K Number
K162331
Device Name
Xpert Xpress Flu/RSV, Xpert Nasopharyngeal Sample Collection Kit, GeneXpert Dx Systems (GX-I, GX-II, GX-IV, GX-XVI), GeneXpert Infinity-48 System and GeneXpert Infinity-48s System, GeneXpert Infinity-80 System
Manufacturer
Date Cleared
2017-02-09

(174 days)

Product Code
Regulation Number
866.3980
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdparty
Intended Use
The Cepheid Xpert® Xpress Flu/RSV Assay, performed on the GeneXpert® Instrument Systems, is an automated, multiplex real-time, reverse transcriptase chain reaction (RT-PCR) assay intended for the in vitro qualitative detection and differentiation of influenza B. and respiratory syncytial virus (RSV) viral RNA. The Xpert Xpress Flu/ RSV Assay uses nasopharyngeal (NP) swab specimens with signs and symptoms of respiratory infection. The Xpert Xpress Flu/RSV Assav 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 preclude influenza virus or RSV 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 or the Xpert Xpress Flu/RSV Assay.
Device Description
The Xpert Xpress Flu/RSV Assay is a rapid, automated in vitro diagnostic test for qualitative detection and differentiation of influenza A (Flu A), influenza B (Flu B), and respiratory syncytial virus (RSV) viral RNA directly from nasopharyngeal (NP) swab specimens. The assay is performed on the Cepheid GeneXpert® Instrument Systems. The Xpert Xpress Flu/RSV Assay includes reagents for the simultaneous detection and differentiation of the target viruses. The primers and probes in the Xpert Xpress Flu/RSV Assay detect the presence of nucleic acid sequences for Flu A, Flu B, and RSV 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/RSV 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 and RSV 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.
More Information

No
The device description and performance studies focus on standard RT-PCR technology for detecting viral RNA. There is no mention of AI or ML algorithms being used for analysis, interpretation, or any other function of the device.

No.

Explanation: This device is an in vitro diagnostic test designed for the qualitative detection and differentiation of specific viral RNA as an aid in diagnosis, not for providing medical treatment or therapy.

Yes

Explanation: The "Intended Use / Indications for Use" section explicitly states that the assay "is intended as an aid in the diagnosis of influenza and respiratory syncytial virus infections." Additionally, the "Device Description" calls it an "in vitro diagnostic test."

No

The device is an in vitro diagnostic (IVD) assay that includes reagents and is performed on a specific hardware instrument system (GeneXpert® Instrument Systems). While software is involved in the automated process and result generation, it is not a standalone software-only medical device.

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 B. and respiratory syncytial virus (RSV) viral RNA." The term "in vitro" is a key indicator of an IVD. It also states it is "intended as an aid in the diagnosis of influenza and respiratory syncytial virus infections."
  • Device Description: The "Device Description" section also clearly states that the Xpert Xpress Flu/RSV Assay is a "rapid, automated in vitro diagnostic test."
  • Purpose: The device is designed to analyze biological specimens (nasopharyngeal swabs) outside of the body to provide information for the diagnosis of disease (influenza and RSV infections).

These points directly align with the definition of an In Vitro Diagnostic device.

N/A

Intended Use / Indications for Use

The Cepheid Xpert® Xpress Flu/RSV Assay, performed on the GeneXpert® Instrument Systems, is an automated, multiplex real-time, reverse transcriptase chain reaction (RT-PCR) assay intended for the in vitro qualitative detection and differentiation of influenza B. and respiratory syncytial virus (RSV) viral RNA. The Xpert Xpress Flu/ RSV Assay uses nasopharyngeal (NP) swab specimens with signs and symptoms of respiratory infection. The Xpert Xpress Flu/RSV Assav 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 preclude influenza virus or RSV 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 or the Xpert Xpress Flu/RSV Assay.

Product codes (comma separated list FDA assigned to the subject device)

OCC, OOI, JSM

Device Description

The Xpert Xpress Flu/RSV Assay is a rapid, automated in vitro diagnostic test for qualitative detection and differentiation of influenza A (Flu A), influenza B (Flu B), and respiratory syncytial virus (RSV) viral RNA directly from nasopharyngeal (NP) swab specimens. The assay is performed on the Cepheid GeneXpert® Instrument Systems.

The Xpert Xpress Flu/RSV Assay includes reagents for the simultaneous detection and differentiation of the target viruses. The primers and probes in the Xpert Xpress Flu/RSV Assay detect the presence of nucleic acid sequences for Flu A, Flu B, and RSV 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/RSV 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 and RSV 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) swab specimens, nasal aspirate/wash specimens

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

Performance characteristics of the Xpert Xpress Flu/RSV Assay were evaluated at eleven institutions in the U.S. during the 2015-2016 influenza season. Due to the low prevalence of influenza viruses and the difficulty in obtaining fresh influenza and RSVpositive specimens, the specimen population for this study was supplemented with consecutively collected, frozen specimens.

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 and/or RSV testing. For eligible subjects, aliquots of leftover specimens were obtained for testing with the Xpert Xpress Flu/RSV Assay and reference testing, and patient management continued at the site per their standard practice.
    The Xpert Xpress Flu/RSV Assay performance was compared to FDA-cleared molecular comparator assay. Bi- directional sequencing was performed on specimens where the Xpert Xpress Flu/RSV Assay and the comparator assay were discrepant, and is provided for informational purposes only.

A total of 2065 NP swab specimens were tested for influenza A, influenza B and RSV by the Xpert Xpress Flu/RSV Assay and the comparator assay. Of the 2065 NP swab specimens, 1142 were fresh, prospectively collected and 923 were consecutively collected, frozen specimens.

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Clinical Comparison Study
Sample Size: 2065 NP swab specimens (1142 fresh, prospectively collected; 923 consecutively collected, frozen specimens).
Key Results:
For fresh, prospectively collected NP swab specimens:

  • 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 99.1% (CI:98.3-99.5)
  • RSV: PPA 100.0% (CI:81.6-100.0), NPA 99.6% (CI:99.0-99.8)

For consecutively collected, frozen NP swab specimens:

  • 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)
  • RSV: PPA 97.9% (CI:89.1-99.6), NPA 97.7% (CI:96.5-98.5)

For combined dataset:

  • 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)
  • RSV: PPA 98.5% (CI:91.8-99.7), NPA 98.8% (CI:98.2-99.2)

Overall assay success rate: 99.7% (2065/2071). Initial indeterminate rate: 1.59% (33/2071). Overall indeterminate rate after retesting: 0.3% (6/2071).

