(85 days)
I'm sorry, but without the actual text input, I cannot identify the Predicate Device(s) K/DEN numbers. The input you provided is "Not Found". Please provide the text from which you'd like me to extract the information.
Not Found
No
The description details a standard RT-PCR assay with fluorescent detection and a threshold-based positive/negative determination. There is no mention of algorithms that learn from data or adapt their performance.
No
This device is an in vitro diagnostic (IVD) tool designed to detect and differentiate influenza A and B viral RNA. Its purpose is to aid in diagnosis, not to provide therapy or treatment.
Yes
The "Intended Use / Indications for Use" section states that the assay is "intended for use as an aid in the differential diagnosis of influenza A and influenza B viral infections." This explicitly identifies it as a tool used in the diagnostic process.
No
The device description clearly outlines the use of physical components like nasal/nasopharyngeal swabs, reagents, a NucliSENS easyMAG system for extraction, and a Cepheid SmartCycler II platform for amplification and detection. This indicates it is a hardware-based diagnostic system, not a software-only device.
Yes, this device is an IVD (In Vitro Diagnostic).
The intended use statement explicitly states that the Quidel® Molecular Influenza A+B assay is for "in vitro qualitative detection and differentiation of influenza A and influenza B viral RNA". The term "in vitro" is a key indicator of an IVD, meaning it is used to test samples outside of the body. The purpose of the test is to aid in the diagnosis of influenza infections, which is a typical function of an IVD.
N/A
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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Quidel Corporation
MAR 1 5 2012 K113777
Quidel Molecular Influenza A + B Assay
12/16/11 Page 1 of 17
Section 05, 510(k) Summary
Applicant:
Quidel Corporation 10165 McKellar Court San Diego, California 92121 Telephone: 858-552-7910 Fax: 858-646-8045
Contact Information:
Ronald H. Lollar, Senior Director Clinical and Quality Affairs 1055 East State Street Suite 100 Athens, Ohio 45701 740-589-3300 - Corporate number 740-589-3373 – Desk phone 740-593-8437 — Fax lollar@dhiusa.com
Date of preparation of 510(k) summary:
December 16, 2011
Device Name:
· Trade name - Quidel Molecular Influenza A + B Assay Classification name - Respiratory viral panel multiplex nucleic acid assay Product Code - OZE Regulation - 21 CFR 866.3980
Legally marketed devices to which equivalence is claimed:
Gen-Probe Prodesse ProFlu+ (K092500)
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 ·
1
decisions. It is recommended that negative RSV results be confirmed by culture.
Performance characteristics for Influenza A Virus were established when Influenza A/H3 and A/H1 were the predominant Influenza A viruses in circulation. 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.
Intended Use:
The Quidel® Molecular Influenza A+B assay is a multiplex Real Time RT-PCR assay for the in vitro qualitative detection and differentiation of influenza A and influenza B viral RNA in nasal and nasopharyngeal swabs from patients with signs and symptoms of respiratory infection. This test is intended for use as an aid in the differential diagnosis of influenza A and influenza B viral infections in humans in conjunction with clinical and epidemiological risk factors. The assay does not detect the presence of influenza C virus.
Negative results do not preclude influenza virus infection and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.
Performance characteristics for influenza A were established during the 2010 to 2011 influenza season when influenza A/H3 and 2009 H1N1 influenza were the predominant influenza A viruses in circulation. 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 Description:
The Quidel Molecular Influenza A+B Assay detects viral RNA that have been extracted from a patient sample using the NucliSENS® easyMAG® automated
2
extraction platform. A multiplex RT-PCR reaction is carried out under optimized conditions in a single tube generating amplicons for each of the target viruses present in the sample. This reaction is performed utilizing the Cepheid SmartCycler® II platform. Identification of influenza A occurs by the use of target specific primers and a fluorescent- labeled probe that hybridizes to a conserved influenza A sequence within the matrix protein gene. Identification of influenza B occurs by the use of target specific primers and fluorescentlabeled probes that will hybridize to a conserved influenza B sequence within the neuraminidase gene.
The following is a summary of the procedure:
-
- Sample Collection: Obtain nasal swabs and nasopharyngeal swabs specimens using standard techniques from symptomatic patients. These specimens are transported, stored, and processed according to established laboratory procedures.
-
- Nucleic Acid Extraction: Extract Nucleic Acids from the specimens with the NucliSENS easyMAG System following the manufacturer's instructions using the appropriate reagents.
Prior to the extraction procedure add 20 µL of the Process Control (PRC) to each 180 uL aliquot of specimen. The PRC serves to monitor inhibitors in the extracted specimen, assures that adequate amplification has taken place and that nucleic acid extraction was sufficient.
