(164 days)
No
The device description and performance studies focus on RT-PCR technology and standard statistical analysis of results, with no mention of AI or ML algorithms.
No
This device is an in vitro diagnostic test intended for the qualitative detection and differentiation of influenza viral RNA, aiding in diagnosis. It does not directly provide therapy or treatment.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device is "intended as an aid in the diagnosis of influenza infections."
No
The device is an in vitro diagnostic test that includes reagents and is performed on a specific instrument system (GeneXpert® Instrument Systems), indicating it is not software-only.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the assay is "intended for the 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's used to test specimens outside of the body.
- Device Description: The "Device Description" also refers to the assay as a "rapid, automated in vitro diagnostic test."
- Specimen Type: The assay uses "nasopharyngeal (NP) swab specimens," which are biological samples taken from a patient for testing.
- Purpose: The assay is intended as "an aid in the diagnosis of influenza infections," which is a diagnostic purpose.
All of these points align with the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The Cepheid Xpert® Xpress Flu Assay, performed on the GeneXpert® Instrument Systems, is an automated, multiplex real-time, reverse transcriptase polymerase chain reaction (RT-PCR) assay intended for the in vitro qualitative detection and differentiation of influenza A and influenza B viral RNA. The Xpert Xpress Flu Assay uses nasopharyngeal (NP) swab specimens collected from patients with signs and symptoms of respiratory infection. The Xpert Xpress Flu Assay is intended as an aid in the diagnosis of influenza infections in conjunction with clinical and epidemiological risk factors.
Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions.
Performance characteristics for influenza A were established during the 2015-2016 influenza season. When other novel 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.
Ancillary Specimen Collection Kit
The Xpert® Nasopharyngeal Sample Collection Kit is designed to collect, preserve, and transport nasopharyngeal swab specimens and to preserve and transport nasal aspirate/wash specimens containing viruses from patients with signs and symptoms of respiratory infection prior to analysis with the Xpert Flu Assay or the Xpert Flu/RSV XC Assay.
The Xpert® Nasopharyngeal Sample Collection Kit is designed to collect, preserve, and transport nasopharyngeal swab specimens containing viruses from patients with signs and symptoms of respiratory infection prior to analysis with the Xpert Flu+RSV Xpress Assay, Xpert Xpress Flu/RSV Assay or the Xpert Xpress Flu Assay.
Product codes (comma separated list FDA assigned to the subject device)
OCC, OOI, JSM
Device Description
The Xpert Xpress Flu Assay is a rapid, automated in vitro diagnostic test for qualitative detection and differentiation of influenza A (Flu A) and influenza B (Flu B) viral RNA directly from nasopharyngeal (NP) swab specimens. The assay is performed on the Cepheid GeneXpert® Instrument Systems.
The Xpert Xpress Flu Assay includes reagents for the simultaneous detection and differentiation of the target viruses. The primers and probes in the Xpert Xpress Flu Assay detect the presence of nucleic acid sequences for Flu A and Flu B directly from NP swab specimens collected from patients with signs and symptoms of respiratory infection. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are internal controls utilized by the GeneXpert Instrument System platform. The SPC is present in every assay to control for adequate processing of the target viruses and to monitor for the presence of inhibitor(s) in the PCR assay to avoid false-negative results. The PCC verifies reagent rehydration, real-time PCR tube filling in the cartridge, probe integrity, and dye stability.
The specimens are collected in viral transport medium and transported to the GeneXpert area. The specimen is prepared according to package insert instructions and transferred to the sample chamber (large opening) of the Xpert Xpress Flu Assay cartridge. The GeneXpert cartridge is loaded onto the GeneXpert Instrument System platform, which performs hands-off automated sample processing and real-time RT-PCR for detection of Flu viral RNA. Summary and detailed test results are obtained in approximately 30 minutes or less. The results are automatically generated at the end of the process in a report that can be viewed and printed.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Nasopharyngeal (NP)
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Laboratory users in moderate and high complexity laboratory settings.
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
Clinical Comparison Study
Specimens were collected from the following:
- Individuals exhibiting signs and symptoms of respiratory infection who provided informed consent for the collection of a NP swab specimen.
- Individuals with signs and symptoms of respiratory infection and whose routine care called for collection of NP swab specimens for influenza testing. For eligible subjects, aliquots of leftover specimens were obtained for testing with the Xpert Xpress Flu Assay and reference testing, and patient management continued at the site per their standard practice.
A total of 2065 NP swab specimens were tested for influenza A and influenza B by the Xpert Xpress Flu Assay and the comparator assay. Of the 2065 NP swab specimens, 1142 were fresh, prospectively collected and 923 were consecutively collected, frozen specimens.
Bi-directional sequencing was performed on specimens where the Xpert Xpress Flu Assay and the comparator assay were discrepant, and is provided for informational purposes only.
Reproducibility Study
A 5-member specimen panel consisting of a negative control and two each of simulated nasal matrix spiked with influenza A, or influenza B at 1X (low pos) and 2-3X (mod pos) the respective LODs was used. Testing was performed at three sites (one internal, two external) using the GeneXpert Dx system, the Infinity-48 system, and the Infinity-80 system. Two operators at each site tested one panel in duplicate two times per day (equivalent to four replicates per day) over six, not necessarily consecutive days. Three lots of Xpert Xpress Flu cartridges were used, with each lot representing approximately two days of testing.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Non-Clinical Studies: Analytical Sensitivity (Limit of Detection)
The analytical limit of detection (LoD) of the Xpert Xpress Flu Assay was determined using two influenza A H3N2 strains, two influenza A 2009 H1N1 strains and two influenza B strains. Viruses were diluted into negative pooled NP swab clinical matrix for testing. The LoD is defined as the lowest concentration (tissue culture infective dose, TCID50/mL) per sample that can be reproducibly distinguished from negative samples with 95% confidence or the lowest concentration at which 19 of 20 replicates were positive. Each strain was tested in replicates of 20 per concentration of virus.
