Predicate Devices

Reference Devices

AI/ML (Artificial Intelligence / Machine Learning)

No
The description focuses on automated RT-PCR technology and internal controls, with no mention of AI or ML algorithms for data analysis or interpretation.

Therapeutic

No
This device is an in vitro diagnostic test intended for the qualitative detection and differentiation of influenza A, influenza B, and RSV viral RNA, used as an aid in diagnosis, not for therapy or treatment.

Diagnostic

Yes

The intended use explicitly states, "The Xpert Xpress Flu/RSV Assay is intended as an aid in the diagnosis of influenza and respiratory syncytial virus infections."

SaMD (Software as a Medical Device)

No

The device is an in vitro diagnostic (IVD) assay that includes reagents and is performed on a specific hardware system (GeneXpert® Xpress System). While it involves automated processing and reporting, it is not solely software.

IVD (In Vitro Diagnostic)

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, influenza B, and respiratory syncytial virus (RSV) viral RNA." The term "in vitro" means "in glass" or "in the lab," referring to tests performed outside of a living organism.
Device Description: The "Device Description" section also refers to the device as a "rapid, automated in vitro diagnostic test."
Specimen Type: The assay uses nasopharyngeal and nasal swab specimens, which are collected from the patient but tested in a laboratory setting.
Purpose: The assay is used to detect and differentiate viral RNA, which is a diagnostic process performed on biological samples.

All of these points align with the definition of an In Vitro Diagnostic device, which is a medical device intended for use in vitro for the examination of specimens derived from the human body solely or principally for the purpose of providing information concerning a physiological or pathological state, or concerning a congenital abnormality, or to determine the safety and compatibility of transfused blood, or to monitor therapeutic measures.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The Cepheid Xpert® Xpress Flu/RSV Assay, performed on the GeneXpert® Xpress System, 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 and nasal swab (NS) 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 2016-2017 influenza season when influenza A/H3N2 and A/HINI pandemic were the predominant influenza A viruses in circulation. 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 Nasopharyngeal Swab Specimen Collection Kit for Viruses:
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.

Ancillary Nasal Swab Specimen Collection Kit for Viruses:
The Xpert® Nasal Sample Collection Kit is designed to collect, preserve, and transport nasal swab specimens containing viruses from patients with signs and symptoms of respiratory infection prior to analysis with the Xpert Xpress Flu/RSV Assay and the Xpert Xpress Flu Assay.

Product codes

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 and nasal swab (NS) specimens. The assay is performed on the Cepheid GeneXpert® Xpress System.

The Xpert Xpress Flu/RSV Assay includes reagents for the detection and differentiation of influenza A, influenza B, and RSV viral RNA directly from NP swab and NS specimens from patients with signs and symptoms of respiratory tract infection. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are internal controls utilized by the GeneXpert Xpress System platform. The SPC is present to control for an adequate extraction and processing of the target sequences and to monitor for the presence of inhibitor in the PCR reaction. The PCC verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dye stability.

The specimens are collected in viral transport medium and transported to the GeneXpert Xpress 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 Xpress 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, nasal

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Untrained operators with no clinical lab experience.

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

Not Found

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

Non-Clinical Studies:

Analytical Sensitivity (Limit of Detection): 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 and NS clinical matrices 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 in each matrix in NP swab and NSclinical matrix.
- Confirmed LoD results for Influenza A 2009 H1N1 (NP Swab: 0.020-0.040 TCID50/mL, NS: 0.018-0.04 TCID50/mL), Influenza A H3N2 (NP Swab: 0.013-0.750 TCID50/mL, NS: 0.006-0.21 TCID50/mL), Influenza B (NP Swab: 0.190-0.400 TCID50/mL, NS: 0.07-0.17 TCID50/mL), Respiratory Syncytial Virus A (NP Swab: 0.870-1.100 TCID50/mL, NS: 0.32-0.45 TCID50/mL), and Respiratory Syncytial Virus B (NP Swab: 0.790-2.300 TCID50/mL, NS: 0.29-0.35 TCID50/mL).
Analytical Specificity (Exclusivity): Evaluated against a panel of 44 cultures (16 viral, 26 bacterial, and two yeast strains). Three replicates of all bacterial and yeast strains were tested at concentrations of ≥ 1 x 10^6 CFU/mL (except one at 1 x 10^5 CFU/mL). Three replicates of all viruses were tested at concentrations of ≥ 1 x 10^5 TCID50/mL.
- The analytical specificity was 100%. All tested organisms showed negative results for Influenza A, Influenza B, and RSV.
Analytical Reactivity (Inclusivity): Evaluated against multiple strains of influenza A (H1N1 seasonal, H1N1 pandemic 2009, H3N2 seasonal, avian influenza A), influenza B (Victoria and Yamagata lineages), and respiratory syncytial virus subgroups A and B. A total of 53 strains (48 influenza viruses, 5 RSV strains) were tested with three replicates for each strain near the analytical LoD.
- 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.
Potentially Interfering Substances: Evaluated 15 substances (e.g., blood, mucin, medications) by testing negative samples (n=8) and positive samples (n=8) spiked with influenza and RSV strains at 3X the analytical LoD, compared to simulated background matrix controls.
- None of the substances caused interference of the assay at the concentrations tested. All positive and negative replicates were identified correctly.
Carry-Over Contamination: Demonstrated that single-use, self-contained GeneXpert cartridges prevent carry-over. A negative sample was followed by a very high positive influenza A or RSV A sample in the same module. This was repeated 20 times on two GeneXpert modules (total of 82 runs: 40 positive, 42 negative).
- All 40 positive samples were correctly reported as positive for the target virus and negative for others. All 42 negative samples were correctly reported as negative for all targets.
Competitive Interference Study: Evaluated the effect of two targets being present at the same time. Influenza strains and RSV strains were tested near their LoD in the presence of different influenza strains at a higher concentration in a simulated background matrix. Replicates of 20 were tested for each target-competitor combination.
- Competitive inhibitory effects were observed for Flu B when combined with high concentration Flu A; for RSV-A when combined with high concentration Flu A; and for RSV-B when combined with high concentration Flu A or Flu B. The competitive inhibitory effect is addressed in the Limitations section of the Package Insert.