Reproducibility Study
Study Type: Multi-center, blinded study using a seven-member specimen panel.
Sample Set: Negative control, and low and moderate positive simulated nasal matrix spikes for influenza A, influenza B, and RSV.
Key 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: 98.6% (142/144)
  • RSV - Low Pos: 94.4% (135/143)
  • RSV - Mod Pos: 100% (143/143)

Non-Clinical Studies: Analytical Sensitivity (Limit of Detection)
The analytical limit of detection (LoD) of the Xpert Xpress Flu/RSV Assay was determined using probit analysis, with verification.
Key Results:

  • 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)
  • RSV A: RSV A/2/Australia/61 (0.87 TCID50/mL), RSV A/Long/MD/56 (1.10 TCID50/mL)
  • RSV B: RSV B/Wash/18537/62 (0.79 TCID50/mL), RSV B/9320/MA/77 (2.30 TCID50/mL)

Non-Clinical Studies: Analytical Specificity (Exclusivity)
Evaluated a panel of 44 cultures (16 viral, 26 bacterial, and 2 yeast strains).
Key Results: Analytical specificity was 100%.

Non-Clinical Studies: Analytical Reactivity (Inclusivity)
Evaluated 53 strains (48 influenza viruses, 5 RSV strains) at levels near analytical LoD.
Key Results:
All Flu and RSV 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
Evaluated 16 potentially interfering substances.
Key Results: None of the substances caused interference of the assay at the concentrations tested. All positive and negative replicates were identified correctly.

Non-Clinical Studies: Carry-Over Contamination
Demonstrated that single-use, self-contained GeneXpert cartridges prevent carry-over contamination.
Key Results: All 40 positive samples were correctly reported, and all 42 negative samples were correctly reported.

Non-Clinical Studies: Fresh vs. Frozen Sample Equivalency Study
Evaluated fresh and frozen specimen equivalency at three different concentrations (2X LoD, 5X LoD, 10X LoD).
Key Results: No difference in performance between fresh virus dilutions and two sequential freeze-thaw cycles. All positive and negative replicates were correctly identified.

Non-Clinical Studies: Competitive Interference Study
Evaluated competitive interference when two targets are present.
Key Results:

  • Flu A/Victoria/361/2011: No competitive inhibitory effects in presence of high concentrations of Flu B or RSV.
  • Flu B/Mass/2/2012: Competitive inhibitory effects observed with 1x103 TCID50/mL of Flu A/Victoria/361/2011. No effects with lower Flu A or RSV.
  • RSV-A/2/Australia/61: Competitive inhibitory effects observed with 1x103 TCID50/mL of Flu A/Victoria/361/2011. No effects with lower Flu A or Flu B.
  • RSV-B/Wash/18537/62: Competitive inhibitory effects observed with 1x102 TCID50/mL of Flu A/Victoria/361/2011 or 1x103 TCID50/mL of Flu B/Mass/2/2012. No effects with lower concentrations.
    Competitive inhibitory effects on the targets (Flu A, Flu B, and RSV) are addressed in the Limitations section of the package insert.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

PPA (Positive Percent Agreement), NPA (Negative Percent Agreement).

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.

K142045, K151226

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.

K132129

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.

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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 an abstract image of three human profiles facing to the right, resembling a bird-like shape.

February 9, 2017

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - W 066-G609 Silver Spring, MD 20993-0002

Public Health Service

CEPHEID SCOTT A. CAMPBELL CORPORATE VICE PRESIDENT & CHIEF REGULTORY OFFICER 904 CARIBBEAN DRIVE SUNNYVALE, CA 94089

Re: K162331 Trade/Device Name: Xpert® Xpress Flu/RSV Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory viral panel multiplex nucleic acid assay Regulatory Class: II Product Code: OCC, OOI, JSM Dated: August, 18 2016 Received: August 23, 2016

Dear Dr. Campbell:

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 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/ResourcesforYou/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

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Indications for Use

510(k) Number (if known)

K162331

Device Name

Xpert Xpress Flu/RSV

Indications for Use (Describe)

The Cepheid Xpert® Xpress Flu/RSV Assay, performed on the GeneXpert® Instrument Systems, is an automated, multiplex real-time, reverse transcriptase chain reaction (RT-PCR) assay intended for the in vitro qualitative detection and differentiation of influenza B. and respiratory syncytial virus (RSV) viral RNA. The Xpert Xpress Flu/ RSV Assay uses nasopharyngeal (NP) swab specimens with signs and symptoms of respiratory infection. The Xpert Xpress Flu/RSV Assav 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 preclude influenza virus or RSV 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 or the Xpert Xpress Flu/RSV Assay.

Type of Use (Select one or both, as applicable)

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)

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DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

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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: | August 18, 2016 |
| Device: | |
| Trade name: | Xpert® Xpress Flu/RSV |
| Common name: | Xpert Xpress Flu/RSV 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,
influenza B, and respiratory syncytial virus (RSV) viral RNA. |
| Regulation number/
Classification name/
Product code: | 866.3980/Respiratory viral panel multiplex nucleic acid
assay/OCC
866.2570/Instrumentation for clinical multiplex test
systems/OOI
866.2390/Culture Media, Non-propagating
Transport/JSM |
| Classification
Advisory Panel | Class II
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]

  1. For the Sample Collection Kits:

Cepheid Xpert Nasopharyngeal Sample Collection Kit |

[510(k) # K151226]

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Device Description:

The Xpert Xpress Flu/RSV Assay is a rapid, automated in vitro diagnostic test for qualitative detection and differentiation of influenza A (Flu A), influenza B (Flu B), and respiratory syncytial virus (RSV) viral RNA directly from nasopharyngeal (NP) swab specimens. The assay is performed on the Cepheid GeneXpert® Instrument Systems.

The Xpert Xpress Flu/RSV Assay includes reagents for the simultaneous detection and differentiation of the target viruses. The primers and probes in the Xpert Xpress Flu/RSV Assay detect the presence of nucleic acid sequences for Flu A, Flu B, and RSV 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/RSV 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 and RSV 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/RSV 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, influenza B, and respiratory syncytial virus (RSV) viral RNA. The Xpert Xpress Flu/RSV Assay uses nasopharyngeal (NP) swab specimens collected from patients with signs and symptoms of respiratory infection. The Xpert Xpress Flu/RSV 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 preclude influenza virus or RSV 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

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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 or the Xpert Xpress Flu/RSV Assay.