- Influenza A 2009 H1N1:
- A/California/7/2009: 0.02 TCID50/mL
- A/Florida/27/2011: 0.04 TCID50/mL
- Influenza A H3N2:
- A/Perth/16/2009: 0.01 TCID50/mL
- A/Victoria/361/2011: 0.75 TCID50/mL
- Influenza B:
- B/Mass/2/2012: 0.40 TCID50/mL
- B/Wisconsin/01/2011: 0.19 TCID50/mL
Non-Clinical Studies: Analytical Specificity (Exclusivity)
The analytical specificity of the Xpert Xpress Flu Assay was evaluated by testing a panel of 44 cultures consisting of 16 viral, 26 bacterial, and two yeast strains representing common respiratory pathogens or those potentially encountered in the nasopharynx. Three replicates of each bacterial and yeast strain were tested at concentrations of ≥ 1 x 10^6 CFU/mL (except Chlamydia pneumoniae at 1 x 10^5 CFU/mL). Three replicates of each virus were tested at concentrations of ≥ 1 x 10^5 TCID50/mL.
The analytical specificity was 100%. All tested organisms showed NEG results for Influenza A and Influenza B.
Non-Clinical Studies: Analytical Reactivity (Inclusivity)
The analytical reactivity of the Xpert Xpress Flu Assay was evaluated against multiple strains of influenza A H1N1 (seasonal pre-2009), influenza A H1N1 (pandemic 2009), influenza A H3N2 (seasonal), avian influenza A (H5N1, H5N2, H6N2, H7N2, H7N3, H2N2, H7N9, and H9N2) and influenza B (both Victoria and Yamagata lineages) at levels near the analytical LoD. A total of 48 strains (35 influenza A and 13 Influenza B) were tested. Three replicates were tested for each strain.
All Flu strains tested positive in all three replicates, except for one Flu A H1N1 strain (A/New Jersey/8/76), which tested positive in 2 of 3 replicates at 0.1 TCID50/mL.
Non-Clinical Studies: Potentially Interfering Substances
Potentially interfering substances present in the nasopharynx (blood, nasal secretions, medications) were evaluated. Negative samples (n=8) were tested per substance to determine the effect on the sample processing control (SPC). Positive samples (n=8) were tested per substance with six influenza strains (four influenza A and two influenza B) spiked at 3X the analytical LoD.
None of the substances caused interference of the assay at the tested concentrations. All positive and negative replicates were identified correctly.
Non-Clinical Studies: Carry-Over Contamination
A study demonstrated that single-use, self-contained GeneXpert cartridges prevent carry-over contamination. This involved processing a negative sample immediately followed by a very high influenza A sample (A/Victoria/361/2011, 2x10^7 TCID50/mL) in the same module. This was repeated 20 times, resulting in 20 positive and 21 negative specimens.
All 20 positive samples were correctly reported as Flu A POSITIVE; Flu B NEGATIVE. All 21 negative samples were correctly reported as Flu A NEGATIVE; Flu B NEGATIVE.
Non-Clinical Studies: Fresh vs. Frozen Sample Equivalency Study
Equivalency was evaluated by testing individual influenza strains at low (2X LoD), moderate (5X LoD), and high (10X LoD) positives, and negative samples, in pooled negative NP swab clinical matrix. One seasonal Flu A H3N2 strain (A/Victoria/361/2011) and one Flu B strain (B/Mass/2/2012) were used. Replicates of 20 were tested for each specimen type and concentration, fresh, after one freeze-thaw cycle, and after two freeze-thaw cycles.
There was no difference in performance between fresh virus dilutions and two sequential freeze-thaw cycles for positive and negative samples. All positive and negative replicates were correctly identified.
Non-Clinical Studies: Competitive Interference Study
Competitive interference caused by the presence of two targets in the Xpert Xpress Flu Assay was evaluated. Individual influenza strains near the LoD were tested in the presence of different influenza strains at a higher concentration in a simulated nasal matrix. 20 replicates were tested for each target strain and competitive strain combination.
With Flu A/Victoria/361/2011 at 0.8 TCID50/mL, no competitive inhibitory effects were observed in the presence of 1x10^3 TCID50/mL of Flu B/Mass/2/2012.
With Flu B/Mass/2/2012 at 0.45 TCID50/mL, competitive inhibitory effects were observed in the presence of 1x10^3 TCIDs0mL of Flu A/Victoria/361/2011. No competitive inhibitory effects were observed in the presence of 1x10^2 TCID50/mL of Flu A/Victoria/361/2011.
Competitive inhibitory effects were observed on the targets (Flu A and Flu B) in the presence of two targets for the Xpert Xpress Flu Assay under the study conditions. This is addressed in the Limitations section of the package insert.
Clinical Studies: Clinical Comparison Study
Performance evaluated at eleven U.S. institutions during the 2015-2016 influenza season. 2065 NP swab specimens were tested (1142 fresh, prospectively collected; 923 frozen, consecutively collected).
