Xpert Respiratory Panel
Device Facts
| Record ID | K261336 |
|---|---|
| Device Name | Xpert Respiratory Panel |
| Applicant | Cepheid |
| Product Code | QOF · Microbiology |
| Decision Date | Sep 25, 2026 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 866.3981 |
| Device Class | Class 2 |
Regulatory Classification
Identification
A device to detect and identify nucleic acid targets in respiratory specimens from microbial agents that cause the SARS-CoV-2 respiratory infection and other microbial agents when in a multi-target test is an in vitro diagnostic device intended for the detection and identification of SARS-CoV-2 and other microbial agents when in a multi-target test in human clinical respiratory specimens from patients suspected of respiratory infection who are at risk for exposure or who may have been exposed to these agents. The device is intended to aid in the diagnosis of respiratory infection in conjunction with other clinical, epidemiologic, and laboratory data or other risk factors.
Special Controls
*Classification.* Class II (special controls). The special controls for this device are:(1) The intended use in the labeling required under § 809.10 of this chapter must include a description of the following: Analytes and targets the device detects and identifies, the specimen types tested, the results provided to the user, the clinical indications for which the test is to be used, the specific intended population(s), the intended use locations including testing location(s) where the device is to be used (if applicable), and other conditions of use as appropriate. (2) Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of specimen types claimed by this device; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device. (3) The labeling required under § 809.10(b) of this chapter must include: (i) A detailed device description, including reagents, instruments, ancillary materials, all control elements, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens; (ii) Detailed descriptions of the performance characteristics of the device for each specimen type claimed in the intended use based on analytical studies including the following, as applicable: Limit of Detection, inclusivity, cross-reactivity, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, precision, reproducibility, and clinical studies; (iii) Detailed descriptions of the test procedure(s), the interpretation of test results for clinical specimens, and acceptance criteria for any quality control testing; (iv) A warning statement that viral culture should not be attempted in cases of positive results for SARS-CoV-2 and/or any similar microbial agents unless a facility with an appropriate level of laboratory biosafety ( *e.g.,* BSL 3 and BSL 3+, etc.) is available to receive and culture specimens; and(v) A prominent statement that device performance has not been established for specimens collected from individuals not identified in the intended use population ( *e.g.,* when applicable, that device performance has not been established in individuals without signs or symptoms of respiratory infection).(vi) Limiting statements that indicate that: (A) A negative test result does not preclude the possibility of infection; (B) The test results should be interpreted in conjunction with other clinical and laboratory data available to the clinician; (C) There is a risk of incorrect results due to the presence of nucleic acid sequence variants in the targeted pathogens; (D) That positive and negative predictive values are highly dependent on prevalence; (E) Accurate results are dependent on adequate specimen collection, transport, storage, and processing. Failure to observe proper procedures in any one of these steps can lead to incorrect results; and (F) When applicable ( *e.g.,* recommended by the Centers for Disease Control and Prevention, by current well-accepted clinical guidelines, or by published peer-reviewed literature), that the clinical performance may be affected by testing a specific clinical subpopulation or for a specific claimed specimen type.(4) Design verification and validation must include: (i) Detailed documentation, including performance results, from a clinical study that includes prospective (sequential) samples for each claimed specimen type and, as appropriate, additional characterized clinical samples. The clinical study must be performed on a study population consistent with the intended use population and compare the device performance to results obtained using a comparator that FDA has determined is appropriate. Detailed documentation must include the clinical study protocol (including a predefined statistical analysis plan), study report, testing results, and results of all statistical analyses. (ii) Risk analysis and documentation demonstrating how risk control measures are implemented to address device system hazards, such as Failure Modes Effects Analysis and/or Hazard Analysis. This documentation must include a detailed description of a protocol (including all procedures and methods) for the continuous monitoring, identification, and handling of genetic mutations and/or novel respiratory pathogen isolates or strains ( *e.g.,* regular review of published literature and periodic in silico analysis of target sequences to detect possible mismatches). All results of this protocol, including any findings, must be documented and must include any additional data analysis that is requested by FDA in response to any performance concerns identified under this section or identified by FDA during routine evaluation. Additionally, if requested by FDA, these evaluations must be submitted to FDA for FDA review within 48 hours of the request. Results that are reasonably interpreted to support the conclusion that novel respiratory pathogen strains or isolates impact the stated expected performance of the device must be sent to FDA immediately.(iii) A detailed description of the identity, phylogenetic relationship, and other recognized characterization of the respiratory pathogen(s) that the device is designed to detect. In addition, detailed documentation describing how to interpret the device results and other measures that might be needed for a laboratory diagnosis of respiratory infection. (iv) A detailed device description, including device components, ancillary reagents required but not provided, and a detailed explanation of the methodology, including molecular target(s) for each analyte, design of target detection reagents, rationale for target selection, limiting factors of the device ( *e.g.,* saturation level of hybridization and maximum amplification and detection cycle number, etc.), internal and external controls, and computational path from collected raw data to reported result (*e.g.,* how collected raw signals are converted into a reported signal and result), as applicable.(v) A detailed description of device software, including software applications and hardware-based devices that incorporate software. The detailed description must include documentation of verification, validation, and hazard analysis and risk assessment activities, including an assessment of the impact of threats and vulnerabilities on device functionality and end users/patients as part of cybersecurity review. (vi) For devices intended for the detection and identification of microbial agents for which an FDA recommended reference panel is available, design verification and validation must include the performance results of an analytical study testing the FDA recommended reference panel of characterized samples. Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses. (vii) For devices with an intended use that includes detection of Influenza A and Influenza B viruses and/or detection and differentiation between the Influenza A virus subtypes in human clinical specimens, the design verification and validation must include a detailed description of the identity, phylogenetic relationship, or other recognized characterization of the Influenza A and B viruses that the device is designed to detect, a description of how the device results might be used in a diagnostic algorithm and other measures that might be needed for a laboratory identification of Influenza A or B virus and of specific Influenza A virus subtypes, and a description of the clinical and epidemiological parameters that are relevant to a patient case diagnosis of Influenza A or B and of specific Influenza A virus subtypes. An evaluation of the device compared to a currently appropriate and FDA accepted comparator method. Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses. (5) When applicable, performance results of the analytical study testing the FDA recommended reference panel described in paragraph (b)(4)(vi) of this section must be included in the device's labeling under § 809.10(b) of this chapter. (6) For devices with an intended use that includes detection of Influenza A and Influenza B viruses and/or detection and differentiation between the Influenza A virus subtypes in human clinical specimens in addition to detection of SARS-CoV-2 and similar microbial agents, the required labeling under § 809.10(b) of this chapter must include the following: (i) Where applicable, a limiting statement that performance characteristics for Influenza A were established when Influenza A/H3 and A/H1-2009 (or other pertinent Influenza A subtypes) were the predominant Influenza A viruses in circulation. (ii) Where applicable, a warning statement that reads 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. (iii) Where the device results interpretation involves combining the outputs of several targets to get the final results, such as a device that both detects Influenza A and differentiates all known Influenza A subtypes that are currently circulating, the device's labeling must include a clear interpretation instruction for all valid and invalid output combinations, and recommendations for any required followup actions or retesting in the case of an unusual or unexpected device result. (iv) A limiting statement that if a specimen yields a positive result for Influenza A, but produces negative test results for all specific influenza A subtypes intended to be differentiated ( *i.e.,* H1-2009 and H3), this result requires notification of appropriate local, State, or Federal public health authorities to determine necessary measures for verification and to further determine whether the specimen represents a novel strain of Influenza A.(7) If one of the actions listed at section 564(b)(1)(A) through (D) of the Federal Food, Drug, and Cosmetic Act occurs with respect to an influenza viral strain, or if the Secretary of Health and Human Services determines, under section 319(a) of the Public Health Service Act, that a disease or disorder presents a public health emergency, or that a public health emergency otherwise exists, with respect to an influenza viral strain: (i) Within 30 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation, the manufacturer must have testing performed on the device with those influenza viral samples in accordance with a standardized protocol considered and determined by FDA to be acceptable and appropriate. (ii) Within 60 days from the date that FDA notifies manufacturers that characterized influenza viral samples are available for test evaluation and continuing until 3 years from that date, the results of the influenza emergency analytical reactivity testing, including the detailed information for the virus tested as described in the certificate of authentication, must be included as part of the device's labeling in a tabular format, either by: (A) Placing the results directly in the device's labeling required under § 809.10(b) of this chapter that accompanies the device in a separate section of the labeling where analytical reactivity testing data can be found, but separate from the annual analytical reactivity testing results; or (B) In a section of the device's label or in other labeling that accompanies the device, prominently providing a hyperlink to the manufacturer's public website where the analytical reactivity testing data can be found. The manufacturer's website, as well as the primary part of the manufacturer's website that discusses the device, must provide a prominently placed hyperlink to the website containing this information and must allow unrestricted viewing access.
Submission Summary (Full Text)
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[LOGO]
FDA
U.S. FOOD & DRUG
ADMINISTRATION
# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
## DECISION SUMMARY
ASSAY AND INSTRUMENT
### I Background Information:
#### A 510(k) Number
K261336
#### B Applicant
Cepheid
#### C Proprietary and Established Names
Xpert Respiratory Panel
#### D Regulatory Information
| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| QOF | Class II | 21 CFR 866.3981 - Device To Detect And Identify Nucleic Acid Targets In Respiratory Specimens From Microbial Agents That Cause The Sars-Cov-2 Respiratory Infection And Other Microbial Agents When In A Multi-Target Test | MI - Microbiology |
### II Submission/Device Overview:
#### A Purpose for Submission:
To demonstrate that the Xpert Respiratory Panel is substantially equivalent to the QIAstat-Dx Respiratory Panel Plus (K233100) on the GeneXpert Instrument Systems and to obtain clearance for the Xpert Respiratory Panel.
#### B Measurand:
The Xpert Respiratory Panel detects and identifies nucleic acids from the following pathogens:
Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
www.fda.gov
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- Adenovirus (A-E)
- Coronavirus (HKU1, NL63, 229E, OC43)
- Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
- Human Metapneumovirus
- Rhinovirus/Enterovirus
- Parainfluenza (1-4)
- Influenza A
- Influenza B
- Respiratory Syncytial Virus (A and B)
- Bordetella pertussis
- Bordetella parapertussis
- Mycoplasma pneumoniae
- Chlamydia pneumoniae
### C Type of Test:
Qualitative reverse transcriptase polymerase chain reaction (RT-PCR) and polymerase chain reaction (PCR)
### III Intended Use/Indications for Use:
#### A Intended Use(s):
See Indications for Use below.
#### B Indication(s) for Use:
The Xpert Respiratory Panel test, performed on the GeneXpert Instrument Systems, is a qualitative multiplexed in vitro diagnostic test for the simultaneous detection and identification of DNA and RNA from multiple bacteria and/or viruses in nasopharyngeal swab (NPS) specimens obtained from individuals with clinical signs and symptoms of respiratory tract infection.
The following organism types and subtypes are detected and identified using the Xpert Respiratory Panel test:
- Adenovirus (A-E)
- Coronavirus (HKU1, NL63, 229E, OC43)
- SARS-CoV-2
- Human Metapneumovirus
- Rhinovirus/Enterovirus
- Parainfluenza (1-4)
- Influenza A
- Influenza B
- Respiratory Syncytial Virus (A and B)
- Bordetella pertussis
- Bordetella parapertussis
- Mycoplasma pneumoniae
- Chlamydia pneumoniae
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Nucleic acids from viral and bacterial organisms identified by this test are generally detectable in NPS specimens during the acute phase of infection. Detecting and identifying specific viral and bacterial nucleic acids from individuals presenting with signs and symptoms of a respiratory infection aids in the diagnosis of respiratory infection, if used in conjunction with other clinical, epidemiological and laboratory findings. The results of this test should not be used as the sole basis for diagnosis, treatment or other patient management decisions.
Negative results in the presence of a respiratory illness may be due to infection with pathogens that are not detected by the test, or due to lower respiratory tract infection that is not detected by a NPS specimen.
Conversely, positive results are indicative of the presence of the identified microorganism, but do not rule out co-infection with other pathogens not detected by the Xpert Respiratory Panel. The agent(s) detected by the Xpert Respiratory Panel may not be the definite cause of disease.
The use of additional laboratory testing (e.g., bacterial and viral culture, immunofluorescence, and radiography) may be necessary when evaluating a patient with possible respiratory tract infection.
### C Special Conditions for Use Statement(s):
Rx – For Prescription Use Only
For In Vitro Diagnostic Use Only
### D Special Instrument Requirements:
For use with the GeneXpert Instrument Systems (GeneXpert Dx System, GeneXpert Infinity System and GeneXpert System with Touchscreen), equipped with GeneXpert 10-color modules running Dx software version 6.6 and higher, Xpertise software version 7.2 or higher, and Cepheid OS software 2.3 or higher, respectively
### IV Device/System Characteristics:
### A Device Description:
The Xpert Respiratory Panel test is performed on GeneXpert Instrument Systems (GeneXpert Dx System, GeneXpert Infinity System and GeneXpert System with Touchscreen), equipped with GeneXpert 10-color modules running Dx software version 6.6 and higher, Xpertise software version 7.2 or higher, and Cepheid OS software 2.3 or higher, respectively.