Substantial Equivalence:

The Xpert Xpress Flu/RSV Assay is substantially equivalent to the current Xpert® Flu/RSV XC Assay [510(k) #K142045]. The Xpert Xpress Flu/RSV Assay detects influenza A. influenza B. and RSV A/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 aspirates/washes (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 multicenter clinical study was conducted to determine the performance characteristics of the Xpert Xpress Flu/RSV 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/RSV Assay and the reference method Prodesse ProFlu+ Assay [510(k) # K132129] were analyzed by bi-directional sequencing using primers different from those used in the Xpert Xpress Flu/RSV Assay. The study results showed that the Xpert Xpress Flu/RSV Assay is substantially equivalent to the predicate device.

Table 8-1 shows the similarities and differences between the Xpert Xpress Flu/RSV Assay and the predicate devices.

8

Similarities
DevicePredicate
ItemCepheid Xpert® Xpress
Flu/RSVCepheid Xpert® Flu/RSV XC
510(k)# K142045
Regulation866.3980Same
Product CodeOCC, OOISame
Device ClassIISame
Technology
Principle of
OperationMultiplex real time RT-PCRSame
Intended UseThe Cepheid Xpert® Xpress
Flu/RSV 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, influenza B, and
respiratory syncytial virus
(RSV) viral RNA. The Xpert
Xpress Flu/RSV Assay uses
nasopharyngeal (NP) swab
specimens collected from
patients with signs and
symptoms of respiratory
infection. The Xpert Xpress
Flu/RSV 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 notThe 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
DevicePredicate
ItemCepheid Xpert® Xpress
Flu/RSVCepheid Xpert® Flu/RSV XC
510(k)# K142045
preclude influenza virus or
RSV
infection and should not be
used as the sole basis for
treatment or other patient
management decisions.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 2015-
2016 influenza season. When
other novel influenza A
viruses are emerging,
performance characteristics
may vary.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.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
DevicePredicate
ItemCepheid Xpert® Xpress
Flu/RSVCepheid Xpert® Flu/RSV XC
510(k)# K142045
Indications for
UsePatients with signs and
symptoms of respiratory
infection in conjunction with
clinical and epidemiological
risk factorsSame
Assay TargetsInfluenza A Virus, Influenza
B Virus, and RSV viral RNASame
Nucleic Acid
ExtractionYesSame
Extraction
MethodsSample preparation integrated
in GeneXpert Cartridge and
GeneXpert Instrumentation
SystemSame
Assay ResultsQualitativeSame
Instrument
SystemCepheid GeneXpert
Instrument Systems; same
Cepheid I-core technologySame
Assay ControlsEncapsulated (armored) RNA
pseudovirus as a sample
processing 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.Same
Primers and
probesPrimers and probes to detect
the presence of nucleic acid
sequences of influenza A,
influenza B, and RSV.Primers and probes to detect
the presence of influenza A,
influenza A subtype H7N9,
influenza B and RSV.
Laboratory
UsersLaboratory users in moderate
and high complexity
laboratory settings.Same
Similarities
DevicePredicate
ItemCepheid Xpert® Xpress
Flu/RSVCepheid Xpert® Flu/RSV XC
510(k)# K142045
Sample
PreparationSelf-contained and automated
after mixed specimen is added
to cartridge. All other
reagents are contained in the
cartridge.Same
Primers and
probes for
influenza A,
influenza B,
and influenza
A subtype
H1N1Primers and probes to detect
the presence of nucleic acid
sequences of influenza A,
influenza B, and RSV A/B.
The Xpert Xpress Flu/RSV
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.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
SequenceInfluenza 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 proteinSame
Internal
ControlsSample processing control
(SPC) and probe check
control (PCC).Same
Combinatorial
Assay
SelectionsYes, user may select
combined assay with all
targets or a Flu only assay or a
RSV only assay.Same
Early assay
termination
functionOn Flu only or RSV only
assay selectionsSame
Differences
DevicePredicate
ItemCepheid Xpert Flu/RSV XCCepheid Xpert Flu/RSV XC
Specimen
TypesNasopharyngeal (NP) swab
specimensNasal aspirate/wash (NA/W)
specimens and
Nasopharyngeal (NP) swab
specimens
Time to obtain
test resultsApproximately 30 minutes or
less for sample preparation
and RT-PCRApproximately 60 minutes or
less for sample preparation and
RT-PCR

Table 8-1: Comparison of Similarities and Differences of the Xpert Xpress Flu/RSV Assay with the Predicate Devices

9

10

11

12

The Xpert Xpress Flu/RSV Assay has the same intended use and technological characteristics as the predicate device. The clinical study demonstrates that the Xpert Xpress Flu/RSV 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.

13

Similarities
DevicePredicate
ItemXpert® Nasopharyngeal
Sample Collection KitXpert® Nasopharyngeal Sample
Collection Kit
510(k)# K151226
Intended UseThe 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 and the
Xpert Xpress Flu/RSV Assay.
The Xpert Nasopharyngeal
Sample Collection Kit has been
cleared for use only with the
Xpert Flu Assay, Xpert
Flu/RSV XC Assay, Xpert
Flu+RSV Xpress Assay and
Xpert Xpress Flu/RSV 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.
The Xpert Nasopharyngeal
Sample Collection Kit has been
cleared for use only with the
Xpert Flu Assay, Xpert Flu/RSV
XC Assay and Xpert Flu+RSV
Xpress Assay.
Single-use DeviceYesSame
Similarities
ItemDevice
Xpert® Nasopharyngeal Sample Collection KitPredicate
Xpert® Nasopharyngeal Sample Collection Kit
510(k)# K151226
Transport Medium
FormulationHank's Balanced Salt Solution
Bovine Serum Albumin
L-cysteine
Gelatin
Sucrose
L-glutamic acid
HEPES buffer
Vancomycin
Amphotericin B
Colistin
Phenol redSame
pH$7.3 \pm 0.2$Same
Storage Temperature2 - 25°C (refrigerated
and room temperature)Same
Volume3 mlSame
Glass Beads3 x 3 mmSame
ContainerPlastic (medical-grade
polypropylene)Same
Product ConfigurationMedium 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

14

15

Differences
DevicePredicate
ItemXpert Nasopharyngeal
Sample Collection KitXpert Nasopharyngeal
Sample
Collection Kit
510(k)# K151226
Intended UseFor 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 and Xpert Xpress
Flu/RSV 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.