For fresh, prospectively collected NP swab specimens (n=1142):
- Flu A: PPA 94.6% (CI:82.3-98.5), NPA 99.3% (CI:98.6-99.6)
- Flu B: PPA 100.0% (CI:91.6-100.0), NPA 99.2% (CI:98.5-99.6)
For frozen, consecutively collected NP swab specimens (n=923): - Flu A: PPA 100.0% (CI:94.7-100.0), NPA 97.2% (CI:95.9-98.1)
- Flu B: PPA 100.0% (CI:90.4-100.0), NPA 98.2% (CI:97.1-98.9)
For the combined dataset (n=2065): - Flu A: PPA 98.1% (CI:93.4-99.5), NPA 98.4% (CI:97.7-98.8)
- Flu B: PPA 100.0% (CI:95.3-100.0), NPA 98.7% (CI:98.1-99.1)
Overall assay success rate was 99.7% (2065/2071). Initial indeterminate rate was 1.59% (33/2071), reducing to 0.3% (6/2071) after retesting.
Clinical Studies: Reproducibility Study
A multi-center, blinded study using a 5-member specimen panel tested at three sites with three different GeneXpert systems (DX, Infinity-48, Infinity-80).
Summary of Reproducibility Results (Total Agreement by Sample):
- Negative: 100% (144/144)
- Flu A - Low Pos: 93.7% (134/143)
- Flu A - Mod Pos: 100% (142/142)
- Flu B - Low Pos: 95.1% (137/144)
- Flu B - Mod Pos: 99.3% (143/144)
Reproducibility rates for fluorescence signal (Ct values) showed low CVs across sites, lots, days, and operators for all panel members, indicating high precision.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA).
For Fresh, prospectively collected NP swab specimens:
Flu A: PPA 94.6%, NPA 99.3%
Flu B: PPA 100.0%, NPA 99.2%
For Frozen, consecutively collected NP swab specimens:
Flu A: PPA 100.0%, NPA 97.2%
Flu B: PPA 100.0%, NPA 98.2%
For Combined dataset:
Flu A: PPA 98.1%, NPA 98.4%
Flu B: PPA 100.0%, NPA 98.7%
Overall assay success rate: 99.7%
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
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
Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized symbol that resembles three human profiles facing to the right, stacked on top of each other.
February 13, 2017
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
Cepheid Jim Kellv. PhD Executive Director, Regulatory Affairs 904 Caribbean Drive Sunnyvale, CA 94089
Re: K162456
Trade/Device Name: Xpert® Xpress Flu Assay Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory viral panel multiplex nucleic acid assay Regulatory Class: II Product Code: OCC. OOI. JSM Dated: January 10, 2017 Received: January 11, 2017
Dear Dr. Kelly:
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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
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 Parts 801 and 809); medical device reporting (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.
1
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education 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. 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 Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Steven R. Gitterman -S
Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known)
Device Name
Xpert Xpress Flu
Indications for Use (Describe)
The Cepheid Xpert Xpress Flu Assay, performed on the GeneXpert® Instrument Systems, is an automated, multiplex real-time, reverse transcriptase polymerase chain reaction (RT-PCR) assay intended for the in virro qualitative detection and differentiation of influenza B viral RNA. The Xpert Xpress Flu Assay uses nasopharyngeal (NP) swab specimens collected from patients with signs and symptoms of respiratory infection. The Xpert Xpress Flu Assay is intended as an aid in the diagnosis of influenza infections in clinical and epidemiological risk factors.
Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions.
Performance characteristics for influenza A were established during the 2015-2016 influenza season. When other novel 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.
Ancillary Collection Kit Indications for Use:
The Xpert" Nasopharyngeal Sample Collection Kit is designed to collect, preserve, and transport nasopharyngeal swab specimens and to preserve and transport nasal aspirate/wash specimens containing viruses from patients with signs and symptoms of respiratory infection prior to analysis with the Xpert Flu Assay or the Xpert Flu/RSV XC Assay.
The Xpert" Nasopharyngeal Sample Collection Kit is designed to collect, preserve, and transport nasopharyngeal swab specimens containing viruses from patients with signs and symptoms of respiratory infection prior to analysis with the Xpert Flu+RSV Xpress Assay, Xpert Xpress Flu/RSV Assay or the Xpert Xpress Flu Assay.
2 Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.
FOR FDA USE ONLY
Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)
3
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4
8.0 510(k) Summary
As required by 21 CFR Section 807.92(c).
| Submitted by: | Cepheid
904 Caribbean Drive
Sunnyvale, CA 90489
Phone number: (847) 228-3299
Fax number: (847) 890-6589 |
|--------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact: | Scott A. Campbell, PhD, MBA |
| Date of Preparation: | September 01, 2016 |
| Device: | |
| Trade name: | Xpert® Xpress Flu |
| Common name: | Xpert Xpress Flu Assay |
| Type of Test: | Automated, multiplex real-time reverse transcription-
polymerase chain reaction (RT-PCR) assay intended for the in
vitro qualitative detection and differentiation of influenza A
and influenza B viral RNA. |
| Regulation number/
Classification name/ | 866.3980/Respiratory viral panel multiplex nucleic acid
assay/OCC |
| Product code: | 866.2570/Instrumentation for clinical multiplex test
systems/OOI |
| | 866.2390/Culture Media, Non-Propagating
Transport |
| Classification | Class II |
| Advisory Panel | Microbiology (83) |
| Prescription Use | Yes |
| Predicate Devices
Assay: | 1) For the detection and differentiation of influenza A,
influenza B, and RSV A/B viral RNA in nasopharyngeal
swab specimens:
Xpert® Flu/RSV XC Assay [510(k) #K142045] |
| | 2) For the Sample Collection Kits:
Cepheid Xpert® Nasopharyngeal Sample Collection Kit
[510(k) # K151226] |
5
Device Description:
The Xpert Xpress Flu Assay is a rapid, automated in vitro diagnostic test for qualitative detection and differentiation of influenza A (Flu A) and influenza B (Flu B) viral RNA directly from nasopharyngeal (NP) swab specimens. The assay is performed on the Cepheid GeneXpert® Instrument Systems.
