Xpert CT/NG, GeneXpert Dx System, GeneXpert Infinity-48s and GeneXpert Infinity-80 Systems, GeneXpert Infinity-48 System, Xpert Vaginal/Endocervical Specimen Collection, Xpert Urine Specimen Collection Kit, Xpert Swab Specimen Collection Kit
Device Facts
| Record ID | K190441 |
|---|---|
| Device Name | Xpert CT/NG, GeneXpert Dx System, GeneXpert Infinity-48s and GeneXpert Infinity-80 Systems, GeneXpert Infinity-48 System, Xpert Vaginal/Endocervical Specimen Collection, Xpert Urine Specimen Collection Kit, Xpert Swab Specimen Collection Kit |
| Applicant | Cepheid |
| Product Code | QEP · Microbiology |
| Decision Date | May 23, 2019 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 866.3393 |
| Device Class | Class 2 |
Indications for Use
The Xpert® CT/NG test, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro real-time PCR test for the automated detection and differentiation of genomic DNA from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) to aid in the diagnosis of chlamydial and gonorrheal disease in the urogenital tract and extragenital sites (pharynx and rectum). The assay may be used to test the following specimens from asymptomatic and symptomatic individuals: female and male urine, patient-collected vaginal swabs (collected in a clinical setting), clinician-collected endocervical swabs, and female and male pharyngeal and rectal swabs.
Device Story
Xpert CT/NG is an automated in vitro diagnostic test for qualitative detection and differentiation of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) DNA. The device utilizes the GeneXpert Instrument System (Dx, Infinity-48, Infinity-48s, or Infinity-80) to perform sample purification, nucleic acid amplification, and real-time PCR detection. The system uses single-use disposable cartridges containing PCR reagents, a syringe drive for fluidics, an ultrasonic horn for cell/spore lysis, and an I-CORE thermocycler. The device is used in clinical settings by healthcare professionals. The system includes internal controls: Sample Processing Control (SPC) for inhibition/processing, Sample Adequacy Control (SAC) for human cell presence, and Probe Check Control (PCC) for reagent/dye integrity. Results are viewed on a connected PC. The output aids clinicians in diagnosing chlamydial and gonorrheal infections, enabling timely patient management and treatment.
Clinical Evidence
Prospective multi-site study (9 US institutions) comparing Xpert CT/NG to an Anatomic Site Infected Status (ASIS) algorithm (composite of two comparator NAATs). Enrolled 2,767 participants; 2,575 pharyngeal and 2,538 rectal specimens analyzed. Pharyngeal CT sensitivity 95.9%, specificity 99.7%. Rectal CT sensitivity 86.0%, specificity 99.4%. Pharyngeal NG sensitivity 94.7%, specificity 98.8%. Rectal NG sensitivity 91.2%, specificity 99.6%. Valid reporting rate 99.1%.
Technological Characteristics
Multiplex real-time PCR assay. Components: single-use disposable cartridges, GeneXpert Instrument System (syringe drive, ultrasonic horn, I-CORE thermocycler). Controls: Sample Processing Control (SPC), Sample Adequacy Control (SAC), Probe Check Control (PCC). Connectivity: networked/standalone instrument systems. Software: preloaded on integrated PC.
Indications for Use
Indicated for symptomatic and asymptomatic individuals, including males and females, for the detection and differentiation of Chlamydia trachomatis and Neisseria gonorrhoeae DNA in urogenital (urine, endocervical, vaginal) and extragenital (pharyngeal, rectal) specimens to aid in the diagnosis of chlamydial and gonorrheal infections.
Regulatory Classification
Identification
A device to detect nucleic acids from non-viral microorganism(s) causing sexually transmitted infections and associated resistance marker(s) is an in vitro diagnostic device intended for the detection and identification of nucleic acids from non-viral microorganism(s) and their associated resistance markers in clinical specimens collected from patients suspected of sexually transmitted infections. The device is intended to aid in the diagnosis of non-viral sexually transmitted infections in conjunction with other clinical and laboratory data. These devices do not provide confirmation of antibiotic susceptibility since mechanisms of resistance may exist that are not detected by the device.
