Xpert Xpress Flu, Xpert Nasopharyngeal Sample Collection Kit, Xpert Nasal Sample Collection Kit, GeneXpert Xpress II, GeneXpert Xpress IV

Q: Who is the manufacturer of Xpert Xpress Flu, Xpert Nasopharyngeal Sample Collection Kit, Xpert Nasal Sample Collection Kit, GeneXpert Xpress II, GeneXpert Xpress IV?

Cepheid filed the 510(k) submission for Xpert Xpress Flu, Xpert Nasopharyngeal Sample Collection Kit, Xpert Nasal Sample Collection Kit, GeneXpert Xpress II, GeneXpert Xpress IV (K171552).

Q: What is the FDA product code for Xpert Xpress Flu, Xpert Nasopharyngeal Sample Collection Kit, Xpert Nasal Sample Collection Kit, GeneXpert Xpress II, GeneXpert Xpress IV?

OCC. It is classified under 21 CFR 866.3980 as a Class 2 device in the Microbiology panel.

Q: What is the regulatory pathway for Xpert Xpress Flu, Xpert Nasopharyngeal Sample Collection Kit, Xpert Nasal Sample Collection Kit, GeneXpert Xpress II, GeneXpert Xpress IV?

510(k) clearance (submission type: Dual Track).

Q: What are the predicate devices for Xpert Xpress Flu, Xpert Nasopharyngeal Sample Collection Kit, Xpert Nasal Sample Collection Kit, GeneXpert Xpress II, GeneXpert Xpress IV?

Xpert® Flu+RSV Xpress Assay (K151226); Cepheid Xpert® Nasopharyngeal Sample Collection Kit for Viruses (K162456); Copan Universal Transport Medium (UTM-RT) System (K042970).

Q: Who can help prepare an FDA FDA submission like Xpert Xpress Flu, Xpert Nasopharyngeal Sample Collection Kit, Xpert Nasal Sample Collection Kit, GeneXpert Xpress II, GeneXpert Xpress IV?

Innolitics — a medical-device software consultancy — provides regulatory and engineering support for FDA FDA submissions. See https://innolitics.com/services/regulatory/ or contact https://innolitics.com/contact.

K171552 · Cepheid · OCC · Dec 19, 2017 · Microbiology

Device Facts

Record ID	K171552
Device Name	Xpert Xpress Flu, Xpert Nasopharyngeal Sample Collection Kit, Xpert Nasal Sample Collection Kit, GeneXpert Xpress II, GeneXpert Xpress IV
Applicant	Cepheid
Product Code	OCC · Microbiology
Decision Date	Dec 19, 2017
Decision	SESE
Submission Type	Dual Track
Regulation	21 CFR 866.3980
Device Class	Class 2

Intended Use

The Cepheid Xpert® Xpress Flu 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 and influenza B viral RNA. The Xpert Xpress Flu 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 infections in conjunction with clinical and epidemiological risk factors. Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions. Performance characteristics for influenza A were established during the 2016-2017 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.

Device Story

The Xpert Xpress Flu Assay is an automated, multiplex real-time RT-PCR test performed on the GeneXpert Xpress System. It processes nasopharyngeal or nasal swab specimens collected in universal transport medium. The system uses self-contained, single-use cartridges to perform automated sample processing, nucleic acid extraction, and real-time RT-PCR amplification. The assay targets specific RNA sequences for influenza A (Matrix, PB2, PA) and influenza B (Matrix, NS1, NS2). Internal controls (SPC and PCC) monitor sample processing and reagent integrity. Results are generated in approximately 30 minutes. The device is used in clinical settings by operators, including those without specialized lab experience. The output is a qualitative report of influenza A and B presence, which aids clinicians in diagnosing respiratory infections and guiding patient management decisions.