The Xpert Xpress Flu Assay includes reagents for the simultaneous detection and differentiation of the target viruses. The primers and probes in the Xpert Xpress Flu Assay detect the presence of nucleic acid sequences for Flu A and Flu B directly from NP swab specimens collected from patients with signs and symptoms of respiratory infection. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are internal controls utilized by the GeneXpert Instrument System platform. The SPC is present in every assay to control for adequate processing of the target viruses and to monitor for the presence of inhibitor(s) in the PCR assay to avoid false-negative results. The PCC verifies reagent rehydration, real-time PCR tube filling in the cartridge, probe integrity, and dye stability.
The specimens are collected in viral transport medium and transported to the GeneXpert area. The specimen is prepared according to package insert instructions and transferred to the sample chamber (large opening) of the Xpert Xpress Flu Assay cartridge. The GeneXpert cartridge is loaded onto the GeneXpert Instrument System platform, which performs hands-off automated sample processing and real-time RT-PCR for detection of Flu viral RNA. Summary and detailed test results are obtained in approximately 30 minutes or less. The results are automatically generated at the end of the process in a report that can be viewed and printed.
6
Device Intended Use:
The Cepheid Xpert® Xpress Flu Assay, performed on the GeneXpert® Instrument Systems, is an automated, multiplex real-time, reverse transcriptase polymerase chain reaction (RT-PCR) assay intended for the in vitro qualitative detection and differentiation of influenza A and influenza B viral RNA. The Xpert Xpress Flu Assay uses nasopharyngeal (NP) swab specimens collected from patients with signs and symptoms of respiratory infection. The Xpert Xpress Flu Assay is intended as an aid in the diagnosis of influenza infections in conjunction with clinical and epidemiological risk factors.
Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions.
Performance characteristics for influenza A were established during the 2015-2016 influenza season. When other novel 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.
Ancillary Specimen Collection Kit
The Xpert® Nasopharyngeal Sample Collection Kit is designed to collect, preserve, and transport nasopharyngeal swab specimens and to preserve and transport nasal aspirate/wash specimens containing viruses from patients with signs and symptoms of
7
respiratory infection prior to analysis with the Xpert Flu Assay or the Xpert Flu/RSV XC Assay.
The Xpert® Nasopharyngeal Sample Collection Kit is designed to collect, preserve, and transport nasopharyngeal swab specimens containing viruses from patients with signs and symptoms of respiratory infection prior to analysis with the Xpert Flu+RSV Xpress Assay, Xpert Xpress Flu/RSV Assay or the Xpert Xpress Flu Assay.
Substantial Equivalence:
The Xpert Xpress Flu Assay is substantially equivalent to the current Xpert® Flu/RSV XC Assay [510(k) #K142045]. The Xpert Xpress Flu Assay detects influenza A and influenza B from nasopharyngeal (NP) swab specimens and the Xpert® Flu/RSV XC Assay detects influenza A, influenza B, and RSV from both NP swab specimens and nasal aspirate/wash (NA/W) specimens. Both assays utilize the same technology by determining the presence of the target organisms through real-time RT-PCR amplification and fluorogenic target-specific hybridization detection. A multi-center clinical study was conducted and obtained data using the Xpert Xpress Flu/RSV Assay which was then reanalyzed with the Xpert Xpress Flu Assay Definition File (ADF). The reanalyzed data was used to determine the performance characteristics of the Xpert Xpress Flu Assay relative to the predicate device, which has been FDA cleared for NP swab and NA/W specimens. Discordant results between the Xpert Xpress Flu Assay and the reference method Prodesse ProFlu+ Assay [510(k) #K132129] were analyzed by bidirectional sequencing using primers different from those used in the Xpert Xpress Flu Assay. The study results showed that the Xpert Xpress Flu Assay is substantially equivalent to the predicate device.
Table 8-1 shows the similarities and differences between the Xpert Xpress Flu Assay and the predicate device.