-
- Rehydration of Master Mix: Rehydrate the lyophilized Master Mix using 135uL of Rehydration Solution. The Master Mix contains oligonucleotide primers. fluorophore and quencher-labeled probes targeting highly conserved regions of the influenza A and influenza B viruses as well as the process control sequence. The primers are complementary to highly specific and conserved regions in the genome of these viruses. The probes are dual labeled with a reporter dye attached to the 5'end and a quencher attached to the 3' end. The rehydrated Master Mix is sufficient for eight reactions.
-
- Nucleic Acid Amplification and Detection: Add 15 µL of the rehydrated Master Mix to each reaction tube. SuL of extracted nucleic acids (specimen with PRC) is then added to the tube. Then place the tube into the Cepheid SmartCycler® II.
Once the reaction tubes are added to the instrument, the assay protocol is initiated. This protocol initiates reverse transcription of the RNA targets generating complementary DNA, and the subsequent amplification of the target amplicons occurs. The Quidel Molecular Influenza A+B assay is
3
Quidel Molecular Influenza A + B Assay
based on TaqMan® chemistry, and uses an enzyme with reverse transcriptase, DNA polymerase, and 5'-3' exonuclease activities. During DNA amplification, this enzyme cleaves the probe bound to the complementary DNA sequence, separating the quencher dye from the reporter dye. This step generates an increase in fluorescent signal upon excitation by a light source of the appropriate wavelength. With each cycle, additional dye molecules are separated from their quenchers resulting in additional signal. If sufficient fluorescence is achieved by 45 cycles, the sample is reported as positive for the detected nucleic acid.
Device Comparison
The Quidel Molecular Influenza A+B assay was compared to Prodesse ProFlu+ ("Comparator Device"). The characteristics of Quidel Molecular Influenza A+B assay ("Subject Device") and Prodesse ProFlu+ ("Predicate Device") are described in Table 5.1, below:
| Table 5.1: Device Comparison | ||
|---|---|---|
| Item | Subject Device | |
| Quidel Molecular Influenza | ||
| A+B Assay | Comparator Device | |
| Prodesse ProFlu+ | ||
| Intended Use | The Quidel® Influenza A and | |
| B virus RT-PCR Kit is a | ||
| multiplex Real Time RT-PCR | ||
| assay for the in vitro | ||
| qualitative detection and | ||
| identification of influenza A | ||
| and influenza B viral RNA in | ||
| nasal and nasopharyngeal | ||
| swabs from patients with signs | ||
| and symptoms of respiratory | ||
| infection. This test is | ||
| intended for use as an aid in | ||
| the differential diagnosis of | ||
| influenza A and influenza B | ||
| viral infections in humans in | ||
| conjunction with clinical and | ||
| epidemiological risk factors. | ||
| The assay does not detect the | ||
| presence of influenza C virus. | ||
| Negative results do not | ||
| preclude influenza virus | 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 | ||
| Table 5.1: Device Comparison | ||
| Item | Subject Device | |
| Quidel Molecular Influenza | ||
| A+B Assay | Comparator Device | |
| Prodesse ProFlu+ | ||
| infection and should not be | ||
| used as the sole basis for | ||
| diagnosis, treatment or other | ||
| patient management decisions. | ||
| Performance characteristics for | ||
| influenza A were established | ||
| during the 2010 to 2011 | ||
| influenza season when | ||
| influenza A/H3 and 2009 | ||
| H1N1 influenza were the | ||
| predominant influenza A | ||
| viruses in circulation. 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 | ||
| departments for testing. Viral | ||
| culture should not be | ||
| attempted in these cases unless | ||
| a BSL3+ facility is available to | ||
| receive and culture specimens. | virus infection and should not | |
| be used as the sole basis for | ||
| treatment or other | ||
| management decisions. It is | ||
| recommended that negative | ||
| RSV results be confirmed by | ||
| culture. | ||
| Performance characteristics | ||