Special Controls
A device to detect nucleic acids from non-viral microorganism(s) causing sexually transmitted infections and associated resistance marker(s) must comply with the following special controls: (1) The intended use for the 21 CFR 809.10 labeling must include a detailed description of targets the device detects, the results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended. (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 21 CFR 809.10(b) labeling 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 discussion of the performance characteristics of the device for all claimed specimen types based on analytical studies, including, but not limited to. Limit of Detection, inclusivity, cross-reactivity, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, with-in lab precision, and reproducibility, as appropriate; (iii) Detailed descriptions of the test procedure, the interpretation of test results for clinical specimens, and acceptance criteria for any quality control testing. (iv) Limiting statements indicating 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) reliable results are dependent on adequate specimen collection, transport, storage, and processing. Failure to observe procedures in any one of these steps can lead to incorrect results; and (D)if appropriate (e.g., recommended by CDC, by current well-accepted clinical guidelines, or by published peer reviewed research), that the clinical performance is inferior in a specific clinical subpopulation or for a specific claimed specimen type. (v) If the device is intended to detect antimicrobial resistance markers, limiting statements, as appropriate, indicating that: (A)negative results for claimed resistance markers do not indicate susceptibility of detected microorganisms, as resistance markers not measured by the assay or other potential mechanisms of antibiotic resistance may be present; (B) detection of resistance markers cannot be definitively linked to specific microorganisms and the source of a detected resistance marker may be an organism not detected by the assay, including colonizing flora; (C) detection of antibiotic resistance markers may not correlate with phenotypic gene expression; and (D) therapeutic failure or success cannot be determined based on the assay results, since nucleic acid may persist following appropriate antimicrobial therapy. (4) Design verification and validation must include: (i) Detailed device description documentation, including, but not limited to, methodology from obtaining sample to result, design of primer/probe sequences, rationale for target sequence selection, and computational path from collected raw data to reported result (e.g., how collected raw signals are converted into a reported result). (ii) Detailed documentation of analytical studies including but not limited to, Limit of Detection, inclusivity, cross-reactivity, microbial interference, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, with-in lab precision, and reproducibility, as appropriate. (iii) Detailed documentation and performance results from a clinical study that includes prospective (sequential) samples for each claimed specimen type and, when determined to be appropriate by FDA, additional characterized clinical samples. The study must be performed on a study population consistent with the intended use population and compare the device performance to results obtained from FDA accepted comparator methods. Documentation from the clinical studies must include the clinical study protocol (including a predefined statistical analysis plan) study report, testing results, and results of all statistical analyses. (iv) A detailed description of the impact of any software, including, but not limited to, software applications and hardware-based devices that incorporate software, on the device's functions.
*Classification.* Class II (special controls). The special controls for this device are:(1) The intended use for the labeling required under § 809.10 of this chapter must include a detailed description of targets the device detects, the results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended. (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 discussion of the performance characteristics of the device for all claimed specimen types based on analytical studies, including Limit of Detection, inclusivity, cross-reactivity, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, within lab precision, and reproducibility, as appropriate; (iii) Detailed descriptions of the test procedure, the interpretation of test results for clinical specimens, and acceptance criteria for any quality control testing; (iv) Limiting statements indicating 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) Reliable 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 (D) If appropriate ( *e.g.,* recommended by the Centers for Disease Control and Prevention, by current well-accepted clinical guidelines, or by published peer reviewed research), that the clinical performance is inferior in a specific clinical subpopulation or for a specific claimed specimen type; and(v) If the device is intended to detect antimicrobial resistance markers, limiting statements, as appropriate, indicating that: (A) Negative results for claimed resistance markers do not indicate susceptibility of detected microorganisms, as resistance markers not measured by the assay or other potential mechanisms of antibiotic resistance may be present; (B) Detection of resistance markers cannot be definitively linked to specific microorganisms and the source of a detected resistance marker may be an organism not detected by the assay, including colonizing flora; (C) Detection of antibiotic resistance markers may not correlate with phenotypic gene expression; and (D) Therapeutic failure or success cannot be determined based on the assay results, since nucleic acid may persist following appropriate antimicrobial therapy. (4) Design verification and validation must include: (i) Detailed device description documentation, including methodology from obtaining sample to result, design of primer/probe sequences, rationale for target sequence selection, and computational path from collected raw data to reported result ( *e.g.,* how collected raw signals are converted into a reported result).(ii) Detailed documentation of analytical studies, including, Limit of Detection, inclusivity, cross-reactivity, microbial interference, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, within lab precision, and reproducibility, as appropriate. (iii) Detailed documentation and performance results from a clinical study that includes prospective (sequential) samples for each claimed specimen type and, when determined to be appropriate by FDA, additional characterized clinical samples. The study must be performed on a study population consistent with the intended use population and compare the device performance to results obtained from FDA accepted comparator methods. Documentation from the clinical studies must include the clinical study protocol (including a predefined statistical analysis plan) study report, testing results, and results of all statistical analyses. (iv) A detailed description of the impact of any software, including software applications and hardware-based devices that incorporate software, on the device's functions.