8
| Similarities | ||
|---|---|---|
| Device | Predicate | |
| Item | Cepheid Xpert® Xpress Flu | Cepheid Xpert® Flu/RSV XC |
| 510(k)# K142045 | ||
| Regulation | 866.3980 | Same |
| Product Code | OCC, OOI | Same |
| Device Class | II | Same |
| Technology | ||
| Principle of | ||
| Operation | Multiplex real time RT-PCR | Same |
| Intended Use | The Cepheid Xpert® Xpress | |
| Flu Assay, performed on the | ||
| GeneXpert® Instrument | ||
| Systems, is an automated, | ||
| multiplex real-time, reverse | ||
| transcriptase polymerase | ||
| chain reaction (RT-PCR) | ||
| assay intended for the in vitro | ||
| qualitative detection and | ||
| differentiation of influenza A | ||
| and influenza B viral RNA. | ||
| The Xpert Xpress Flu Assay | ||
| uses nasopharyngeal (NP) | ||
| swab specimens collected | ||
| from patients with signs and | ||
| symptoms of respiratory | ||
| infection. The Xpert Xpress | ||
| Flu Assay is intended as an | ||
| aid in the diagnosis of | ||
| influenza infections in | ||
| conjunction with clinical and | ||
| epidemiological risk factors. | ||
| Negative results do not | ||
| preclude influenza virus | ||
| infection and should not be | The Cepheid Xpert® Flu/RSV | |
| XC Assay is an automated, | ||
| multiplex real-time, reverse | ||
| transcriptase polymerase chain | ||
| reaction (RT-PCR) assay | ||
| intended for the in vitro | ||
| qualitative detection and | ||
| differentiation of | ||
| influenza A, influenza B, and | ||
| respiratory syncytial virus | ||
| (RSV) viral RNA. The Xpert | ||
| Flu/RSV XC Assay uses | ||
| nasopharyngeal swab and | ||
| nasal aspirate/wash specimens | ||
| collected from patients with | ||
| signs and symptoms of | ||
| respiratory infection. The | ||
| Xpert Flu/RSV XC Assay is | ||
| intended as an aid in the | ||
| diagnosis of influenza and | ||
| respiratory syncytial virus | ||
| infections in conjunction with | ||
| clinical and epidemiological | ||
| risk factors. | ||
| Negative results do not | ||
| Similarities | ||
| Device | Predicate | |
| Item | Cepheid Xpert® Xpress Flu | Cepheid Xpert® Flu/RSV XC |
| 510(k)# K142045 | ||
| used as the sole basis for | ||
| treatment or other patient | ||
| management decisions. | ||
| Performance characteristics | ||
| for influenza A were | ||
| established during the 2015- | ||
| 2016 influenza season. When | ||
| other novel 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. | preclude influenza virus or | |
| respiratory syncytial virus | ||
| infection and should not be | ||
| used as the sole basis for | ||
| treatment or other patient | ||
| management decisions. | ||
| Performance characteristics for | ||
| influenza A were established | ||
| during the 2013-2014 | ||
| influenza season. When other | ||
| novel 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. | ||
| Similarities | ||
| Item | Device | |
| Cepheid Xpert® Xpress Flu | Predicate | |
| Cepheid Xpert® Flu/RSV XC | ||
| 510(k)# K142045 | ||
| Indications for Use | Patients with signs and symptoms of respiratory infection in conjunction with clinical and epidemiological risk factors | Same |
| Nucleic Acid Extraction | Yes | Same |
| Extraction Methods | Sample preparation integrated in GeneXpert Cartridge and GeneXpert Instrumentation System | Same |
| Assay Results | Qualitative | Same |
| Instrument System | Cepheid GeneXpert Instrument Systems; same Cepheid I-core technology | Same |
| Primers and probes | Primers and probes to detect the presence of nucleic acid sequences of influenza A, influenza B, and RSV. Only results for influenza A and influenza B are reported. | Primers and probes to detect the presence of influenza A, influenza A subtype H7N9, influenza B and RSV. Results for influenza A, influenza B and RSV analytes are reported. |
| Laboratory Users | Laboratory users in moderate and high complexity laboratory settings. | Same |
| Sample Preparation | Self-contained and automated after mixed specimen is added to cartridge. All other reagents are contained in the cartridge. | Same |
| Similarities | ||
| Item | Device | |
| Cepheid Xpert® Xpress Flu | Predicate | |
| Cepheid Xpert® Flu/RSV XC | ||
| 510(k)# K142045 | ||
| Primers and | ||
| probes for | ||
| influenza A, | ||
| influenza B | Primers and probes to detect | |
| the presence of nucleic acid | ||
| sequences of influenza A, | ||
| influenza B, and RSV A/B. | ||
| The Xpert Xpress Flu Assay | ||
| contains primers and probes to | ||
| detect additional RNA | ||
| segments in order to protect | ||
| the assay sensitivity and | ||
| specificity from mutations in | ||
| the influenza genome due to | ||
| antigenic drifts and shifts. | ||
| Only results for influenza A | ||
| and influenza B are reported. | Primers and probes to detect | |
| the presence of nucleic acid | ||
| sequences of influenza A, | ||
| influenza B, and RSV A/B. | ||
| The Xpert Flu/RSV XC Assay | ||
| contains primers and probes to | ||
| detect additional RNA | ||
| segments in order to protect | ||
| the assay sensitivity and | ||
| specificity from mutations in | ||
| the influenza genome due to | ||
| antigenic drifts and shifts. | ||
| Target | ||
| Sequences | Influenza A: Matrix protein | |
| (MP),basic polymerase (PB2) | ||
| and acidic protein (PA) |
Influenza B: Matrix protein
(MP) and Non-structural
proteins (NS 1 and NS 2)
RSV A and RSV B:
Nucleocapsid protein
Only results for influenza A
and influenza B are reported. | Influenza A: Matrix protein
(MP),basic polymerase (PB2)
and acidic protein (PA)
Influenza B: Matrix protein
(MP) and Non-structural
proteins (NS 1 and NS 2)
RSV A and RSV B:
Nucleocapsid protein |
| Internal
Controls | Sample processing control
(SPC) and probe check
control (PCC). | Same |
| Early assay
termination
function | Yes | Yes |
| Differences | | |
| | Device | Predicate |
| Item | Cepheid Xpert® Xpress Flu | Cepheid Xpert® Flu/RSV XC |
| Assay Targets | Influenza A Virus and
Influenza B Virus viral RNA | Influenza A Virus, Influenza B
Virus, and RSV viral RNA |
| Specimen
Types | Nasopharyngeal (NP) swab
specimens | Nasal aspirate/wash (NA/W)
specimens and
Nasopharyngeal (NP) swab
specimens |
| Assay Controls | Encapsulated (armored) RNA
pseudovirus as a sample
processing control. | Encapsulated (armored) RNA
pseudovirus as a sample
processing control. |
| | Available but not provided are
inactivated virus controls for
influenza A/B as external
positive controls, and
Coxsackie virus as an external
negative control. | Available but not provided are
inactivated virus controls for
influenza A/B and RSV as
external positive controls, and
Coxsackie virus as an external
negative control. |
| Time to obtain
test results | Approximately 30 minutes or
less for sample preparation
and RT-PCR | Approximately 60 minutes or
less for sample preparation and
RT-PCR |
| Combinatorial
Assay
Selections | Not applicable | Yes, user may select combined
assay with all targets or a Flu
only assay or a RSV only
assay. |
Table 8-1: Comparison of Similarities and Differences of the Xpert Xpress Flu Assay with the Predicate Device
9
10
11
12
13
The Xpert Xpress Flu Assay and the predicate device have the same general intended use and technological characteristics, and both detect influenza A and influenza B viral RNA from NP swab specimens. The clinical study demonstrates that the Xpert Xpress Flu Assay is substantially equivalent to the predicate device.