Both devices have the same general intended use and use the same technology to collect, store and transport clinical specimens, including viruses, to the laboratory for further testing. The prospective component of the multi-center clinical study of the Xpert Xpress Flu/RSV 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/RSV Assay with two lots of reagents across three testing days. The higher LoD 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

16

testing days. LoD was established using two influenza A H3N2 strains, two influenza A 2009 H1N1 strains, two influenza B strains, two respiratory syncytial virus A (RSV A) strains and two respiratory syncytial virus B (RSV 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 – 8-7.

| Virus
Strain | Confirmed
LoD
(TCID50/mL) |
|-------------------------------|---------------------------------|
| Influenza A/California/7/2009 | 0.02 |
| Influenza A/Florida/27/2011 | 0.04 |

Table 8-3 Confirmed LoD (TCID50/mL):
Influenza A 2009 H1N1

| Virus
Strain | Confirmed LoD
(TCID50/mL) |
|-------------------------------|------------------------------|
| Influenza A/Perth/16/2009 | 0.01 |
| Influenza A/Victoria/361/2011 | 0.75 |

| Virus
Strain | Confirmed LoD
(TCID50/mL) |
|-------------------------------|------------------------------|
| Influenza B/Mass/2/2012 | 0.40 |
| Influenza B/Wisconsin/01/2011 | 0.19 |

17

| Virus Strain | Confirmed LoD
(TCID50/mL) |
|----------------------|------------------------------|
| RSV A/2/Australia/61 | 0.87 |
| RSV A/Long/MD/56 | 1.10 |

Table 8-6 Confirmed LoD (TCID50/mL) Respiratory Syncytial Virus A

Table 8-7 Confirmed LoD (TCID50/mL): Respiratory Syncytial Virus B

| Virus Strain | Confirmed LoD
(TCID50/mL) |
|---------------------|------------------------------|
| RSV B/Wash/18537/62 | 0.79 |
| RSV B/9320/MA/77 | 2.30 |

Analytical Specificity (Exclusivity)

The analytical specificity of the Xpert Xpress Flu/RSV 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 8-8.

18

OrganismConcentrationResult
Influenza AInfluenza BRSV
No Template ControlN/ANEGNEGNEG
Adenovirus Type 11.12E+06 TCID50/mLNEGNEGNEG
Adenovirus Type 71.87E+05 TCID50/mLNEGNEGNEG
Human coronavirus OC432.85E+05 TCID50/mLNEGNEGNEG
Human coronavirus 229E1.00E+05 TCID50/mLNEGNEGNEG
Cytomegalovirus1.00E+05 TCID50/mLNEGNEGNEG
Echovirus3.31E+07 TCID50/mLNEGNEGNEG
Enterovirus3.55E+05 TCID50/mLNEGNEGNEG
Epstein Barr Virus7.16E+07 TCID50/mLNEGNEGNEG
HSV8.90E+05 TCID50/mLNEGNEGNEG
Measles6.31E+05 TCID50/mLNEGNEGNEG
Human metapneumovirus1.00E+05 TCID50/mLNEGNEGNEG
Mumps virus6.31E+06 TCID50/mLNEGNEGNEG
Human parainfluenza Type 11.15E+06 TCID50/mLNEGNEGNEG
Human parainfluenza Type 26.31E+05 TCID50/mLNEGNEGNEG
Human parainfluenza Type 33.55E+06 TCID50/mLNEGNEGNEG
Rhinovirus Type 1A1.26E+05 TCID50/mLNEGNEGNEG
Acinetobacter baumannii1.00E+06 CFU/mLNEGNEGNEG
Burkholderia cepacia3.30E+06 CFU/mLNEGNEGNEG
Candida albicans3.20E+06 CFU/mLNEGNEGNEG
Candida parapsilosis3.00E+06 CFU/mLNEGNEGNEG
Bordetella pertussis3.30E+06 CFU/mLNEGNEGNEG
Chlamydia pneumoniae1.00E+05 CFU/mLNEGNEGNEG
Citrobacter freundii3.30E+06 CFU/mLNEGNEGNEG
Corynebacterium sp.3.30E+06 CFU/mLNEGNEGNEG
Escherichia coli1.00E+07 CFU/mLNEGNEGNEG
Enterococcus faecalis1.30E+06 CFU/mLNEGNEGNEG
Haemophilus influenzae1.00E+06 CFU/mLNEGNEGNEG
Lactobacillus reuteri1.00E+06 CFU/mLNEGNEGNEG
Legionella spp.1.00E+06 CFU/mLNEGNEGNEG
Moraxella catarrhalis1.00E+07 CFU/mLNEGNEGNEG
Mycobacterium tuberculosis
(avirulent)1.00E+06 CFU/mLNEGNEGNEG
Mycoplasma pneumoniae1.00E+06 CFU/mLNEGNEGNEG
OrganismConcentrationResult
Influenza AInfluenza BRSV
Neisseria meningitidis2.15E+06 CFU/mLNEGNEGNEG
Neisseria mucosa1.00E+07 CFU/mLNEGNEGNEG
Propionibacterium acnes2.40E+07 CFU/mLNEGNEGNEG
Pseudomonas aeruginosa3.70E+06 CFU/mLNEGNEGNEG
Staphylococcus aureus
(protein A producer)2.20E+06 CFU/mLNEGNEGNEG
Staphylococcus epidermidis3.40E+06 CFU/mLNEGNEGNEG
Staphylococcus haemolyticus4.00E+06 CFU/mLNEGNEGNEG
Streptococcus agalactiae3.50E+06 CFU/mLNEGNEGNEG
Streptococcus pneumoniae1.00E+06 CFU/mLNEGNEGNEG
Streptococcus pyogenes1.00E+07 CFU/mLNEGNEGNEG
Streptococcus salivarius1.00E+07 CFU/mLNEGNEGNEG
Streptococcus sanguinis3.10E+06 CFU/mLNEGNEGNEG

Table 8-8 Analytical Specificity of the Xpert Xpress Flu/RSV Assay

19

Analytical Reactivity (Inclusivity)

The analytical reactivity of the Xpert Xpress Flu/RSV 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), influenza B (representing strains from both Victoria and Yamagata lineages), and respiratory syncytial virus subgroups A and B (RSV A and RSV B) at levels near the analytical LoD. A total of 53 strains comprised of 48 influenza viruses (35 influenza A and 13 influenza B) and 5 RSV strains were tested in this study with the Xpert Xpress Flu/RSV Assay. Three replicates were tested for each strain. All Flu and RSV 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 8-9.

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.