The GeneXpert Instrument Systems automate and integrate sample preparation, nucleic acid extraction and amplification, and detection of multiple bacterial/viral target sequences in simple or complex samples using real-time reverse transcription (RT)-polymerase chain reaction (PCR) for RNA targets and PCR for DNA targets. Depending on the instrument, the GeneXpert Instrument Systems can have from 1 and up to 80 randomly accessible modules, each capable of performing separate sample preparation and real-time RT-PCR and PCR tests. Each module
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contains a syringe drive for dispensing fluids (i.e., the syringe drive activates the plunger that works in concert with the rotary valve in the cartridge to move fluids between chambers), an ultrasonic horn for lysing cells or spores, and a proprietary I-CORE thermocycler for performing real-time RT-PCR and PCR as well as detection. The systems require the use of single-use disposable cartridges that hold the RT-PCR reagents and host sample purification, nucleic acid amplification, and detection of the target sequences. Because the cartridges are self-contained, cross-contamination between samples is minimized.
The Xpert Respiratory Panel test includes reagents for the detection of DNA and RNA from Adenovirus, Coronavirus, SARS-CoV-2, Human Metapneumovirus, Rhinovirus/Enterovirus, Parainfluenza, Influenza A, Influenza B, RSV, Bordetella pertussis, Bordetella parapertussis, Chlamydia pneumoniae and Mycoplasma pneumoniae from nasopharyngeal swab (NPS) specimens. The primers and probes in the Xpert Respiratory Panel test are designed to amplify and detect unique genetic sequences for each on-panel analyte.
# B Principle of Operation:
The Xpert Respiratory Panel test, performed on Cepheid GeneXpert Instrument Systems, is an automated in vitro diagnostic test for qualitative detection and differentiation of multiple bacteria and/or viruses in nasopharyngeal swab (NPS) specimens collected from individuals suspected of having respiratory tract infection (RTI).
# C Instrument Description Information:
# 1. Instrument Name:
GeneXpert Instrument Systems (GeneXpert Dx System, GeneXpert Infinity System and GeneXpert System with Touchscreen), equipped with GeneXpert 10-color modules running Dx software version 6.6 and higher, Xpertise software version 7.2 or higher, and Cepheid OS software 2.3 or higher, respectively.
# 2. Specimen Sampling and Handling:
The ancillary specimen collection kits, swabs and transport media validated for use with the Xpert Respiratory Panel test included:
# Nasopharyngeal Sample Collection Kit
- Copan UTM 3C057N (Flexible Minitip Flocked Swab with UTM Medium)
- Copan eNAT Molecular Collection and Preservation Medium P/N 6U074S01
- BD™ Becton Dickinson Specimen Collection and Transport System P/N 220531 (Flexible Minitip Flocked Swab with UVT Medium)
Alternatively, swabs and transport media can be obtained separately:
- Nylon flocked swab (Copan P/N 503CS01)
- Viral transport medium (Copan P/N 3C047N, Remel MicroTest M4RT, M5 and M6 Transport Medium, PrimeStore Molecular Transport Medium)
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# 3. Calibration:
Not applicable.
# 4. Quality Control:
Internal Controls
The assay uses Sample Processing Control (SPC) to control for adequate processing of the sample and to monitor for the presence of potential inhibitor(s) in the RT-PCR reaction. The SPC also ensures that the RT-PCR reaction conditions (temperature and time) are appropriate for the amplification reaction and that the RT-PCR reagents are functional. In addition, SPC also functions as a control for the melt curve analysis. The assay uses a Probe Check Control (PCC) to verify reagent rehydration, PCR tube filling, and confirms that all reaction components are present in the cartridge including monitoring for probe integrity and dye stability.
External Controls
External controls are not provided with the Xpert Respiratory Panel. External controls in the form of inactivated bacteria and viruses are available from ZeptoMetrix (Buffalo, NY) for optional use with the Xpert Respiratory Panel test.
- External Positive Control – NATtrol Respiratory Positive Control; Cat # NATRSPPOS-8C-IVD
- External Negative Control – NATtrol Respiratory Negative Control; Cat # NATRSPNEG-8C-IVD
The following information on external control testing is included in the Instructions for Use, "Quality control requirements must be performed in conformance with local, state, and/or federal regulations or accreditation requirements and your laboratory's standard quality control procedures."
# V Substantial Equivalence Information:
# A Predicate Device Name(s):
QIAstat-Dx Respiratory Panel Plus
# B Predicate 510(k) Number(s):
K233100
# C Comparison with Predicate(s):
| Device & Predicate Device(s): | K261336 | K233100 |
| --- | --- | --- |
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| Device Trade Name | Xpert Respiratory Panel | QIAstat-Dx Respiratory Panel Plus |
| --- | --- | --- |
| General Device Characteristic Similarities | | |
| Technology/Detection | Qualitative multiplex reverse transcription polymerase chain reaction (RT-PCR) with both amplification and melt detected targets | Nucleic acid extraction, nucleic acid amplification, and detection of amplified targets that use an increase in fluorescence to generate the assay results |
| Intended Use / Indications for Use | The Xpert Respiratory Panel test, performed on the GeneXpert Instrument Systems, is a qualitative multiplexed in vitro diagnostic test for the simultaneous detection and identification of DNA and RNA from multiple bacteria and/or viruses in nasopharyngeal swab (NPS) specimens obtained from individuals with clinical signs and symptoms of respiratory tract infection. The following organism types and subtypes are detected and identified using the Xpert Respiratory Panel test: - Adenovirus (A-E) - Coronavirus (HKU1, NL63, 229E, OC43) - SARS-CoV-2 - Human Metapneumovirus - Rhinovirus/Enterovirus - Parainfluenza (1-4) | The QIAstat-Dx Respiratory Panel Plus is a multiplexed nucleic acid test intended for use with the QIAstat-Dx system for the simultaneous in vitro qualitative detection and identification of multiple respiratory viral and bacterial nucleic acids in nasopharyngeal swabs (NPS) obtained from individuals with clinical signs and symptoms of respiratory tract infection, including SARS-CoV-2. The following organism types and subtypes are identified using the QIAstat-Dx Respiratory Panel Plus: - Adenovirus, Human Coronavirus 229E, Human Coronavirus HKU1, Human Coronavirus NL63, |
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| | - Influenza A - Influenza B - Respiratory Syncytial Virus (A and B) - *Bordetella pertussis* - *Bordetella parapertussis* - *Mycoplasma pneumoniae* - *Chlamydia pneumoniae*Nucleic acids from viral and bacterial organisms identified by this test are generally detectable in NPS specimens during the acute phase of infection. Detecting and identifying specific viral and bacterial nucleic acids from individuals presenting with signs and symptoms of a respiratory infection aids in the diagnosis of respiratory infection, if used in conjunction with other clinical, epidemiological and laboratory findings. The results of this test should not be used as the sole basis for diagnosis, treatment or other patient management decisions.Negative results in the presence of a respiratory illness may be due to infection with pathogens that are not detected by the test, or due to lower respiratory | Human Coronavirus OC43, Human Metapneumovirus, Influenza A, Influenza A H1, Influenza A H1N1 pdm09, Influenza A H3, Influenza B, Parainfluenza virus 1, Parainfluenza virus 2, Parainfluenza virus 3, Parainfluenza virus 4, Respiratory Syncytial Virus, Human Rhinovirus/Enterovirus (not differentiated), Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), *Bordetella pertussis*, *Chlamydophila pneumoniae* *Mycoplasma pneumoniae*Nucleic acids from viral and bacterial organisms identified by this test are generally detectable in NPS specimens during the acute phase of infection. Detecting and identifying specific viral and bacterial nucleic acids from |
| --- | --- | --- |
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| | tract infection that is not detected by a NPS specimen. Conversely, positive results are indicative of the presence of the identified microorganism, but do not rule out co-infection with other pathogens not detected by the Xpert Respiratory Panel. The agent(s) detected by the Xpert Respiratory Panel may not be the definite cause of disease. The use of additional laboratory testing (e.g., bacterial and viral culture, immunofluorescence, and radiography) may be necessary when evaluating a patient with possible respiratory tract infection. | individuals presenting with signs and symptoms of a respiratory infection aids in the diagnosis of respiratory infection, if used in conjunction with other clinical, epidemiological and laboratory findings. The results of this test should not be used as the sole basis for diagnosis, treatment or other patient management decisions. Negative results in the presence of a respiratory illness may be due to infection with pathogens that are not detected by the test or due to lower respiratory tract infection that is not detected by a NPS specimen. Conversely, positive results are indicative of the presence of the identified microorganism, but do not rule out co-infection with other pathogens not detected by the QIAstat-Dx Respiratory Panel Plus. The agent(s) detected by the QIAstat-Dx Respiratory Panel Plus may not be the definite cause of disease. The use of additional |
| --- | --- | --- |
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| | | laboratory testing (e.g., bacterial and viral culture, immunofluorescence and radiography) may be necessary when evaluating a patient with possible respiratory tract infection. |
| --- | --- | --- |
| Intended User / Environment | The Xpert Respiratory Panel test is intended to be performed by laboratory and healthcare professionals trained on the use of the test. This test is for use in a laboratory environment. | The QIAstat-Dx Respiratory Panel Plus is to be used by laboratory professionals trained in the use of the QIAstat-Dx Analyzer 1.0, QIAstat-Dx Analyzer 2.0, or QIAstat-Dx Rise. |
| Specimen Type | Same | Nasopharyngeal swab (NPS) |
| Transport Media | • Universal Transport Medium (UTM)/ Viral Transport Medium (VTM) • eNAT | Universal Transport Medium (UTM) |
| Test Automation | Same | Automated Nucleic Acid Extraction, Detection and Results Interpretation |
| Test Format | Same | Single Use |
| Internal Controls | • Sample Processing Control (SPC) • Probe Check Control (PCC) | Titered MS2 bacteriophage that provides verification that all steps of the analysis process |
| Assay Targets | • Adenovirus (A-E) • Coronavirus (HKU1, NL63, 229E, OC43) • SARS-CoV-2 • Human Metapneumovirus • Rhinovirus/Enterovirus • Parainfluenza (1-4) | • Adenovirus • Human Coronavirus 229E, Human Coronavirus HKU1, Human Coronavirus NL63, Human Coronavirus OC43, • Human Metapneumovirus • Influenza A |
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| | - Influenza A - Influenza B - Respiratory Syncytial Virus (A and B) - *Bordetella pertussis* - *Bordetella parapertussis* - *Mycoplasma pneumoniae* - *Chlamydia pneumoniae* | - Influenza A H1 - Influenza A H1N1 pdm09 - Influenza A H3 - Influenza B - Parainfluenza virus 1, Parainfluenza virus 2, Parainfluenza virus 3, Parainfluenza virus 4, - Respiratory Syncytial Virus, - Human Rhinovirus/Enterovirus (not differentiated) - Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) - *Bordetella pertussis* - *Chlamydophila pneumoniae**Mycoplasma pneumoniae* |
| --- | --- | --- |
| **Assay Results** | Same | Qualitative |
| **Test Access** | Same | Prescription Use Only |
| **Time to Result** | ~56 minutes | ~60 minutes |
| **Instrument Systems** | GeneXpert Instrument Systems: - GeneXpert Dx System - GeneXpert Infinity Systems (48s and 80)GeneXpert System with Touchscreen | - QIAstat-Dx Analyzer 1.0 - QIAstat-Dx Analyzer 2.0 - QIAstat-Dx Rise |
| **Systems Software for Instrument Family** | - GeneXpert Dx software version 6.6 or higher - GeneXpert Xpertise software 7.2 or higher | - For QIAstat-Dx Analyzer 1.0, use software version 1.4 or 1.5 - For QIAstat-Dx Analyzer 2.0, use |
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| | Cepheid OS software version 2.3 or higher | software version 1.6 or later For QIAstat-Dx Rise, use software version 2.4 or later |
| --- | --- | --- |
#### **D Standards/Guidance Documents Referenced:**
- • 21 CFR 866.3981 – Device to detect and identify nucleic acid targets in respiratory specimens from microbial agents that cause the SARS-CoV-2 respiratory infection and other microbial agents when in a multi-target test.
- • FDA Class II Special Controls Guidance: Respiratory Viral Panel Multiplex Nucleic Acid Assay – Class II Special Controls Guidance for Industry and FDA Staff (DEN200031).
