(22 days)
The ProFAST™+ Assay is a multiplex Real Time RT-PCR in vitro diagnostic test for the qualitative detection and discrimination of seasonal Influenza A/H1, seasonal Influenza A/H3 and 2009 H1N1 Influenza viral nucleic acids isolated and purified from nasopharyngeal (NP) swab specimens from human patients with signs and symptoms of respiratory infection in conjunction with clinical and epidemiological risk factors. This assay targets conserved regions of the Hemagglutinin (HA) gene for seasonal Influenza A/H1, seasonal Influenza A/H3 and 2009 H1N1 Influenza Virus, respectively. This assay is not intended to detect Influenza B or Influenza C Viruses.
A negative ProFAST+ Assay result is a presumptive negative result for Influenza A. These results should be confirmed by an FDA cleared nucleic acid-based test (NAT) detecting Influenza A.
Negative results do not preclude Influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions.
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.
The ProFAST+ Assay enables detection and discrimination of Influenza A Virus subtypes: seasonal H1, seasonal H3, and 2009 H1N1.
An overview of the procedure is as follows:
- Collect nasopharyngeal swab specimens from symptomatic patients using a polyester, ravon, or nylon tipped swab and place into viral transport medium (refer to Materials Required but not Provided section of this Instruction for Use).
- Add an Internal Control (IC) to every sample to monitor for inhibitors present in the specimens.
- Perform isolation and purification of nucleic acids using a MagNA Pure LC Instrument (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 the ProFAST+ Supermix along with enzymes included in the ProFAST+ kit. The ProFAST+ Supermix contains target-specific oligonucleotide primers and probes. The primers are complementary to conserved regions of the Hemagglutinin (HA) gene for seasonal influenza A/H1, seasonal influenza A/H3 and 2009 H1N1 Influenza Virus (swine-origin), respectively. The probes are dual-labeled with a reporter dye and a quencher dye (see table below).
- 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 ProFAST+ 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 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.
Here's a summary of the acceptance criteria and study details for the ProFAST+ Assay based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the "Positive Percent Agreement" and "Negative Percent Agreement" values, along with their 95% Confidence Intervals. For the reproducibility study, the acceptance criterion is an "overall percent agreement with the expected result" of 99.7%.
| Analyte (Clinical Performance - Prospective Study) | Acceptance Criteria (Implied) | Reported Device Performance (95% CI) |
|---|---|---|
| Seasonal Influenza A/H1 (Positive) | High Positive Percent Agreement | 100.0% (93.2% - 100.0%) |
| Seasonal Influenza A/H1 (Negative) | High Negative Percent Agreement | 99.0% (98.0% - 99.5%) |
| Seasonal Influenza A/H3 (Positive) | High Positive Percent Agreement | 100.0% (86.7% - 100.0%) |
| Seasonal Influenza A/H3 (Negative) | High Negative Percent Agreement | 99.6% (98.9% - 99.9%) |
| 2009 H1N1 Influenza (Positive) | High Positive Percent Agreement | 95.4% (87.3% - 98.4%) |
| 2009 H1N1 Influenza (Negative) | High Negative Percent Agreement | 100.0% (99.5% - 100.0%) |
| Analyte (Clinical Performance - Retrospective Study) | Acceptance Criteria (Implied) | Reported Device Performance (95% CI) |
| Seasonal Influenza A/H1 (Positive) | High Positive Percent Agreement | 94.4% (74.3% - 99.0%) |
| Seasonal Influenza A/H1 (Negative) | High Negative Percent Agreement | 99.3% (96.1% - 99.9%) |
| Seasonal Influenza A/H3 (Positive) | High Positive Percent Agreement | 100.0% (94.9% - 100.0%) |
| Seasonal Influenza A/H3 (Negative) | High Negative Percent Agreement | 100.0% (95.8% - 100.0%) |
| 2009 H1N1 Influenza (Positive) | High Positive Percent Agreement | 100.0% (86.7% - 100.0%) |
| 2009 H1N1 Influenza (Negative) | High Negative Percent Agreement | 100.0% (97.2% - 100.0%) |
| Reproducibility | Overall Percent Agreement ≥ 99.7% with expected result | 99.7% (628/630) (95% CI: 98.8% - 99.9%) |
2. Sample Size Used for the Test Set and Data Provenance
- Prospective Study:
- Sample Size: 842 eligible prospective NP swab specimens (initially 874, but 32 were excluded).