Predicate Devices
- Aptima Mycoplasma genitalium Assay (DEN180047)
- Xpert Vaginal/Endocervical Specimen Collection Kit (K173840)
- BD MAX UVE Specimen Collection Kit (K043144)
Related Devices
Submission Summary (Full Text)
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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
A. 510(k) Number:
K190441
B. Purpose for Submission:
To obtain a Substantial Equivalence Determination for a new 510(k) application for Xpert CT/NG performed on the Cepheid GeneXpert Instrument Systems for new specimen types; rectal swab and pharyngeal swab.
C. Measurand:
Unique sequences in the genomic DNA for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG).
D. Type of Test:
Automated, multiplex real-time polymerase chain reaction (PCR) assay intended for the in vitro qualitative detection and differentiation of DNA from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG).
E. Applicant:
Cepheid
F. Proprietary and Established Names:
Xpert CT/NG
Xpert CT/NG Assay
G. Regulatory Information:
1. Regulation section:
866.3393 Device to detect nucleic acids from non-viral microorganism(s) causing sexually transmitted infections and associated resistance marker(s)
2. Classification:
Class II
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3. Product codes:
QEP: Nucleic Acid Detection System For Non-Viral Microorganism(s) Causing Sexually Transmitted Infections
LSL: DNA-Reagents, Neisseria
MKZ: DNA Probe, Nucleic Acid Amplification, Chlamydia
OOI: Real Time Nucleic Acid Amplification System
QBD: Microbial Nucleic Acid Storage and Stabilization Device
4. Panel:
Microbiology (83)
H. Intended Use:
1. Intended use(s):
Device Intended Use:
The Xpert® CT/NG test, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro real-time PCR test for the automated detection and differentiation of genomic DNA from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) to aid in the diagnosis of chlamydial and gonorrheal disease in the urogenital tract and extragenital sites (pharynx and rectum). The assay may be used to test the following specimens from asymptomatic and symptomatic individuals: female and male urine, patient-collected vaginal swabs (collected in a clinical setting), clinician-collected endocervical swabs, and female and male pharyngeal and rectal swabs.
Ancillary Collection Kits:
Xpert Vaginal/Endocervical Specimen Collection Kit
The Cepheid Xpert® Swab Specimen Collection Kit is designed to collect, preserve, and transport Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis DNA in endocervical swab specimens (collected by a clinician) and patient-collected vaginal swab specimens (collected in a clinical setting) from symptomatic and asymptomatic women prior to analysis with the Xpert CT/NG Assay and the Xpert TV Assay.
Xpert Urine Specimen Collection Kit
The Cepheid Xpert® Urine Specimen Collection Kit is designed to preserve and transport Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis DNA in first-catch female and male urine specimens from symptomatic and asymptomatic individuals prior to analysis with the Xpert CT/NG Assay and the Xpert TV Assay.
Xpert Swab Specimen Collection Kit
The Xpert® Swab Specimen Collection Kit is designed to collect, preserve, and transport endocervical, vaginal, pharyngeal, and rectal swab specimens. This transport system is for use for testing with Xpert tests.
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2. Indication(s) for use:
Same as Intended Use
3. Special conditions for use statement(s):
For Prescription Use Only
4. Special instrument requirements:
Gene Xpert System
I. Device Description:
The Xpert CT/NG test is an automated *in vitro* diagnostic test for qualitative detection and differentiation of DNA from *Chlamydia trachomatis* (CT) and/or *Neisseria gonorrhoeae* (NG). The test is performed on the Cepheid GeneXpert Instrument Systems. The Xpert CT/NG test on the GeneXpert Instrument System automates and performs the following procedures; sample purification, nucleic acid amplification through real-time polymerase chain reaction (PCR), and detection of the target sequences. The system consists of an instrument, personal computer, and preloaded software for running the tests and viewing the results. The system requires the use of single-use disposable cartridges that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained, cross-contamination between samples is minimized.