Clinical Studies:

Clinical Comparison Study: Performance characteristics were evaluated at fourteen institutions in the U.S. during the 2016-2017 influenza season. Specimens were collected from individuals with signs and symptoms of respiratory infection who provided informed consent for NS or NP swab specimens. The Xpert Xpress Flu/RSV Assay performance was compared to an FDA-cleared molecular comparator assay.
- Sample Size: 3265 total specimens (1598 NS and 1667 NP swab) were tested for influenza A and B. 3103 total specimens (1543 NS and 1560 NP swab) were tested for RSV.
- Key Results (PPA, NPA):
  - Flu A:
    - NS: PPA 98.9% (96.2-99.7), NPA 97.5% (96.6-98.2)
    - NP: PPA 97.6% (94.4-99.0), NPA 98.2% (97.4-98.8)
    - Overall: PPA 98.2% (96.4-99.1), NPA 97.9% (97.3-98.3)
  - Flu B:
    - NS: PPA 98.4% (91.7-99.7), NPA 99.3% (98.7-99.6)
    - NP: PPA 97.3% (90.6-99.2), NPA 99.6% (99.1-99.8)
    - Overall: PPA 97.8% (93.8-99.3), NPA 99.4% (99.1-99.6)
  - RSV:
    - NS: PPA 98.2% (95.8-99.2), NPA 99.1% (98.4-99.5)
    - NP: PPA 98.2% (95.9-99.2), NPA 98.5% (97.7-99.0)
    - Overall: PPA 98.2% (96.7-99.0), NPA 98.8% (98.3-99.1)
- Assay Success Rate: 98.0% (3212/3279) on first attempt. The overall rate of assay success was 99.6% (3265/3279). The overall indeterminate rate was 0.4%.
Reproducibility Study: Multi-center, blinded study using a 7-member specimen panel tested at three sites with three operators each, over five days, with one lot of cartridges. Each operator tested each panel twice per day.
- Sample Size: 90 replicates for each sample type (except for Flu A Low Pos (89) and Flu B Low Pos (90), RSV Low Pos (90)).
- Key Results (Total Agreement by Sample):
  - Negative: 100% (90/90)
  - Flu A Low Pos: 91.0% (81/89)
  - Flu A Mod Pos: 100% (90/90)
  - Flu B Low Pos: 93.3% (84/90)
  - Flu B Mod Pos: 100% (90/90)
  - RSV Low Pos: 91.0% (82/90)
  - RSV Mod Pos: 100% (90/90)
- Reproducibility in Ct values: Mean Ct, SD, and CV presented for each panel member for Between-Site, Between-Day, Between-Operator, Within-Assay, and Total variability. CVs ranged from 0% to 4.9%.

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

Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) were provided in the Clinical Comparison Study.
Flu A:

NS: PPA 98.9% (96.2-99.7), NPA 97.5% (96.6-98.2)
NP: PPA 97.6% (94.4-99.0), NPA 98.2% (97.4-98.8)
Overall: PPA 98.2% (96.4-99.1), NPA 97.9% (97.3-98.3)

Flu B:

NS: PPA 98.4% (91.7-99.7), NPA 99.3% (98.7-99.6)
NP: PPA 97.3% (90.6-99.2), NPA 99.6% (99.1-99.8)
Overall: PPA 97.8% (93.8-99.3), NPA 99.4% (99.1-99.6)

RSV:

NS: PPA 98.2% (95.8-99.2), NPA 99.1% (98.4-99.5)
NP: PPA 98.2% (95.9-99.2), NPA 98.5% (97.7-99.0)
Overall: PPA 98.2% (96.7-99.0), NPA 98.8% (98.3-99.1)

Predicate Device(s)

Xpert® Flu+RSV Xpress Assay [510(k) #K151226]
Cepheid Xpert® Nasopharyngeal Sample Collection Kit for Viruses[510(k) # K171552]
Cepheid Xpert® Nasal Sample Collection Kit for Viruses [510(k) # K171552]

Reference Device(s)

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information

Not Found

Regulation Number and Section

§ 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.

Summary

0

Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

July 24, 2018

Cepheid Jim Kelly, Ph.D. Executive Director, Regulatory Affairs 904 Caribbean Drive Sunnyvale, California 94089

Re: K180218

Trade/Device Name: Xpert Xpress Flu/RSV, Xpert Nasopharyngeal Sample Collection Kit, Xpert Nasal Sample Collection Kit, GeneXpert Xpress II, GeneXpert Xpress IV Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory viral panel multiplex nucleic acid assay Regulatory Class: Class II Product Code: OCC, OOI, JSM Dated: January 24, 2018 Received: January 25, 2018

Dear Jim 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 Part 801 and Part 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

1

Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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 comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely.

Steven R. Gitterman -S for

Uwe Scherf, 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) K180218

Device Name Cepheid Xpert® Xpress Flu/RSV Assay

Indications for Use (Describe) Device Intended Use:

The Cepheid Xpert® Xpress Flu/RSV Assay, performed on the GeneXpert® Xpress System, 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 B, and respiratory syncytial virus (RSV) viral RNA. The Xpert Xpress Flul RSV Assay uses nasopharyngeal (NP) swab and nasal swab (NS) 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 and should not be used as for treatment or other patient management decisions.

Performance characteristics for influenza A were established during the 2016-2017 influenza A/ H3N2 and A/HINI pandemic were the predominant influenza A viruses in circulation. 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 Nasopharyngeal Swab Specimen Collection Kit for Viruses:

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.

Ancillary Nasal Swab Specimen Collection Kit for Viruses:

The Xpert® Nasal Sample Collection Kit is designed to collect, preserve, and transport nasal swab specimens containing viruses from patients with signs and symptoms of respiratory infection prior to analysis with the Xpert Xpress Flu/RSV Assay and the Xpert Xpress Flu Assay.