20

VirusStrainTargetResult
Flu AFlu BRSV
No Template Controln/aNEGNEGNEG
Influenza
A H1N1
(pre-2009)A/swine/Iowa/15/300.1 TCID50/mLPOSNEGNEG
A/WS/330.1 TCID50/mLPOSNEGNEG
A/PR/8/340.1 TCID50/mLPOSNEGNEG
A/Mal/302/540.1 TCID50/mLPOSNEGNEG
A/Denver/1/570.1 TCID50/mLPOSNEGNEG
A/New Jersey/8/760.1 TCID50/mLPOSNEGNEG
A/New Caledonia/20/19990.1 TCID50/mLPOSNEGNEG
A/New York/55/20040.1 TCID50/mLPOSNEGNEG
A/Soloman Island/3/20060.1 TCID50/mLPOSNEGNEG
A/Taiwan/42/060.1 TCID50/mLPOSNEGNEG
A/Brisbane/59/20070.1 TCID50/mLPOSNEGNEG
Influenza
A H1N1
(pdm2009)A/swine/NY/02/20090.1 TCID50/mLPOSNEGNEG
A/Colorado/14/20120.1 TCID50/mLPOSNEGNEG
A/Washington/24/20120.1 TCID50/mLPOSNEGNEG
A/Aichi/2/682.0 TCID50/mLPOSNEGNEG
VirusStrainTargetResult
Flu AFlu BRSV
Influenza A
H3N2
(Seasonal)A/HongKong/8/682.0 TCID50/mLPOSNEGNEG
A/Port Chalmers/1/732.0 TCID50/mLPOSNEGNEG
A/Hawaii/15/20012.0 TCID50/mLPOSNEGNEG
A/Wisconsin/67/052.0 TCID50/mLPOSNEGNEG
Influenza
A H3N2
(Seasonal)A/Brisbane/10/20072.0 TCID50/mLPOSNEGNEG
A/Minnesota/11/2010 (H3N2)v2.0 TCID50/mLPOSNEGNEG
A/Indiana/08/2011 (H3N2)v2.0 TCID50/mLPOSNEGNEG
A/Texas/50/20122.0 TCID50/mLPOSNEGNEG
Avian
influenza AA/duck/Hunan/795/2002 (H5N1)≤ 1pg/µLaPOSNEGNEG
A/chicken/Hubei/327/2004 (H5N1)≤ 1pg/µLaPOSNEGNEG
A/Anhui/01/2005 (H5N1)≤ 1pg/µLaPOSNEGNEG
A/Japanese white eye/
HongKong/ 1038/2006≤ 1pg/µLaPOSNEGNEG
A/mallard/WI/34/75 (H5N2)≤ 1pg/µLaPOSNEGNEG
A/chicken/CA431/00 (H6N2)≤ 1pg/µLaPOSNEGNEG
A/duck/LTC-182743/1943 (H7N2)≤ 1pg/µLaPOSNEGNEG
A/chicken/NJ/15086-3/94 (H7N3)≤ 1pg/µLaPOSNEGNEG
VirusStrainTargetResult
Flu AFlu BRSV
A/Anhui/1/2013 (H7N9)N/APOSNEGNEG
A/Shanghai/1/2013 (H7N9)N/APOSNEGNEG
A/chicken/Korea/38349-p96323/1996 (H9N2)≤ 1pg/μLaPOSNEGNEG
A/Mallard/NY/6750/78 (H2N2)≤ 1pg/μLaPOSNEGNEG
Influenza BB/Lee/401.0 TCID50/mLNEGPOSNEG
B/Allen/451.0 TCID50/mLNEGPOSNEG
B/GL/1739/541.0 TCID50/mLNEGPOSNEG
B/Maryland/1/591.0 TCID50/mLNEGPOSNEG
B/Panama/45/90c1.0 TCID50/mLNEGPOSNEG
B/Florida/07/2004d1.0 TCID50/mLNEGPOSNEG
B/Florida/02/06c1.0 TCID50/mLNEGPOSNEG
B/Florida/04/06d1.0 TCID50/mLNEGPOSNEG
B/Hong Kong/5/721.0 TCID50/mLNEGPOSNEG
B/Wisconsin/01/2010d1.0 TCID50/mLNEGPOSNEG
B/Malaysia/2506/04c1.0 TCID50/mLNEGPOSNEG
B/Taiwan/2/621.0 TCID50/mLNEGPOSNEG
B/Brisbane/60/2008c1.0 TCID50/mLNEGPOSNEG
RSV-A/NY (Clinical unknown)NEGNEGPOS
3.0 TCID50/mL
TargetResult
VirusStrainFlu AFlu BRSV
RSV ARSV-A/WI/629-8-2/20073.0 TCID50/mLNEGNEGPOS
RSV-A/WI/629-11-1/20083.0 TCID50/mLNEGNEGPOS
RSV BRSV-B/WV14617/857.0 TCID50/mLNEGNEGPOS
RSV-B/CH93(18)-187.0 TCID50/mLNEGNEGPOS

Table 8-9 Analytical Reactivity (Inclusivity) of the Xpert Xpress Flu/RSV Assay

21

22

23

Purified viral RNA in simulated background matrix was used for avian influenza A viruses due to biosafety regulations. a.

Inactivated avian influenza A (H7N9) viruses without 100,000 fold in simulated background matrix and tested due to biosafety regulations. b.

c. Known Victoria lineage.

d. Known Yamagata lineage.

24

Potentially Interfering Substances

In a non-clinical study, potentially interfering substances that may be present in the nasopharynx were evaluated directly relative to the performance of the Xpert Xpress Flu/RSV Assay. Potentially interfering substances in the nasopharynx may include, but are not limited to: blood, nasal secretions or mucus, and nasal and throat medications used to relieve congestion, nasal dryness, irritation, or asthma and allergy symptoms, as well as antibiotics and antivirals. Negative samples (n = 8) were tested per each substance to determine the effect on the performance of the sample processing control (SPC). Positive samples (n = 8) were tested per substance with six influenza (four influenza A and two influenza B) and four RSV (two RSV A and two RSV B) strains spiked at 3X the analytical LoD determined for each strain. All results were compared to positive and negative simulated nasal matrix controls. The simulated nasal matrix consisted of 2.5% (w/v) porcine mucin, 1% (v/v) human whole blood in 0.85% sodium chloride (NaCl) formulated in 1x PBS solution with 15% glycerol, which was then diluted 1:5 in UTM. The evaluated substances are listed in Table 8-10 with active ingredients and concentrations tested shown. None of the substances caused interference of the assay at the concentrations tested in this study. All positive and negative replicates were identified correctly using the Xpert Xpress Flu/RSV Assay.

