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

Q: Who is the manufacturer of 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 filed the 510(k) submission for 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 (K181289).

Q: What is the FDA product code for 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?

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 Dx Systems (GX-I, GX-II, GX-IV, GX-XVI), GeneXpert Infinity-48S System and GeneXpert Infinity-80 System?

510(k) clearance (submission type: Traditional).

Q: What are the predicate devices for 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?

Xpert® Flu/RSV XC Assay (K142045); Cepheid Xpert® Nasopharyngeal Sample Collection Kit for Viruses (K171552); Cepheid Xpert® Nasal Sample Collection Kit for Viruses (K171552).

Q: Who can help prepare an FDA 510(k) submission like 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?

Innolitics — a medical-device software consultancy — provides regulatory and engineering support for FDA 510(k) submissions. See https://innolitics.com/services/510ks/ or contact https://innolitics.com/contact.

K181289 · Cepheid · OCC · Aug 15, 2018 · Microbiology

Device Facts

Record ID	K181289
Device Name	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
Applicant	Cepheid
Product Code	OCC · Microbiology
Decision Date	Aug 15, 2018
Decision	SESE
Submission Type	Traditional
Regulation	21 CFR 866.3980
Device Class	Class 2

Intended Use

The Cepheid Xpert® Xpress Flu Assay, performed on the GeneXpert® Instrument Systems, is an automated, multiplex real-time, reverse transcriptase polymerase chain reaction (RT-PCR) assay intended for the in vitro qualitative detection and differentiation of influenza A and influenza B viral RNA. The Xpert Xpress Flu Assay uses nasopharyngeal (NP) swab 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 2015-2016 influenza season for NP swab specimens and the 2016-2017 influenza season for NS specimens. 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

Xpert Xpress Flu Assay is an automated, in vitro diagnostic test for qualitative detection/differentiation of influenza A and B viral RNA. Input: nasopharyngeal or nasal swab specimens collected in viral transport medium. Operation: specimen transferred to GeneXpert cartridge; GeneXpert Instrument System performs automated sample processing and real-time RT-PCR. Output: qualitative test results generated in ~30 minutes. Used in clinical laboratory settings; operated by laboratory personnel. Results aid clinicians in diagnosing influenza infections alongside clinical/epidemiological risk factors. Benefits: rapid, automated diagnosis to inform patient management decisions.

Clinical Evidence

Clinical study evaluated performance at 11-14 U.S. institutions using 2051 NP swabs and 1598 NS specimens. Combined NP swab PPA/NPA: 98.1%/98.8% (Flu A), 100%/99.1% (Flu B). NS specimen PPA/NPA: 98.9%/97.6% (Flu A), 98.4%/99.3% (Flu B). Comparator: FDA-cleared molecular assay. Study included fresh and frozen specimens.

Technological Characteristics

Multiplex real-time RT-PCR assay. Materials: medical-grade polypropylene cartridges. Sensing: fluorogenic target-specific hybridization. Energy: electrical (GeneXpert instrument). Connectivity: standalone/networked GeneXpert systems. Software: automated processing/analysis. Sterilization: N/A (reagents).

Indications for Use

Indicated for patients with signs and symptoms of respiratory infection to detect and differentiate influenza A and influenza B viral RNA from nasopharyngeal and nasal swab specimens. Intended as an aid in diagnosis in conjunction with clinical and epidemiological risk factors.

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 XC Assay (K142045)
Cepheid Xpert® Nasopharyngeal Sample Collection Kit for Viruses (K171552)
Cepheid Xpert® Nasal Sample Collection Kit for Viruses (K171552)

Reference Devices

Prodesse ProFlu+ Assay (K132129)
Lyra Influenza A+B Assay (K131728)

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
K171552 — Xpert Xpress Flu, Xpert Nasopharyngeal Sample Collection Kit, Xpert Nasal Sample Collection Kit, GeneXpert Xpress II, GeneXpert Xpress IV · Cepheid · Dec 19, 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
K120911 — XPERT FLU GENEXPERT DX SYSTEMS (GX-I, GX-IV) · Cepheid · May 18, 2012
K162331 — Xpert Xpress Flu/RSV, Xpert Nasopharyngeal Sample Collection Kit, GeneXpert Dx Systems (GX-I, GX-II, GX-IV, GX-XVI), GeneXpert Infinity-48 System and GeneXpert Infinity-48s System, GeneXpert Infinity-80 System · Cepheid · Feb 9, 2017

Submission Summary (Full Text)