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

X Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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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: (408) 400-6838 |
|-------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact: | Yi-Ping Lin, PhD |
| Date of Preparation: | May 18, 2018 |
| 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 |
| 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 Xpress Assay [510(k) #K151226] |
| | 2) For the Sample Collection Kits:
Cepheid Xpert® Nasopharyngeal Sample Collection Kit
for Viruses[510(k) # K171552] |
| | Cepheid Xpert® Nasal Sample Collection Kit for Viruses
[510(k) # K171552] |

5

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 and nasal swab (NS) specimens. The assay is performed on the Cepheid GeneXpert® Xpress System.

The Xpert Xpress Flu/RSV Assay includes reagents for the detection and differentiation of influenza A, influenza B, and RSV viral RNA directly from NP swab and NS specimens from patients with signs and symptoms of respiratory tract infection. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are internal controls utilized by the GeneXpert Xpress System platform. The SPC is present to control for an adequate extraction and processing of the target sequences and to monitor for the presence of inhibitor in the PCR reaction. The PCC verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dye stability.

The specimens are collected in viral transport medium and transported to the GeneXpert Xpress 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 Xpress 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® Xpress System, 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 and nasal swab (NS) 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 2016-2017 influenza season when influenza A/H3N2 and A/HINI pandemic were the predominant influenza A viruses in circulation. 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 Nasopharyngeal Swab Specimen Collection Kit for Viruses

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.

Ancillary Nasal Swab Specimen Collection Kit for Viruses

The Xpert® Nasal Sample Collection Kit is designed to collect, preserve, and transport nasal swab specimens containing viruses from patients with signs and symptoms of respiratory infection prior to analysis with the Xpert Xpress Flu/RSV Assay and the Xpert Xpress Flu Assay.

Substantial Equivalence:

The Xpert Xpress Flu/RSV Assay is substantially equivalent to the current Xpert® Flu+RSV Xpress Assay [510(k) #K151226]. The Xpert Xpress Flu/RSV Assay detects influenza A, influenza B, and RSV from nasopharyngeal (NP) swab and nasal swab (NS) specimens and the Xpert® Flu+RSV Xpress Assay detects influenza A, influenza B, and RSV from NP swab 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. The data were used to determine the performance characteristics of the Xpert Xpress Flu/RSV Assay relative to the reference test. The reference test was FDA cleared for testing for Flu with NP swab and NS specimens and for testing for RSV with NP swab specimens. For these studies the reference test was also validated for testing for RSV with NS specimens. The study results showed that the Xpert Xpress Fly/RSV Assay is acceptable for its intended use and 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 device.

8

Similarities
	Device	Predicate
Item	Cepheid Xpert® Xpress
Flu/RSV	Cepheid Xpert® Flu+RSV
Xpress Assay
510(k)# K151226
Regulation	866.3980	Same
Product Code	OCC, OOI	Same
Device Class	II	Same
Technology
Principle of
Operation	Multiplex real time RT-PCR	Same
Similarities
	Device	Predicate
Item	Cepheid Xpert® Xpress
Flu/RSV	Cepheid Xpert® Flu+RSV
Xpress Assay
510(k)# K151226
Intended Use	The Cepheid Xpert® Xpress
Flu/RSV Assay, performed on
the GeneXpert® Xpress
System, 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
and nasal swab (NS)
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 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 2016-	The Cepheid Xpert® Flu+RSV
Xpress Assay, performed on
the GeneXpert® Xpress
System, 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
Xpress Assay uses
nasopharyngeal swab
specimens collected from
patients with signs and
symptoms of respiratory
infection. The Xpert Flu+RSV
Xpress Assay is intended as an
aid in the diagnosis of
influenza and respiratory
syncytial virus in conjunction
with clinical and
epidemiological risk factors.
Negative results do not
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 2014-2015
Similarities
	Device	Predicate
Item	Cepheid Xpert® Xpress
Flu/RSV	Cepheid Xpert® Flu+RSV
Xpress Assay
510(k)# K151226
	2017 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. | 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. |
| Indication 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 Xpress System | Same |
| Similarities | | |
| Item | Device
Cepheid Xpert® Xpress
Flu/RSV | Predicate
Cepheid Xpert® Flu+RSV
Xpress Assay
510(k)# K151226 |
| Assay Results | Qualitative | Same |
| Instrument
System | Cepheid GeneXpert Xpress
System (instrument model
GX-II and GX-IV); Cepheid
I-core technology | Cepheid GeneXpert Xpress
System (instrument model
GX-I); Cepheid I-core
technology |
| Primers and
probes | Primers and probes to detect
the presence of nucleic acid
sequences of influenza A,
influenza B, and RSV. | Same |
| Laboratory
Users | Untrained operators with no
clinical lab experience. | Same |
| Sample
Preparation | Self-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 | 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. | Same |
| Similarities | | |
| | Device | Predicate |
| Item | Cepheid Xpert® Xpress
Flu/RSV | Cepheid Xpert® Flu+RSV
Xpress Assay
510(k)# K151226 |
| 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 | Same |
| Internal
Controls | Sample processing control
(SPC) and probe check
control (PCC). | Same |
| Early assay
termination
function | Yes | Yes |
| Assay Targets | Influenza A, Influenza B, and
RSV viral RNA | Same |
| Assay Controls | Encapsulated (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 |
| Combinatorial
Assay
Selections | Yes, user may select
combined assay with all
targets or a Flu only assay or
a RSV only assay. | Same |
| Differences | | |
| | Device | Predicate |
| Item | Cepheid Xpert® Xpress
Flu/RSV | Cepheid Xpert® Flu+RSV
Xpress Assay
510(k)# K151226 |
| Specimen
Types | Nasopharyngeal (NP) swab
and nasal swab (NS)
specimens | Nasopharyngeal (NP) swab
specimens |
| Time to obtain
test results | Approximately 30 minutes or
less for sample preparation
and RT-PCR | Approximately 60 minutes for
sample preparation and real-
time 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

13

The Xpert Xpress Flu/RSV Assay and the predicate device have the same general intended use and technological characteristics, and both detect influenza A, influenza B, and RSV viral RNA from NP swab specimens. The clinical study demonstrates that the Xpert Xpress Flu/RSV Assay is acceptable for its intended use and is substantially equivalent to the predicate device.