The predicate device for the ancillary specimen collection kit, the Xpert® Nasopharyngeal Sample Collection Kit is the Cepheid Nasopharyngeal Sample Collection Kit, [510(k) # K151226]. The similarities and differences are shown in Table 8-2.
14
| Similarities | ||
|---|---|---|
| Device | Predicate | |
| Item | Xpert® Nasopharyngeal | |
| Sample Collection Kit | Xpert® Nasopharyngeal | |
| Sample Collection Kit | ||
| 510(k)# K151226 | ||
| Intended Use | The Xpert® Nasopharyngeal | |
| Sample Collection Kit is | ||
| designed to collect, preserve, | ||
| and transport nasopharyngeal | ||
| swab specimens and to preserve | ||
| and transport nasal | ||
| aspirate/wash specimens | ||
| containing viruses from patients | ||
| with signs and symptoms of | ||
| respiratory infection prior to | ||
| analysis with the Xpert Flu | ||
| Assay or the Xpert Flu/RSV XC | ||
| Assay. The Xpert® | ||
| Nasopharyngeal Sample | ||
| Collection Kit is designed to | ||
| collect, preserve, and transport | ||
| nasopharyngeal swab specimens | ||
| containing viruses from patients | ||
| with signs and symptoms of | ||
| respiratory infection prior to | ||
| analysis with the Xpert | ||
| Flu+RSV Xpress Assay, Xpert | ||
| Xpress Flu/RSV Assay or the | ||
| Xpert Xpress Flu Assay. | The Xpert® Nasopharyngeal | |
| Sample Collection Kit is designed | ||
| to collect, preserve, and transport | ||
| nasopharyngeal swab specimens | ||
| and to preserve and transport | ||
| nasal aspirate/wash specimens | ||
| containing viruses from patients | ||
| with signs and symptoms of | ||
| respiratory infection prior to | ||
| analysis with the Xpert Flu Assay | ||
| or the Xpert Flu/RSV XC Assay. | ||
| The Xpert® Nasopharyngeal | ||
| Sample Collection Kit is designed | ||
| to collect, preserve, and transport | ||
| nasopharyngeal swab specimens | ||
| containing viruses from patients | ||
| with signs and symptoms of | ||
| respiratory infection prior to | ||
| analysis with the Xpert Flu+RSV | ||
| Xpress Assay. | ||
| Similarities | ||
| Device | Predicate | |
| Item | Xpert® Nasopharyngeal | |
| Sample Collection Kit | Xpert® Nasopharyngeal | |
| Sample Collection Kit | ||
| 510(k)# K151226 | ||
| Transport Medium | ||
| Formulation | Hank's Balanced Salt Solution | |
| Bovine Serum Albumin | ||
| L-cysteine | ||
| Gelatin | ||
| Sucrose | ||
| L-glutamic acid | ||
| HEPES buffer | ||
| Vancomycin | ||
| Amphotericin B | ||
| Colistin | ||
| Phenol red | Same | |
| pH | 7.3 ± 0.2 | Same |
| Storage Temperature | 2 - 25°C (refrigerated | |
| and room temperature) | Same | |
| Volume | 3 ml | Same |
| Glass Beads | 3 x 3 mm | Same |
| Container | Plastic (medical-grade | |
| polypropylene) | Same | |
| Product Configuration | Medium Tube in Kit with | |
| individually-wrapped sterile | ||
| swab. | Same |
Table 8-2: Comparison of Similarities and Differences of the Xpert Nasopharyngeal Sample Collection Kit with the Predicate Device
15
16
| Differences | ||
|---|---|---|
| Device | Predicate | |
| Item | Xpert® Nasopharyngeal | |
| Sample Collection Kit | Xpert® Nasopharyngeal | |
| Sample | ||
| Collection Kit | ||
| 510(k)# K151226 | ||
| Intended Use | For collection, preservation | |
| and transport of | ||
| nasopharyngeal swab | ||
| specimens and to preserve | ||
| and transport nasal | ||
| aspirate/wash specimens | ||
| containing viruses from | ||
| patients with signs and | ||
| symptoms of respiratory | ||
| infection prior to analysis | ||
| with the Xpert Flu Assay, | ||
| Xpert Flu/RSV XC Assay, | ||
| Xpert Flu+RSV Xpress | ||
| Assay, Xpert Xpress | ||
| Flu/RSV Assay and Xpert | ||
| Xpress Flu Assay. | For collection, preservation | |
| and transport of | ||
| nasopharyngeal swab | ||
| specimens and to preserve | ||
| and transport nasal | ||
| aspirate/wash specimens | ||
| containing viruses from | ||
| patients with signs and | ||
| symptoms of respiratory | ||
| infection prior to analysis | ||
| with the Xpert Flu Assay, | ||
| Xpert Flu/RSV XC Assay and | ||
| Xpert Flu+RSV Xpress | ||
| Assay. |
The proposed collection kit and predicate collection kit have the same general intended use and the same technology to collect, store and transport clinical specimens, including viruses, to the laboratory for further testing. The prospective component of the multicenter clinical study of the Xpert Xpress Flu Assay was conducted using Xpert Nasopharyngeal Sample Collection Kit [510(k) # K151226] demonstrating that the Xpert Nasopharyngeal Sample Collection Kit is substantially equivalent to the predicate device.