- • ANSI/AAMI/ISO 14971:2019. Medical devices – Application of risk management to medical devices. (FDA Recognized Standard 5-125)
- • CLSI EP12-A2. User Protocol for Evaluation of Qualitative Test Performance; Approved Guideline – Second Edition. (FDA Recognized Standard 7-152)
- • CLSI EP17-A2. Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline – Second Edition. (FDA Recognized Standard 7-233)
- • CLSI EP24-A2. Assessment of the Diagnostic Accuracy of Laboratory Tests Using Receiver Operating Characteristic Curves; Approved Guideline – Second Edition. (FDA Recognized Standard 7-234)
- • CLSI EP25-A. Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline. (FDA Recognized Standard 7-235)
- • CLSI EP05-A3. Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition. (Reaffirmed: September 2019) (FDA Recognized Standard 7-251)
- • CLSI MM03, 3rd Edition. Molecular Diagnostic Methods for Infectious Diseases; Approved Guideline. (FDA Recognized Standard 7-260)
- • CLSI EP07, 3rd Edition. Interference Testing in Clinical Chemistry. (FDA Recognized Standard 7-275)
- • CLSI MM17, 2nd Edition. Verification and Validation of Multiplex Nucleic Acid Assays. (FDA Recognized Standard 7-289)
- • CLSI MM13, 2nd Edition. Collection Transport Preparation and Storage of Specimens for Molecular Methods. (FDA Recognized Standard 7-300)
- • ANSI/AAMI IEC 62304:2006/A1:2016. Medical device software – Software life cycle processes [Including Amendment 1 (2016)]. (FDA Recognized Standard 13-79)
- • ANSI/AAMI IEC 60601-1-2:2014 [Including AMD 1:2021]. Medical electrical equipment Part 1-2: General requirements for basic safety and essential performance – Collateral Standard: Electromagnetic disturbances – Requirements and tests. (FDA Recognized Standard 19-36)
- • IEC 61326-1, Edition 3.0 2020-10. Electrical equipment for measurement, control and laboratory use – EMC requirements – Part 1: General requirements. (FDA Recognized Standard 19-42)
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- IEC 61326-2-6, Edition 3.0 2020-10. Electrical equipment for measurement, control and laboratory use – EMC requirements – Part 2-6: Particular requirements – In vitro diagnostic (IVD) medical equipment. (FDA Recognized Standard 19-43)
# VI Performance Characteristics (if/when applicable):
# A Analytical Performance:
# 1. Precision/Reproducibility:
# Reproducibility
The reproducibility of the Xpert Respiratory Panel test was established at 3 sites (1 internal, 2 external) using 7-member panels, each panel includes 1 negative sample, 3 low positive and 3 moderate positive samples. Collectively, the 3 positive panel members at each level included one strain per on-panel analyte for a total of 14 analytes detected by the Xpert Respiratory Panel. Positive panel members consisted of 5 – 6 different analytes, contrived in simulated NPS matrix to a low (~1x LoD) or moderate (~3x LoD) level. The negative sample consisted of simulated NPS matrix only. Testing was performed across 6 non-consecutive days, using 3 lots of cartridges. Each site had 2 operators who tested 2 runs of 2 replicates per testing day to yield a total of 144 observations per panel member (3 Sites × 2 Operators × 3 Lots × 2 Days /Lot × 2 Run × 2 Replicates = 144 test results/panel member).
Table 1 presents the qualitative summary of the reproducibility testing. The nested ANOVA analysis of the internal continuous response in the Xpert Respiratory Panel test (either Ct values or melt curve measurements) are presented by analyte in Table 2. The results of the study demonstrate acceptable assay precision and reproducibility.
Table 1: Summary of Reproducibility Results - Percent Agreement
| Analyte | Level | Site 01 | | | Site 02 | | | Site 03 | | | Total Agreement with 95% CI |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | Op 1 | Op 2 | Subtotal | Op 1 | Op 2 | Subtotal | Op 1 | Op 2 | Subtotal | |
| PIV | Low Pos (~1x LoD) | 95.8% 23/24 | 95.8% 23/24 | 95.8% 46/48 | 100% 24/24 | 100% 23/23 | 100% 47/47 | 100% 24/24 | 95.8% 23/24 | 97.9% 47/48 | 97.9% (140/143) 94.0-99.3% |
| | Mod Pos | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% (144/144) 97.4-100% |
| CoV | Low Pos (~1x LoD) | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 23/23 | 100% 47/47 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% (143/143) 97.4-100% |
| | Mod Pos | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% (144/144) 97.4-100% |
| B. parapertussis | Low Pos (~1x LoD) | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 23/23 | 100% 47/47 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% (143/143) 97.4-100% |
| | Mod Pos | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% (144/144) 97.4-100% |
| Flu A | Low Pos | 95.8% | 100% | 97.9% | 100% | 100% | 100% | 95.8% | 100% | 97.9% | 98.6% |
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{12}
| Analyte | Level | Site 01 | | | Site 02 | | | Site 03 | | | Total Agreement with 95% CI |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | Op 1 | Op 2 | Subtotal | Op 1 | Op 2 | Subtotal | Op 1 | Op 2 | Subtotal | |
| | (~1x LoD) | 23/24 | 24/24 | 47/48 | 24/24 | 23/23 | 47/47 | 23/24 | 24/24 | 47/48 | (141/143) 95.0-99.6% |
| | Mod Pos | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% (144/144) 97.4-100% |
| RSV | Low Pos (~1x LoD) | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 23/23 | 100% 47/47 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% (143/143) 97.4-100% |
| | Mod Pos | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% (144/144) 97.4-100% |
| *C. pneumoniae* | Low Pos (~1x LoD) | 91.7% 22/24 | 100% 24/24 | 95.8% 46/48 | 87.5% 21/24 | 95.8% 23/24 | 91.7% 44/48 | 95.8% 23/24 | 100% 24/24 | 97.9% 47/48 | 95.1% (137/144) 90.3-97.6% |
| | Mod Pos | 100% 24/24 | 100% 24/24 | 100% 48/48 | 95.8% 23/24 | 100% 24/24 | 97.9% 47/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 99.3% (143/144) 96.2-99.9% |
| Flu A H1N1-09 | Low Pos (~1x LoD) | 100% 24/24 | 100% 24/24 | 100% 48/48 | 95.8% 23/24 | 95.8% 23/24 | 95.8% 46/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 98.6% (142/144) 95.1-99.6% |
| | Mod Pos | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% (144/144) 97.4-100% |
| hMPV | Low Pos (~1x LoD) | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% (144/144) 97.4-100% |
| | Mod Pos (~3x LoD) | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% (144/144) 97.4-100% |
| AdV | Low Pos (~1x LoD) | 95.8% 23/24 | 95.8% 23/24 | 95.8% 46/48 | 91.7% 22/24 | 95.8% 23/24 | 93.8% 45/48 | 100% 24/24 | 95.8% 23/24 | 97.9% 47/48 | 95.8% (138/144) 91.2-98.1% |
| | Mod Pos (~3x LoD) | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% (144/144) 97.4-100% |
| RV/EV | Low Pos (~1x LoD) | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% (144/144) 97.4-100% |
| | Mod Pos (~3x LoD) | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% (144/144) 97.4-100% |
| Flu B | Low Pos (~1x LoD) | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% (144/144) 97.4-100% |
| | Mod Pos (~3x LoD) | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% (144/144) 97.4-100% |
| *B. pertussis* | Low Pos (~1x LoD) | 100% 24/24 | 100% 24/24 | 100% 48/48 | 95.8% 23/24 | 95.8% 23/24 | 95.8% 46/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 98.6% (142/144) 95.1-99.6% |
| | Mod Pos (~3x LoD) | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 95.8% 23/24 | 97.9% 47/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 99.3% (143/144) 96.2-99.9% |
| *M. pneumoniae* | Low Pos (~1x LoD) | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% (144/144) 97.4-100% |
| | Mod Pos (~3x LoD) | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 95.8% 23/24 | 97.9% 47/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 99.3% (143/144) 96.2-99.9% |
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| Analyte | Level | Site 01 | | | Site 02 | | | Site 03 | | | Total Agreement with 95% CI |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | Op 1 | Op 2 | Subtotal | Op 1 | Op 2 | Subtotal | Op 1 | Op 2 | Subtotal | |
| SARS-CoV-2 | Low Pos (~1x LoD) | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% (144/144) 97.4-100% |
| | Mod Pos (~3x LoD) | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 100% (144/144) 97.4-100% |
| Negative | N/A | 100% 24/24 | 95.8% 23/24 | 97.9% 47/48 | 95.8% 23/24 | 100% 23/23 | 97.9% 46/47 | 100% 24/24 | 100% 24/24 | 100% 48/48 | 98.6% (141/143) 95.0-99.6% |
Table 2: Summary of Nested ANOVA by Coefficient of Variation
| Analyte (Level) | Response | N | Mean | Variance Source | | | | | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | Site | | OP | | Lot | | Day | | Run | | Within-Run | | Total | |
| | | | | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) |
| PIV (Low Pos) | Ct | 140^{ab} | 39.2 | 0.2 | 0.6 | 0.0 | 0.0 | 0.7 | 1.7 | 0.2 | 0.4 | 0.0 | 0.0 | 1.2 | 3.1 | 1.4 | 3.7 |
| PIV (Mod Pos) | Ct | 144 | 38.5 | 0.0 | 0.0 | 0.0 | 0.0 | 0.6 | 1.5 | 0.0 | 0.0 | 0.5 | 1.2 | 1.2 | 3.0 | 1.4 | 3.6 |
| CoV (Low Pos) | Ct | 143^{a} | 39 | 0.0 | 0.0 | 0.0 | 0.0 | 0.4 | 1.1 | 0.2 | 0.6 | 0.0 | 0.0 | 0.8 | 2.2 | 1.0 | 2.5 |