The predicate device for the ancillary specimen collection kit, the Xpert Nasopharyngeal Sample Collection Kit for Viruses is the Cepheid Nasopharyngeal Sample Collection Kit for Viruses, [510(k) # K171552]. The similarities are shown in Table 8-2. There is no

14

difference between the Nasopharyngeal Sample Collection Kit for Viruses cleared in 510(k) # K171552 and this 510(k).

The predicate device for the ancillary specimen collection kit, the Xpert Nasal Sample Collection Kit for Viruses is the Xpert Nasal Sample Collection Kit for Viruses, [510(k) # K171552]. The similarities and differences are shown in Table 8-3.

15

Table 8-2: Comparison of Similarities of the Xpert Nasopharyngeal Sample

Similarities
	Device	Predicate
Item	Xpert® Nasopharyngeal
Sample Collection Kit for
Viruses	Xpert® Nasopharyngeal
Sample Collection Kit for
Viruses
510(k)# K171552
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.	Same
Single-use Device	Yes	Same

Collection Kit with the Predicate Device

16

Similarities
Item	Device	Predicate
	Xpert® Nasopharyngeal
Sample Collection Kit for
Viruses	Xpert® Nasopharyngeal
Sample Collection Kit for
Viruses
510(k)# K171552
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	$7.3 \pm 0.2$	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

17

Similarities
	Device	Predicate
Item	Xpert® Nasal Sample
Collection Kit for Viruses	Xpert® Nasal Sample
Collection Kit for Viruses
510(k)# K171552
Intended Use	The Xpert® Nasal Sample
Collection Kit is designed to
collect, preserve, and transport
nasal swab specimens
containing viruses from patients
with signs and symptoms of
respiratory infection prior to
analysis with the Xpert Xpress
Flu/RSV and the Xpert Xpress
Flu Assay.	The Xpert® Nasal Sample
Collection Kit is designed to
collect, preserve, and transport
nasal swab specimens containing
viruses from patients with signs
and symptoms of respiratory
infection prior to analysis with the
Xpert Xpress Flu Assay.
Single-use Device	Yes	Same
Similarities
Item	Device	Predicate
	Xpert® Nasal Sample
Collection Kit for Viruses	Xpert® Nasal Sample
Collection Kit for Viruses
510(k)# K171552
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	$7.3 \pm 0.2$	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
Swab	Nylon flocked	Same
Differences
	Device	Predicate
Item	Xpert Nasal Sample
Collection Kit for Viruses	Xpert® Nasal Sample
Collection Kit for Viruses
510(k)# K171552
Intended Use	For collection, preservation
and transport of nasal swab
specimens containing viruses
from patients with signs and
symptoms of respiratory
infection prior to analysis
with the Xpert Xpress
Flu/RSV and the Xpert
Xpress Flu Assay.	For collection, preservation and
transport of nasal swab
specimens containing viruses
from patients with signs and
symptoms of respiratory
infection prior to analysis with
the Xpert Xpress Flu.

Table 8-3: Comparison of Similarities and Differences of the Xpert Nasal Sample

Collection Kit for Viruses with the Predicate Device

18

19

The proposed collection kits and predicate collection kits 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/RSV Assay was conducted using Xpert Nasopharyngeal Sample Collection Kit for Viruses [510(k) # K171552] and Xpert Nasal Sample Collection Kit for Viruses [510(k) # K171552] demonstrating that the Xpert Nasopharyngeal Sample Collection Kit for Viruses and Xpert Nasal Sample Collection Kit for Viruses are acceptable for their intended use and substantially equivalent to the predicate devices.

Non-Clinical Studies:

Analytical Sensitivity (Limit of Detection)

20

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 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, 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 and NS clinical matrices 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 in each matrix in NP swab and NSclinical matrix. The LoD point values for each strain tested are summarized in Tables 8-4 - 8-6.

| Virus Strain | Confirmed LoD Probit
(TCID50/mL) | |
|-------------------------------|-------------------------------------|-------|
| | NP Swab | NS |
| Influenza A/California/7/2009 | 0.020 | 0.018 |
| Influenza A/Florida/27/2011 | 0.040 | 0.04 |

Table 8-4 Confirmed LoD (TCIDso/mL):
Influenza A 2009 H1N1

Table 8-5 Confirmed LoD (TCID50/mL): Influenza A H3N2
	Confirmed LoD

| Virus Strain | Confirmed LoD
Probit
(TCID50/mL) | |
|-------------------------------|----------------------------------------|-------|
| | NP Swab | NS |
| Influenza A/Perth/16/2009 | 0.013 | 0.006 |
| Influenza A/Victoria/361/2011 | 0.750 | 0.21 |

Table 8-6 Confirmed LoD (TCID50/mL): Influenza B

21

| Virus Strain | Confirmed LoD
Probit
(TCID50/mL) | |
|-------------------------------|----------------------------------------|------|
| | NP Swab | NS |
| Influenza B/Mass/2/2012 | 0.400 | 0.07 |
| Influenza B/Wisconsin/01/2011 | 0.190 | 0.17 |

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

| Virus Strain | Confirmed LoD
Probit
(TCID50/mL) | |
|----------------------|----------------------------------------|------|
| | NP Swab | NS |
| RSV A/2/Australia/61 | 0.870 | 0.32 |
| RSV A/Long/MD/56 | 1.100 | 0.45 |

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

| Virus Strain | Confirmed LoD
Probit
(TCID50/mL) | |
|---------------------|----------------------------------------|------|
| | NP Swab | NS |
| RSV B/Wash/18537/62 | 0.790 | 0.29 |
| RSV B/9320/MA/77 | 2.300 | 0.35 |

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 nasal passage and nasopharynx. Three replicates of all bacterial and yeast strains 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 all viruses

22

were tested at concentrations of ≥ 1 x 105 TCID50/mL. The analytical specificity was 100%. Results are shown in Table 8-7.