| for Influenza A Virus were | ||
| established when Influenza | ||
| A/H3 and A/H1 were the | ||
| predominant Influenza A | ||
| viruses in circulation. 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 | ||
| departments for testing. Viral | ||
| culture should not be | ||
| attempted in these cases | ||
| unless a BSL 3+ facility is | ||
| available to receive and | ||
| culture specimens. | ||
| Assay Target | Influenza A virus, influenza B | |
| virus | Influenza A virus, influenza B | |
| virus, respiratory syncytial | ||
| virus | ||
| Table 5.1: Device Comparison | ||
| Item | Subject Device | |
| Quidel Molecular Influenza | ||
| A+B Assay | Comparator Device | |
| Prodesse ProFlu+ | ||
| Sample Types | nasal swab and | |
| nasopharyngeal swab | nasopharyngeal swab | |
| Extraction | ||
| Methods | bioMérieux easyMAG | |
| Automated Magnetic | ||
| Extraction Reagents | Roche MagNA Pure LC Total | |
| Nucleic Acid Isolation Kit or | ||
| the bioMérieux easyMAG | ||
| Automated Magnetic | ||
| Extraction Reagents | ||
| Assay | ||
| Methodology | PCR-based system for | |
| detecting the presence or | ||
| absence of viral RNA in | ||
| clinical specimens | PCR-based system for | |
| detecting the presence or | ||
| absence of viral RNA in | ||
| clinical specimens | ||
| Detection | ||
| Techniques | Multiplex assay using different | |
| reporter dyes for each target | Multiplex assay using | |
| different reporter dyes for | ||
| each target | ||
| Viral Targets | Influenza A: Matrix Gene; | |
| Influenza B: Neuraminidase | ||
| Gene | Influenza A: Matrix Gene; | |
| Influenza B: Non-structural | ||
| NS1 and NS2 | ||
| LoD | The analytical sensitivity (limit | |
| of detection or LoD) of the | ||
| Quidel Molecular Influenza | ||
| A+B assay was determined | ||
| using quantified (TCID50/mL) | ||
| cultures of 3 influenza A | ||
| strains (1 H1N1, 1 2009H1N1 | ||
| and 1 H3N2), 3 influenza B | ||
| strains, serially diluted in | ||
| negative nasopharyngeal | ||
| matrix. Each dilution was | ||
| extracted in replicates of 20 | ||
| per concentration of virus | ||
| using the NucliSENS | ||
| easyMAG System and tested | ||
| on Cepheid SmartCycler® II. | ||
| Analytical sensitivity (LoD), | The analytical sensitivity | |
| (limit of detection or LoD) of | ||
| the ProFlu+ Assay was | ||
| determined using quantified | ||
| (TCID50/mL) cultures of 4 | ||
| Influenza A (2 H1N1 and 2 | ||
| H3N2), 2 Influenza B, 2 | ||
| Respiratory Syncytial Virus | ||
| Type A, and 2 Respiratory | ||
| Syncytial Virus Type B | ||
| strains serially diluted in | ||
| nasopharyngeal clinical | ||
| matrix. Each viral strain was | ||
| extracted using the Roche | ||
| MagNA Pure LC instrument | ||
| and tested in replicates of 20 | ||
| per concentration of virus. | ||
| Analytical sensitivity (LoD), | ||
| Table 5.1: Device Comparison | ||
| Item | Subject Device | |
| Quidel Molecular Influenza | ||
| A+B Assay | Comparator Device | |
| Prodesse ProFlu+ | ||
| concentration at which 95% of | ||
| all replicates tested positive, | ||
| ranged from 101 to 100 | ||
| TCID50/mL. | as defined as the lowest | |
| concentration at which 95% | ||
| of all replicates tested | ||
| positive, ranged from 102 to | ||
| 101 TCID50/mL. |
4
·
5
6
Quidel Moiecular Influenza A + B Assay
Analytical Performance:
Precision/Reproducibility:
The reproducibility of the Quidel Molecular Influenza A and B assay was evaluated at 3 laboratory sites. Reproducibility was assessed using a panel of 4 simulated samples that include medium (5x LoD) and low (2x LoD), high negative (0.3x LoD) influenza A (A/Mexico/4108/2009), influenza B (B/Florida/04/2006) and negative samples. Panels and controls were tested at each site by 2 operators for 5 days (triplicate testing x 2 operators x 5 days x 3 sites = 90 results per level for each virus). The LoD values are based on the values obtained in the LoD study. The panels and controls were extracted using the bioMérieux easyMAG system and tested on the Cepheid SmartCycler II.