Non-Clinical Studies:
Analytical Sensitivity (Limit of Detection)
Studies were performed to determine the analytical limit of detection (LoD) of the Xpert Xpress Flu Assay with two lots of reagents across three testing days. The higher LoD
17
observed per strain and per lot as determined by probit analysis was selected for verification. Verification of the estimated LoD claim was performed on one reagent lot across a minimum of three testing days. LoD was established using two influenza A H3N2 strains, two influenza A 2009 H1N1 strains and two influenza B strains. Viruses were diluted into negative pooled NP swab clinical matrix for testing. The LoD is defined as the lowest concentration (tissue culture infective dose, TCID50/mL) per sample that can be reproducibly distinguished from negative samples with 95% confidence or the lowest concentration at which 19 of 20 replicates were positive. Each strain was tested in replicates of 20 per concentration of virus. The LoD values for each strain tested are summarized in Tables 8-3 – 8-5.
| Table 8-3 Confirmed LoD (TCID50/mL):
| Influenza A 2009 H1N1 | |
|---|---|
| T 7 ------- | Confirmed |
| Virus
Strain | Confirmed
LoD
(TCID50/mL) |
|-------------------------------|---------------------------------|
| Influenza A/California/7/2009 | 0.02 |
| Influenza A/Florida/27/2011 | 0.04 |
Table 8-4 Confirmed LoD (TCID50/mL): Influenza A H3N2
| Virus
Strain | Confirmed LoD
(TCID50/mL) |
|-------------------------------|------------------------------|
| Influenza A/Perth/16/2009 | 0.01 |
| Influenza A/Victoria/361/2011 | 0.75 |
Table 8-5 Confirmed LoD (TCID50/mL): Influenza B
| Virus
Strain | Confirmed
LoD
(TCID50/mL) |
|-------------------------------|---------------------------------|
| Influenza B/Mass/2/2012 | 0.40 |
| Influenza B/Wisconsin/01/2011 | 0.19 |
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Analytical Specificity (Exclusivity)
The analytical specificity of the Xpert Xpress Flu Assay was evaluated by testing a panel of 44 cultures consisting of 16 viral, 26 bacterial, and two yeast strains representing common respiratory pathogens or those potentially encountered in the nasopharynx. Three replicates of each bacterial and yeast strain were tested at concentrations of ≥ 1 x 106 CFU/mL with the exception of one strain that was tested at 1 x 105 CFU/mL (Chlamydia pneumoniae). Three replicates of each virus were tested at concentrations of ≥ 1 x 105 TCID50/mL. The analytical specificity was 100%. Results are shown in Table 8-6.
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| Result | |||
|---|---|---|---|
| Organism | Concentration | ||
| (per cartridge) | Influenza | ||
| A | Influenza | ||
| B | |||
| No Template Control | N/A | NEG | NEG |
| Adenovirus Type 1 | 1.12E+06 TCID50/mL | NEG | NEG |
| Adenovirus Type 7 | 1.87E+05 TCID50/mL | NEG | NEG |
| Human coronavirus OC43 | 2.85E+05 TCID50/mL | NEG | NEG |
| Human coronavirus 229E | 1.00E+05 TCID50/mL | NEG | NEG |
| Cytomegalovirus | 1.00E+05 TCID50/mL | NEG | NEG |
| Echovirus | 3.31E+07 TCID50/mL | NEG | NEG |
| Enterovirus | 3.55E+05 TCID50/mL | NEG | NEG |
| Epstein Barr Virus | 7.16E+07 TCID50/mL | NEG | NEG |
| HSV | 8.90E+05 TCID50/mL | NEG | NEG |
| Measles | 6.31E+05 TCID50/mL | NEG | NEG |
| Human metapneumovirus | 1.00E+05 TCID50/mL | NEG | NEG |
| Mumps virus | 6.31E+06 TCID50/mL | NEG | NEG |
| Human parainfluenza Type 1 | 1.15E+06 TCID50/mL | NEG | NEG |
| Human parainfluenza Type 2 | 6.31E+05 TCID50/mL | NEG | NEG |
| Human parainfluenza Type 3 | 3.55E+06 TCID50/mL | NEG | NEG |
| Rhinovirus Type 1A | 1.26E+05 TCID50/mL | NEG | NEG |
| Acinetobacter baumannii | 1.00E+06 CFU/mL | NEG | NEG |
| Burkholderia cepacia | 3.30E+06 CFU/mL | NEG | NEG |
| Candida albicans | 3.20E+06 CFU/mL | NEG | NEG |
| Candida parapsilosis | 3.00E+06 CFU/mL | NEG | NEG |
| Bordetella pertussis | 3.30E+06 CFU/mL | NEG | NEG |
| Chlamydia pneumoniae | 1.00E+05 CFU/mL | NEG | NEG |
| Citrobacter freundii | 3.30E+06 CFU/mL | NEG | NEG |