23

| Organism (per cartridge) | Result |----------------------- | | No Template Control | Adenovirus Type 1 | Adenovirus Type 7 | Human coronavirus OC43 | Human coronavirus 229E | Cytomegalovirus | Echovirus | Enterovirus | Epstein Barr Virus | HSV | Measles | Human metapneumovirus | Mumps virus | Human parainfluenza Type 1 | Human parainfluenza Type 2 | Human parainfluenza Type 3 | Rhinovirus Type 1A | Acinetobacter baumannii | Burkholderia cepacia | Candida albicans | Candida parapsilosis | Bordetella pertussis | Chlamydia pneumoniae | Citrobacter freundii | Corynebacterium sp. | Escherichia coli | Enterococcus faecalis | Hemophilus influenzae | Lactobacillus reuteri | Legionella spp. | Moraxella catarrhalis | | Organism A | Influenza
B | RSV |
| Mycobacterium tuberculosis
(avirulent) | 1.00E+06 CFU/mL | Mycoplasma pneumoniae | Neisseria meningitides | Neisseria mucosa | Propionibacterium acnes | Pseudomonas aeruginosa | Staphylococcus aureus (protein A
producer) | 2.20E+06 CFU/mL | Staphylococcus epidermidis | Staphyloccus haemolyticus | Streptococcus agalactiae | Streptococcus pneumoniae | Streptococcus pyogenes | Streptococcus salivarius | Streptococcus sanguinis | Concentration
| | |
------------------------|----------------------------------|----------------|----------------|-----|
| | Influenza A | Influenza B | RSV |
| N/A | NEG | NEG | NEG |
| 1.12E+06 TCID50/mL | NEG | NEG | NEG |
| 1.87E+05 TCID50/mL | NEG | NEG | NEG |
| 2.85E+05 TCID50/mL | NEG | NEG | NEG |
| 1.00E+05 TCID50/mL | NEG | NEG | NEG |
| 1.00E+05 TCID50/mL | NEG | NEG | NEG |
| 3.31E+07 TCID50/mL | NEG | NEG | NEG |
| 3.55E+05 TCID50/mL | NEG | NEG | NEG |
| 7.16E+07 TCID50/mL | NEG | NEG | NEG |
| 8.90E+05 TCID50/mL | NEG | NEG | NEG |
| 6.31E+05 TCID50/mL | NEG | NEG | NEG |
| 1.00E+05 TCID50/mL | NEG | NEG | NEG |
| 6.31E+06 TCID50/mL | NEG | NEG | NEG |
| 1.15E+06 TCID50/mL | NEG | NEG | NEG |
| 6.31E+05 TCID50/mL | NEG | NEG | NEG |
| 3.55E+06 TCID50/mL | NEG | NEG | NEG |
| 1.26E+05 TCID50/mL | NEG | NEG | NEG |
| 1.00E+06 CFU/mL | NEG | NEG | NEG |
| 3.30E+06 CFU/mL | NEG | NEG | NEG |
| 3.20E+06 CFU/mL | NEG | NEG | NEG |
| 3.00E+06 CFU/mL | NEG | NEG | NEG |
| 3.30E+06 CFU/mL | NEG | NEG | NEG |
| 1.00E+05 CFU/mL | NEG | NEG | NEG |
| 3.30E+06 CFU/mL | NEG | NEG | NEG |
| 3.30E+06 CFU/mL | NEG | NEG | NEG |
| 1.00E+07 CFU/mL | NEG | NEG | NEG |
| 1.30E+06 CFU/mL | NEG | NEG | NEG |
| 1.00E+06 CFU/mL | NEG | NEG | NEG |
| 1.00E+06 CFU/mL | NEG | NEG | NEG |
| 1.00E+06 CFU/mL | NEG | NEG | NEG |
| 1.00E+07 CFU/mL | NEG | NEG | NEG |
| Concentration | Result | | |
| (per cartridge) | Influenza
| NEG | NEG | NEG |
| 1.00E+06 CFU/mL | NEG | NEG | NEG |
| 2.15E+06 CFU/mL | NEG | NEG | NEG |
| 1.00E+07 CFU/mL | NEG | NEG | NEG |
| 2.40E+07 CFU/mL | NEG | NEG | NEG |
| 3.70E+06 CFU/mL | NEG | NEG | NEG |
| NEG | NEG | NEG |
| 3.40E+06 CFU/mL | NEG | NEG | NEG |
| 4.00E+06 CFU/mL | NEG | NEG | NEG |
| 3.50E+06 CFU/mL | NEG | NEG | NEG |
| 1.00E+06 CFU/mL | NEG | NEG | NEG |
| 1.00E+07 CFU/mL | NEG | NEG | NEG |
| 1.00E+07 CFU/mL | NEG | NEG | NEG |
| 3.10E+06 CFU/mL | NEG | NEG | NEG |

Table 8-7 Analytical Specificity of the Xpert Xpress Flu/RSV Assay

24

25

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 8-8.

Predicted cross reactivity from in silico analyses showed 100% sequence homology for additional pH1N1 strains.

26

			Result
Virus	Strain	Target
Concentration	Flu A	Flu B	RSV
	No Template Control	n/a	NEG	NEG	NEG
	A/swine/Iowa/15/30	0.1 TCID50/mL	POS	NEG	NEG
	A/WS/33	0.1 TCID50/mL	POS	NEG	NEG
	A/PR/8/34	0.1 TCID50/mL	POS	NEG	NEG
	A/Mal/302/54	0.1 TCID50/mL	POS	NEG	NEG
	A/Denver/1/57	0.1 TCID50/mL	POS	NEG	NEG
	A/New Jersey/8/76	0.1 TCID50/mL	POS	NEG	NEG
Influenza A
H1N1
(pre-2009)	A/New Caledonia/20/1999	0.1 TCID50/mL	POS	NEG	NEG
	A/New York/55/2004	0.1 TCID50/mL	POS	NEG	NEG
	A/Soloman Island/3/2006	0.1 TCID50/mL	POS	NEG	NEG
	A/Taiwan/42/06	0.1 TCID50/mL	POS	NEG	NEG
	A/Brisbane/59/2007	0.1 TCID50/mL	POS	NEG	NEG
	A/swine/NY/02/2009	0.1 TCID50/mL	POS	NEG	NEG
Influenza A
H1N1
(pdm2009)	A/Colorado/14/2012	0.1 TCID50/mL	POS	NEG	NEG
	A/Washington/24/2012	0.1 TCID50/mL	POS	NEG	NEG