{0}------------------------------------------------ # Indications for Use 510(k) Number (if known) Device Name Indications for Use (Describe) Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) #### CONTINUE ON A SEPARATE PAGE IF NEEDED. 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." {1}------------------------------------------------ #### 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 14, 2018 | | 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 virus. | | 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 XC Assay [510(k) #K142045] 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] | {2}------------------------------------------------ ### Device Description: The Xpert Xpress Flu Assay is a rapid, automated in vitro diagnostic test for qualitative detection and differentiation of influenza A (Flu A) and influenza B (Flu B) viral RNA directly from nasopharyngeal (NP) swab and nasal swab (NS) specimens. The assay is performed on the Cepheid GeneXpert® Instrument Systems. The Xpert Xpress Flu Assay includes reagents for the detection and differentiation of influenza A and influenza B 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 Instrument 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 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. {3}------------------------------------------------ #### Device Intended Use: The Cepheid Xpert® Xpress Flu Assay, performed on the GeneXpert® Instrument Systems, is an automated, multiplex real-time, reverse transcriptase polymerase chain reaction (RT-PCR) assay intended for the in vitro qualitative detection and differentiation of influenza A and influenza B viral RNA. The Xpert Xpress Flu Assay uses nasopharyngeal (NP) swab 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 2015-2016 influenza season for NP swab specimens and the 2016-2017 influenza season for NS specimens. 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 {4}------------------------------------------------ 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 Assay. #### Substantial Equivalence: The Xpert Xpress Flu Assay is substantially equivalent to the current Xpert® Flu/RSV XC Assay [510(k) #K142045]. The Xpert Xpress Flu Assay detects influenza A and influenza B from NP swab and NS specimens and the Xpert® Flu/RSV XC Assay detects influenza A, influenza B, and RSV from NP swab specimens and nasal aspirate/wash (NA/W) specimens. Both assays utilize the same technology by determining the presence of the target organisms through real-time RT-PCR amplification and fluorogenic target-specific hybridization detection. A multi-center clinical study was conducted and obtained data using the Xpert Xpress Flu/RSV Assay which was then reanalyzed with the Xpert Xpress Flu Assay Definition File (ADF). The reanalyzed data was used to determine the performance characteristics of the Xpert Xpress Flu Assay relative to the comparator Flu tests. Discordant results between the Xpert Xpress Flu Assay and the comparator methods Prodesse ProFlu+ Assay [510(k) #K132129] for NP swabs (FDA cleared for NP swabs) and Lyra Influenza A+B Assay [510(k) #K131728] for NS (FDA cleared for NP swabs and NS) were analyzed by bi-directional sequencing using primers different from those used in the Xpert Xpress Flu Assay. 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. {5}------------------------------------------------ | Similarities | | | |-----------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | | Device | Predicate | | Item | Cepheid Xpert® Xpress Flu | Cepheid Xpert® Flu/RSV XC 510(k)# K142045 | | Regulation | 866.3980 | Same | | Product Code | OCC, OOI | Same | | Device Class | II | Same | | Technology Principle of Operation | Multiplex real time RT-PCR | Same | | Intended Use | The Cepheid Xpert® Xpress Flu Assay, performed on the GeneXpert® Instrument Systems, is an automated, multiplex real-time, reverse transcriptase polymerase chain reaction (RT-PCR) assay intended for the in vitro qualitative detection and differentiation of influenza A and influenza B viral RNA. The Xpert Xpress Flu Assay uses nasopharyngeal (NP) swab 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. | The Cepheid Xpert® Flu/RSV XC Assay is an automated, multiplex real-time, reverse transcriptase polymerase chain reaction (RT-PCR) assay intended for the in vitro qualitative detection and differentiation of influenza A, influenza B, and respiratory syncytial virus (RSV) viral RNA. The Xpert Flu/RSV XC Assay uses nasopharyngeal swab and nasal aspirate/wash specimens collected from patients with signs and symptoms of respiratory infection. The Xpert Flu/RSV XC Assay is intended as an aid in the diagnosis of influenza and respiratory syncytial virus infections in conjunction with clinical and epidemiological risk factors. | | Similarities | | | | Item | Device | Predicate | | | Cepheid Xpert® Xpress Flu | Cepheid