| CoV (Mod Pos) | Ct | 144 | 38.2 | 0.1 | 0.4 | 0.0 | 0.0 | 0.5 | 1.4 | 0.2 | 0.5 | 0.0 | 0.0 | 0.7 | 1.8 | 0.9 | 2.3 |
| *B. parapertussis* (Low Pos) | MP | 143^{a} | 15.9 | 0.7 | 4.3 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 2.9 | 18.0 | 2.9 | 18.5 |
| | MV | 143^{a} | 14 | 0.7 | 4.7 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.5 | 3.4 | 2.5 | 18.0 | 2.6 | 18.9 |
| *B. parapertussis* (Mod Pos) | MP | 144 | 16.9 | 1.3 | 7.6 | 0.0 | 0.0 | 0.3 | 2.0 | 0.0 | 0.0 | 0.9 | 5.2 | 2.7 | 15.7 | 3.1 | 18.4 |
| | MV | 144 | 15 | 1.2 | 8.0 | 0.1 | 0.7 | 0.3 | 1.8 | 0.0 | 0.0 | 1.0 | 6.6 | 2.4 | 16.1 | 2.9 | 19.2 |
| Flu A (Low Pos) | Ct | 142^{ab} | 37 | 0.1 | 0.4 | 0.0 | 0.0 | 0.5 | 1.5 | 0.1 | 0.3 | 0.0 | 0.0 | 0.9 | 2.4 | 1.0 | 2.8 |
| Flu A (Mod Pos) | Ct | 144 | 36.4 | 0.0 | 0.0 | 0.0 | 0.0 | 0.3 | 0.9 | 0.0 | 0.0 | 0.1 | 0.4 | 5.3 | 14.5 | 0.6 | 1.8 |
| RSV (Low Pos) | Ct | 143^{a} | 35.9 | 0.2 | 0.7 | 0.0 | 0.0 | 0.0 | 0.0 | 0.5 | 1.3 | 0.1 | 0.4 | 1.3 | 3.5 | 1.4 | 3.8 |
| RSV (Mod Pos) | Ct | 144 | 35.4 | 0.1 | 0.3 | 0.0 | 0.0 | 0.5 | 1.4 | 0.0 | 0.0 | 0.0 | 0.0 | 1.0 | 2.8 | 1.1 | 3.1 |
| *C. pneumoniae* (Low Pos) | MP | 137^{c} | 9.1 | 0.0 | 0.0 | 0.0 | 0.0 | 0.5 | 6.0 | 0.1 | 1.1 | 0.5 | 5.2 | 1.0 | 11.4 | 1.3 | 13.9 |
| | MV | 137^{c} | 4.6 | 0.0 | 0.0 | 0.0 | 0.0 | 0.5 | 11.7 | 0.0 | 0.0 | 0.5 | 11.7 | 0.8 | 18.1 | 1.1 | 24.5 |
| *C. pneumoniae* (Mod Pos) | MP | 143^{c} | 9.7 | 0.0 | 0.0 | 0.0 | 0.0 | 0.4 | 4.3 | 0.0 | 0.0 | 0.2 | 2.3 | 1.2 | 11.9 | 1.2 | 12.8 |
| | MV | 143^{c} | 5.1 | 0.0 | 0.0 | 0.0 | 0.0 | 0.5 | 9.4 | 0.0 | 0.0 | 0.2 | 3.9 | 1.0 | 18.9 | 1.1 | 21.4 |
| hMPV (Low Pos) | MP | 144 | 7 | 1.4 | 19.6 | 0.0 | 0.0 | 0.3 | 4.0 | 0.0 | 0.0 | 0.0 | 0.0 | 2.0 | 28.4 | 2.4 | 34.8 |
| | MV | 144 | 6.7 | 1.3 | 19.1 | 0.0 | 0.0 | 0.3 | 4.5 | 0.0 | 0.0 | 0.0 | 0.0 | 2.0 | 29.5 | 2.4 | 35.4 |
| hMPV (Mod Pos) | MP | 144 | 8.1 | 1.4 | 17.8 | 0.1 | 1.2 | 0.0 | 0.0 | 0.1 | 1.7 | 0.9 | 10.6 | 1.6 | 20.1 | 2.3 | 29.0 |
| | MV | 144 | 7.8 | 1.4 | 17.3 | 0.2 | 2.6 | 0.0 | 0.0 | 0.0 | 0.0 | 0.9 | 11.4 | 1.5 | 19.5 | 2.2 | 28.6 |
| AdV (Low Pos) | Ct | 138^{b} | 39.8 | 0.3 | 0.7 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.2 | 0.5 | 1.1 | 2.9 | 1.2 | 3.0 |
| AdV (Mod Pos) | Ct | 144 | 39.2 | 0.4 | 0.9 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.4 | 1.0 | 1.1 | 2.9 | 1.3 | 3.2 |
| RV/EV (Low Pos) | Ct | 144 | 36.4 | 0.1 | 0.3 | 0.0 | 0.0 | 0.3 | 0.7 | 0.0 | 0.0 | 0.1 | 0.4 | 0.4 | 1.0 | 0.5 | 1.3 |
K261336 - Page 14 of 38
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| Analyte (Level) | Response | N | Mean | Variance Source | | | | | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | Site | | OP | | Lot | | Day | | Run | | Within-Run | | Total | |
| | | | | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) |
| RV/EV (Mod Pos) | Ct | 144 | 35.8 | 0.0 | 0.0 | 0.0 | 0.0 | 0.3 | 0.9 | 0.1 | 0.4 | 0.0 | 0.0 | 0.3 | 0.9 | 0.5 | 1.4 |
| Flu B (Low Pos) | Ct | 144 | 37.2 | 0.0 | 0.0 | 0.0 | 0.0 | 0.7 | 1.8 | 0.0 | 0.0 | 0.0 | 0.0 | 0.4 | 1.2 | 0.8 | 2.2 |
| Flu B (Mod Pos) | Ct | 144 | 36.5 | 0.0 | 0.0 | 0.0 | 0.0 | 0.7 | 1.8 | 0.0 | 0.0 | 0.1 | 0.3 | 0.3 | 0.8 | 0.7 | 2.0 |
| B. pertussis (Low Pos) | MP | \( 142^c \) | 14.1 | 0.9 | 6.3 | 0.0 | 0.0 | 0.8 | 5.5 | 0.2 | 1.6 | 0.0 | 0.0 | 2.2 | 15.7 | 0.8 | 5.6 |
| | MV | \( 142^c \) | 11.6 | 0.7 | 6.3 | 0.0 | 0.0 | 0.7 | 6.0 | 0.1 | 1.2 | 0.0 | 0.0 | 1.8 | 15.6 | 2.1 | 18.0 |
| B. pertussis (Mod Pos) | MP | \( 143^c \) | 14.4 | 1.2 | 8.1 | 0.0 | 0.0 | 1.1 | 7.6 | 0.0 | 0.0 | 0.0 | 0.0 | 2.3 | 15.6 | 2.8 | 19.2 |
| | MV | \( 143^c \) | 11.9 | 1.0 | 8.1 | 0.0 | 0.0 | 1.0 | 8.3 | 0.3 | 2.4 | 0.0 | 0.0 | 1.9 | 15.7 | 2.3 | 19.7 |
| M. pneumoniae (Low Pos) | MP | 144 | 16.3 | 0.8 | 50.6 | 0.9 | 5.7 | 0.1 | 0.9 | 0.7 | 4.2 | 1.6 | 9.7 | 3.8 | 23.4 | 4.4 | 26.7 |
| | MV | 144 | 18.6 | 0.8 | 4.6 | 0.8 | 4.5 | 1.2 | 6.6 | 0.8 | 4.5 | 2.0 | 10.9 | 4.3 | 23.2 | 5.1 | 27.6 |
| M. pneumoniae (Mod Pos) | MP | \( 143^c \) | 19.5 | 0.4 | 2.3 | 0.0 | 0.0 | 1.1 | 5.7 | 0.0 | 0.0 | 1.5 | 7.5 | 3.6 | 18.7 | 4.1 | 21.1 |
| | MV | \( 143^c \) | 22.6 | 0.7 | 2.9 | 0.0 | 0.0 | 1.6 | 6.9 | 0.0 | 0.0 | 1.6 | 6.9 | 4.2 | 18.5 | 4.8 | 21.1 |
| SARS-CoV-2 (Low Pos) | Ct | 144 | 35.9 | 0.1 | 0.4 | 0.0 | 0.0 | 0.5 | 1.5 | 0.2 | 0.5 | 0.2 | 0.7 | 0.9 | 2.5 | 1.1 | 3.1 |
| SARS-CoV-2 (Mod Pos) | Ct | 144 | 35.1 | 0.2 | 0.6 | 0.0 | 0.0 | 0.5 | 1.4 | 0.0 | 0.0 | 0.0 | 0.0 | 0.9 | 2.6 | 1.0 | 3.0 |
Abbreviations: Ct, cycle threshold; CV, coefficient of variation; Low Pos, low positive ~1xLoD; MP, melt peak; Mod Pos, moderate positive ~3xLoD; MV, melt valley; SD, standard deviation
\( ^{a} \) Sample excluded due to an ND result.
\( ^{b} \) Sample excluded due to 0 Ct value.
\( ^{c} \) Sample excluded due to missing melt peak and melt valley values.
### 2. Linearity:
Not applicable. This is a qualitative assay.
### 3. Analytical Specificity/Interference:
### Analytical Reactivity (Inclusivity)
### Wet-Testing
The inclusivity of the Xpert Respiratory Panel test was evaluated through testing of multiple strains of each target analyte. A total of 169 strains were initially tested at near LoD concentrations: 14 Adenovirus strains, 11 Coronavirus strains, 14 SARS-CoV-2 strains, 9 hMPV strains, 46 RV and EV strains, 11 PIV strains, 31 Influenza A virus strains, 7 Influenza B virus strains, 5 RSV strains, 4 Bordetella parapertussis strains, 8 Bordetella pertussis strains, 3 Chlamydia pneumoniae strains, and 6 Mycoplasma pneumoniae strains. Each analyte was individually spiked into negative simulated NPS matrix and five (5) replicates were tested for each strain. If less than \(100\%\) reactivity was observed during testing, the strain was prepared at a higher concentration and tested until \(100\%\) reactivity was achieved. Table 3 presents the lowest concentration of the viral or bacterial strain/isolate at which all 5 replicates reported positive
K261336 - Page 15 of 38
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results.
Table 4: Analytical Reactivity (Inclusivity) of the Xpert Respiratory Panel Test
| Adenovirus | Type/ Strain | Vendor | Part Number | Lowest Concentration With 100% Positivity (N=5) |
| --- | --- | --- | --- | --- |
| A | 12 | ATCC | VR-863 | 544 Copies/mL |
| | 18 | ATCC | VR-19 | 272 Copies/mL |
| | 31 | ZeptoMetrix | 0810073CF | 544 Copies/mL |
| B | 3 | ZeptoMetrix | 0810062CF | 1,719 Copies/mLa |
| | 7A | ZeptoMetrix | 0810021CF | 91 Copies/mL |
| | 16 | ATCC | VR-17 | 27.2 Copies/mL |
| | 34 | ATCC | VR-716 | 11,625 Copies/mLa |
| | 35 | ATCC | VR-718 | 3,913 Copies/mLa |
| C | 2 | ATCC | VR-846 | 272 Copies/mL |
| | 5 | ZeptoMetrix | 0810020CF | 897 Copies/mL |
| | 6 | ATCC | VR-6 | 30 Copies/mL |
| D | 8 | ZeptoMetrix | 0810069CF | 272 Copies/mL |
| | 20 | ZeptoMetrix | 0810115CF | 272 Copies/mL |
| | 37 | ZeptoMetrix | 0810119CF | 544 Copies/mL |
| Coronavirus | Type/ Strain | Vendor | Part Number | Lowest Concentration With 100% Positivity (N=5) |
| 229E | 229E | ATCC | VR-740 | 0.2 TCID50/mL |
| | 229E | ZeptoMetrix | 0810229CF | 0.001 TCID50/mL |
| | 229E | Clinical Specimen | NA | 991 Copies/mL |
| HKU1 | HKU1 | Clinical specimen | NA | 50 Copies/mL |
| | HKU1 | Clinical Specimen | NA | 100 Copies/mL |
| NL63 | NL63/Amsterdam/2003 | BEI | NR-470 | 0.0006 TCID50/mL |
| | NL63 | ZeptoMetrix | 0810228CF | 0.002 TCID50/mL |
| | NL63 | Clinical Specimen | NA | 248 Copies/mL |
| OC43 | OC43 | ATCC | VR-1558 | 0.03 TCID50/mL |
| | OC43 | ZeptoMetrix | 0810024CF | 0.5 TCID50/mL |
| | OC43 | Clinical Specimen | NA | 495 Copies/mL |
| SARS-CoV-2 | Type/ Strain | Vendor | Part Number | Lowest Concentration With 100% Positivity (N=5) |
| SARS-CoV-2 | Italy-INMI1 | ZeptoMetrix | 0810589CFHI | 12 TCID50/mL |
| | USA-WA1/2020 | ZeptoMetrix | 0810587CFHI | 0.6 TCID50/mL |
| | Alpha | ZeptoMetrix | 0810614CFHI | 0.09 TCID50/mL |
| | Beta | ZeptoMetrix | 0810613CFHI | 0.9 TCID50/mL |
| | Delta | ZeptoMetrix | 0810624CFHI | 0.1 TCID50/mL |
| | Gamma | ZeptoMetrix | 0810616CFHI | 0.2 TCID50/mL |
| | Iota | ZeptoMetrix | 0810620CFHI | 0.7 TCID50/mL |
| | Kappa | ZeptoMetrix | 0810623CFHI | 12 TCID50/mL |
| | Zeta | ZeptoMetrix | 0810618CFHI | 0.3 TCID50/mL |
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| | SARS-CoV-2, Omicron- hCoV-19/USA/New York/PV96109/2023 | BEI | NR-59693 | 0.6 TCID_{50}/mL |
| --- | --- | --- | --- | --- |
| | SARS-CoV-2, Omicron hCoV-19/USA/ CA-Stanford -165 S29/2023 | BEI | NR-59709 | 0.2 TCID_{50}/mL |
| | SARS-CoV-2, Omicron hCoV-19/USA/MD-HP49152/2023 | BEI | NR-59703 | 0.03 TCID_{50}/mL |
| | SARS-CoV-2, Omicron hCoV-19/USA/MD-HP47946/2023 | BEI | NR-59503 | 0.6 TCID_{50}/mL |
| | SARS-CoV-2, Omicron | ZeptoMetrix | 0810682CFHI | 0.1 TCID_{50}/mL |
| Human Metapneumovirus | Type/ Strain | Vendor | Part Number | Lowest Concentration With 100% Positivity (N=5) |
| A | A1, Strain 9 | ZeptoMetrix | 0810161CF | 20 Copies/mL |
| | A1, Strain 16 | ZeptoMetrix | 0810160CF | 39 Copies/mL |
| | A2, Strain 20 | ZeptoMetrix | 0810163CF | 78 Copies/mL |
| | A2, Strain 27 | ZeptoMetrix | 0810164CF | 20 Copies/mL |
| B | B1, Strain 3 | ZeptoMetrix | 0810156CF | 78 Copies/mL |
| | B1, Strain 5 | ZeptoMetrix | 0810158CF | 39 Copies/mL |