	A/Aichi/2/68	2.0 TCID50/mL	POS	NEG	NEG
	A/HongKong/8/68	2.0 TCID50/mL	POS	NEG	NEG
	A/Port Chalmers/1/73	2.0 TCID50/mL	POS	NEG	NEG
	A/Hawaii/15/2001	2.0 TCID50/mL	POS	NEG	NEG
Influenza A
H3N2
(Seasonal)	A/Wisconsin/67/05	2.0 TCID50/mL	POS	NEG	NEG
	A/Brisbane/10/2007	2.0 TCID50/mL	POS	NEG	NEG
	A/Minnesota/11/2010 (H3N2)v	2.0 TCID50/mL	POS	NEG	NEG
	A/Indiana/08/2011 (H3N2)v	2.0 TCID50/mL	POS	NEG	NEG
	A/Texas/50/2012	2.0 TCID50/mL	POS	NEG	NEG
Avian influenza	A/duck/Hunan/795/2002 (H5N1)	$≤ 10g/μLa$	POS	NEG	NEG
	Strain	Target
Concentration	Result
Virus			Flu A	Flu B	RSV
A	A/chicken/Hubei/327/2004
(H5N1)	≤ 1pg/μLa	POS	NEG	NEG
	A/Anhui/01/2005 (H5N1)	≤ 1pg/μLa	POS	NEG	NEG
	A/Japanese white eye/ Hong
Kong/ 1038/2006 (H5N1)	≤ 1pg/μLa	POS	NEG	NEG
	A/mallard/WI/34/75 (H5N2)	≤ 1pg/μLa	POS	NEG	NEG
	A/chicken/CA431/00 (H6N2)	≤ 1pg/μLa	POS	NEG	NEG
	A/duck/LTC-10-82743/1943
(H7N2)	≤ 1pg/μLa	POS	NEG	NEG
	A/chicken/NJ/15086-3/94 (H7N3)	≤ 1pg/μLa	POS	NEG	NEG
	A/Anhui/1/2013 (H7N9)	N/Ab	POS	NEG	NEG
	A/Shanghai/1/2013 (H7N9)	N/Ab	POS	NEG	NEG
	A/chicken/Korea/38349-p96323/
1996 (H9N2)	≤ 1pg/μLa	POS	NEG	NEG
	A/Mallard/NY/6750/78 (H2N2)	≤ 1pg/μLa	POS	NEG	NEG
	B/Lee/40	1.0 TCID50/mL	NEG	POS	NEG
	B/Allen/45	1.0 TCID50/mL	NEG	POS	NEG
	B/GL/1739/54	1.0 TCID50/mL	NEG	POS	NEG
	B/Maryland/1/59	1.0 TCID50/mL	NEG	POS	NEG
	B/Panama/45/90c	1.0 TCID50/mL	NEG	POS	NEG
	B/Florida/07/2004d	1.0 TCID50/mL	NEG	POS	NEG
	B/Florida/02/06c	1.0 TCID50/mL	NEG	POS	NEG
	B/Florida/04/06d	1.0 TCID50/mL	NEG	POS	NEG
	B/Hong Kong/5/72	1.0 TCID50/mL	NEG	POS	NEG
Influenza B	B/Wisconsin/01/2010d	1.0 TCID50/mL	NEG	POS	NEG
	B/Malaysia/2506/04c	1.0 TCID50/mL	NEG	POS	NEG
	B/Taiwan/2/62	1.0 TCID50/mL	NEG	POS	NEG
Virus	Strain	Target
Concentration	Result
			Flu A	Flu B	RSV
	B/Brisbane/60/2008c	1.0 TCID50/mL	NEG	POS	NEG

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

27

28

Purified viral RNA in simulated background matrix was used for avian influenza A viruses due to a. biosafety regulations.
b. Inactivated avian influenza A (H7N9) viruses without viral titer was diluted 100,000 fold in simulated background matrix and tested due to biosafety regulations.

Known Victoria lineage. C.

Known Yamagata lineage. d.

Potentially Interfering Substances

In a non-clinical study, potentially interfering substances that may be present in the nasal passage and nasopharynx were evaluated directly relative to the performance of the Xpert Xpress Flu/RSV Assay. Potentially interfering substances in the nasal passage and 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 background matrix controls. The simulated background 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 8-9 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.

29

| Substance/Class | Description/Active
Ingredient | Concentration
Tested |
|---------------------------------------------------|--------------------------------------------------------------------------------|-------------------------------------------------|
| Control | Simulated background
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) |
| BD™ 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 drug | 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 8-9 Potentially Interfering Substances in the Xpert Xpress Flu Assay

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 TCIDso/mL) or a very high RSV A

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sample (A/Long/MD/26, 1x104 TCID50/mL) spiked into a simulated background 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.

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 strains and RSV strains near the LoD in the presence of different influenza strains at a higher concentration in a simulated background matrix. Analytical competitive interference was assessed using one (1) seasonal Flu A H3 strain (H3/Victoria/361/2011) at 0.8 TCID50/mL, one (1) Flu B strain (B/Mass/2/2012) at 0.45 TCID50/mL, one (1) RSV A strain (RSV-A/2/Australia/61) at 1.1 TCID50/mL and one (1) RSV B strain (RSV-B/Wash/18537/62) at 0.9 TCID50/mL; the strains were tested at in the presence of competing strains at either 1 x 102 TCID50/mL or 1 x 102 TCID50/mL. 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=0.95 (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 TCID50/mL of Flu

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A/Victoria/361/2011. No competitive inhibitory effects were observed in the presence of 1x102 TCID50/mL of Flu A/Victoria/361/2011; 1x103 TCID50/mL of RSV-A/2/Australia/6; or 1x103 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 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 TCID50/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 this Package Insert.