Xpert® Flu/RSV XC 510(k)# K142045 | | | Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions. | 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 2015- 2016 influenza season for NP swab specimens and the 2016- 2017 influenza season for NS specimens. When other novel influenza A viruses are emerging, performance characteristics may vary. | Performance characteristics for influenza A were established during the 2013-2014 influenza season. When other novel influenza A viruses are emerging, performance characteristics may vary. | | | If infection with a novel influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent influenza viruses and sent to state or local health departments for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens. | If infection with a novel influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent influenza viruses and sent to state or local health departments for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens. | # Table 8-1: Comparison of Similarities and Differences of the Xpert Xpress Flu Assay with the Predicate Devices {6}------------------------------------------------ {7}------------------------------------------------ | Similarities | | | | | |----------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--|--| | | Device | Predicate | | | | Item | Cepheid Xpert® Xpress Flu | Cepheid Xpert® Flu/RSV XC 510(k)# K142045 | | | | 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 Instrumentation System | Same | | | | Assay Results | Qualitative | Same | | | | Instrument System | Cepheid GeneXpert Instrument Systems; same Cepheid I-core technology | Same | | | | Primers and probes | Primers and probes to detect the presence of nucleic acid sequences of influenza A, influenza B, and RSV. Only results for influenza A and influenza B are reported. | Primers and probes to detect the presence of influenza A, influenza A subtype H7N9, influenza B and RSV. Results for influenza A, influenza B and RSV analytes are reported. | | | | Laboratory Users | Laboratory users in moderate and high complexity laboratory settings. | Same | | | | Sample Preparation | Self-contained and automated after mixed specimen is added to cartridge. All other reagents are contained in the cartridge. | Same | | | {8}------------------------------------------------ | Similarities | | | |----------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Item | Device | Predicate | | Primers and probes for influenza A, influenza B | Primers and probes to detect the presence of nucleic acid sequences of influenza A, influenza B, and RSV A/B. The Xpert Xpress Flu Assay contains primers and probes to detect additional RNA segments in order to protect the assay sensitivity and specificity from mutations in the influenza genome due to antigenic drifts and shifts. Only results for influenza A and influenza B are reported. | Primers and probes to detect the presence of nucleic acid sequences of influenza A, influenza B, and RSV A/B. The Xpert Flu/RSV XC Assay contains primers and probes to detect additional RNA segments in order to protect the assay sensitivity and specificity from mutations in the influenza genome due to antigenic drifts and shifts. | | Target Sequences | Influenza A: Matrix protein (MP),basic polymerase (PB2) and acidic protein (PA) Influenza B: Matrix protein (MP) and Non-structural proteins (NS 1 and NS 2) RSV A and RSV B: Nucleocapsid protein Only results for influenza A and influenza B are reported. | Influenza A: Matrix protein (MP),basic polymerase (PB2) and acidic protein (PA) Influenza B: Matrix protein (MP) and Non-structural proteins (NS 1 and NS 2) RSV A and RSV B: Nucleocapsid protein | | Internal Controls | Sample processing control (SPC) and probe check control (PCC). | Same | | Early assay termination function | Yes | Yes | | | Cepheid Xpert® Xpress Flu | Cepheid Xpert® Flu/RSV XC 510(k)# K142045 | | Differences | | | | | Device | Predicate | | Item | Cepheid Xpert® Xpress Flu | Cepheid Xpert® Flu/RSV XC 510(k)# K142045 | | Assay Targets | Influenza A Virus and Influenza B Virus | Influenza A Virus, Influenza B Virus, and RSV viral RNA | | Specimen Types | Nasopharyngeal (NP) swab and nasal swab (NS) specimens | Nasal aspirate/wash (NA/W) specimens and 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 or less for sample preparation and RT-PCR | | Combinatorial Assay Selections | Not applicable | Yes, user may select combined assay with all targets or a Flu only assay or a RSV only assay. | {9}------------------------------------------------ {10}------------------------------------------------ The Xpert Xpress Flu Assay and the predicate device have the same general intended use and technological characteristics, and both detect influenza Aand influenza B viral RNA from NP swab specimens. The clinical study demonstrates that the Xpert Xpress Flu 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 