- Data Provenance: U.S. clinical laboratories (4 sites), collected between December 2009 and May 2010. Also included prospectively collected archived samples (from January-March, 2008, February-March, 2009, and October-November, 2009) due to absence of seasonal influenza during the 2009-2010 winter season. These represented "excess, remnants of nasopharyngeal (NP) swab specimens that were prospectively collected from symptomatic individuals suspected of respiratory infection, and were submitted for routine care or analysis by each site, and that otherwise would have been discarded."
- Retrospective Study:
- Sample Size: 160 retrospective nasopharyngeal (NP) swab samples.
- Data Provenance: Two clinical sites, collected from January-March, 2008, January-November 2009, and March 2010.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not specify the number or qualifications of experts involved in establishing the ground truth. The ground truth was established by a "composite comparator/reference method."
4. Adjudication Method for the Test Set
The document does not describe an explicit adjudication method between human experts, as the ground truth was established by a composite of laboratory tests rather than expert consensus on interpretation. It mentions that samples were "considered as any sample that was tested positive for Influenza A by the ProFlu+ Assay, and had bidirectional sequencing data meeting pre-defined quality acceptance criteria."
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not performed. This is a diagnostic test (RT-PCR assay) intended for standalone use, not an imaging device requiring human reader interpretation, so this type of study would not be applicable.
6. If a Standalone Study Was Done
Yes, a standalone study (algorithm/device-only performance without human-in-the-loop performance) was done. The ProFAST+ Assay's performance was compared directly against a composite reference method. The clinical performance data (Positive and Negative Percent Agreements) reflect the standalone performance of the device.
7. The Type of Ground Truth Used
The ground truth used was a composite comparator/reference method consisting of:
- FDA cleared ProFlu+ Assay (another nucleic acid-based test for Influenza A).
- Individual well-characterized Influenza A subtype-specific RT-PCR assays.
- Bi-directional sequencing (targeting different regions of the hemagglutinin gene than the ProFAST+ Assay).
"True" positives required:
- Positive for Influenza A by ProFlu+ Assay
- And bidirectional sequencing data meeting pre-defined quality acceptance criteria, matching seasonal A/H1, A/H3, or A/2009 H1N1 sequences in the NCBI GenBank database with acceptable E-values.
"True" negatives required:
- Negative for Influenza A by ProFlu+ Assay
- OR positive for Influenza A by ProFlu+ Assay but negative by the respective Influenza A subtype-specific RT-PCR assay followed by bi-directional sequencing.
8. The Sample Size for the Training Set
The document does not explicitly state the sample size used for a training set. The clinical performance studies describe the evaluation of the device using prospective and retrospective samples, implying these are test sets rather than training sets. Typically for an in vitro diagnostic (IVD) assay like this, development and optimization (which might use internal "training-like" datasets) are usually completed before the formal clinical validation described in the 510(k) summary.
9. How the Ground Truth for the Training Set Was Established
Since a distinct "training set" is not explicitly mentioned as part of this premarket notification validation, the method for establishing its ground truth is not detailed. For typical IVD development, internal positive and negative controls, spiked samples, and characterized clinical samples would be used during development and optimization phases.
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Page 1 of 7 Date: July 21, 2010
Attachment D 510(k) SUMMARY
CONTACT
Karen Harrington Gen-Probe Prodesse, Inc. W229 N1870 Westwood Dr. Waukesha, WI 53186
JUL 2 3 2010
NAME OF DEVICE
| Trade Name: |
|---|
| Regulation Number: |
| Classification Name: |
ProFAST+TM Assay 21 CFR 866.3980 Respiratory viral panel multiplex nucleic acid assay
PREDICATE DEVICE
- K063765, K081483, K091677 ID Tag Respiratory Virus Panel, Luminex Molecular . Diagnostics
- K080570 Human Influenza Virus Real Time RT-PCR Detection and Characterization . Panel. CDC
- K100148 Simplexa Influenza A H1N1 (2009), Focus Diagnostics .
