.8 | 36.6 | |
| | Overall
% CV | 1.8 | 3.1c | 2.2 | 1.6 | 2.1 | 6.1c | 2.6 | 3.3 | 4.5 | 1.7 | 1.1 | |
4Mean Cr calculated from Universal Internal Control
'Number of positive samples
· Average and %CV based on number of positive samples
4Does not include intermediate samples as those are at a concentration that is not reproducible
*Performed study using the bioMérieux NucliSENS easyMAG
Performed study using the Roche MagNA Pure
5
Image /page/5/Picture/0 description: The image shows the logo for the Department of Health & Human Services USA. The logo features a stylized eagle with three stripes representing the department's mission. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the eagle.
Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-0609 Silver Spring, MD 20993-0002
Gen-Probe Prodesse, Inc. c/o Emily Ziegler Research Associate III W229 N1870 Westwood Dr. Waukesha. WI 53186
DEC - 3 2010
Re: K102952
| Trade/Device Name: | ProAdeno™+ |
|---|---|
| Regulation Number: | 21 CFR §866.3980 |
| Regulation Name: | Respiratory viral panel multiplex nucleic acid assay |
| Regulatory Class: | Class II |
| Product Code: | OCC |
| Dated: | October 4, 2010 |
| Received: | October 5, 2010 |
Dear Ms. Ziegler:
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 In Incolumn include 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 1 (1) The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbrandi, insand adulteration.
ff 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 notification. The FDA finding of substantial equivalence of your device to a legally marketed
6
Page 2 - Emily Ziegler
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/McdicalDevices/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,
Satiyagn
Sally A. Hojvat, M.Sc., P Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
7
Indications for Use
510(k) Number (if known): K102952
Device Name: ProAdeno™+ Assay
Indication for Use:
The ProAdeno™+ Assay is a multiplex Real Time PCR in vitro diagnostic test for the qualitative detection of human Adenovirus (HAdV) DNA isolated and purified from nasopharyngeal (NP) swab specimens obtained from individuals exhibiting signs and symptoms of acute respiratory infection. This test is intended for use to aid in the diagnosis of HAdV infections in humans in conjunction with other clinical and laboratory findings. The test detects, but does not differentiate, serotypes 1-51.
Negative results do not preclude HAdV infection and should not be used as the sole basis for treatment or other patient 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)
Uve Schuf
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) lo2952