Clinical Studies

Clinical Comparison Study

Performance characteristics of the Xpert Xpress Flu/RSV Assay were evaluated at fourteen institutions in the U.S. during the 2016-2017 influenza season.

Specimens were collected from the following:

Individuals exhibiting signs and symptoms of respiratory infection who provided .

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informed consent for the collection of a NS or NP swab specimen.

The Xpert Xpress Flu/RSV Assay performance was compared to FDA-cleared molecular comparator assay.

Overall Results

A total of 3265 specimens (1598 NS and 1667 NP swab) were tested for influenza A, influenza B by the Xpert Xpress Flu/RSV Assay and the comparator method.

For NS specimens, the Xpert Xpress Flu/RSV Assay demonstrated a positive percent agreement (PPA) and a negative percent agreement (NPA) relative to the comparator method of 98.9% and 97.5% for the detection of influenza A and 98.4% and 99.3% for influenza B, respectively (Table 8-10).

For NP swab specimens, the Xpert Xpress Flu/RSV Assay demonstrated a PPA and NPA relative to the comparator method of 97.6% and 98.2% for the detection of influenza A and 97.3% and 99.6% for influenza B, respectively (Table 8-10).

For the combined dataset, the Xpert Xpress Flu/RSV Assay demonstrated a PPA and NPA relative to the comparator method of 98.2% and 97.9% for the detection of influenza A and 97.8% and 99.4% for influenza B, respectively (Table 8-10).

A total of 3103 specimens (1543 NS and 1560 NP swab) were tested for RSV by the Xpert Xpress Flu/RSV Assay and the comparator assay.

For NS specimens, the Xpert Xpress Flu/RSV Assay demonstrated a PPA and NPA relative to the comparator method of 98.2% and 99.1% for detection of RSV, respectively (Table 8-10).

For NP swab specimens, the Xpert Xpress Flu/RSV Assay demonstrated a PPA and NPA relative to the comparator method of 98.2% and 98.5% for detection of RSV, respectively (Table 8-10).

For the combined dataset, the Xpert Xpress Flu/RSV Assay demonstrated a PPA and NPA relative to the comparator method of 98.2% and 98.8% for the detection of RSV, respectively (Table 8-10).

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| Targeta | Specimen
Type | N | TP | FN | TN | FP | PPA
(95% CI) | NPA
(95% CI) |
|---------|------------------|------|-----|-----|------|-----|----------------------|----------------------|
| Flu A | NS | 1598 | 186 | 2b | 1375 | 35c | 98.9
(96.2-99.7) | 97.5%
(96.6-98.2) |
| | NP | 1667 | 200 | 5d | 1436 | 26e | 97.6%
(94.4-99.0) | 98.2%
(97.4-98.8) |
| | Overall | 3265 | 386 | 7f | 2811 | 61g | 98.2%
(96.4-99.1) | 97.9%
(97.3-98.3) |
| Flu B | NS | 1598 | 63 | 1h | 1523 | 11i | 98.4%
(91.7-99.7) | 99.3%
(98.7-99.6) |
| | NP | 1667 | 71 | 2j | 1587 | 7k | 97.3%
(90.6-99.2) | 99.6%
(99.1-99.8) |
| | Overall | 3265 | 134 | 3l | 3110 | 18m | 97.8%
(93.8-99.3) | 99.4%
(99.1-99.6) |
| RSV | NS | 1543 | 269 | 5n | 1257 | 12o | 98.2%
(95.8-99.2) | 99.1%
(98.4-99.5) |
| | NP | 1560 | 275 | 5p | 1261 | 19q | 98.2%
(95.9-99.2) | 98.5%
(97.7-99.0) |
| | Overall | 3103 | 544 | 10r | 2518 | 31s | 98.2%
(96.7-99.0) | 98.8%
(98.3-99.1) |

Table 8-10 Xpert Xpress Flu/RSV Assay Performance

a Five specimens were positive for both Flu A and Flu B.

bDiscrepant Testing: 1 of 2 Flu A NEG: 1 of 2 Flu A POS.

· Discrepant Testing: 17 of 35 Flu A NEG; 11 of 35 Flu A POS; 7 of 35 inconclusive.

dDiscrepant Testing: 3 of 5 Flu A NEG; 2 of 5 Flu A POS.

6Discrepant Testing: 11 of 26 Flu A NEG; 9 of 26 Flu A POS; 6 of 26 inconclusive.

fDiscrepant Testing: 4 of 7 Flu A NEG; 3 of 7 Flu A POS.

8Discrepant Testing: 26 of 61 Flu A NEG; 22 of 61 Flu A POS; 13 of 61 inconclusive

hDiscrepant Testing: 1 of 1 inconclusive.

Discrepant Testing: 5 of 11 Flu B POS; 6 of 11 inconclusive.

Discrepant Testing: 1 of 2 Flu B POS; 1 of 2 inconclusive.

*Discrepant Testing: 1 of 7 Flu B NEG; 5 of 7 Flu B POS; 1 of 7 inconclusive.

1Discrepant Testing: 1 of 3 Flu B POS; 2 of 3 inconclusive

™Discrepant Testing: 1 of 18 Flu B NEG; 10 of 18 Flu B POS; 7 of 18 inconclusive

"Discrepant Testing: 3 of 5 RSV NEG; 1 of 5 inconclusive; 1 of 5 not done.

0Discrepant Testing: 5 of 12 RSV NEG; 3 of 12 RSV POS, 4 of 12 inconclusive.

PDiscrepant Testing: 2 of 5 RSV NEG; 2 of 5 inconclusive; 1 of 5 not done.

9Discrepant Testing: 6 of 19 RSV NEG; 2 of 19 RSV POS, 6 of 19 inconclusive; 5 of 19 not done.

'Discrepant Testing: 5 of 10 RSV NEG; 3 of 10 inconclusive; 2 of 10 not done.

9Discrepant Testing: 11 of 31 RSV NEG; 5 of 31 RSV POS; 10 of 31 inconclusive; 5 of 31 not done.