Clinical Evidence

Clinical performance was evaluated at 14 U.S. institutions during the 2016-2017 season using 3,229 specimens (1,582 nasal, 1,647 NP). Compared to an FDA-cleared molecular assay, the device showed: Flu A PPA 98.2% (95% CI: 96.3-99.1) and NPA 97.7% (95% CI: 97.1-98.2); Flu B PPA 97.8% (95% CI: 93.8-99.3) and NPA 99.4% (95% CI: 99.0-99.6). Reproducibility was confirmed across three sites with 100% agreement for negative samples and high agreement for positive samples.

Technological Characteristics

Multiplex real-time RT-PCR assay. Uses GeneXpert Xpress System (GX-II/GX-IV) with I-core technology. Reagents contained in single-use, self-contained cartridges. Internal controls: Sample Processing Control (SPC) and Probe Check Control (PCC). Targets: Influenza A (MP, PB2, PA) and Influenza B (MP, NS1, NS2). Ancillary collection kits use medical-grade polypropylene containers, Hank's Balanced Salt Solution-based transport medium, and nylon flocked swabs.

Indications for Use

Indicated for qualitative detection and differentiation of influenza A and B viral RNA in nasopharyngeal and nasal swab specimens from patients with respiratory infection symptoms. Intended as an aid in diagnosis alongside clinical/epidemiological risk factors. Not for sole basis of treatment decisions.

Regulatory Classification

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.

Special Controls

*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.

Predicate Devices

Xpert® Flu+RSV Xpress Assay (K151226)
Cepheid Xpert® Nasopharyngeal Sample Collection Kit for Viruses (K162456)
Copan Universal Transport Medium (UTM-RT) System (K042970)

Related Devices

K162456 — Xpert Xpress Flu, 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 · Cepheid · Feb 13, 2017
K180218 — Xpert Xpress Flu/RSV, Xpert Nasopharyngeal Sample Collection Kit, Xpert Nasal Sample Collection Kit, GeneXpert Xpress II, GeneXpert Xpress IV · Cepheid · Jul 24, 2018
K181289 — Xpert Xpress Flu, Xpert Nasopharyngeal Sample Collection Kit, Xpert Nasal Sample Collection Kit, GeneXpert Dx Systems (GX-I, GX-II, GX-IV, GX-XVI), GeneXpert Infinity-48S System and GeneXpert Infinity-80 System · Cepheid · Aug 15, 2018
K151226 — Xpert Flu+RSV Xpress, Xpert Nasopharyngeal Sample Collection Kit, GeneXpert Xpress System (GX-I) · Cepheid · Dec 3, 2015
K120911 — XPERT FLU GENEXPERT DX SYSTEMS (GX-I, GX-IV) · Cepheid · May 18, 2012

Submission Summary (Full Text)