| | B1, PP947667 (Synthetic ssDNA) | IDT | NA | 1,510 Copies/mL^{b} |
| | B2, Strain 4 | ZeptoMetrix | 0810157CF | 78.4 Copies/mL |
| | B2, Strain 8 | ZeptoMetrix | 0810159CF | 78.4 Copies/mL |
| Rhinovirus/ Enterovirus | Type/ Strain | Vendor | Part Number | Lowest Concentration With 100% Positivity (N=5) |
| Rhinovirus A | A1 | ZeptoMetrix | 0810012CFN | 130 Copies/mL |
| | A2 | ATCC | VR-482 | 130 Copies/mL |
| | A7 | ATCC | VR-1601 | 130 Copies/mL |
| | A16 | ATCC | VR-283 | 260 Copies/mL |
| | A57 | ATCC | VR-1600 | 13,023 Copies/mL |
| | A63 OK649395 Synthetic ssDNA | IDT | NA | 39,070 Copies/mL |
| | A77 | ATCC | VR-1187 | 260 Copies/mL |
| Rhinovirus B | B14 | ATCC | VR-284 | 203 Copies/mL |
| | B17 | ATCC | VR-1663 | 33 Copies/mL |
| | B27 | ATCC | VR-1137 | 130 Copies/mL |
| | B42 | ATCC | VR-1950 | 65 Copies/mL |
| | B83 | ATCC | VR3341 | 43 Copies/mL |
| | B85 | ATCC | VR-1195 | 65 Copies/mL |
| Rhinovirus C | Clinical sample PC4S1GES50113 | NA | NA | 1,390 Copies/mL^{c} |
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| | Clinical sample PC4S1GES50210 | NA | NA | 10,000 Copies/mL\( ^c \) |
| --- | --- | --- | --- | --- |
| | Clinical Sample PC4S1GES50258 | NA | NA | 1,000 Copies/mL\( ^c \) |
| | Clinical Sample PC4S1GES50332 | NA | NA | 861 Copies/mL\( ^c \) |
| | C7 OM001438 Synthetic ssDNA | IDT | NA | 1,628 Copies/mL |
| | C20 MZ427502 Synthetic ssDNA | IDT | NA | 1,736,000 Copies/mL\( ^d \) |
| | C36 PP158746 Synthetic ssDNA | IDT | NA | 407 Copies/mL |
| Coxsackievirus | A1 | ZeptoMetrix | 0810140CF | 1,884 Copies/mL |
| | A9 | ZeptoMetrix | 0810017CF | 3,768 Copies/mL |
| | A15, strain 'G-19' | ZeptoMetrix | 0810144CF | 55,000 Copies/mL |
| | A21 | ATCC | VR-850 | 3,768Copies/mL |
| | CoxA4 ON730810 Synthetic ssDNA | IDT | NA | 5,652 Copies/mL |
| | CoxA10 PP078948 Synthetic ssDNA | IDT | NA | 1,884 Copies/mL |
| | CoxB5 OQ408283 Synthetic ssDNA | IDT | NA | 1,884 Copies/mL |
| Echovirus | Type 6 | ZeptoMetrix | 0810076CF | 1,884 Copies/mL |
| | Type 9 | ZeptoMetrix | 0810077CF | 3,768 Copies/mL |
| | Type 11 | ZeptoMetrix | 0810023CF | 5,652 Copies/mL |
| | Type 13, H06368-226 | ZeptoMetrix | 0810607CF | 628 Copies/mL |
| | Type 14, H08330539 | ZeptoMetrix | 0810502CF | 3,768 Copies/mL |
| | Type 18, H07218-472 | ZeptoMetrix | 0810608CF | 314 Copies/mL |
| | Type 30 | ZeptoMetrix | 0810078CF | 1,884 Copies/mL |
| Enterovirus | A71 | ZeptoMetrix | 0810236CF | 628 Copies/mL |
| | A71 OR791510 Synthetic ssDNA | IDT | NA | 1,884 Copies/mL |
| | D68 Major Group, 9/2014 Isolate 3 | ZeptoMetrix | 0810303CF | 1,884 Copies/mL |
| | HEV-D68/ Fermon | BEI | NR-51430 | 30,094 Copies/mL\( ^e \) |
| | D68/US/MO/14-18949 | BEI | NR-49130 | 1,884 Copies/mL |
| | D68/US/IL/14-18952 | BEI | NR-49131 | 940 Copies/mL |
| | D68/USA/2018-23089 | BEI | NR-51998 | 3,762 Copies/mL |
| | D68/US/KY/14-18953 | BEI | NR-49132 | 5,966 Copies/mL |
| | Sabin monovalent Polio vaccine type 1 (1st International Standard) | NIBSC | Code 16/196 | 188,390 Copies/mL\( ^f \) |
| | Poliovirus OPV reference mOPV 3 | NIBSC | Code 16/202 | 56,517 Copies/mL\( ^f \) |
| | Poliovirus OP410429 Synthetic ssDNA | IDT | NA | 31,398 Copies/mL\( ^f \) |
| | Poliovirus PV557050 Synthetic ssDNA | IDT | NA | NA\( ^f \) |
| Parainfluenza Virus | Type/ Strain | Vendor | Part Number | Lowest Concentration |
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| | | | | With 100% Positivity (N=5) |
| --- | --- | --- | --- | --- |
| PIV1 | Type 1 | ZeptoMetrix | 0810014CF | 275 Copies/mL |
| | Type 1, strain FRA/29221106/2009 | BEI | NR-48680 | 1,240 Copies/mL |
| PIV2 | Type 2 | ZeptoMetrix | 0810015CF | 35 TCID\( _{50} \)/mL |
| | Type 2, strain Greer | BEI | NR-5994 | 0.04 TCID\( _{50} \)/mL |
| PIV3 | Type 3 | ZeptoMetrix | 0810016CF | 248 Copies/mL |
| | Type 3, NIH Wash/47885/57 | BEI | NR-3233 | 6,614 Copies/mL |
| PIV4 | Type 4A | ATCC | VR-1378 | 69 Copies/mL |
| | Type 4A, strain M-25 | BEI | NR-3237 | 207 Copies/mL |
| | Type 4B CH19503 | ATCC | VR-1377 | 69 Copies/mL |
| | Type 4B | ZeptoMetrix | 0810060BCF | 28 Copies/mL |
| | PV224554 Synthetic ssDNA | IDT | NA | 411 Copies/mL |
| Influenza A | Type/ Strain | Vendor | Part Number | Lowest Concentration With 100% Positivity (N=5) |
| H3N2 | A/New York/21/2020 | IRR | FR-1761 | 4 FFU/mL |
| | A/Tasmania/503/2020 | IRR | FR-1790 | 1 FFU/mL |
| | A/Darwin/06/2021 | IRR | FR-1837 | 1.6 FFU/mL |
| | A/Darwin/9/2021 | IRR | FR-1845 | 2.7 CEID\( _{50} \)/mL |
| | A/Massachusetts/18/2022 | IRR | FR-1859 | 0.4 FFU/mL |
| | A/Florida/57/2022 | IRR | FR-1861 | 0.05 TCID\( _{50} \)/mL |
| | A/New York/66/2022 | IRR | FR-1868 | 1.3 FFU/mL |
| | A/Michigan/60/2022 | IRR | FR-1871 | 1.5 FFU/mL |
| | A/Montana/08/2023 | IRR | FR-1873 | 6.5 FFU/mL |
| | A/Macha/O1237/2021 | BEI | NR-59461 | 0.2 FFU/mL |
| | A/Baltimore/JH-0586/2022 | BEI | NR-59462 | 17 TCID\( _{50} \)/mL |
| H1N1-09 | A/Indiana/02/2020 | IRR | FR-1763 | 670 CEID\( _{50} \)/mL |
| | A/Macha/O1453/2021 | BEI | NR-59464 | 40 TCID\( _{50} \)/mL |
| | A/Baltimore/JH-22377/2022 | BEI | NR-59465 | 67 CEID\( _{50} \)/mL |
| | A/Baltimore/JH-22400/2022 | BEI | NR-59466 | 9.6 CEID\( _{50} \)/mL |
| | Clinical specimen/2020 | NA | NA | 77 Copies/mL |
| | Clinical specimen/2020 | NA | NA | 77 Copies/mL |
| | Clinical specimen/2020 | NA | NA | 77 Copies/mL |
| | Clinical specimen/2020 | NA | NA | 77 Copies/mL |
| | Clinical specimen/2020 | NA | NA | 67 Copies/mL |
| | Clinical specimen/2020 | NA | NA | 168 Copies/mL |
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| H1N1 | Swine 1976/31 | ATCC | VR-99 | 3 CEID\( _{50} \)/mL |
| --- | --- | --- | --- | --- |
| | A/Texas/14/2008 | IRR | FR-587 | 67 CEID\( _{50} \)/mL |
| H5N1 | A/duck/Hunan/795/2002 | IRR | FR-265 (219) | 65 Copies/mL |
| | A/Japanese white eye/Hong Kong/1038/2006 | IRR | FR-270 | 258 Copies/mL |
| | A/bovine/Ohio/B24O SU-439/2024 (genomic RNA) | BEI | NR-59885 | 65 Copies/mL |
| H5N2 | A/pheasant/New Jersey/1355/1998-PR8-IBCDC-4 | IRR | FR-729 | 59 CEID\( _{50} \)/mL |
| H7N2 | A/turkey/Virginia/45 29/2002-PR8-IBCDC-5 | IRR | FR-730 | 36 CEID\( _{50} \)/mL |
| H7N7 | A/mallard/Netherlands/12/2000/PR8-IBCDC-1 | IRR | FR-731 | 8.2 CEID\( _{50} \)/mL |
| H7N9 | A/Shanghai/2/2013-PR8-IDCDC-RG32A | IRR | FR-1389 | 7.7 CEID\( _{50} \)/mL |
| H9N2 | A/chicken/Hong Kong/G9/1997-PR8-IBCDC-2 | IRR | FR-732 | 104 CEID\( _{50} \)/mL |
| Influenza B | Type/ Strain | Vendor | Part Number | Lowest Concentration With 100% Positivity (N=5) |
| Victoria Lineage | B/Washington/02/2019 | IRR | FR-1709 | 6.7 CEID\( _{50} \)/mL |
| | B/Hawaii/01/2018 (NA D197N) | IRR | FR-1661 | 0.8 TCID\( _{50} \)/mL |
| | B/New Hampshire/01/2021 | IRR | FR-1796 | 0.03 TCID\( _{50} \)/mL |
| | B/Michigan/01/2021 | IRR | FR-1800 | 0.05 TCID\( _{50} \)/mL |
| Yamagata Lineage | B/Oklahoma/10/2018 (NA D197N) | IRR | FR-1660 | 1.7 TCID\( _{50} \)/mL |
| NA | Clinical specimen/2020 | NA | NA | 17 Copies/mL |
| | Clinical specimen/2020 | NA | NA | 25 Copies/mL |
| Respiratory Syncytial Virus | Type/ Strain | Vendor | Part Number | Lowest Concentration With 100% Positivity (N=5) |
| RSV A | Type A2 | ATCC | VR1540 | 2 PFU/mL |
| | Type A Long | ATCC | VR-26 | 2 PFU/mL |
| RSV B | Type B WV/ 14617/85 | ATCC | VR-1400 | 0.3 TCID\( _{50} \)/mL |
| | Type B 9320 | ATCC | VR-955 | 0.2 PFU/mL |
| | Type B 18537 | ATCC | VR-1580 | 0.01 PFU/mL |
| Bordetella parapertussis | Type/ Strain | Vendor | Part Number | Lowest Concentration With 100% Positivity (N=5) |
| B. parapertussis | E595 | ZeptoMetrix | 801462 | 118 CFU/mL |
| | 508 and 344 (NCTC 10853) | ATCC | 15237 | 29 CFU/mL |
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| | NCTC 5952 (522) | ATCC | 15311 | 88 CFU/mL |
| --- | --- | --- | --- | --- |
| | 12822 | ATCC | BAA-587 | 24 CFU/mL |
| Bordetella pertussis | Type/ Strain | Vendor | Part Number | Lowest Concentration With 100% Positivity (N=5) |
| B. pertussis | E431 | ZeptoMetrix | 801460 | 275 CFU/mL |
| | F | ATCC | 8467 | 2 CFU/mL |
| | 5 (17921) | ATCC | 9340 | 824 CFU/mL |
| | 18323 (NCTC 10739) | ATCC | 9797 | 0.5 CFU/mL |
| | 10-536 | ATCC | 10380 | 8 CFU/mL |
| | CNCTC Hp 12/63 (623) | ATCC | 51445 | 1 CFU/mL |
| | MN2531 | ATCC | BAA-1335 | 2 CFU/mL |
| Chlamydia pneumoniae | Type/ Strain | Vendor | Part Number | Lowest Concentration With 100% Positivity (N=5) |
| C. pneumoniae | TW-183 | ATCC | VR-2282 | 132 IFU/mL |
| | CWL-029 | ATCC | VR-1310 | 66 IFU/mL |
| | AR-39 | ATCC | 53592 | 17 IFU/mL |
| Mycoplasma pneumoniae | Type/ Strain | Vendor | Part Number | Lowest Concentration With 100% Positivity (N=5) |
| M. pneumoniae | Type1 M129-B7 | ATCC | 29342 | 321 Copies/mL |
| | Type 2 Mac | ATCC | 15492 | 321 Copies/mL |
| | M52 | ATCC | 15293 | 321 Copies/mL |
| | Bru | ATCC | 15377 | 642 Copies/mL |
| | Mutant 22 | ATCC | 39505 | 321 Copies/mL |
| | UTMB-10P | ATCC | 49894 | 642 Copies/mL |
\( ^{a} \) Adenovirus B3, B34, and B35 were detected at 19x, 128x, and 43x LoD, respectively. Adenovirus B34 and B35 are uncommonly recovered from humans with respiratory tract infection.
\( ^{b} \) Human metapneumovirus B1 synthetic ssDNA was detected at 900x LoD. Infectious hMPV B1 was detected at <0.1x LoD.