| Table 5.2: Reproducibility Results | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Panel | ||||||||||
| Member ID | Site 1 | Site 2 | Site 3 | Total | ||||||
| Results | ||||||||||
| Results | AVE | |||||||||
| Ct | %CV | Results | AVE | |||||||
| Ct | %CV | Results | AVE | |||||||
| Ct | %CV | |||||||||
| Influenza A | ||||||||||
| High | ||||||||||
| Negative | ||||||||||
| 0.3x LoD | 3/30 | |||||||||
| (3 positive | ||||||||||
| results) | 44.27 | 1.2 | 4/30 | |||||||
| (4 | ||||||||||
| positive | ||||||||||
| results) | 43.45 | 4.5 | 2/30 | |||||||
| (2 positive | ||||||||||
| results) | 42.65 | 0.50 | 9/90 | |||||||
| Influenza A | ||||||||||
| Low | ||||||||||
| Positive | ||||||||||
| 2x LoD | 30/30 | 37.72 | 2.7 | 30/30 | 38.05 | 3.8 | 30/30 | 37.40 | 4.5 | 90/90 |
| Influenza A | ||||||||||
| Med | ||||||||||
| Positive | ||||||||||
| 5x LoD | 30/30 | 35.36 | 1.9 | 30/30 | 36.05 | 3.3 | 30/30 | 34.95 | 1.6 | 90/90 |
| Influenza A | ||||||||||
| Negative | 0/30 | N/A | N/A | 0/30 | N/A | N/A | 0/30 | N/A | N/A | 0/90 |
| Influenza B | ||||||||||
| High | ||||||||||
| Negative | ||||||||||
| 0.3x LoD | 0/30 | N/A | N/A | 1/30 | ||||||
| (1 | ||||||||||
| positive | ||||||||||
| results) | 39.9 | N/A | 4/30 | |||||||
| (4 positive | ||||||||||
| results) | 42.43 | 3.2 | 4/90 |
Sec05_QM_FluA-B Li.doc
7
Quidei Molecular Influenza A + B Assay
| Table 5.2: Reproducibility Results | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Panel | ||||||||||
| Member ID | Site 1 | Site 2 | Site 3 | Total | ||||||
| Results | ||||||||||
| Results | AVE | |||||||||
| Ct | %CV | Results | AVE | |||||||
| Ct | %CV | Results | AVE | |||||||
| Ct | %CV | |||||||||
| result) | ||||||||||
| Influenza B | ||||||||||
| Low | ||||||||||
| Positive | ||||||||||
| 2x LoD | 30/30 | 35.42 | 1.14 | 30/30 | 36.06 | 3.1 | 30/30 | 34.86 | 3.6 | 90/90 |
| Influenza B | ||||||||||
| Med | ||||||||||
| Positive | ||||||||||
| 5x LoD | 30/30 | 33.46 | 1.2 | 30/30 | 33.86 | 1.6 | 30/30 | 33.01 | 1.3 | 90/90 |
| Influenza B | ||||||||||
| Negative | 0/30 | N/A | N/A | 0/30 | N/A | N/A | 0/30 | N/A | N/A | 0/90 |
| Influenza A | ||||||||||
| Positive | ||||||||||
| Control | 30/30 | 29.19 | 1.2 | 30/30 | 29.47 | 1.9 | 30/30 | 29.25 | 1.5 | 90/90 |
| Influenza B | ||||||||||
| Positive | ||||||||||
| Control | 30/30 | 27.76 | 1.1 | 30/30 | 28.05 | 2.7 | 30/30 | 27.57 | 1.5 | 90/90 |
| Negative | ||||||||||
| Control | 0/30 | N/A | N/A | 0/30 | N/A | N/A | 0/30 | N/A | N/A | 0/90 |
The data from the combined sites indicates that the Quidel Molecular assay generates reproducible results for both influenza A and influenza B viruses when tested with the Cepheid SmartCycler II.
Limit of Detection
The analytical sensitivity (limit of detection or LoD) of the Quidel Molecular Influenza A+B assay was determined using quantified (TCIDsN/mL) cultures of three influenza A strains (1 H1N1, 1 2009H1N1 and 1 H3N2) and three influenza B strains, serially diluted in negative nasopharyngeal matrix. Each dilution was extracted using the NucliSENS easyMAG System in replicates of 20 per concentration of virus and tested on the Cepheid SmartCycler II platform. Analytical sensitivity (LoD) is defined as the lowest concentration at which 95% of all replicates tested positive.
| Table 5.3: Final TCID50 LoD | |
|---|---|
| Strain | Final LOD (TCID50/mL) |
| A1/Mal/302/54 | 7.00E+00 |
| A/Mexico/4108/2009 | 2.40E+01 |
| A/Victoria/3/75 | 3.10E+01 |
| B/Florida/04/2006 | 6.00E+00 |
| B/RCHIN 8/05 | 1.80E+00 |
| B/Malaysia/25/06/04 | 1.30E+00 |
8
Analytical reactivity (inclusivity)
The reactivity of the Quidel Molecular Influenza A+B assay was evaluated against multiple strains of influenza A, and influenza B viruses. The clinical panel consisted of 10 Influenza A subtype H1N1, 2 Influenza A subtype 2009H1N1, 8 Influenza A subtype H3N2, 2 Influenza A subtype H5N1, 13 Influenza B. strains. An additional panel of non-clinical restricted isolates was also tested. Each panel member was extracted using the NucliSens easyMAG instrument and tested in triplicate.