25

| Substance/Class | Assay
Description/Active
Ingredient | Concentration
Tested |
|---------------------------------------------------|--------------------------------------------------------------------------------|-------------------------------------------------|
| Control | Simulated nasal
matrix | 100% (v/v) |
| Beta-adrenergic bronchodilator | Albuterol Sulfate | 0.83 mg/mL
(equivalent to 1
dose per day) |
| Blood | Blood (Human) | 2% (v/v) |
| BDTM Universal Viral
Transport System | Transport Media | 100% (v/v) |
| Remel M4® | Transport Media | 100% (v/v) |
| Remel M4RT® | Transport Media | 100% (v/v) |
| Remel M5® | Transport Media | 100% (v/v) |
| Remel M6® | Transport Media | 100% (v/v) |
| Throat lozenges, oral
anesthetic and analgesic | Benzocaine, Menthol | 1.7 mg/mL |
| Mucin | Purified Mucin protein
(Bovine or porcine
submaxillary gland) | 2.5% (w/v) |
| Antibiotic, nasal ointment | Mupirocin | 10 mg/mL |
| Saline Nasal Spray | Sodium Chloride (0.65%) | 15% (v/v) |
| Anefrin Nasal Spray | Oxymetazoline, 0.05% | 15% (v/v) |
| PHNY Nasal Drops | Phenylephrine, 0.5% | 15% (v/v) |
| Tamiflu Anti-viral drugs | Zanamivir | 7.5 mg/mL |
| Antibacterial, systemic | Tobramycin | 4 µg/mL |
| Zicam Nasal Gel | Luffa opperculata,
Galphimia glauca,
Histaminum
hydrochloricum Sulfur | 15% (w/v) |
| Nasal corticosteroid | Fluticasone Propionate | 5 µg/mL |

Table 8-10 Potentially Interfering Substances in the Xpert Xpress Flu/RSV Assav

26

Carry-Over Contamination

A study was conducted to demonstrate that single-use, self-contained GeneXpert cartridges prevent carry-over contamination of negative samples when followed by very high positive samples in the same GeneXpert module. The study consisted of a negative sample processed in the same GeneXpert module immediately followed by a very high influenza A sample (A/Victoria/361/2011, 2x107 TCID50/mL) or a very high RSV A sample (A/Long/MD/26, 1x104 TCID50/mL) spiked into a simulated nasal matrix. This testing scheme was repeated 20 times on two GeneXpert modules for a total of 82 runs resulting in 40 positive and 42 negative specimens for each virus type. All 40 positive samples were correctly reported as Flu A POSITIVE; Flu B NEGATIVE; RSV NEGATIVE or Flu A NEGATIVE; Flu B NEGATIVE;RSV POSITIVE. All 42 negative samples were correctly reported as Flu A NEGATIVE; Flu B NEGATIVE; RSV NEGATIVE.

Fresh vs. Frozen Sample Equivalency Study

Fresh and frozen specimen equivalency in the Xpert Xpress Flu/RSV Assay was evaluated by testing individual influenza and RSV strains at three different concentrations representing low positives (2X LoD), moderate positives (5X LoD), and high positives (10X LoD) in pooled negative NP swab clinical matrix. Negative samples consisted of pooled negative NP swab clinical matrix only. Fresh and frozen specimen equivalency was determined using one seasonal Flu A H3N2 strain (A/Victoria/361/2011), one Flu B strain (B/Mass/2/2012), one RSV A strain (RSV-A/2/Australia/61), and one RSV B strain (RSV-B/Wash/18537/62). Replicates of 20 were tested for each specimen type and concentration. All positive and negative specimens were tested fresh, after one freeze- thaw cycle, and after two freeze-thaw cycles. There was no difference in the performance of the Xpert Xpress Flu/RSV Assay between fresh virus dilutions and two sequential freeze thaw

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cycles for positive and negative samples. All positive and negative replicates were correctly identified using the Xpert Xpress Flu/RSV Assay.

Competitive Interference Study

Competitive interference of the assay caused by the presence of two targets in the Xpert Xpress Flu/RSV Assay was evaluated by testing individual influenza and RSV strains near the LoD in the presence of different influenza or RSV strains at a higher concentration in a simulated nasal matrix. The concentration of each strain at LoD ranged from 0.45 TCID50/mL to 1.6 TCID50/mL and the concentration of the competitive strains ranged from 101 TCID50/mL to 104 TCID50/mL. Analytical competitive interference was assessed using one (1) seasonal Flu A H3 strain (H3/Victoria/361/2011), one (1) Flu B strain (B/Mass/2/2012), one (1) RSV A strain (RSV-A/2/Australia/61), and one (1) RSV B strain (RSV-B/Wash/18537/62). Replicates of 20 were tested for each target strain and each competitive strain combination. The normal binomial distribution with 20 replicate samples at LoD is between 17 and 20 positive results based on the binomial distribution with N=20, p=.95 (X~Bin(20,0.95)). Therefore, sets of 20 with 16 or less positives would be rare and an indication of a competitive inhibitory effect due to high levels of a competing analyte.

  • With Flu A/Victoria/361/2011 at a concentration of 0.8 TCID50/mL no . competitive inhibitory effects were observed in the presence of 1x103 TCID50/mL of Flu B/Mass/2/2012; 1x103 TCID50/mL of RSV-A/2/Australia/6; or 1x104 TCID50/mL of RSV-B/Wash/18537/62.
  • . With Flu B/Mass/2/2012 at a concentration of 0.45 TCID50/mL competitive inhibitory effects were observed in the presence of 1x103 TCIDso/mL of Flu A/Victoria/361/2011. No competitive inhibitory effects were observed in the presence of 1x102 TCID50mL of Flu A/Victoria/361/2011; 1x103 TCID50/mL of RSV-A/2/Australia/6; or 1x102 TCID50/mL of RSV-B/Wash/18537/62.
  • With RSV-A/2/Australia/6 at a concentration of 1.1 TCID50/mL competitive . inhibitory effects were observed in the presence of 1x103 TCID50/mL of Flu

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A/Victoria/361/2011. No competitive inhibitory effects were observed in the presence of 1x102 TCID50mL of Flu A/Victoria/361/2011; or 1x103 TCID50/mL of Flu B/Mass/2/2012.