\( ^{c} \) Due to limited volume of Rhinovirus clinical specimen, this specimen was run in replicates of 3 instead of 5.
\( ^{d} \) Rhinovirus C20 synthetic ssDNA was detected at 400x LoD. Rhinovirus C20 is uncommonly recovered from humans with respiratory tract infection.
\( ^{e} \) Enterovirus D68 “Feron” strain was detected at 48x LoD. This is an unknown clade. Known D68 clades A2/D, B1, B2, and B3 were all detected at \( \leq \) 10x LoD.
\( ^{f} \) Polioviruses and poliovirus synthetic ssDNA were detected at \( \geq50x \) LoD or not detected. Polioviruses are not associated with respiratory tract infection.
### In Silico Analyses
The inclusivity of the Xpert Respiratory Panel was evaluated using in silico analysis of the oligonucleotide sequences for SARS-CoV-2 against SARS-CoV-2 sequence records in NCBI Datasets v18.9.0 accessed on January 4, 2026. The analysis of the three SARS-CoV-2 targets (E, N2 and RdRP) was conducted with over 1.6 million SARS-CoV-2 genomic RNA sequences. Results of the in-silico analysis predict that the Xpert Respiratory Panel will detect greater than \(99.99\%\) of SARS-CoV-2 variants.
### Analytical Specificity (Exclusivity)
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### Wet-Testing
Cross reactivity (exclusivity) of the Xpert Respiratory Panel test was evaluated by testing a panel of 52 non-target microorganisms (8 viruses, 39 bacteria, 5 fungi) and nasal wash (Table 4) to determine the assay's ability to detect on panel analytes in the presence of related pathogens, high prevalence disease agents, and normal or pathogenic microorganisms reasonably likely to be present in a clinical NPS sample. Each non-target organism was tested in triplicates. The bacterial and yeast strains were tested at concentrations of \(\geq 1\mathrm{E}6\) units/mL (CFU/mL, IFU/mL, copies/mL or CCU/mL) and viral strains were tested at \(\geq 1\mathrm{E}5\) units/mL (TCID\(_{50}\)/mL or copies/mL) in simulated nasopharyngeal swab (NPS) matrix, except for Ureaplasma urealyticum which was tested at 2E4 copies/mL. As no quantified stock was available, SARS-CoV-1 was tested at a dilution of 1:100. A non-target organism was considered negative if all three replicates were negative for all analytes detected by the Xpert Respiratory Panel test. If an exclusivity microorganism was reported POSITIVE with the Xpert Respiratory Panel test, the test was repeated with a lower concentration of the exclusivity microorganisms and the highest concentration that did not produce a false positive result was recorded.
The results of the analytical specificity study demonstrated that the primer/probe sets do not cross-react with the nucleic acids from non-intended respiratory microorganisms or phylogenetically related respiratory pathogens detected by the Xpert Respiratory Panel test. The one exception was SARS-CoV-1 which yielded the expected SARS-CoV-2 POSITIVE test result. Based on the in silico analysis, cross-reactivity with the E gene target of SARS-CoV-1 was expected due to the highly conserved E gene target shared among coronaviruses in the B lineage Betacoronavirus. Although the nasal wash sample reported Parainfluenza POSITIVE results in all replicates tested, sequencing result confirmed the presence of Parainfluenza in this diverse microbial human flora.
Table 5: Organisms Evaluated in Cross-Reactivity and Microbial Interference Study by Wet Testing
| Count | Exclusivity Strain | Concentration Tested |
| --- | --- | --- |
| 0 | Negative Control | Not Applicable |
| 1 | Escherichia coli | 2E6 CFU/mL |
| 2 | Lactobacillus plantarum | 2E6 CFU/mL |
| 3 | Legionella longbeacheae | 2E6 CFU/mL |
| 4 | Pseudomonas aeruginosa | 2E6 CFU/mL |
| 5 | Enterobacter aerogenes | 2E6 CFU/mL |
| 6 | Legionella pneumophila | 2E6 CFU/mL |
| 7 | Staphylococcus epidermidis | 2E6 CFU/mL |
| 8 | Stenotrophomonas maltophilia | 2E6 CFU/mL |
| 9 | Klebsiella oxytoca | 2E6 CFU/mL |
| 10 | Neisseria elongata | 2E6 CFU/mL |
| 11 | Serratia marcescens | 2E6 CFU/mL |
| 12 | Streptococcus pyogenes | 2E6 CFU/mL |
| 13 | Klebsiella pneumoniae | 2E6 CFU/mL |
| 14 | Mycoplasma hominis | 2E6 CCU/mL |
| 15 | Proteus mirabilis | 2E6 CFU/mL |
| 16 | Streptococcus pneumoniae | 2E6 CFU/mL |
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| Count | Exclusivity Strain | Concentration Tested |
| --- | --- | --- |
| 17 | Candida albicans | 2E6 CFU/mL |
| 18 | Mycoplasma orale | 2E6 CFU/mL |
| 19 | Corynebacterium diphtheriae | 2E6 CFU/mL |
| 20 | Streptococcus salivarus | 2E6 CFU/mL |
| 21 | Neisseria gonorrhoeae | 2E6 CFU/mL |
| 22 | Acinetobacter calcoaceticus | 2E6 CFU/mL |
| 23 | Haemophilus influenzae | 2E6 CFU/mL |
| 24 | Lactobacillus acidophilus | 2E6 CFU/mL |
| 25 | Moraxella catarrhalis | 2E6 CFU/mL |
| 26 | Neisseria meningitidis | 2E6 CFU/mL |
| 27 | Streptococcus agalactiae | 2E6 CFU/mL |
| 28 | Chlamydia trachomatis | 2E6 IFU/mL |
| 29 | Aspergillus flavus | 2E6 CFU/mL |
| 30 | Aspergillus fumigatus | 2E6 CFU/mL |
| 31 | Cryptococcus neoformans | 2E6 CFU/mL |
| 32 | Pneumocystis jirovecii | 2E6 CFU/mL |
| 33 | Bordetella avium | 2E6 CFU/mL |
| 34 | Bordetella hinzii | 2E6 CFU/mL |
| 35 | Bordetella bronchiseptica | 2E6 CFU/mL |
| 36 | Bordetella holmesii | 2E6 CFU/mL |
| 37 | Bocavirus | 2E5 Cp/mL |
| 38 | Measles Virus | 2E5 TCID\( _{50} \)/mL |
| 39 | Cytomegalovirus (CMV) | 2E5 Cp/mL |
| 40 | Epstein-Barr Virus (EBV) | 2E5 Cp/mL |
| 41 | Mycobacterium tuberculosis | 2E6 Cp/mL |
| 42 | Mycoplasma genitalium | 2E6 Cp/mL |
| 43 | Ureaplasma urealyticum | 2E4 Cp/mL |
| 44 | Staphylococcus aureus | 2E6 CFU/mL |
| 45 | Mumps | 2E5 TCID\( _{50} \)/mL |
| 46 | Herpes Simplex Virus 1 | 1E6 TCID\( _{50} \)/mL |
| 47 | Middle East Respiratory (MERS) | 2E5 Cp/mL |
| 48 | SARS-CoV-1 | Not Applicable |
| 49 | Legionella bozemanii | 2E6 CFU/mL |
| 50 | Legionella dumofii | 2E6 CFU/mL |
| 51 | Legionella feeleii | 2E6 CFU/mL |
| 52 | Legionella micdadei | 2E6 CFU/mL |
| 53 | Nasal wash | Not Applicable |
### In Silico Analysis
An in silico assessment was performed using the NCBI BLAST Core Nucleotide Database (January 9, 2026) to evaluate potential cross-reactivity of the Xpert Respiratory Panel primers and probes. All primer probe combinations across the multiplex panel were examined.
The predicted cross-reactivity was limited to a small number of non-target organisms with close
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genetic relatedness to the test's intended targets, including non-human Mastadenovirus, embecoviruses related to Coronavirus OC43/HKU1, parainfluenza 3 and respirovirus, enteroviruses and other picornaviruses, and SARS-related coronaviruses. Additionally, cross-reactivity was predicted for human adenoviruses F and G, a few Bordetella species and Achromobacter denitrificans, which are known to infect humans (see limitation section). A summary of potential cross-reactivity is provided in Table 5.
Table 6: Summary of Predicted Cross-Reactivity
| Oligonucleotide Target | Predicted Cross-Reactivity |
| --- | --- |
| Adenovirus | Non-human Mastadenovirus species (e.g., simian, bovine, porcine, lemur, bat) and enteric human adenoviruses (types 40, 41, 52) |
| Coronavirus OC43/HKU1 | Non-human embecoviruses (e.g., bovine, canine respiratory, yak, dromedary camel, equine, and sambar deer coronaviruses) |
| SARS-CoV-2 | SARS-related coronaviruses (e.g., bat SARS-like, bat SARS, civet SARS coronavirus, and other SARS-related betacoronaviruses) |
| Parainfluenza 1 / Parainfluenza 3 | Non-human parainfluenza and respirovirus species (e.g., caprine parainfluenza virus 3, Respirovirus bovis, swine and wild boar parainfluenza virus 3) |
| RSV A / RSV B | Bovine orthopneumovirus and bovine respiratory syncytial virus (did not meet primer mismatch criteria of no more than 4) |
| Rhinovirus/Enterovirus | Non-human enteroviruses and other picornaviruses (e.g., canine, porcine, simian, bat, and rodent associated sequences) |
| Bordetella pertussis | Bordetella bronchiseptica and Bordetella holmesii |
| Bordetella parapertussis | Bordetella bronchiseptica and Achromobacter denitrificans |
### Microbial Interference
The microbial interference of the Xpert Respiratory Panel test was evaluated by testing the same panel of 52 pathogens (8 viruses, 39 bacteria, 5 fungi) used in the analytical specificity / exclusivity study (Table 4), in the presence of individual on-panel analyte at a concentration of ~3x LoD in simulated nasopharyngeal swab (NPS) matrix. Each on-panel analyte was tested in different pools of pathogens, with 6 replicates per pool. A sample was considered positive if all 6 replicates were positive for the on-panel analyte tested. The bacterial and yeast strains were tested at concentrations of ≥ 1E6 units/mL (CFU/mL, IFU/mL, copies/mL or CCU/mL) and viral strains were tested at ≥ 1E5 units/mL (TCID50/mL or copies/mL) in simulated nasopharyngeal swab (NPS) matrix, except for Ureaplasma urealyticum which was tested at 2E4 copies/mL. As no quantified stock was available, SARS-CoV-1 was tested at a dilution of 1:100. The pathogens tested are listed in Table 4. No microbial interference was observed.
### Competitive Interference
A competitive interference study was conducted to evaluate the ability of the Xpert Respiratory Panel test to detect a low-level analyte (3 x LoD) in the presence of a high-level (1E5 copies/mL for viral strains and 1E6 CFU/mL or IFU/mL for bacterial strains) on-panel organism. Samples were prepared in simulated NPS matrix. Testing was performed in 5 replicates, and the results are shown in Table 6.
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Table 7: Combinations Tested for Competitive Interference
| Combination | Analyte at 3x LoD | | | Competitive Analyte at High Titer | Number of Positive Results / Total Valid Replicates |
| --- | --- | --- | --- | --- | --- |
| | Target Pathogen | Conc. | Conc. (Copies/mL) | | |
| 1 | Adenovirus | 10.4 TCID\( _{50} \)/mL | 272 | Rhinovirus | 5/5 |
| 2 | Respiratory Syncytial Virus | 0.66 TCID\( _{50} \)/mL | 11,943 | Rhinovirus | 5/5 |
| 3 | Coronavirus | 0.94 TCID\( _{50} \)/mL | 7.7 | Rhinovirus | 5/5 |
| 4 | Respiratory Syncytial Virus | 0.66 TCID\( _{50} \)/mL | 11,943 | Adenovirus | 5/5 |
| 5 | Adenovirus | 10.4 TCID\( _{50} \)/mL | 272 | SARS-CoV-2 | 5/5 |
| 6 | Rhinovirus | 30.6 TCID\( _{50} \)/mL | 13,023 | SARS-CoV-2 | 5/5 |
| 7 | Human Metapneumovirus | 0.26 TCID\( _{50} \)/mL | 5,018 | SARS-CoV-2 | 5/5 |
| 8 | Respiratory Syncytial Virus | 0.66 TCID\( _{50} \)/mL | 11,943 | SARS-CoV-2 | 5/5 |
| 9 | Rhinovirus | 30.6 TCID\( _{50} \)/mL | 13,023 | Adenovirus | 5/5 |
| 10 | Rhinovirus | 30.6 TCID\( _{50} \)/mL | 13,023 | Respiratory Syncytial Virus | 5/5 |
| 11 | Rhinovirus | 30.6 TCID\( _{50} \)/mL | 13,023 | Coronavirus | 5/5 |
| 12 | Adenovirus | 10.4 TCID\( _{50} \)/mL | 272 | Respiratory Syncytial Virus | 5/5 |
| 13 | SARS-CoV-2 | 3.8 TCID\( _{50} \)/mL | 1,169 | Adenovirus | 5/5 |
| 14 | SARS-CoV-2 | 3.8 TCID\( _{50} \)/mL | 1,169 | Rhinovirus | 5/5 |
| 15 | SARS-CoV-2 | 3.8 TCID\( _{50} \)/mL | 1,169 | Human Metapneumovirus | 5/5 |
| 16 | SARS-CoV-2 | 3.8 TCID\( _{50} \)/mL | 1,169 | Respiratory Syncytial Virus | 5/5 |
| 17 | C. pneumoniae | 131.9 IFU/mL | NA | B. pertussis | 5/5 |
| 18 | B. pertussis | 16.5 CFU/mL | NA | C. pneumoniae | 5/5 |
### Interfering Substances
The performance of the Xpert Respiratory Panel test was evaluated in the presence of endogenous and exogenous substances that may be commonly found in NPS specimens. Each substance was tested individually in the presence and absence of 6 representative on-panel viruses and bacteria (Adenovirus, SARS-CoV-2, Human Metapneumovirus, Rhinovirus, Influenza A, and Chlamydia pneumoniae), prepared at \(\sim 3\mathrm{x}\) LoD in simulated nasopharyngeal swab (NPS) matrix. The viruses and bacteria were either tested in a pool of 4 pathogens or individually (e.g., SARS-CoV-2 and Rhinovirus). Positive and negative samples were tested with 6 replicates per substance. Positive and negative controls were also included in the study. A total of 34 substances were tested with the Xpert Respiratory Panel
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test, and 32 demonstrated no interference with assay performance. Two substances, FluMist (6.7%) and Saline Nasal Gel (15%), showed interference with the Xpert Respiratory Panel test performance. As a safety precaution, a maximum bleach concentration of 1% is included as a limitation. The substances and concentrations tested are presented in Table 7.