The Ouidel Molecular Influenza A+B assay detected 100% of the influenza A (38/38) and influenza B strains (15/15) at 102 to 103 TCID50 levels including novel, pandemic and avian influenza A strains and recent circulating influenza B strains.
| Table 5.4: Clinical Panel Influenza A viruses | ||||
|---|---|---|---|---|
| Subtype | Strain | TCID50 | A | B |
| 2009 H1N1 | H1N1 | |||
| A/California/07/2009 | 1.45E+02 | Positive | Negative | |
| H1N1 | A/New | |||
| Caledonia/20/1999 | 1.12E+02 | Positive | Negative | |
| H1N1 | A/New Jersey/8/76 | 3.80E+02 | Positive | Negative |
| H1N1 | A/PR/8/34 | 5.89E+02 | Positive | Negative |
| H1N1 | A/NWS/33 | NA | Positive | Negative |
| H1N1 | A/Denver/1/57 | 1.26E+02 | Positive | Negative |
| H1N1 | A/FM/1/47 | 3.80E+02 | Positive | Negative |
| 2009 H1N1 | A/Mexico/4108/2009 | 1.40E+02 | Positive | Negative |
| H1N1 | A1/Mal/302/54 | 4.19E+02 | Positive | Negative |
| H1N1 | A/Taiwan/42/06 | 3.39E+02 | Positive | Negative |
| H1N1 | A/Brisbane/59/07 | 7.24E+01 | Positive | Negative |
| H1N1 | A/Solomon | |||
| Islands/3/06 | 1.41E+01 | Positive | Negative | |
| H3N2 | A/Hong Kong/8/68 | 1.15E+02 | Positive | Negative |
| H3N2 | A/Wisconsin/67/2005 | 7.24E+02 | Positive | Negative |
| H3N2 | A/Aichi/2/68 | 4.17E+02 | Positive | Negative |
9
Quidel Molecular Influenza A + B Assay
12/01/11 . Page 10 of 17
:
:
| Table 5.4: | Clinical Panel Influenza A viruses | |||
|---|---|---|---|---|
| Subtype | Strain | TCID50 | A | B |
| H3N2 | A/Port Chalmers/1/73 | 4.57E+02 | Positive | Negative |
| H3N2 | A/Perth/16/2009 | 9.83E+02 | Positive | Negative |
| H3N2 | A/Uruguay/7/16/2007 | 1.03E+02 | Positive | Negative |
| H3N2 | A/Victoria/3/75 | 2.19E+02 | Positive | Negative |
| H3N2 | A/Brisbane/10/07 | 4.17E+02 | Positive | Negative |
:
Sec05_QM_FIuA-B Li.doc
the control control control of the control of
· .
10
Quidel Molecular Influenza A + B Assay
| Table 5.5: | Clinical Panel Influenza B viruses | ||
|---|---|---|---|
| Strain | TCID50 | A | B |
| B/HongKong/5/72 | 6.67E+02 | Negative | Positive |
| B/Panama/45/90 | 1.02E+02 | Negative | Positive |
| B/Florida/02/2006 | 3.16E+02 | Negative | Positive |
| B/Florida/04/2006 | 3.80E+02 | Negative | Positive |
| B/Florida/07/2004 | 1.26E+02 | Negative | Positive |
| B/Malaysia/25/06/04 | 3.41E+02 | Negative | Positive |
| B/Maryland/1/59 | 1.15E+02 | Negative | Positive |
| B/Allen/45 | 4.17E+02 | Negative | Positive |
| B/Taiwan/2/62 | 1.51E+02 | Negative | Positive |
| B/Russia/69 | 2.19E+02 | Negative | Positive |
| B/Mass/3/66 | 1.38E+02 | Negative | Positive |
| B/Lee/40 | 1.95E+02 | Negative | Positive |
| B/GL/1739/54 | 6.30E+02 | Negative | Positive |
| Table 5.6: Non-clinical Restricted viruses | ||||
|---|---|---|---|---|
| Subtype | Strain | TCID50 | A | B |
| A/WI/629-9/2008 | 2.00E+02 | Positive | Negative | |
| H3N2 | A/WI/629-2/2008 | |||
| (H3N2) | 2.00E+02 | Positive | Negative | |
| H1N1 | A/WI/629-S7(D02473)/2009 | |||
| (H1N1pdm) | 2.00E+02 | Positive | Negative | |
| H1N1 | A/WI/629-S5(D02312)/2009 | |||
| (H1N1pdm) | 2.00E+02 | Positive | Negative | |
| H2N2 | A/Mallard/NY/6750/7 | |||
| 8 (H2N2) | 2.00E+02 | Positive | Negative | |
| H7N3 | A/Chicken/NJ/15086-3/94 (H7N3) | 2.00E+02 | Positive | Negative |
11
| Table 5.6: Non-clinical Restricted viruses | ||||
|---|---|---|---|---|
| Subtype | Strain | TCID50 | A | B |
| H9N2 | A/Chicken/NJ/12220/ | |||
| 97 (H9N2) | 2.00E+02 | Positive | Negative | |
| H4N8 | A/Mallard/OH/338/86 | |||
| (H4N8) | 2.00E+02 | Positive | Negative | |
| H6N2 | A/Chicken/CA/431/00 | |||
| (H6N2) | 2.00E+02 | Positive | Negative | |
| H8N4 | A/Blue Winged | |||
| Teal/LA/B174/86 | ||||