| Corynebacterium sp. | 3.30E+06 CFU/mL | NEG | NEG |
| Escherichia coli | 1.00E+07 CFU/mL | NEG | NEG |
| Enterococcus faecalis | 1.30E+06 CFU/mL | NEG | NEG |
| Haemophilus influenzae | 1.00E+06 CFU/mL | NEG | NEG |
| Lactobacillus reuteri | 1.00E+06 CFU/mL | NEG | NEG |
| Legionella spp. | 1.00E+06 CFU/mL | NEG | NEG |
| Moraxella catarrhalis | 1.00E+07 CFU/mL | NEG | NEG |
| Organism | Concentration | ||
| (per cartridge) | Result | ||
| Influenza | |||
| A | Influenza | ||
| B | |||
| Mycobacterium tuberculosis | |||
| (avirulent) | 1.00E+06 CFU/mL | NEG | NEG |
| Mycoplasma pneumoniae | 1.00E+06 CFU/mL | NEG | NEG |
| Neisseria meningitidis | 2.15E+06 CFU/mL | NEG | NEG |
| Neisseria mucosa | 1.00E+07 CFU/mL | NEG | NEG |
| Propionibacterium acnes | 2.40E+07 CFU/mL | NEG | NEG |
| Pseudomonas aeruginosa | 3.70E+06 CFU/mL | NEG | NEG |
| Staphylococcus aureus (protein A | |||
| producer) | 2.20E+06 CFU/mL | NEG | NEG |
| Staphylococcus epidermidis | 3.40E+06 CFU/mL | NEG | NEG |
| Staphylococcus haemolyticus | 4.00E+06 CFU/mL | NEG | NEG |
| Streptococcus agalactiae | 3.50E+06 CFU/mL | NEG | NEG |
| Streptococcus pneumoniae | 1.00E+06 CFU/mL | NEG | NEG |
| Streptococcus pyogenes | 1.00E+07 CFU/mL | NEG | NEG |
| Streptococcus salivarius | 1.00E+07 CFU/mL | NEG | NEG |
| Streptococcus sanguinis | 3.10E+06 CFU/mL | NEG | NEG |
Table 8-6 Analytical Specificity of the Xpert Xpress Flu Assay
20
21
Analytical Reactivity (Inclusivity)
The analytical reactivity of the Xpert Xpress Flu Assay was evaluated against multiple strains of influenza A H1N1 (seasonal pre-2009), influenza A H1N1 (pandemic 2009), influenza A H3N2 (seasonal), avian influenza A (H5N1, H5N2, H6N2, H7N2, H7N3, H2N2, H7N9, and H9N2) and influenza B (representing strains from both Victoria and Yamagata lineages) at levels near the analytical LoD. A total of 48 strains comprised of 35 influenza A and 13 Influenza B strains were tested in this study with the Xpert Xpress Flu Assay. Three replicates were tested for each strain. All Flu strains tested positive in all three replicates, except for one Flu A H1N1 strain (A/New Jersey/8/76), which tested positive in 2 of 3 replicates at 0.1 TCID50/mL. Results are shown in Table 8-7.
Further in silico analysis was conducted to determine the predicted cross reactivity of additional influenza A 2009 H1N1-like strains. The results showed 100% sequence homology for all primer target nucleotide sequences analyzed.
22
| Virus | Strain | Target
Concentration | Result | |
|-----------------------------------|----------------------------------|-------------------------|---------------|-----|
| | No Template Control | n/a | NEG | NEG |
| | A/swine/Iowa/15/30 | 0.1 TCID50/mL | POS | NEG |
| | A/WS/33 | 0.1 TCID50/mL | POS | NEG |
| | A/PR/8/34 | 0.1 TCID50/mL | POS | NEG |
| | A/Mal/302/54 | 0.1 TCID50/mL | POS | NEG |
| | A/Denver/1/57 | 0.1 TCID50/mL | POS | NEG |
| | A/New Jersey/8/76 | 0.1 TCID50/mL | POS | NEG |
| Influenza
A H1N1
(pre-2009) | A/New Caledonia/20/1999 | 0.1 TCID50/mL | POS | NEG |
| | A/New York/55/2004 | 0.1 TCID50/mL | POS | NEG |
| | A/Soloman Island/3/2006 | 0.1 TCID50/mL | POS | NEG |
| | A/Taiwan/42/06 | 0.1 TCID50/mL | POS | NEG |
| | A/Brisbane/59/2007 | 0.1 TCID50/mL | POS | NEG |
| | A/swine/NY/02/2009 | 0.1 TCID50/mL | POS | NEG |
| | Influenza
A H1N1
(pdm2009) | A/Colorado/14/2012 | 0.1 TCID50/mL | POS |
| | | A/Washington/24/2012 | 0.1 TCID50/mL | POS |
| | | A/Aichi/2/68 | 2.0 TCID50/mL | POS |
| | A/HongKong/8/68 | 2.0 TCID50/mL | POS | NEG |
| | A/Port Chalmers/1/73 | 2.0 TCID50/mL | POS | NEG |
| | A/Hawaii/15/2001 | 2.0 TCID50/mL | POS | NEG |
| Influenza
A H3N2
(Seasonal) | A/Wisconsin/67/05 | 2.0 TCID50/mL | POS | NEG |
| | A/Brisbane/10/2007 | 2.0 TCID50/mL | POS | NEG |
| | A/Minnesota/11/2010 (H3N2)v | 2.0 TCID50/mL | POS | NEG |
| | A/Indiana/08/2011 (H3N2)v | 2.0 TCID50/mL | POS | NEG |
| | A/Texas/50/2012 | 2.0 TCID50/mL | POS | NEG |
Table 8-7 Analytical Reactivity (Inclusivity) of the Xpert Xpress Flu Assay
23