Table 8: Potentially Interfering Substances Tested
| Substance ID | Substance/Class | Highest Concentration Tested Without Interference |
| --- | --- | --- |
| Control NPS Simulated Matrix | No substance | 100%^{a} |
| Human whole blood K2-EDTA | Endogenous substance | 10 % v/v |
| Mucin | Endogenous substance | 1% v/v^{b} |
| Human genomic DNA | Endogenous substance | 20 ng/mL |
| Tobramycin | Antibiotic | 0.6 mg/mL |
| Mupirocin | Antibiotic | 2% w/v |
| Saline Nasal Spray | Nasal spray | 1% v/v |
| Nasal Decongestant Spray Oxymetazoline HCl 0.05% | Nasal spray | 1% v/v^{c} |
| Analgesic ointment (Vicks® VapoRub®) | Analgesic ointment | 1% w/v |
| Petroleum Jelly (Vaseline®) | Topical ointment | 1% w/v |
| Snuff (Nasal Tobacco) | Nasal tobacco | 1% w/v |
| Zinc | Zinc supplement | 0.1 μg/mL |
| FluMist | Influenza vaccine | 6.7% v/v^{d} |
| Zanamivir | Antiviral drug | 7.5 mg/mL |
| Nasonex (mometasone furoate) | Allergy medication | 1% v/v |
| Saline Nasal Gel | Nasal gel | 15% w/v^{b} |
| Throat lozenges | Throat lozenge | 1.7 mg/mL |
| Bleach | Disinfectant | 5% v/v |
| Disinfecting wipes | Disinfectant | 0.5 inches^{2} (3.23 cm^{2}) |
| Ethanol (70%) | Disinfectant | 7% v/v |
| DNAZap™ | Nucleic acid degrading reagent | 1% v/v |
| RNAseOUT™ | Nucleic acid degrading reagent | 1% v/v |
| Nasopharyngeal swab 168C | Specimen collection device | 1 swab^{b} |
| FloQSwab 552C | Specimen collection device | 1 swab |
| Nasopharyngeal swab 175KS01 | Specimen collection device | 1 swab |
| Eswab 480c | Specimen collection device | 1 swab |
| Puritan® Calgiswab® 25-800 A 50c | Specimen collection device | 1 swab |
| Microtest™ M4-RT transport media | Transport media | 100%^{a} |
| UTM | Transport media | 100%^{a} |
| eNAT® | Transport media | 100%^{a} |
| BD universal viral transport medium | Transport media | 100%^{a} |
| Sigma Virocult transport medium | Transport media | 100%^{a} |
| Microtest™ M6 transport media | Transport media | 100%^{a} |
| Microtest™ M5 transport media | Transport media | 100%^{a} |
| PrimeStore® molecular transport medium | Transport media | 100%^{a} |
$^{a}$ Test concentration of 100% denotes the use of the substance directly and undiluted as a sample matrix.
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\( ^{b} \) Interference was observed when testing Chlamydia pneumoniae in a representative mix of on-panel analytes. No interference was observed when testing Chlamydia pneumoniae as a single analyte.
\( ^{c} \) Interference was observed when testing Influenza A in a representative mix of on-panel analytes. No interference was observed when testing Influenza A as a single analyte.
\( ^{d} \) False positive results for Influenza A and Influenza B were observed with FluMist at 6.7% v/v.
4. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):
a) Controls
See Section IV.C.5. Quality Control.
b) Sample Stability
Sample stability testing demonstrated that NPS specimens can be stored and transported at the conditions listed below:
- Room temperature (15–30 °C) for up to 12 hours in UTM/VTM or up to 24 hours in eNAT until testing is performed on the GeneXpert Instrument Systems.
- Refrigerated (2–8 °C) up to 4 days in UTM/VTM or up to 7 days in eNAT until testing is performed on the GeneXpert Instrument Systems.
c) Freeze/Thaw Stability
Freeze/Thaw stability testing demonstrated that NPS specimens in UTM/VTM are stable for up to 2 freeze/thaw cycle when stored at -20 °C.
d) Kit Stability
Real-time kit stability data supports the recommended shelf-life stability claim when stored at 2–28 °C for up to 10 months.
5. Detection Limit:
The analytical sensitivity of the Xpert Respiratory Panel test was evaluated using two reagent lots per strain and testing limiting dilutions of on-panel viruses and bacteria (4 Adenovirus strains, 4 Human Coronavirus strains, 2 SARS-CoV-2 strains, 1 Human Metapneumovirus strain, 1 human Rhinovirus strain, 1 Enterovirus strain, 4 Parainfluenza subtypes, 1 Influenza A strain, 2 Influenza B strains [1 Yamagata and 1 Victoria lineage], one strain each of Respiratory Syncytial Virus A and B, one Bordetella pertussis strain, one Bordetella parapertussis strain, one Mycoplasma pneumoniae strain, and one Chlamydia pneumoniae strain) in pooled negative clinical nasopharyngeal swab (NPS) in Universal Transport Media (UTM) matrix. Preliminary LoD was established using Probit regression analysis on the dilution series test result for each target viral strain. The LoD of each analyte was confirmed as the dilution level where the level below reported positivity rate of \(< 95\%\) and the level above resulted in a positivity rate of \(100\%\) through additional serial dilution testing of 20 replicates at each tested dilutions. Confirmed LoD are shown in Table 8.
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Table 9: Xpert Respiratory Panel Limit of Detection in Clinical NPS-UTM Matrix
| Virus/Bacteria Strain | LoD Concentration |
| --- | --- |
| Adenovirus B, Wan | 3.0 TCID\( _{50} \)/mL |
| Adenovirus 1C | 3.5 TCID\( _{50} \)/mL |
| Adenovirus 4(E) | 0.62 TCID\( _{50} \)/mL |
| First WHO International Standard for human Adenovirus DNA for nucleic acid amplification techniques (NIBSC code: 16/324) | 1,345 IU/mL |
| Coronavirus 229E | 0.015 TCID\( _{50} \)/mL |
| Coronavirus HKU1 | 133.2 Cp/mL |
| Coronavirus NL63 | 0.0057 TCID\( _{50} \)/mL |
| Coronavirus OC43 | 0.31 TCID\( _{50} \)/mL |
| Second WHO International Standard for SARS-CoV-2 RNA (NIBSC code: 22/252) | 2,584 IU/mL |
| SARS-CoV-2 Hong Kong/VM20001061/2020 | 1.32 TCID\( _{50} \)/mL |
| Human Metapneumovirus (hMPV) 18 B2, IA18-2003 | 0.088 TCID\( _{50} \)/mL |
| Human Rhinovirus 3, FEB | 10.2 TCID\( _{50} \)/mL(7.1 PFU/mL) |
| Enterovirus D68, US/MO/14-18947 | 11.2 TCID\( _{50} \)/mL |
| Parainfluenza 1, C35 | 5.2 TCID\( _{50} \)/mL |
| Parainfluenza 2, Greer | 0.8 TCID\( _{50} \)/mL |
| Parainfluenza 3, C 243 | 11.7 TCID\( _{50} \)/mL |
| Parainfluenza 4A | 1.2 TCID\( _{50} \)/mL |
| Influenza A/Wisconsin/04/2018 (H3N2) | 104 CEID\( _{50} \)/mL |
| Influenza B/Missouri/12/2018 (NA D197E) (Victoria Lineage) | 1.4 TCID\( _{50} \)/mL |
| Influenza B/Indiana/17/2017 (NA I221T) (Yamagata Lineage) | 4.4 TCID\( _{50} \)/mL |
| Respiratory Syncytial Virus (RSV) A | 0.2 TCID\( _{50} \)/mL |
| Respiratory Syncytial Virus (RSV) B, WV/14617/85 | 0.02 TCID\( _{50} \)/mL |
| Bordetella pertussis, A639 | 5.49 CFU/mL |
| Bordetella parapertussis, A747 | 0.2 CFU/mL |
| Mycoplasma pneumoniae, M129 | 50.8 CCU/mL |
| Chlamydia pneumoniae, CM-1 | 0.156 TCID\( _{50} \)/mL(43.97 IFU/mL) |
#### 6. Assay Cut-Off:
The GeneXpert software is responsible for converting RT-PCR/PCR data from the test instrument into test results. Results for each analyte are reported as Detected, Not Detected, INVALID, ERROR, or NO RESULT, based on automated interpretation of the PCR amplification and melt curve data. The Xpert Respiratory Panel test reports Ct values for target pathogens detected by amplification.
### B Comparison Studies:
#### 1. Method Comparison with Predicate Device:
Not applicable.
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# 2. Matrix Comparison:
# Simulated Matrix Equivalence
Equivalent performance of simulated NPS matrix and natural clinical NPS matrix was established by testing three positive sample prepared by spiking 4-5 respiratory organisms into 3 pools of negative matrix at concentration levels of 5x LoD, 1-2x LoD and <1x LoD and tested with one Xpert Respiratory Panel reagent lot. Equivalent testing performance was observed for each organism and overall matrix equivalence was observed.
# Collection Media Equivalence
The Xpert Respiratory Panel test was validated for use with nasopharyngeal swab (NPS) specimens collected in Universal Transport Medium (UTM)/Viral Transport Medium (VTM) or eNAT Molecular Collection and Preservation Medium. Clinical performance of the Xpert Respiratory Panel test was established using NPS specimens collected in UTM/VTM. Performance in Copan eNAT, Remel MicroTest M4RT, M5, and M6 transport media was established in analytical studies only; clinical performance in these media types was not established. Transport media containing guanidine thiocyanate (GTC), except for Copan eNAT, has not been evaluated with the Xpert Respiratory Panel test and may yield invalid or inaccurate results.
# C Clinical Studies:
1. Clinical Sensitivity:
Not applicable
2. Clinical Specificity:
Not applicable
3. Clinical Cut-Off
Not applicable
4. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):
# Prospective Clinical Study
The clinical performance of the Xpert Respiratory Panel test was evaluated using clinical specimen prospectively collected in a multi-site study including 19 geographically diverse sites (15 U.S. sites and 4 O.U.S. sites). NPS specimens in UTM/VTM from leftover standard of care testing of pediatric and adult patients exhibiting clinical signs and symptoms of respiratory tract infection were enrolled prospectively from November 2024 to February 2025. Prospective frozen specimens were collected from January to March 2024 and during the month of September 2024. The results of the Xpert Respiratory Panel test were compared to results from an FDA-cleared molecular respiratory panel (NAAT 1) except for B.
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parapertussis. PPA and NPA for B. parapertussis detection were determined by comparing results with a different FDA-cleared molecular respiratory panel (NAAT 2). Discrepant results for all analytes except B. parapertussis were investigated using NAAT 2. Discrepant B. parapertussis results were investigated using a molecular test for B. parapertussis (NAAT-Bordetella).
Initial enrollment included a total of 2643 unique prospectively collected specimens that met the pre-determined inclusion criteria. Of these, a total of 12 (0.45 %) specimens were excluded due to protocol deviations with specimen collection. Table 9 provides a summary of the demographic information for the remaining 2,631 subjects included in the data analysis. Of the 2,631 samples included in the data analysis, 84% (2,231/2,631) were tested fresh while 16% (400/2,631) were tested frozen. Clinical performance of the Xpert Respiratory Panel with prospectively collected samples is presented in Table 10.