The Xpert CT/NG test includes reagents for the detection and differentiation of CT and NG. A Sample Processing Control (SPC), a Sample Adequacy Control (SAC), and a Probe Check Control (PCC) are also included. The SPC is present to control for adequate processing of the target bacteria and to monitor the presence of inhibitors in the PCR reaction. The SAC reagents detect the presence of a single copy human gene and monitor whether the specimen contains human cells. The PCC verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dye stability.
The GeneXpert Instrument Systems, comprised of the GeneXpert Dx Systems, the GeneXpert Infinity-48 System, GeneXpert Infinity-48s, and the GeneXpert Infinity-80 System, have 1 to 80 randomly accessible modules, depending upon the instrument, that are each capable of performing separate sample preparation and real-time PCR tests.
Each module 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 PCR and detection.
The ancillary specimen collection kits for use with the Xpert CT/NG test are the Xpert Vaginal/Endocervical Specimen Collection Kit, Xpert Swab Specimen Collection kit, and the Xpert Urine Specimen Collection kit.
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# J. Substantial Equivalence Information:
1. Predicate device name(s): Aptima Mycoplasma Genitalium Assay
2. Predicate 510(k) number(s): DEN180047
3. Comparison with predicate:
Table 1. Similarities between device and predicate.
| Similarities | | |
| --- | --- | --- |
| | Device | Predicate Device |
| Item | Cepheid Xpert CT/NG | Aptima Mycoplasma Genitalium Assay |
| Nucleic Acid Extraction | Yes | Yes |
| Assay Results | Qualitative | Same |
| Indication for Use | Asymptomatic and symptomatic patients | Same |
Table 2. Differences between device and the predicate
| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate Device |
| | Cepheid Xpert CT/NG | Aptima Mycoplasma Genitalium Assay |
| Technology/ Detection | Multiplex real-time polymerase chain reaction (PCR) | Transcription -mediated nucleic acid amplification and hybridization |
| Specimen Type | Female and male urine, endocervical swab, patient-collected vaginal swab (collected in a clinical setting), and female and male pharyngeal and rectal swabs | Clinician-collected and self-collected vaginal swabs (in a clinical setting), clinician-collected endocervical swabs, female and male urine, clinician-collected male urethral swabs, and self-collected penile meatal swabs (in a clinical setting) |
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| Intended Use | The Xpert® CT/NG test, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro real-time PCR test for the automated detection and differentiation of genomic DNA from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) to aid in the diagnosis of chlamydial and gonorrheal disease in the urogenital tract and extragenital sites (pharynx and rectum). The assay may be used to test the following specimens from asymptomatic and symptomatic individuals: female and male urine, patient-collected vaginal swabs (collected in a clinical setting), clinician-collected endocervical swabs, and female and male pharyngeal and rectal swabs. | The Aptima Mycoplasma genitalium assay is an in vitro nucleic acid amplification test (NAAT) for the qualitative detection of ribosomal RNA (rRNA) from Mycoplasma genitalium on the fully automated Panther system. It is intended for use as an aid in the diagnosis of M. genitalium urogenital infections in male and female patients suspected of M. genitalium infection. The assay may be used to test the following specimens: clinician-collected and self-collected vaginal swabs (in a clinical setting), clinician-collected endocervical swabs, female and male urine, clinician-collected male urethral swabs, and self-collected penile meatal swabs (in a clinical setting). For females, a vaginal swab is the preferred specimen type due to higher clinical sensitivity for detecting M. genitalium than other specimen types; however, female urine or clinician-collected endocervical swabs may be used as alternative specimens when vaginal swab specimens are not available. If female urine or clinician-collected endocervical swab specimens test negative, testing with a vaginal swab may be indicated, if M. genitalium infection is suspected. |
| --- | --- | --- |
| Assay Targets | DNA from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) | Ribosomal RNA from Mycoplasma genitalium |
| Instrument System | Cepheid GeneXpert Instrument System | Panther System |
| Assay Controls | Internal sample processing control (SPC), sample adequacy control (SAC), and probe check control (PCC). External controls available. | Internal Control (IC). External calibrators available. |
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K. Standard/Guidance Document Referenced (if applicable):
N/A
L. Test Principle:
The assay detects bacterial genomic DNA that has been extracted from a patient sample. A multiplex real-time PCR reaction is carried out under optimized conditions generating amplicons for *Chlamydia trachomatis* and/or *Neisseria gonorrhoeae* and the Sample Process Control (SPC). Identification of *Chlamydia trachomatis*, *Neisseria gonorrhoeae*, and the SPC occurs by the use of target-specific primers and fluorescent-labeled probes that hybridize to conserved regions in the genomes.