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Of the Xpert Xpress Flu/RSV Assay runs performed with eligible specimens, 98.0% (3212/3279) of these specimens were successful on the first attempt. The remaining 67 gave indeterminate results on the first attempt (38 NO RESULT-REPEAT TEST results and 29 INSTRUMENT ERROR). Fifty-eight of the 67 indeterminate cases were retested, of which 53 yielded valid results upon repeat testing; nine specimens were not retested. The overall rate of assay success was 99.6% (3265/3279). The overall indeterminate rate was 0.4%.

Reproducibility Study

Reproducibility was established in a multi-center, blinded study using a 7-member specimen panel. Testing was performed at three sites using the GeneXpert Xpress System.

Testing was conducted for five (not necessarily consecutive) days, with one lot of Xpert Xpress Flu/RSV cartridges. Each site had three operators, who tested each panel twice each day. Results are summarized in Table 8-11.

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| Sample | Titer of
Virus
(TCID50/mL) | Site 1 | | | | Site 2 | | | | Site 3 | | | | % Total
Agreement
by Samplea |
|---------------|----------------------------------|-----------------|-----------------|-----------------|------------------|-----------------|-----------------|-----------------|------------------|-----------------|-----------------|-----------------|------------------|------------------------------------|
| | | Op 1 | Op 2 | Op 3 | Site | Op 1 | Op 2 | Op 3 | Site | Op 1 | Op 2 | Op 3 | Site | |
| Neg | 0 | 100%
(10/10) | 100%
(10/10) | 100%
(10/10) | 100%
(30/30) | 100%
(10/10) | 100%
(10/10) | 100%
(10/10) | 100%
(30/30) | 100%
(10/10) | 100%
(10/10) | 100%
(10/10) | 100%
(30/30) | 100%
(90/90) |
| Flu A Low Pos | 0.75 | 100%
(10/10) | 100%
(10/10) | 90.0%
(9/10) | 96.7%
(29/30) | 70.0%
(7/10) | 100%
(10/10) | 100%
(10/10) | 90.0%
(27/30) | 70.0%
(7/10) | 100%
(10/10) | 88.9%
(8/9) | 86.2%
(25/29) | 91.0%
(81/89) |
| Flu A Mod Pos | 1.5 | 100%
(10/10) | 100%
(10/10) | 100%
(10/10) | 100%
(30/30) | 100%
(10/10) | 100%
(10/10) | 100%
(10/10) | 100%
(30/30) | 100%
(10/10) | 100%
(10/10) | 100%
(10/10) | 100%
(30/30) | 100%
(90/90) |
| Flu B Low Pos | 0.2 | 90.0%
(9/10) | 100%
(10/10) | 90.0%
(9/10) | 93.3%
(28/30) | 100%
(10/10) | 100%
(10/10) | 90.0%
(9/10) | 96.7%
(29/30) | 100%
(10/10) | 70.0%
(7/10) | 100%
(10/10) | 90.0%
(27/30) | 93.3%
(84/90) |
| Flu B Mod Pos | 0.4 | 100%
(10/10) | 100%
(10/10) | 100%
(10/10) | 100%
(30/30) | 100%
(10/10) | 100%
(10/10) | 100%
(10/10) | 100%
(30/30) | 100%
(10/10) | 100%
(10/10) | 100%
(10/10) | 100%
(30/30) | 100%
(90/90) |
| RSV Low Pos | 1.1 | 80.0%
(8/10) | 90.0%
(9/10) | 100%
(10/10) | 90.0%
(27/30) | 100%
(10/10) | 80.0%
(8/10) | 100%
(10/10) | 93.3%
(28/30) | 90.0%
(9/10) | 80.0%
(8/10) | 100%
(10/10) | 90.0%
(27/30) | 91.0%
(82/90) |
| RSV Mod Pos | 2.2 | 100%
(10/10) | 100%
(10/10) | 100%
(10/10) | 100%
(30/30) | 100%
(10/10) | 100%
(10/10) | 100%
(10/10) | 100%
(30/30) | 100%
(10/10) | 100%
(10/10) | 100%
(10/10) | 100%
(30/30) | 100%
(90/90) |

Table 8-11 Summary of Reproducibility Results

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

b. One sample 2x indeterminate (Flu A Low Pos)

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) between-sites, betweendays, between-lots and between-operators for each panel member are presented in Table 8-12.

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| Sample | Assay Channel
(Analyte) | Na | Mean
Ct | Between-Site | | Between-Day | | Between-Operator | | Within-Assay | | Total | |
|---------------|----------------------------|----|------------|--------------|-----------|-------------|-----------|------------------|-----------|--------------|-----------|-------|-----------|
| | | | | SD | CV
(%) | SD | CV
(%) | SD | CV
(%) | SD | CV
(%) | SD | CV
(%) |
| Neg | SPC | 90 | 32.2 | 0.2 | 0.6 | 0.2 | 0.6 | 0.2 | 0.7 | 0.4 | 1.4 | 0.6 | 1.8 |
| Flu A Low Pos | A | 80 | 36.4 | 0.1 | 0.4 | 0 | 0 | 0 | 0 | 1.8 | 4.9 | 1.8 | 4.9 |
| Flu A Mod Pos | A | 90 | 33.7 | 0.1 | 0.2 | 0 | 0 | 0 | 0 | 0.6 | 1.7 | 0.6 | 1.8 |
| Flu B Low Pos | B | 84 | 35.8 | 0 | 0 | 0 | 0 | 0.6 | 1.8 | 1.5 | 4.1 | 1.6 | 4.5 |
| Flu B Mod Pos | B | 90 | 33.7 | 0 | 0.1 | 0.1 | 0.4 | 0 | 0 | 0.5 | 1.6 | 0.6 | 1.7 |
| RSV Low Pos | RSV | 82 | 36.8 | 0.7 | 2.0 | 0.1 | 0.4 | 0 | 0 | 1.1 | 2.9 | 1.3 | 3.6 |
| RSV Mod Pos | RSV | 90 | 33.1 | 0 | 0.1 | 0.2 | 0.6 | 0 | 0 | 0.5 | 1.4 | 0.5 | 1.5 |

Table 8-12 Summary of Reproducibility Data

Results with non-zero Ct values of 90. 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.