- . K073029. K081030. K092500 - ProFlu+ Assav. Gen-Probe Prodesse, Inc.
INTENDED USE
The ProFAST™+ Assay is a multiplex Real Time RT-PCR in vitro diagnostic test for the qualitative detection and discrimination of seasonal Influenza A/H1, seasonal Influenza A/H3 and 2009 H1N1 Influenza viral nucleic acids isolated and purified from nasopharyngeal (NP) swab specimens from human patients with signs and symptoms of respiratory infection in conjunction with clinical and epidemiological risk factors. This assay targets conserved regions of the Hemagglutinin (HA) gene for seasonal Influenza A/H1, seasonal Influenza A/H3 and 2009 H1N1 Influenza Virus, respectively. This assay is not intended to detect Influenza B or Influenza C Viruses.
A negative ProFAST+ Assay result is a presumptive negative result for Influenza A. These results should be confirmed by an FDA cleared nucleic acid-based test (NAT) detecting Influenza A.
Negative results do not preclude Influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions.
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.
{1}------------------------------------------------
PRODUCT DESCRIPTION
The ProFAST+ Assay enables detection and discrimination of Influenza A Virus subtypes: seasonal H1, seasonal H3, and 2009 H1N1.
An overview of the procedure is as follows:
-
- Collect nasopharyngeal swab specimens from symptomatic patients using a polyester, ravon, or nylon tipped swab and place into viral transport medium (refer to Materials Required but not Provided section of this Instruction for Use).
-
- Add an Internal Control (IC) to every sample to monitor for inhibitors present in the specimens.
-
- Perform isolation and purification of nucleic acids using a MagNA Pure LC Instrument (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 the ProFAST+ Supermix along with enzymes included in the ProFAST+ kit. The ProFAST+ Supermix contains target-specific oligonucleotide primers and probes. The primers are complementary to conserved regions of the Hemagglutinin (HA) gene for seasonal influenza A/H1, seasonal influenza A/H3 and 2009 H1N1 Influenza Virus (swine-origin), respectively. The probes are dual-labeled with a reporter dye and a quencher dye (see table below).
-
- 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 ProFAST+ 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 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 | AbsorbancePeak | EmissionPeak |
|---|---|---|---|---|
| Seasonal H1 Influenza A | Hemagglutinin | FAM | 495 nm | 520 nm |
| Seasonal H3 Influenza A | Hemagglutinin | Cal Fluor Orange 560 | 540 nm | 561 nm |
| 2009 H1N1 Influenza Virus | Hemagglutinin | Cal Fluor Red 610 | 595 nm | 615 nm |
| Internal Control | E.coli MS2 Phage A-Protein | Quasar 670 | 647 nm | 667 nm |
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SUBSTANTIAL EQUIVALENCE
Clinical Performance
The clinical performance of the ProFAST+ Assay was established during prospective studies at 4 U.S. clinical laboratories. NP swab samples were collected and tested at three U.S. clinical laboratories during December 2009 thru May 2010. Due to the absence of seasonal (HINI or H3N2) and 2009 H1N1 Influenza A during the typical 2009-2010 winter season, prospectively collected archived samples were also included in the prospective studies. These samples were collected from January - March, 2008, February - March, 2009 and October - November, 2009, and tested at two U.S. clinical laboratories. All specimens used in the study meeting the inclusion and exclusion criteria represented excess, remnants of nasopharyngeal (NP) swab specimens that were prospectively collected from symptomatic individuals suspected of respiratory infection, and were submitted for routine care or analysis by each site, and that otherwise would have been discarded.