| (H8N4) | 2.00E+02 | Positive | Negative | |
| H5N1 | A/Anhui/01/2005(H5 | |||
| N1)-PR8-IBCDC- | ||||
| RG5 | 2.00E+02 | Positive | Negative | |
| H10N7 | A/GWT/LA/169GW/8 | |||
| 8 (H10N7) | 2.00E+02 | Positive | Negative | |
| H11N9 | A/Chicken/NJ/15906- | |||
| 9/96 (H11N9) | 2.00E+02 | Positive | Negative | |
| H12N5 | A/Duck/LA/188D/87 | |||
| (H12N5) | 2.00E+02 | Positive | Negative | |
| H13N6 | A/Gull/MD/704/77 | |||
| (H13N6) | 2.00E+02 | Positive | Negative | |
| H14N5 | A/Mallard/GurjevRus | |||
| sia/262/82 (H14N5) | 2.00E+02 | Positive | Negative | |
| H15N9 | A/Shearwater/Australi | |||
| a/2576/79 (H15N9) | 2.00E+02 | Positive | Negative | |
| H16N3 | A/Shorebird/DE/172/2 | |||
| 006(H16N3) | 2.00E+02 | Positive | Negative |
Analytical specificity (cross-reactivity)
The analytical specificity of the Quidel Molecular Influenza A+B assay was evaluated by testing a panel consisting of 26 viral, 24 bacterial, and 1 yeast strain representing common respiratory pathogens or flora commonly present in nasopharynx. Bacteria and yeast were tested at concentrations of 105 to 1010 CFU/mL. Viruses were tested at concentrations of 103 to 10 TCID50/mL. Samples were extracted using the NucliSens easyMAG instrument and tested in triplicate. Analytical specificity of the Quidel Molecular influenza A+B assay was 100%.
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.
,
| Table 5.7: | Quidel Molecular influenza A+B assay Cross-reactivity Data | ||
|---|---|---|---|
| Organism ID | Final Conc. | Influenza A Result | Influenza B Result |
| hMPV Al | 3.70E+04 | Negative | Negative |
| hMPV B1 | 2.37E+04 | Negative | Negative |
| RSV Long | 4.40E+04 | Negative | Negative |
| RSV Washington | 1.75E+03 | Negative | Negative |
| Adenovirus 1/Adenoid 71 | 5.67E+04 | Negative | Negative |
| Coronavirus 229E | 1.70E+06 | Negative | Negative |
| Coronavirus OC43 | 1.67E+06 | Negative | Negative |
| Coxsackievirus B4 | 2.43E+06 | Negative | Negative |
| Coxsackievirus B5/10/2006 | 2.28E+06 | Negative | Negative |
| Cytomegalovirus | 8.76E+05 | Negative | Negative |
| Echovirus 7 | 5.38E+08 | Negative | Negative |
| Echovirus 9 | 1.50E+06 | Negative | Negative |
| Echovirus 6 | 1.05E+08 | Negative | Negative |
| Echovirus 11 | 1.50E+05 | Negative | Negative |
| Enterovirus 71 | 2.68E+03 | Negative | Negative |
| Enterovirus 70 | 1.66E+05 | Negative | Negative |
| Epstein Barr Virus | 5,000cp/mL | Negative | Negative |
| HSV Type 1 Mac Inytre strain | 1.95E+06 | Negative | Negative |
| HSV Type 2 G strain | 3.67E+06 | Negative | Negative |
| Rubeola | 3.78E+05 | Negative | Negative |
| Mumps virus | 8.43E+04 | Negative | Negative |
| Parainfluenza Type 1 | 2.50E+05 | Negative | Negative |
| Parainfluenza Type 2 | 2.20E+04 | Negative | Negative |
| Parainfluenza Type 3 | 9.10E+05 | Negative | Negative |
| Parainfluenza Type 4 | 9.57E+06 | Negative | Negative |
| Varicella Zoster Virus | 7.50E+02 | Negative | Negative |
| Bordetella pertussis | 1.04E+07 | Negative | Negative |
| Bordetella bronchiseptica | 2.55E+07 | Negative | Negative |
| Chlamydia trachomatis | 2.10E+05 | Negative | Negative |
| Legionella pneumophila | 2.05E+08 | Negative | Negative |
| Mycobacterium intracellulare | 6.90E+08 | Negative | Negative |
| Mycobacterium tuberculosis | 6.60E+07 | Negative | Negative |
| Mycobacterium avium | 1.36E+10 | Negative | Negative |
| Haemophilus influenzae | 5.90E+07 | Negative | Negative |
| Table 5.7: | Quidel Molecular influenza A+B assay Cross-reactivity Data | ||
| Organism ID | Final Conc. | Influenza A | |
| Result | Influenza B | ||
| Result | |||
| Pseudomonas aeruginosa | 5.15E+07 | Negative | Negative |
| Proteus vulgaris | 2.65E+08 | Negative | Negative |