  • With RSV-B/Wash/18537/62 at a concentration of 0.9 TCID50/mL competitive . inhibitory effects were observed in the presence of 1x102 TCIDs%/mL of Flu A/Victoria/361/2011 or 1x103 TCID50/mL of Flu B/Mass/2/2012. No competitive inhibitory effects were observed in the presence of 10 TCID50/mL of Flu A/Victoria/361/2011; or 1x102 TCID50/mL of Flu B/Mass/2/2012. When the concentration of RSV-B/Wash/18537/62 was increased to 1.6 TCID50/mL, no competitive inhibitory effects were observed in the presence of 1x102 TCID50/mL of Flu A/Victoria/361/2011; or 1x103 TCID50/mL of Flu B/Mass/2/2012.
  • Under the conditions of this study, internal competitive inhibitory effects were ● observed on the targets (Flu A, Flu B, and RSV) in the presence of two targets for the Xpert Xpress Flu/RSV Assay. The competitive inhibitory effect on the Xpert Xpress Flu/RSV targets is addressed in the Limitations section of the package insert.

Clinical Studies

Clinical Comparison Study

Performance characteristics of the Xpert Xpress Flu/RSV Assay were evaluated at eleven institutions in the U.S. during the 2015-2016 influenza season. Due to the low prevalence of influenza viruses and the difficulty in obtaining fresh influenza and RSVpositive specimens, the specimen population for this study was supplemented with consecutively collected, frozen specimens.

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.

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  • Individuals with signs and symptoms of respiratory infection and whose routine . care called for collection of NP swab specimens for influenza and/or RSV testing. For eligible subjects, aliquots of leftover specimens were obtained for testing with the Xpert Xpress Flu/RSV Assay and reference testing, and patient management continued at the site per their standard practice.
    The Xpert Xpress Flu/RSV Assay performance was compared to FDA-cleared molecular comparator assay. Bi- directional sequencing was performed on specimens where the Xpert Xpress Flu/RSV Assay and the comparator assay were discrepant, and is provided for informational purposes only.

Overall Results – NP Swab Specimens

A total of 2065 NP swab specimens were tested for influenza A, influenza B and RSV by the Xpert Xpress Flu/RSV Assay and the comparator assay. Of the 2065 NP swab specimens, 1142 were fresh, prospectively collected and 923 were consecutively collected, frozen specimens.

For the fresh, prospectively collected NP swab specimens, the Xpert Xpress Flu/RSV Assay demonstrated a PPA and NPA of 94.6% and 99.3%, detection of influenza A; 100% and 99.1% for influenza B. respectively; and 100% and 99.6%, for RSV, respectively, relative to the comparator assay (Table 8-11).

For the consecutively collected, frozen NP swab specimens, the Xpert Xpress Flu/RSV Assay demonstrated a PPA and NPA of 100% and 97.2% for the detection of influenza A, respectively; 100% and 98.2% for influenza B, respectively; and 97.9% and 97.7% for RSV, respectively, relative to the comparator assay (Table 8-11).

For the combined dataset, relative to the comparator assay, the Xpert Xpress Flu/RSV Assay demonstrated a PPA and NPA of 98.1% and 98.4% for the detection of influenza A, respectively; 100% and 98.7% for influenza B respectively; and 98.5% and 98.8% for RSV, respectively (Table 8-11).

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Xpert Xpress F

| Specimen
Type | Target | N | TP | FP | TN | FN | PPA
(95% CI) | NPA
(95% CI) |
|---------------------------------------|--------|------|-----|-----|------|----|---------------------------|-------------------------|
| Fresh,
prospectively
collected | Flu A | 1142 | 35 | 8a | 1097 | 2b | 94.6%
(CI:82.3-98.5) | 99.3%
(CI:98.6-99.6) |
| | Flu B | 1142 | 42 | 10c | 1090 | 0 | 100.0%
(CI:91.6-100.0) | 99.1%
(CI:98.3-99.5) |
| | RSV | 1142 | 17 | 5d | 1120 | 0 | 100.0%
(CI:81.6-100.0) | 99.6%
(CI:99.0-99.8) |
| Frozen,
consecutively
collected | Flu A | 923 | 69 | 24e | 830 | 0 | 100.0%
(CI:94.7-100.0) | 97.2%
(CI:95.9-98.1) |
| | Flu B | 923 | 36 | 16f | 871 | 0 | 100.0%
(CI:90.4-100.0) | 98.2%
(CI:97.1-98.9) |
| | RSV | 923 | 47 | 20g | 855 | 1h | 97.9%
(CI:89.1-99.6) | 97.7%
(CI:96.5-98.5) |
| Combined1 | Flu A | 2065 | 104 | 32i | 1927 | 2b | 98.1%
(CI:93.4-99.5) | 98.4%
(CI:97.7-98.8) |
| | Flu B | 2065 | 78 | 26j | 1961 | 0 | 100.0%
(CI:95.3-100.0) | 98.7%
(CI:98.1-99.1) |
| | RSV | 2065 | 64 | 25k | 1975 | 1h | 98.5%
(CI:91.8-99.7) | 98.8%
(CI:98.2-99.2) |

a.Testing results by sequencing: 3 of 8 were Flu A Positive; 1 of 8 insufficient speciment for sequencing.

b Testing results by sequencing: 2 of 2 were Flu A Negative.

c.Testing results by sequencing: 6 of 10 were Flu B Positive; 1 of 10 insufficient specimen for sequencing. d.Testing results by sequencing: 0 of 5 were RSV Negative; 2 of 5 insufficient specimen for sequencing. e.Testing

results by sequencing: 8 of 24 were Flu A Positive; 11 of 24 were Flu A Negative; 5 of 24 insufficient specimen for sequencing.

f. Testing results by sequencing: 7 of 16 were Flu B Positive; 6 of 16 insufficient specimen for sequencing.

g.Testing results by sequencing: 3 of 20 were RSV Positive; 8 of 20 insufficient specimen for sequencing.

h.Testing results by sequencing: 1 of 1 was RSV Negative.

i. Testing results by sequencing: 11 of 32 were Flu A Positive; 6 of 32 insufficient specimen for sequencing.

j. Testing results by sequencing: 13 of 26 were Flu B Negative; 7 of 26 insufficient specimen for sequencing.

k.Testing results by sequencing: 3 of 25 were RSV Negative; 11 of 25 insufficient specimen for sequencing

  1. Nine specimens (8 Flu A FP; 9 Flu B FP; 7 RSV FP) were positive for all three targets.

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Of the Xpert Xpress Flu/RSV Assay runs performed with eligible specimens, 98.4% (2038/2071) of these specimens were successful on the first attempt. The remaining 33 gave indeterminate results on the first attempt (20 ERROR, 10 INVALID, and 3 NO RESULT). The initial indeterminate rate was 1.59% (33/2071) with the 95% CI 1.14-2.23%. Thirty of the 33 indeterminate cases were retested, of which 27 yielded valid results upon repeat testing; three specimens were not retested. The overall rate of assay success was 99.7% (2065/2071). The overall indeterminate rate after retesting was 0.3% (6/2071) with 95% CI 0.13- 0.63%.