Table 10: Demographic Summary for the Prospective Symptomatic Population
| Characteristics | Symptomatic Subjects |
| --- | --- |
| Total, N | 2643 |
| **Age Group (Years), n (%)** | |
| ≤ 5 yr | 556 (21.0%) |
| 6-17 yr | 365 (13.8%) |
| 18-21 yr | 104 (3.9%) |
| 22-49 yr | 657 (24.9%) |
| 50-64 yr | 374 (14.2%) |
| ≥ 65 yr | 587 (22.2%) |
| **Sex, n (%)** | |
| Male | 1240 (46.9%) |
| Female | 1403 (53.1%) |
| **Ethnicity, n (%)** | |
| Hispanic / Latino | 592 (22.4%) |
| Not Hispanic / Not Latino | 1529 (57.9%) |
| Not Available | 522 (19.8%) |
| **Race, n (%)** | |
| American Indian / Alaskan Native | 9 (0.3%) |
| Asian | 61 (2.3%) |
| Black / African-American | 533 (20.2%) |
| White | 1094 (41.4%) |
| Other or Mixed Race | 15 (0.6%) |
| Not Available | 931 (35.2%) |
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**Table 11: Clinical Performance of Xpert Respiratory Panel in Prospectively Collected Specimens**
| Analyte | | TP | FN | PPA% TP/(TP+FN) | PPA 95% CI | TN | FP | NPA% TN/(TN+FP) | NPA 95% CI |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Adenovirus^{1} | Prospective Overall | 36 | 1 | 97.3% 36/37 | 86.2% - 99.5% | 2448 | 20 | 99.2% 2448/2468 | 98.8% - 99.5% |
| | Fresh | 33 | 1 | 97.1% 33/34 | 85.1% - 99.5% | 2084 | 19 | 99.1% 2084/2103 | 98.6% - 99.4% |
| | Frozen | 3 | 0 | 100% 3/3 | 43.9% - 100% | 364 | 1 | 99.7% 364/365 | 98.5% - 100% |
| Coronavirus^{2} | Prospective Overall | 128 | 4 | 97.0% 128/132 | 92.5% - 98.8% | 2345 | 28 | 98.8% 2345/2373 | 98.3% - 99.2% |
| | Fresh | 115 | 4 | 96.6% 115/119 | 91.7% - 98.7% | 1996 | 22 | 98.9% 1996/2018 | 98.4% - 99.3% |
| | Frozen | 13 | 0 | 100% 13/13 | 77.2% - 100% | 349 | 6 | 98.3% 349/355 | 96.4% - 99.2% |
| SARS-CoV-2^{3} | Prospective Overall | 143 | 6 | 96.0% 143/149 | 91.5% - 98.1% | 2297 | 59 | 97.5% 2297/2356 | 96.8% - 98.1% |
| | Fresh | 53 | 1 | 98.1% 53/54 | 90.2% - 99.7% | 2069 | 14 | 99.3% 2069/2083 | 98.9% - 99.6% |
| | Frozen | 90 | 5 | 94.7% 90/95 | 88.3% - 97.7% | 228 | 45 | 83.5% 228/273 | 78.7% - 87.4% |
| Human Metapneumovirus^{4} | Prospective Overall | 30 | 0 | 100% 30/30 | 88.7% - 100% | 2472 | 3 | 99.9% 2472/2475 | 99.6% - 100% |
| | Fresh | 23 | 0 | 100% 23/23 | 85.7% - 100% | 2113 | 1 | 99.9% 2113/2114 | 99.7% - 100% |
| | Frozen | 7 | 0 | 100% 7/7 | 64.6% - 100% | 359 | 2 | 99.4% 359/361 | 98.0% - 99.8% |
| Rhinovirus/ Enterovirus^{5} | Prospective Overall | 362 | 16 | 95.8% 362/378 | 93.2% - 97.4% | 2056 | 71 | 96.7% 2056/2127 | 95.8% - 97.3% |
| | Fresh | 295 | 11 | 96.4% 295/306 | 93.7% - 98.0% | 1767 | 64 | 96.5% 1767/1831 | 95.6% - 97.3% |
| | Frozen | 67 | 5 | 93.1% 67/72 | 84.8% - 97.0% | 289 | 7 | 97.6% 289/296 | 95.2% - 98.9% |
| Parainfluenza^{6} | Prospective Overall | 57 | 1 | 98.3% 57/58 | 90.9% - 99.7% | 2426 | 21 | 99.1% 2426/2447 | 98.7% - 99.4% |
| | Fresh | 54 | 1 | 98.2% 54/55 | 90.4% - 99.7% | 2063 | 19 | 99.1% 2063/2082 | 98.6% - 99.4% |
| | Frozen | 3 | 0 | 100% 3/3 | 43.9% - 100% | 363 | 2 | 99.5% 363/365 | 98.0% - 99.8% |
| Influenza A^{7} | Prospective Overall | 297 | 5 | 98.3% 297/302 | 96.2% - 99.3% | 2178 | 25 | 98.9% 2178/2203 | 98.3% - 99.2% |
| | Fresh | 222 | 2 | 99.1% 222/224 | 96.8% - 99.8% | 1906 | 7 | 99.6% 1906/1913 | 99.2% - 99.8% |
| | Frozen | 75 | 3 | 96.2% 75/78 | 89.3% - 98.7% | 272 | 18 | 93.8% 272/290 | 90.4% - 96.0% |
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| Analyte | | TP | FN | PPA% TP/(TP+FN) | PPA 95% CI | TN | FP | NPA% TN/(TN+FP) | NPA 95% CI |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Influenza B | Prospective Overall | 8 | 0 | 100% 8/8 | 67.6% - 100% | 2497 | 0 | 100% 2497/2497 | 99.8% - 100% |
| | Fresh | 8 | 0 | 100% 8/8 | 67.6% - 100% | 2129 | 0 | 100% 2129/2129 | 99.8% - 100% |
| | Frozen | 0 | 0 | N/A | N/A | 368 | 0 | 100% 368/368 | 99.0% - 100% |
| Respiratory Syncytial Virus\( ^{8} \) | Prospective Overall | 153 | 6 | 96.2% 153/159 | 92.0% - 98.3% | 2319 | 27 | 98.8% 2319/2346 | 98.3% - 99.2% |
| | Fresh | 152 | 6 | 96.2% 152/158 | 92.0% - 98.2% | 1954 | 25 | 98.7% 1954/1979 | 98.1% - 99.1% |
| | Frozen | 1 | 0 | 100% 1/1 | 20.7% - 100% | 365 | 2 | 99.5% 365/367 | 98.0% - 99.9% |
| Bordetella pertussis\( ^{9} \) | Prospective Overall | 10 | 2 | 83.3% 10/12 | 55.2% - 95.3% | 2488 | 5 | 99.8% 2488/2493 | 99.5% - 99.9% |
| | Fresh | 9 | 1 | 90.0% 9/10 | 59.6% - 98.2% | 2122 | 5 | 99.8% 2122/2127 | 99.5% - 99.9% |
| | Frozen | 1 | 1 | 50.0% 1/2 | 9.4% - 90.6% | 366 | 0 | 100% 366/366 | 99.0% - 100% |
| Bordetella parapertussis\( ^{10} \) | Prospective Overall | 0 | 0 | N/A | N/A | 2613 | 1 | 99.9% 2613/2614 | 99.8% - 100% |
| | Fresh | 0 | 0 | N/A | N/A | 2218 | 0 | 100% 2218/2218 | 99.8% - 100% |
| | Frozen | 0 | 0 | N/A | N/A | 395 | 1 | 99.7% 395/396 | 98.6% - 100% |
| Mycoplasma pneumoniae\( ^{11} \) | Prospective Overall | 66 | 8 | 89.2% 66/74 | 80.1% - 94.4% | 2409 | 22 | 99.1% 2409/2431 | 98.6% - 99.4% |
| | Fresh | 65 | 8 | 89.0% 65/73 | 79.8% - 94.3% | 2043 | 21 | 99.0% 2043/2064 | 98.4% - 99.3% |
| | Frozen | 1 | 0 | 100% 1/1 | 20.7% - 100% | 366 | 1 | 99.7% 366/367 | 98.5% - 100% |
| Chlamydia pneumoniae\( ^{12} \) | Prospective Overall | 1 | 0 | 100% 1/1 | 20.7% - 100% | 2503 | 1 | 99.9% 2503/2504 | 99.8% - 100% |
| | Fresh | 0 | 0 | N/A | N/A | 2137 | 0 | 100% 2137/2137 | 99.8% - 100% |
| | Frozen | 1 | 0 | 100% 1/1 | 20.7% - 100% | 366 | 1 | 99.7% 366/367 | 98.5% - 100% |
\( ^{1} \) Discrepant test results based on NAAT 2: In specimens with FN results, 1/1 AdV negative. In specimens with FP results, 13/20 AdV positive, 7/20 AdV negative.
\( ^{2} \) Discrepant test results based on NAAT 2: In specimens with FN results, 3/4 CoV negative, 1/4 CoV positive. In specimens with FP results, 19/28 CoV positive, 9/28 CoV negative.
\( ^{3} \) Discrepant test results based on NAAT 2: In specimens with FN results, 5/6 SARS-CoV-2 negative, 1/6 SARS-CoV-2 positive. In specimens with FP results, 22/59 SARS-CoV-2 positive, 37/59 SARS-CoV-2 negative.
\( ^{4} \) Discrepant test results based on NAAT 2: In specimens with FP results, 1/3 hMPV positive, 2/3 hMPV negative.
\( ^{5} \) Discrepant test results based on NAAT 2: In specimens with FN results, 3/16 RV/EV negative, 13/16 RV/EV positive. In specimens with FP results, 59/71 RV/EV positive, 12/71 RV/EV negative.
\( ^{6} \) Discrepant test results based on NAAT 2: In specimens with FN results, 1/1 PIV negative. In specimens with FP results, 16/21 PIV positive, 5/21 PIV negative.
\( ^{7} \) Discrepant test results based on NAAT 2: In specimens with FN results, 4/5 Flu A negative, 1/5 Flu A positive. In specimens with FP results, 11/25 Flu A positive, 13/25 Flu A negative, 1/25 with invalid results.
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| Analyte | TP | FN | PPA% TP/(TP+FN) | PPA 95% CI | TN | FP | NPA% TN/(TN+FP) | NPA 95% CI |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
\( ^{8} \) Discrepant test results based on NAAT 2: In specimens with FN results, 3/6 RSV negative, 3/6 RSV positive. In specimens with FP results, 20/27 RSV positive, 7/27 RSV negative.
\( ^{9} \) Discrepant test results based on NAAT 2: In specimens with FN results, 2/2 B. pertussis negative. In specimens with FP results, 5/5 B. pertussis negative.
\( ^{10} \) Discrepant test results based on NAAT-Bordetella: In specimens with FP results, 1/1 not sent for discrepant testing.
\( ^{11} \) Discrepant test results based on NAAT 2: In specimens with FN results, 7/8 M. pneumoniae negative, 1/8 M. pneumoniae positive. In specimens with FP results, 8/22 M. pneumoniae positive, 14/22 M. pneumoniae negative.
\( ^{12} \) Discrepant test results based on NAAT 2: In the specimen with FP results, 1/1 C. pneumoniae positive.
The Xpert Respiratory Panel test detected 2 or more analytes in a total of 215 specimens. Of the 215 specimens with multi-analyte detection, RV/EV was most commonly co-detected with another analyte (47.4%), followed by Flu A (34.0%), and SARS-CoV-2 (31.6%). The positivity rates of multi-analyte detection by Xpert are presented in Table 11.
Table 12: Xpert Positivity Rates of Multi-Analyte Detection
| Analyte | Multi-analyte Detection (N = 215) |
| --- | --- |
| RV/EV | 47.4% (102) |
| Flu A | 34.0% (73) |
| SARS-CoV-2 | 31.6% (68) |
| RSV | 24.7% (53) |
| CoV | 23.7% (51) |
| AdV | 17.2% (37) |
| PIV | 14.4% (31) |
| M. pneumoniae | 12.6% (27) |
| B. pertussis | 4.7% (10) |
| hMPV | 4.7% (10) |
| B. parapertussis | 0.5% (1) |
### Retrospective/Archived Study:
To supplement the clinical study results for analytes with low prevalence (AdV, hMPV, Flu B, B. pertussis, B. parapertussis and C. pneumoniae), pre-selected archived specimens collected from individuals with signs and symptoms of respiratory infection (collection dates May 2009 to September 2025) were tested from January 2023 to August 2026. A summary of the demographic information of the tested retrospective specimens is provided in Table 12 below. A total of 277 archived specimens were tested in this study. The same comparators as the prospective study was used. Clinical performance for archived samples is shown in Table 13.
Table 13: Demographic Results of Archived Specimens…