| Proteus mirabilis | 2.75E+07 | Negative | Negative |
| Neisseria gonorrhoeae | 2.15E+07 | Negative | Negative |
| Neisseria menigitidis | 1.85E+08 | Negative | Negative |
| Neisseria mucosa | 1.85E+08 | Negative | Negative |
| Klebsiella pneumoniae | 3.30E+07 | Negative | Negative |
| Escherichia coli | 6.80E+07 | Negative | Negative |
| Moraxella catarrhalis | 5.85E+07 | Negative | Negative |
| Corynebacterium diptheriae | 6.0E+05 | Negative | Negative |
| Lactobacillus plantarum | 1.03E+08 | Negative | Negative |
| Streptococcus pneumoniae | 4.5E+07 | Negative | Negative |
| Streptococcus pyogenes | 2.05E+08 | Negative | Negative |
| Streptococcus salivarius | 2.50E+06 | Negative | Negative |
| Staphylococcus epidermidis | 2.6E+07 | Negative | Negative |
| Staphylococcus aureus | 5.15E+08 | Negative | Negative |
| Candida albicans | 1.07E+06 | Negative | Negative |
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Clinical Performance:
Prospective Clinical Study
Performance characteristics of the Quidel Molecular Influenza A+B assay using the Cepheid SmartCycler® II instrument were established during a prospective study during the 2010-2011 respiratory virus season (January to March 2011). Samples used for this study were fresh nasal (427) and nasopharyngeal (352) swab specimens that were collected for routine influenza testing at thirteen sites across the United States. A single specimen was collected per patient and tested within 72-hours of collection at one central location.
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A comparator method (a high performance FDA Cleared Influenza A and B molecular test) was used in the evaluation of the Quidel Molecular Influenza A+B assay.
Seven hundred and seventy-nine (779) fresh specimens (427 nasal swabs and 352 nasopharyngeal swabs) were tested by both the subject and comparator device for influenza A and influenza B virus viral RNA. Twelve of these specimens were invalid on initial testing with the subject device (1.5%). Retesting of the specimens according to the Interpretation algorithm described above also yielded invalid results. Twenty-three specimens were invalid on initial and repeat testing (as per the device's PI) on the comparator device (3.0%). Nine specimens were invalid in both devices, therefore, a total of twenty-six invalid specimens have been removed from additional analysis. The table below details the results for the remaining 753 specimens.
| Table 5.8: Influenza A | |||
|---|---|---|---|
| Fresh nasal and | |||
| nasopharyngeal swabs | |||
| (N=753) | Comparator: FDA Cleared RT-PCR device | ||
| Quidel Molecular | Positive | Negative | Total |
| Positive | 157 | 8* | 165 |
| Negative | 0 | 588 | 588 |
| Total | 157 | 596 | 753 |
| 95% CI | |||
| Positive Percent Agreement | 157/157 | 100% | 97.7% to 100% |
| Negative Percent Agreement | 588/596 | 98.7% | 97.4% to 99.4% |
*Eight specimens were negative by FDA Cleared RT-PCR device but positive for influenza A by sequence analysis.
| Table 5.9:
| Influenza B | |||
|---|---|---|---|
| Fresh nasal and | |||
| nasopharyngeal swabs | |||
| (N=753) | Comparator: FDA Cleared RT-PCR device | ||
| Quidel Molecular | Positive | Negative | Total |
| Positive | 123 | 28* | 151 |
| Negative | 2 | 600 | 602 |
| Total | 125 | 628 | 753 |
| 95% CI | |||
| Positive Percent Agreement | 123/125 | 98.4% | 94.3% to 99.8% |
| Negative Percent Agreement | 600/628 | 95.5% | 93.6% to 97.0% |
*Twenty-six specimens were negative by FDA Cleared RT-PCR device but positive for influenza B by sequence analysis. Two specimens were negative by FDA Cleared RT-PCR device but negative for influenza B by sequence analysis.