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 are shown in Table 8-3. There is no difference between the Nasal Sample Collection Kit for Viruses cleared in 510(k) # K171552 and this 510(k). {11}------------------------------------------------ | 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 | # Table 8-2: Comparison of Similarities of the Xpert Nasopharyngeal Sample Collection Kit with the Predicate Device {12}------------------------------------------------ | 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 | {13}------------------------------------------------ | 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 Assay. | Same | | Single-use Device | Yes | Same | | 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 | | Similarities | | | | Item | Device | Predicate | | Product Configuration | Xpert® Nasal Sample Collection Kit for Viruses Medium Tube in Kit with individually-wrapped sterile swab. | Xpert® Nasal Sample Collection Kit for Viruses 510(k)# K171552 | | Swab | Nylon flocked | Same | # Table 8-3: Comparison of Similarities and Differences of the Xpert Nasal Sample Collection Kit for Viruses with the Predicate Device {14}------------------------------------------------ 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 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) 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 {15}------------------------------------------------ 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 Table 8-4 through Table 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 (TCID50/mL): Influenza A 2009 H1N1 Table 8-5: Confirmed LoD (TCID50/mL): Influenza A H3N2 | 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 | |--|---------------------------------------------------| |--|---------------------------------------------------| | 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 | {16}------------------------------------------------ # Analytical Specificity (Exclusivity) The analytical specificity of the Xpert Xpress Flu Assay was evaluated by testing a panel of 44 cultures consisting of 16 viral, 26 bacterial, and two yeast strains representing common respiratory pathogens or those potentially encountered in the 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. {17}------------------------------------------------ | | | Result | | |-----------------------------------------------|----------------------------------|----------------|----------------| | Organism | Concentration (per cartridge) | Influenza A | Influenza B | | No Template Control | N/A | NEG | NEG | | Adenovirus Type 1 | 1.12E+06 TCID50/mL | NEG | NEG | | Adenovirus Type 7 | 1.87E+05 TCID50/mL | NEG | NEG | | Human coronavirus OC43 | 2.85E+05 TCID50/mL | NEG | NEG | | Human coronavirus 229E | 1.00E+05 TCID50/mL | NEG | NEG | | Cytomegalovirus | 1.00E+05 TCID50/mL | NEG | NEG | | Echovirus | 3.31E+07 TCID50/mL | NEG | NEG | | Enterovirus | 3.55E+05 TCID50/mL | NEG | NEG | | Epstein Barr Virus | 7.16E+07 TCID50/mL | NEG | NEG | | HSV | 8.90E+05 TCID50/mL | NEG | NEG | | Measles | 6.31E+05 TCID50/mL | NEG | NEG | | Human metapneumovirus | 1.00E+05 TCID50/mL | NEG | NEG | | Mumps virus | 6.31E+06 TCID50/mL | NEG | NEG | | Human parainfluenza Type 1 | 1.15E+06 TCID50/mL | NEG | NEG | | Human parainfluenza Type 2 | 6.31E+05 TCID50/mL | NEG | NEG | | Human parainfluenza Type 3 | 3.55E+06 TCID50/mL | NEG | NEG | | Rhinovirus Type 1A | 1.26E+05 TCID50/mL | NEG | NEG | | Acinetobacter baumannii | 1.00E+06 CFU/mL | NEG | NEG | | Burkholderia cepacia | 3.30E+06 CFU/mL | NEG | NEG | | Candida albicans | 3.20E+06 CFU/mL | NEG | NEG | | Candida parapsilosis | 3.00E+06 CFU/mL | NEG | NEG | | Bordetella pertussis | 3.30E+06 CFU/mL | NEG | NEG | | Chlamydia pneumoniae | 1.00E+05 CFU/mL | NEG | NEG | | Citrobacter freundii | 3.30E+06 CFU/mL | NEG | NEG | | Corynebacterium sp. | 3.30E+06 CFU/mL | NEG | NEG | | Escherichia coli | 1.00E+07 CFU/mL | NEG | NEG | | Enterococcus faecalis | 1.30E+06 CFU/mL | NEG | NEG | | 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 | | Organism | Concentration (per cartridge) | Result | | | | | Influenza A | Influenza B | | Mycobacterium tuberculosis (avirulent) | 1.00E+06 CFU/mL | NEG | NEG | | Mycoplasma pneumoniae | 1.00E+06 CFU/mL | NEG | NEG | | Neisseria 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 | | Staphyloccus haemolyticus | 4.00E+06 CFU/mL | NEG | NEG | | Streptococcus agalactiae | 3.50E+06 CFU/mL | NEG | NEG | | Streptococcus pneumoniae | 1.00E+06 CFU/mL | NEG | NEG | | Streptococcus pyogenes | 1.00E+07 CFU/mL | NEG | NEG | | Streptococcus salivarius | 1.00E+07 CFU/mL | NEG | NEG | | Streptococcus sanguinis | 3.10E+06 CFU/mL | NEG | NEG | # Table 8-7: Analytical Specificity of the Xpert Xpress Flu/RSV Assay {18}------------------------------------------------ {19}------------------------------------------------ # Analytical Reactivity (Inclusivity) The analytica…