{0}------------------------------------------------ Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo features the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text. December 19, 2017 Cepheid Jim Kelly, PhD Executive Director, Regulatory Affairs 904 Caribbean Drive Sunnyvale, California 94089-1189 Re: K171552 Trade/Device Name: Xpress Flu, Xpert Nasopharyngeal Sample Collection Kit, Xpert Nasal Sample Collection Kit 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: May 24, 2017 Received: May 26, 2017 Dear Dr. Kelly: We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading. If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR 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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance. 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) K171552 Device Name Xpert Xpress Flu #### Indications for Use (Describe) The Cepheid Xpert Xpress Flu 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 and influenza B viral RNA. The Xpert Xpress Flu 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 infections in conjunction with clinical and epidemiological risk factors. Negative results do not prection 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 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 for Nasopharyngeal Swabs 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/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 Collection Kit for Nasal Swabs Indications for 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 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) | #### CONTINUE ON A SEPARATE PAGE IF NEEDED. - {3}------------------------------------------------ This section applies only to requirements of the Paperwork Reduction Act of 1995. #### *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.* The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to: > Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov "An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number." {4}------------------------------------------------ # 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 24, 2017 | | Device: | | | Trade name: | Xpert® Xpress Flu | | Common name: | Xpert Xpress Flu Assay | | Type of Test: | Automated, multiplex real-time reverse transcription- polymerase chain reaction (RT-PCR) assay intended for the in vitro qualitative detection and differentiation of influenza A and influenza B viral RNA. | | Regulation number/ Classification name/ Product code: | 866.3980/Respiratory viral panel multiplex nucleic acid assay 866.2570/Instrumentation for clinical multiplex test systems OCC; OOI, 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 Xpress Assay [510(k) #K151226] | | | 2) For the Sample Collection Kits: Cepheid Xpert® Nasopharyngeal Sample Collection Kit for Viruses [510(k) # K162456] | | | Copan Universal Transport Medium (UTM-RT) System, [510(k) # K042970] | {5}------------------------------------------------ #### Device Description: The Xpert Xpress Flu Assay is a rapid, automated in vitro diagnostic test for the qualitative detection and differentiation of influenza A (Flu A) and influenza B (Flu B) 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 Assay includes reagents for the simultaneous detection and differentiation of the target viruses. The primers and probes in the Xpert Xpress Flu Assay detect the presence of nucleic acid sequences for Flu A and Flu B directly from NS and 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 Xpress 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 universal 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 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 viral RNA. Summary and detailed test results are obtained in approximately 30 minutes or less. The results are automatically generated at the end of the process in a report that can be viewed and printed. {6}------------------------------------------------ ## Device Intended Use: The Cepheid Xpert® Xpress Flu Assay, performed on the GeneXpert® 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 and influenza B viral RNA. The Xpert Xpress Flu 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 infections in conjunction with clinical and epidemiological risk factors. Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions. Performance characteristics for influenza A were established during the 2016-2017 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. ## Ancillary Collection Kit for Nasal Swabs Indications for 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 Assay. # Ancillary Collection Kit for Nasopharyngeal Swabs 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 {7}------------------------------------------------ Assay. The Xpert® Nasopharyngeal Sample Collection Kit is designed to collect, preserve, and transport nasopharyngeal swab specimens containing viruses from patients with signs and symptoms of respiratory infection prior to analysis with the Xpert Flu+RSV Xpress Assay, Xpert Xpress Flu/RSV Assay or the Xpert Xpress Flu Assay. ### Substantial Equivalence: The Xpert Xpress Flu Assay is substantially equivalent to the current Xpert® Flu+RSV Xpress Assay [510(k) #K151226]. The Xpert Xpress Flu Assay detects influenza A and influenza B from nasopharyngeal (NP) swab and nasal swab (NS) specimens and the Xpert® Flu+RSV Xpress Assay detects influenza A, 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 data obtained using the Xpert Xpress Flu/RSV Assay was then reanalyzed with the Xpert Xpress Flu Assay Definition File (ADF). The reanalyzed data was used to determine the performance characteristics of the Xpert Xpress Flu Assay relative to the reference Flu test, which has been FDA cleared for NP swab and NS specimens. The study results showed that the Xpert Xpress Flu 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 Assay and the predicate device. {8}------------------------------------------------ | Similarities | | | |----------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | | Device | Predicate | | Item | Cepheid Xpert® Xpress Flu | 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 | | 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. Only results for influenza A and influenza B are reported. | Primers and probes to detect the presence of nucleic acid sequences of influenza A, influenza B, and RSV. Results for influenza A, influenza B and RSV analytes are reported. | | 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. Only results for influenza A and influenza B are reported. | Primers and probes to detect the presence of nucleic acid sequences of influenza A, influenza B, and RSV A/B. The Xpert Flu+RSV Xpress 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. Results for influenza A, influenza B and RSV analytes are reported. | | Target Sequences | Influenza A: Matrix protein (MP), basic polymerase (PB2) and acidic protein (PA) Influenza B: Matrix protein (MP) and Non-structural proteins (NS 1 and NS 2) RSV A and RSV B: Nucleocapsid protein Only results for influenza A and influenza B are reported. | Influenza A: Matrix protein (MP), basic polymerase (PB2) and acidic protein (PA) Influenza B: Matrix protein (MP) and Non-structural proteins (NS 1 and NS 2) RSV A and RSV B: Nucleocapsid protein Results for influenza A, influenza B and RSV analytes are reported. | | Internal Controls | Sample processing control (SPC) and probe check control (PCC). | Same | | Early Assay termination function | Yes | Yes | # Table 8-1: Comparison of Similarities and Differences of the Xpert Xpress Flu Assay with the Predicate Devices {9}------------------------------------------------ | Differences | | | |---------------|---------------------------------------|------------------------------------------------| | | Device | Predicate | | Item | Cepheid Xpert® Xpress Flu | Cepheid Xpert® Flu+RSV Xpress Assay | | | | K151226 | | Assay Targets | Influenza A and Influenza B viral RNA | Influenza A, Influenza B, and RSV viral RNA | {10}------------------------------------------------ | Specimen Types | Nasopharyngeal (NP) swab and nasal swab (NS) specimens | Nasopharyngeal (NP) swab specimens | |--------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Assay Controls | Encapsulated (armored) RNA pseudovirus as a sample processing control. Available but not provided are inactivated virus controls for influenza A/B as external positive controls, and Coxsackie virus as an external negative control. | 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. | | 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 | | Combinatorial Assay Selections | Not applicable | Yes, user may select combined assay with all targets or a Flu only assay or a RSV only assay. | | Intended Use | | | | | The Cepheid Xpert® Xpress Flu 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 and influenza B viral RNA. The Xpert Xpress Flu 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 infections in conjunction with clinical and epidemiological risk factors. Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions. Performance characteristics for influenza A were established during the 2016-2017 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 | 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 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 | {11}------------------------------------------------ The Xpert Xpress Flu Assay and the predicate device have the same general intended use and technological characteristics, and both detect influenza A and influenza B viral RNA from NP swab specimens. The clinical study demonstrates that the Xpert Xpress Flu {12}------------------------------------------------ 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) # K162456]. The similarities are shown in Table 8-2. There is no difference between the Nasopharyngeal Sample Collection Kit for Viruses cleared in 510(k) # K162456 and this 510(k). The predicate device for the ancillary specimen collection kit, the Xpert Nasal Sample Collection Kit for Viruses is the Copan Universal Transport Medium (UTM-RT) System, [510(k) # K042970]. The similarities and differences are shown in Table 8-3. Table 8-2: Comparison of Similarities of the Xpert Nasopharyngeal Sample Collection Kit with the Predicate Device | Similarities | | | |--------------|---------------------------------------------------------------|----------------------------------------------------------------------------------| | | Device | Predicate | | Item | Xpert® Nasopharyngeal Sample Collection Kit for Viruses | Xpert® Nasopharyngeal Sample Collection Kit for Viruses 510(k)# K162456 | {13}------------------------------------------------ | 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 | | | Similarities | | | |---------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------|--| | | Device | Predicate | | | Item | Xpert® Nasopharyngeal Sample Collection Kit for Viruses | Xpert® Nasopharyngeal Sample Collection Kit for Viruses 510(k)# K162456 | | | Transport Medium Formulation | Hank's Balanced Salt Solution Bovine Serum Albumin L-cysteine Gelatin Sucrose L-glutamic acid HEPES buffer Vancomycin Amphotericin B Colistin Phenol red | Same | | | pH | 7.3 + 0.2 | Same | | {14}------------------------------------------------ | Storage Temperature | 2 - 25°C (refrigerated and room temperature) | Same | |-----------------------|------------------------------------------------------------------|------| | Volume | 3 ml | Same | | Glass Beads | 3 x 3 mm | Same | | Container | Plastic (medical-grade polypropylene) | Same | | Product Configuration | Medium Tube in Kit with individually-wrapped sterile swab. | Same | # Table 8-3: Comparison of Similarities and Differences of the Xpert Nasal Sample Collection Kit for Viruses with the Predicate Device | Similarities | | | |-------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | | Device | Predicate | | Item | Xpert® Nasal Sample Collection Kit for Viruses | Copan Universal Transport Medium (UTM-RT) System 510(k)# K042970 | | 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 Assay. | Copan Universal Transport Medium (UTM-RT) System is intended for the collection and transport of clinical specimens containing viruses, chlamydiae, mycoplasma or ureaplasma from the collection site to the testing laboratory. UTM-RT can be processed using standard clinical laboratory operating procedures for viral, chlamydial, mycoplasma and ureaplasma culture. | | Single-use Device | Yes | Same | | | Similarities | | |------|---------------------------------------------------|------------------------------------------------------------------------| | | Device | Predicate | | Item | Xpert® Nasal Sample Collection Kit for Viruses | Copan Universal Transport Medium (UTM-RT) System 510(k)# K042970 | {15}------------------------------------------------ | 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 | | Differences | | | |--------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | | Device | Predicate | | Item | Xpert Nasal Sample Collection Kit for Viruses | Copan Universal Transport Medium (UTM-RT) System 510(k)# K042970 | | 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 Assay. | For collection, transport (and preservation of viability) of swab collected clinical specimens containing viruses, chlamydiae, mycoplasma or ureaplasma. UTM-RT can be processed using standard clinical laboratory operating procedures for viral, chlamydial, mycoplasma and ureaplasma culture. | | Product Configuration | Medium Tube in Kit with individually-wrapped sterile swab. | Medium Tubes; Kit with Medium Tubes and Swab Options | | Swab | Nylon flocked | Polyester | 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 multi-[Type here] {16}------------------------------------------------ center clinical study of the Xpert Xpress Flu Assay was conducted using Xpert Nasopharyngeal Sample Collection Kit for Viruses [510(k) # K162456] and Xpert Nasal Sample Collection Kit for Viruses (Copan-manufactured UTM-RT and sterile nylon flocked swab) 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) Studies were performed to determine the analytical limit of detection (LoD) of the Xpert Xpress Flu Assay with two lots of reagents across three testing days. The higher LoD 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 and two influenza 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 NS clinical 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 Matrix | NS Matrix | | Influenza A/California/7/2009 | 0.02 | 0.018 | | Influenza A/Florida/27/2011 | 0.04 | 0.04 | Table 8-4 Confirmed LoD (TCID50/mL): Influenza A 2009 HIN1 {17}------------------------------------------------ | Virus Strain | Confirmed LoD Probit (TCID50/mL) | | |-------------------------------|----------------------------------------|-----------| | | NP Swab Matrix | NS Matrix | | Influenza A/Perth/16/2009 | 0.01 | 0.006 | | Influenza A/Victoria/361/2011 | 0.75 | 0.21 | | Table 8-5 Confirmed LoD (TCID50/mL): Influenza A H3N2 | | | |--------------------------------------------------------|--|--| | | | | Table 8-6 Confirmed LoD (TCID50/mL): Influenza B | Virus Strain | Confirmed LoD Probit (TCID50/mL) | | |-------------------------------|----------------------------------------|-----------| | | NP Swab Matrix | NS Matrix | | Influenza B/Mass/2/2012 | 0.40 | 0.07 | | Influenza B/Wisconsin/01/2011 | 0.19 | 0.17 | The analytical specificity of the Xpert Xpress Flu Assay was evaluated by testing a panel of 44 cultures consisting of 16 viral, 26 bacterial, and two yeast strains representing common respiratory pathogens or those potentially encountered in the 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 were tested at concentrations of ≥ 1 x 105 TCID50/mL. The analytical specificity was 100%. Results are shown in Table 8-7. | Table 8-7 Analytical Specificity of the Xpert Xpress Flu Assay | | | | | | |----------------------------------------------------------------|--|--|--|--|--| |----------------------------------------------------------------|--|--|--|--|--| | | Concentration | Result | | |-----------------------------------------------|--------------------|----------------|----------------| | Organism | (per cartridge) | Influenza A | Influenza B | | No Template Control | N/A | NEG | NEG | | Adenovirus Type 1 | 1.12E+06 TCID50/mL | NEG | NEG | | Adenovirus Type 7 | 1.87E+05 TCID50/mL | NEG | NEG | | Human coronavirus OC43 | 2.85E+05 TCID50/mL | NEG | NEG | | Human coronavirus 229E | 1.00E+05 TCID50/mL | NEG | NEG | | Cytomegalovirus | 1.00E+05 TCID50/mL | NEG | NEG | | Echovirus | 3.31E+07 TCID50/mL | NEG | NEG | | Enterovirus | 3.55E+05 TCID50/mL | NEG | NEG | | Epstein Barr Virus | 7.16E+07 TCID50/mL | NEG | NEG | | HSV | 8.90E+05 TCID50/mL | NEG | NEG | | Measles | 6.31E+05 TCID50/mL | NEG | NEG | | Human metapneumovirus | 1.00E+05 TCID50/mL | NEG | NEG | | Mumps virus | 6.31E+06 TCID50/mL | NEG | NEG | | Human parainfluenza Type 1 | 1.15E+06 TCID50/mL | NEG | NEG | | Human parainfluenza Type 2 | 6.31E+05 TCID50/mL | NEG | NEG | | Human parainfluenza Type 3 | 3.55E+06 TCID50/mL | NEG | NEG | | Rhinovirus Type 1A | 1.26E+05 TCID50/mL | NEG | NEG | | Acinetobacter baumannii | 1.00E+06 CFU/mL | NEG | NEG | | Burkholderia cepacia | 3.30E+06 CFU/mL | NEG | NEG | | Candida albicans | 3.20E+06 CFU/mL | NEG | NEG | | Candida parapsilosis | 3.00E+06 CFU/mL | NEG | NEG | | Bordetella pertussis | 3.30E+06 CFU/mL | NEG | NEG | | Chlamydia pneumoniae | 1.00E+05 CFU/mL | NEG | NEG | | Citrobacter freundii | 3.30E+06 CFU/mL | NEG | NEG | | Corynebacterium sp. | 3.30E+06 CFU/mL | NEG | NEG | | Escherichia coli | 1.00E+07 CFU/mL | NEG | NEG | | Enterococcus faecalis | 1.30E+06 CFU/mL | NEG | NEG | | Hemophilus influenzae | 1.00E+06 CFU/mL | NEG | NEG | | Lactobacillus reuteri | 1.00E+06 CFU/mL | NEG | NEG | | Legionella spp. | 1.00E+06 CFU/mL | NEG | NEG | | Moraxella catarrhalis | 1.00E+07 CFU/mL | NEG | NEG | | Mycobacterium tuberculosis (avirulent) | 1.00E+06 CFU/mL | NEG | NEG | | Mycoplasma pneumoniae | 1.00E+06 CFU/mL | NEG | NEG | | Neisseria meningitides | 2.15E+06 CFU/mL | NEG | NEG | | Neisseria mucosa | 1.00E+07 CFU/mL | NEG | NEG | | Propionibacterium acnes | 2.40E+07 CFU/mL | NEG | NEG | | Pseudomonas aeruginosa | 3.70E+06 CFU/mL | NEG | NEG | | Staphylococcus aureus (protein A producer) | 2.20E+06 CFU/mL | NEG | NEG | | Staphylococcus epidermidis | 3.40E+06 CFU/mL | NEG | NEG | | Streptococcus agalactiae | 3.50E+06 CFU/mL | NEG | NEG | | Streptococcus pneumoniae | 1.00E+06 CFU/mL | NEG | NEG | | Streptococcus pyogen…