Demographic details for the patient population included in the prospective study are summarized in the following table.
| Sex | Number of Subjects |
|---|---|
| Female | 439 (52.1%) |
| Male | 403 (47.9%) |
| Age | |
| ≤ 5 years | 439 (52.1%) |
| 6 - 21 years | 184 (21.9%) |
| 22 - 59 years | 168 (20.0%) |
| ≥ 60 years | 51 (6.0%) |
Gender and Age Demographic Detail for ProFAST+ Prospective Study
Performance of the ProFAST+ Assay was assessed and compared to the composite comparator/reference method of the FDA cleared ProFlu+ Assay and individual well characterized Influenza A subtype specific RT-PCR assays followed by bi-directional sequencing. The sequencing assays targeted different regions of the hemagglutinin gene than the ProF AST+ Assay and were specific for each of the Influenza A subtypes (A/H1, A/H3, and A/2009 HIN1). "True" seasonal A/H1, A/H3 or A/2009 H1N1 RNA positives, were considered as any sample that was tested positive for Influenza A by the ProFlu+ Assay, and had bidirectional sequencing data meeting pre-defined quality acceptance criteria, for both the forward and the reverse sequences that matched seasonal A/H1, A/H3, and A/2009 H1N1 sequences deposited in the National Center for Biotechnology Information (NCBI) GenBank database (www.ncbi.nlm.nih.gov), respectively, with acceptable E-values. "True" seasonal A/H1, A/H3 or A/2009 H1N1 RNA negatives were considered as any sample that was tested negative for Influenza A by the ProFlu+ Assay IVD, or any sample that was tested positive for Influenza A by the ProFlu+ Assay IVD, but was tested negative by the respective Influenza A subtype specific RT-PCR assay followed by bi-directional sequencing. Nucleic acid extractions on the clinical samples were carried out using either the Roche MagNA Pure LC system or the bioMérieux NucliSENS easyMAG during the clinical study.
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A total of 874 prospective NP swab specimens were initially included in the prospective clinical trial. Thirty two (32) samples were excluded from the prospective clinical study data analysis because they remained "Unresolved" after repeat testing for either the ProFlu+ Assay (comparator assay), or the ProFAST+ Assay, or both assays, resulted in a total 842 eligible prospective specimens to be included in the prospective clinical study data analysis.
Of the prospective specimens run using the ProFAST+ Assay, 98.9% (864/874) of these specimens were successful on the first attempt. The remaining 10 (10/874 = 1.1%) gave "Unresolved" results on the first attempt. Unresolved results occur when the sample is negative for all three Influenza A subtype markers and the Internal Control, indicating potentially PCRinhibiting samples. Of the 10 "Unresolved" specimens on the first attempt with sufficient nucleic acid for retest, only 50.0% (5/10) gave a valid result on the second attempt (3 from Site 1, 1 from site 2, and 1 from Site 3). The remaining 5 were "Unresolved" on the second attempt.
| ProFlu+/Sequencing | |||||
|---|---|---|---|---|---|
| Positive Negative | Total | ||||
| oFAST Assay | Positive | રે રે | ga | 61 | Positive PercentAgreement=100.0%(93.2% - 100.0%) 95% CI |
| Negative | 0 | 781 | .781 | Negative PercentAgreement=99.0%(98.0% - 99.5%) 95% CI | |
| Total | રે રે | 789 | 842 |
Seasonal Influenza A/H1 Comparison Results
a Two (2) samples were negative for Influenza A by the ProFlu+ Assay, but positive for seasonal A/H1 by bi-directional sequence analysis. One (1) sample was negative for Influenza A by the ProFlu+ Assay, and negative for seasonal A/H1 by bidirectional sequence analysis, but positive for Influenza A, un-subtyptable, by the FDA cleared CDC rRT-PCR Influenza Panel. Five (5) samples were positive for Influenza A by the ProFlu+ Assay, negative for A/H1, A/H3 and A/2009 H1N1 by bidirectional sequence analysis, but positive for A/H1 by the FDA cleared CDC rRT-PCR Influenza Panel.