In addition, there were 102 pre-selected frozen NP swab specimens tested. The results of this testing were analyzed separately and are as follows: the Xpert Xpress Flu/RSV Assay demonstrated a PPA and NPA of 100% and 95.8%, for influenza A, respectively; 100% and 94.5% for influenza B, respectively; and 100% and 95.7%, for RSV, respectively, relative to the comparator assay.

Reproducibility Study

Reproducibility was established in a multi-center, blinded study using a sevenmember specimen panel consisting of a negative control and two each of simulated nasal matrix spiked with influenza A. influenza B or RSV at 1X (low pos) and 2-3X (mod pos) the respective LODs. 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/RSV cartridges were used, with each lot representing approximately two days of testing. Results are summarized in Table 8-12.

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| Sample ID | Site 1/Infinity-80 | | | Site 2/DX | | | Site 3/Infinity-48 | | | % Total
Agreement by
Samplea |
|-------------------|--------------------|------------------|------------------|------------------|------------------|------------------|--------------------|------------------|------------------|------------------------------------|
| | Op 1 | Op 2 | Site | Op 1 | Op 2 | Site | Op 1 | Op 2 | Site | |
| Negative | 100%
(24/24) | 100%
(24/24) | 100%
(48/48) | 100%
(24/24) | 100%
(24/24) | 100%
(48/48) | 100%
(24/24) | 100%
(24/24) | 100%
(48/48) | 100%
(144/144) |
| Flu A-
Low Pos | 87.5%
(21/24) | 95.8%
(23/24) | 91.7%
(44/48) | 95.7%
(22/23) | 91.7%
(22/24) | 93.6%
(44/47) | 100%
(24/24) | 91.7%
(22/24) | 95.8%
(46/48) | 93.7%
(134/143)b |
| Flu A-
Mod Pos | 100%
(24/24) | 100%
(24/24) | 100%
(48/48) | 100%
(23/23) | 100%
(23/23) | 100%
(46/46) | 100%
(24/24) | 100%
(24/24) | 100%
(48/48) | 100%
(142/142)b |
| Flu B-
Low Pos | 95.8%
(23/24) | 95.8%
(23/24) | 95.8%
(46/48) | 95.8%
(23/24) | 95.8%
(23/24) | 95.8%
(46/48) | 95.8%
(23/24) | 91.7%
(22/24) | 93.8%
(45/48) | 95.1%
(137/144) |
| Flu B-
Mod Pos | 95.8%
(23/24) | 100%
(24/24) | 97.9%
(47/48) | 100%
(24/24) | 100%
(24/24) | 100%
(48/48) | 100%
(24/24) | 95.8%
(23/24) | 97.9%
(47/48) | 98.6%
(142/144)c |
| RSV-
Low Pos | 91.7%
(22/24) | 87.5%
(21/24) | 89.6%
(43/48) | 100%
(23/23) | 100%
(24/24) | 100%
(47/47) | 91.7%
(22/24) | 95.8%
(23/24) | 93.8%
(45/48) | 94.4%
(135/143)b |
| RSV-
Mod Pos | 100%
(24/24) | 100%
(24/24) | 100%
(48/48) | 100%
(23/23) | 100%
(24/24) | 100%
(47/47) | 100%
(24/24) | 100%
(24/24) | 100%
(48/48) | 100%
(143/143)b |

Table 8-12 Summary of Reproducibility Results

Agreement calculated based on expected result: Negative (targeted positivity: 0%); Positive for Low Pos (targeted positivity: 95%) and a. Mod Pos (targeted positivity: 100% ) samples.

Fives samples 2x indeterminate [Flu A Low Pos (1); Flu A Mod Pos (2); RSV Low Pos (1); RSV Mod Pos (1)] b.

c. Two Flu B Mod Pos samples were positive for all three targets

The reproducibility of the Xpert Xpress Flu/RSV Assay was also evaluated in terms of the fluorescence signal expressed in Ct values for each target detected. The mean, standard deviation (SD), and coefficient of variation (CV) betweensites, between- days, between-lots and between-operators for each panel member are presented in Table 8-13.

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| Sample | Assay
Channel
(Analyte) | Na | Mean
Ct | Between-
Site | | Between-Lot | | Between-
Day | | Between-
Operator | | Within-
Assay | | Total | |
|-------------------|-------------------------------|-----|------------|------------------|-----------|-------------|-----------|-----------------|-----------|----------------------|-----------|------------------|-----------|-------|-----------|
| | | | | SD | CV
(%) | SD | CV
(%) | SD | CV
(%) | SD | CV
(%) | SD | CV
(%) | SD | CV
(%) |
| Negative | SPC | 144 | 32.3 | 0 | 0 | 0.7 | 2.1 | 0 | 0 | 0.2 | 0.5 | 0.6 | 1.8 | 0.9 | 2.8 |
| Flu A-
Low Pos | FluA1 | 134 | 35.3 | 0 | 0 | 0.4 | 1.1 | 0.6 | 1.8 | 0.1 | 0.4 | 0.9 | 2.5 | 1.2 | 3.3 |
| Flu A-
Mod Pos | FluA1 | 142 | 33.1 | 0 | 0 | 0.1 | 0.4 | 0.1 | 0.4 | 0 | 0 | 0.6 | 1.9 | 0.7 | 2.0 |
| Flu B-
Low Pos | FluB | 137 | 34.6 | 0 | 0 | 0 | 0 | 0.4 | 1.3 | 0 | 0 | 1.4 | 4.1 | 1.5 | 4.3 |
| Flu B-
Mod Pos | FluB | 144 | 32.2 | 0.2 | 0.5 | 0.2 | 0.7 | 0 | 0 | 0.2 | 0.7 | 1.0 | 3.1 | 1.1 | 3.3 |
| RSV-Low
Pos | RSV | 135 | 36.5 | 0 | 0 | 0.6 | 1.7 | 0 | 0 | 0.5 | 1.3 | 0.9 | 2.6 | 1.2 | 3.3 |
| RSV- Mod
Pos | RSV | 143 | 33.5 | 0.2 | 0.7 | 0.1 | 0.4 | 0 | 0 | 0 | 0 | 1.5 | 4.6 | 1.6 | 4.6 |

Table 8-13 Summary of Reproducibility Data

Results with non-zero Ct values of 144. a.

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Conclusions

The results of the nonclinical analytical and clinical performance studies summarized above demonstrate that the Xpert Xpress Flu/RSV Assay is substantially equivalent to the predicate device.