15
The prospective clinical study had a dual infection rate for Influenza A and Influenza B of 2.4% (18/753) using the Quidel Molecular Influenza A + B Assay. Three of these dual infections were concordant with the FDA Cleared RT-PCR device comparator assay. Three of these dual infections were discordant with the Influenza A results from the FDA Cleared RT-PCR device comparator assay. Twelve of these dual infections were discordant with the Influenza B results from the FDA Cleared RT-PCR device comparator assay.
Retrospective Study
Performance of the Quidel Molecular Influenza A+B assay using the Cepheid SmartCycler® II instrument were also evaluated during a retrospective study of frozen specimens collected during the 2010-2011 respiratory virus season (January to March of 2011). Samples tested in this study were frozen nasopharyngeal (356) swab specimens that were collected for routine influenza testing.
For this study the comparator method was high performance FDA Cleared influenza A and B molecular device.
Three hundred fifty six (356) frozen nasopharyngeal swabs were tested by both the subject and comparator devices for influenza A and influenza B virus viral RNA. Two of these specimens were invalid on initial testing with the subject device (0.6%). Re-testing of the specimens according to the Interpretation algorithm described above also yielded invalid results. Two specimens were invalid on initial and repeat testing (as per the device's PI) on the comparator device (0.6%). The invalid specimens were removed from performance analyses. The table below details the results for the remaining 352 specimens.
| Table 5.10: Influenza A | |||
|---|---|---|---|
| Frozen nasopharyngeal | |||
| swab (N=352) | Comparator: FDA Cleared RT-PCR device | ||
| Quidel Molecular | Positive | Negative | Total |
| Positive | 37 | 0 | 37 |
| Negative | 0 | 315 | 315 |
| Total | 37 | 315 | 352 |
| 95% CI | |||
| Positive Percent Agreement | 37/37 | 100% | 90.5% to 100% |
| Negative Percent Agreement | 315/315 | 100% | 98.8% to 100% |
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| Table 5.11: Influenza B | |||
|---|---|---|---|
| Frozen nasopharyngeal | |||
| swab (N=352) | Comparator: FDA Cleared RT-PCR device | ||
| Quidel Molecular | Positive | Negative | Total |
| Positive | 37 | 5* | 42 |
| Negative | 1 | 309 | 310 |
| Total | 38 | 314 | 352 |
| 95% CI | |||
| Positive Percent Agreement | 37/38 | 97.4% | 86.2% to 99.9% |
| Negative Percent Agreement | 309/314 | 98.4% | 96.3% to 99.5% |
*Five specimens were negative by FDA Cleared RT-PCR device but positive for influenza B by sequence analysis.
CONCLUSIONS
Quidel Molecular Influenza A + B Assay using the Cepheid SmartCycler® II instrument yielded good positive and negative percent agreement when compared to a high performance FDA Cleared Influenza A and B molecular test.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/17/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus symbol, which is a staff with two snakes coiled around it, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" arranged in a circular fashion around the symbol. The text is in all caps and appears to be in a sans-serif font.
Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993
Quidel Corp. Ronald H. Lollar Sr. Director, Clinical and Quality Affairs 10165 McKellar Ct. San Diego. CA 92121
MAR 1 5 2012
Re: K113777
Trade/Device Name: Quidel® Molecular Influenza A+B Assay Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory viral panel multiplex nucleic acid assay Regulatory Class: Class II Product Code: OZE, OOI Dated: December 16, 2011 Received: December 21, 2011
Dear Mr. Lollar:
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
18
Page 2 - Ronald H. Lollar
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 advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
Hall, aittoms
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
19
510(k) Number K113777:
Device Name: Ouidel Molecular Influenza A+B Assay
Indication for Use:
The Ouidel® Molecular Influenza A+B assay is a multiplex Real Time RT-PCR assay for the in vitro qualitative detection and differentiation of influenza A and influenza B viral RNA in nasal and nasopharyngeal swabs from patients with signs and symptoms of respiratory infection. This test is intended for use as an aid in the differential diagnosis of influenza A and influenza B viral infections in humans in conjunction with clinical and epidemiological risk factors. The assay does not detect the presence of influenza C virus.
Negative results do not preclude influenza virus infection and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.
Performance characteristics for influenza A were established during the 2011 influenza season when influenza A/H3 and 2009 H1N1 influenza were the predominant influenza A viruses in circulation. 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 (Part 21 CFR 801 Subpart D)
AND/OR
Over-The-Counter Use (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED
Concurrence of CDRH, Office of In Vitro Diagnostic Devices Evaluation and Safety (OIVD)
Tamara Feldblum
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K 1/3777