Seasonal Influenza A/H3 Comparison Results
| ProFlu+/Sequencing | ||||||
|---|---|---|---|---|---|---|
| Positive | Negative | Total | ||||
| ProFAST+Assay | Positive | 25 | 3a | 28 | Positive PercentAgreement=100.0%(86.7% - 100.0%) 95% CI | |
| Negative | 0 | 814 | 814 | Negative PercentAgreement=99.6%(98.9% - 99.9%) 95% CI | ||
| Total | 25 | 817 | 842 |
4 One (1) sample was negative for Influenza A by the ProFlu+ Assay, also negative for seasonal A/H1 and A/H3, and A/2009 H1N1 by bi-directional sequence analysis. One (1) sample was positive for Influenza A by the ProPlu+ Assay, negative for A/H1, A/H3 and A/2009 H1N1 by bi-directional sequence analysis, but positive for A/H3 by the FDA cleared CDC rRT-PCR Influenza Panel. One (1) sample was positive for Influenza A by the ProFit+ for A/H/ and negative for A/H3 and A/2009 H1N1 by bi-directional sequence analysis.
{4}------------------------------------------------
| 2009 H1N1 Influenza Comparison Results | ||
|---|---|---|
| ProFlu+/Sequencing | ||||||
|---|---|---|---|---|---|---|
| Positive | Negative | Total | ||||
| ProFAST+Assay | Positive | 62 | 0 | 62 | Positive PercentAgreement=95.4%(87.3% - 98.4%) 95% CI | |
| Negative | 3 | 777 | 780 | Negative PercentAgreement=100.0%(99.5% - 100.0%) 95% CI | ||
| Total | 65 | 777 | 842 |
Retrospective Study
In addition to the prospective clinical study, two clinical sites also performed testing using retrospective samples that were collected from January - March, 2008, January - November 2009, and March 2010. The ProFAST+ Assay was compared to the same composite comparator/reference method that was employed for the prospective study to determine clinical Percent Positive Agreement and Percent Negative Agreement. A total of 160 retrospective nasopharyngeal (NP) swab samples were included in the retrospective study.
Demographic details for this patient population are summarized in the table below.
| Gender and Age Demographic Detail for ProFAST+ Retrospective Stuc | |
|---|---|
| Sex | Number of Subjects |
| Female | 74 (46.3%)* |
| Male | 84 (52.5%)* |
| Age | |
| ≤ 5 years | 25 (15.6%) |
| 6 - 21 years | 24 (15.0%) |
| 22 - 59 years | 91 (56.9%) |
| > 60 years | 20(12.5%) |
ー
*For two of the subjects, the gender was unknown.
{5}------------------------------------------------
Seasonal Influenza A/H1 Comparison Results
| ProFlu+/Sequencing | |||||
|---|---|---|---|---|---|
| Positive | Negative | Total | |||
| ProFAST+Assay | Positive | 17 | 1a | 18 | Positive Percent Agreement=94.4%(74.3% - 99.0%) 95% CI |
| Negative | 1 | 141 | 142 | Negative Percent Agreement=99.3%(96.1% - 99.9%) 95% CI | |
| Total | 18 | 142 | 160 |
4 One (1) sample was negative for Influenza A by the ProFlu+ Assay, but positive for seasonal A/H1 by bi-directional sequence analysis.
Seasonal Influenza A/H3 Comparison Results
| ProFlu+/Sequencing | |||||
|---|---|---|---|---|---|
| Positive | Negative | Total | |||
| ProFAST+Assay | Positive | 72 | 0 | 72 | Positive PercentAgreement=100.0%(94.9% - 100.0%) 95% CI |
| Negative | 0 | 88 | 88 | Negative PercentAgreement=100.0%(95.8% - 100.0%) 95% CI | |
| Total | 72 | 88 | 160 |
2009 H1N1 Influenza A Comparison Results
| ProFAST+ Assay | ProFlu+/Sequencing | |||
|---|---|---|---|---|
| Positive | Negative | Total | ||
| Positive | 25 | 0 | 25 | Positive PercentAgreement=100.0%(86.7% - 100.0%) 95% CI |
| Negative | 0 | 135 | 135 | Negative PercentAgreement=100.0%(97.2% - 100.0%) 95% CI |
| Total | 25 | 135 | 160 |
{6}------------------------------------------------
Reproducibility
The reproducibility of the ProFAST+ Assay was evaluated at 3 laboratory sites. Reproducibility was assessed using a panel of 18 simulated samples that included medium positive, low positive (near the assay limit of detection, ≥ 95% positive), and high negative (below the assay limit of detection, < 5% positive) samples for each of the three Influenza A subtypes detected by the assay. Panels and controls were tested at each site by 2 operators for 5 days. Nucleic acid extraction was carried out using either the Roche MagNA Pure LC System or the bioMérieux NucliSENS easyMAG System. The overall percent agreement with the expected result for the ProFAST+ Assay was 99.7%.
| PanelMember ID | Concentration | A/H1 negative(values from IC)0.001X LoD | A/H1 low positive2 XLoD | A/H1 medium positive10XLoD | A/H3 negative(values from IC)'0.001X LoD | A/H3 low positive2 XLoD | A/H3 medium positive10XLOD | A/2009 H1N1 negative(values from IC)0.001,X LOD | A/2009 H1N1 low positive2 XLoD | A/2009 H1N1 medium positive10XLoD | ExtractionControlN/A | Influenza ASubtypingRNA ControlN/A | NegativeControlN/A | Total %Agreement | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/H1 | A/H3 | A/2009H1N1 | A/H1 | A/H3 | A/2009H1N1 | ||||||||||||||
| Site 1 | Agreementwith ExpectedResult | 20/20 | 20/20 | 20/20 | 20/20 | 20/20 | 20/20 | 20/20 | 20/20 | 20/20 | 10/10 | 10/10 | 10/10 | 10/10 | 10/10 | 10/10 | 10/10 | 210/210(100%) | |
| Mean Ct Value | 29.3 | 34.7 | 32.1 | 29.5 | 32.5 | 30.3 | 29.4 | 31.3 | 28.6 | 29.3 | 27.5 | 27.9 | 32.4 | 31.3 | 31.6 | 29.5 | |||
| % CV | 1.54 | 1.16 | 0.58 | 1.77 | 0.96 | 0.58 | 1.52 | 0.76 | 1.45 | 0.78 | 1.01 | 3.04 | 0.79 | 0.79 | 0.89 | 0.71 | |||
| Site 2 | Agreementwith ExpectedResult | 20/20 | 20/20 | 20/20 | 20/20 | 20/20 | 20/20 | 20/20 | 20/20 | 20/20 | 10/10 | 10/10 | 10/10 | 210/210(100%) | |||||
| Mean Ct Value | 27.0 | 34.1 | 31.0 | 27.1 | 31.7 | 29.5 | 26.9 | 30.6 | 28.0 | 28.1 | 26.5 | 27.3 | 32.1 | 31.0 | 31.2 | 26.4 | |||
| % CV | 1.41 | 3.11 | 0.86 | 1.54 | 0.86 | 0.93 | 1.41 | 2.09 | 0.91 | 0.38 | 0.86 | 1.72 | 0.61 | 0.95 | 0.80 | 0.95 | |||
| Site 3 | Agreementwith ExpectedResult | 20/20 | 19/20 | 20/20 | 20/20 | 19/20 | 20/20 | 20/20 | 20/20 | 20/20 | 10/10 | 10/10 | 10/10 | 208/210(99.0%) | |||||
| Mean Ct Value | 28.5 | 36.1 | 32.0 | 28.6 | 32.4 | 30.2 | 28.3 | 31.5 | 28.7 | 28.9 | 27.2 | 29.4 | 32.0 | 30.9 | 31.0 | 28.8 | |||
| % CV | 4.28 | 7.26 | 1.80 | 4.44 | 1.66 | 2.42 | 3.02 | 2.20 | 1.13 | 1.44 | 1.54 | 1.42 | 1.13 | 1.45 | 1.05 | 4.88 | |||
| TotalAgreementwith ExpectedResult | 60/60 | 59/60 | 60/60 | 60/60 | 59/60 | 60/60 | 60/60 | 60/60 | 60/60 | 30/30 | 30/30 | 30/30 | 628/630(99.7%) | ||||||
| 95% CI | 94.0 -100% | 91.1-99.7% | 94.0 -100% | 94.0 -100% | 91.1-99.7% | 94.0 -100% | 94.0 -100% | 94.0 -100% | 94.0 -100% | 88.7% - 100% | 88.7% - 100% | 88.7 -100% | 98.8% -99.9% | ||||||
| Overall MeanCt Value | 28.2 | 34.9 | 31.7 | 28.4 | 32.2 | 30.0 | 28.2 | 31.1 | 28.5 | 28.8 | 27.1 | 28.3 | 32.2 | 31.0 | 31.3 | 28.2 | |||
| Overall% CV | 4.40 | 5.08 | 1.97 | 4.49 | 1.59 | 1.94 | 4.11 | 2.12 | 1.66 | 1.99 | 1.95 | 3.86 | 1.01 | 1.19 | 1.21 | 5.62 |
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Image /page/7/Picture/1 description: The image shows the logo for the Department of Health & Human Services (HHS). The logo features a stylized depiction of an eagle or bird-like figure with outstretched wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the bird symbol. The logo is black and white.
Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-0609 Silver Spring, MD 20993-0002
JUL 2 3 2010
Karen Harrington, Ph.D. Manager, Clinical Affairs Gen-Probe Prodesse Inc. W229 N1870 Westwood Dr. Waukesha, WI, 53186
Re: K101855
| Trade/Device Name: | Prodesse ProFAST+ Assay |
|---|---|
| Regulation Number: | 21 CFR §866.3332 |
| Regulation Name: | Reagents for detection of specific novel influenza A viruses |
| Regulatory Class: | Class II |
| Product Code: | OQW |
| Dated: | June 30, 2010 |
| Received: | July 1, 2010 |
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 additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
{8}------------------------------------------------
Page 2 - Dr. Karen Harrington
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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/MedicalDevices/Resourcesfor You/Industry/default.htm.
Sincerely yours,
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
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Indication for Use
510(k) Number (if known): K101855
Device Name: ProFAST+TM Assay
Indication For Use:
The ProFAST™+ Assay is a multiplex Real Time RT-PCR in vitro diagnostic test for the qualitative detection and discrimination of seasonal Influenza A/H1, seasonal Influenza A/H3 and 2009 H1N1 Influenza viral nucleic acids isolated and purified from nasopharyngeal (NP) swab specimens from human patients with signs and symptoms of respiratory infection in conjunction with clinical and epidemiological risk factors. This assay targets conserved regions of the Hemagglutinin (HA) gene for seasonal Influenza A/H1. seasonal Influenza A/H3 and 2009 H1N1 Influenza Virus, respectively. This assay is not intended to detect Influenza B or Influenza C Viruses.
A negative ProFAST+ Assay result is a presumptive negative result for Influenza A. These results should be confirmed by an FDA cleared nucleic acid-based test (NAT) detecting Influenza A.
Negative results do not preclude Influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions.
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) Over the Counter Use (21 CFR Part 801 Subpart C)
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And/Or
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)
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Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K101855
§ 866.3332 Reagents for detection of specific novel influenza A viruses.
(a)
Identification. Reagents for detection of specific novel influenza A viruses are devices that are intended for use in a nucleic acid amplification test to directly detect specific virus RNA in human respiratory specimens or viral cultures. Detection of specific virus RNA aids in the diagnosis of influenza caused by specific novel influenza A viruses in patients with clinical risk of infection with these viruses, and also aids in the presumptive laboratory identification of specific novel influenza A viruses to provide epidemiological information on influenza. These reagents include primers, probes, and specific influenza A virus controls.(b)
Classification. Class II (special controls). The special controls are:(1) FDA's guidance document entitled “Class II Special Controls Guidance Document: Reagents for Detection of Specific Novel Influenza A Viruses.” See § 866.1(e) for information on obtaining this document.
(2) The distribution of these devices is limited to laboratories with experienced personnel who have training in standardized molecular testing procedures and expertise in viral diagnosis, and appropriate biosafety equipment and containment.