M. Performance Characteristics (if/when applicable):
1. Analytical performance:
Several of the analytical studies in support of this 510(k) submission were conducted for and described in submission K121710. Testing for all analytical studies reported with K121710 was performed using the identical Cepheid Xpert CT/NG Assay, and no changes to the assay were made since the 510(k) clearance of K121710. The additional analytical studies described below were performed in support of the new specimen types included in the Intedned Use for this submission.
a. Precision/Reproducibility:
Please refer to the Decision Summary for submissions K121710.
b. Linearity/assay reportable range:
Please refer to submission K121710.
c. Traceability, Stability, controls and calibrators:
Please refer to submission K121710.
Stability:
Stability studies have been performed to support device performance for the new specimen types:
Sample Stability:
To examine sample stability of pharyngeal and rectal swabs in Cepeid Xpert swab transport reagent (STR), positive samples for two serovars of CT and two strains of NG were generated. Bacteria was seeded at 3xLoD into pooled negative clinical matrix for each sample type. Pooled negative clinical matrix was used for negative samples. Positive and Negative samples were stored at 2°C, 8°C, 15°C and 30°C to represent extremes of refrigerated and room-temperature storage conditions. Replicates of 8 positive and 4 negative samples were tested for each sample type and bacteria at time 0, 1 day, 2 days, 4 days, 8 days, 16 days, 41 days
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and 61 days for each storage condition.
Under the conditions of this study, all positive and negative samples at all storage conditions and temperatures tested were correctly identified using the Xpert CT/NG test.
The following specimen stability claims are supported by study data:
- $2 - 30^{\circ}\mathrm{C}$ for up to 60 days
# Kit Stability:
The following kit stability claims are supported by study data from K121710:
- $2 - 28^{\circ}\mathrm{C}$ until expiration date provided on label
# Cartridge Hold Time:
The following stability claim for prepared samples waiting on the GeneXpert Instrument Systems was confirmed in a new study with pharyngeal and rectal specimen types:
Up to 4.5 hours at room temperature
# Carryover:
Please refer to submission K121710.
# d. Detection limit:
Studies were performed to determine the analytical limit of detection (LoD) of the Xpert CT/NG for rectal swab and pharyngeal swabs. Pooled negative clinical matrix was used for negative samples and was spiked to generate positive samples. Positive pharyngeal and rectal swabs in Cepeid Xpert swab transport reagent (STR) were generated for 2 serovars of CT and 2 strains of NG. Limiting dilutions of titered CT and NG were generated, 5 dilutions per serovar/strain with 20 replicates each. Testing was performed with two reagent lots per bacteria and occurred across 3 testing days. Probit model fit was used to estimate the LoD which was then confirmed with 20 replicates where $\geq 19/20$ replicates were positive.
The LoD point values for each serovar/strain tested in paryngeal and rectal swab matrix are summarized in Tables below.
Table 3. Confirmed LoD (EB/mL): Chlamydia tracomatis
| Organism Strain | Confirmed LoD(EB/mL) | |
| --- | --- | --- |
| | Pharyngeal Swab | Rectal Swab |
| Chlamydia tracomatis serovar D | 161 | 88 |
| Chlamydia tracomatis serovar H | 225 | 161 |
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Table 4. Confirmed LoD (CFU/mL): Neisseria gonorrhoeae
| Organism Strain | Confirmed LoD (CFU/mL) | |
| --- | --- | --- |
| | Pharyngeal Swab | Rectal Swab |
| Neisseria gonorrhoeae ATCC 19424 | 7.1 | 4.9 |
| Neisseria gonorrhoeae ATCC 49226 | 6.4 | 5.3 |
# e. Analytical specificity:
# Analytical Reactivity (inclusivity)
The analytical reactivity of the Xpert CT/NG test was evaluated against 14 CT serovars and 20 NG strains obtained from culture collections in the United States and Europe. Pooled negative clinical matrix was used for negative samples. Positive samples were prepared by spiking negative clinical matrix with bacteria at concentrations near the LoD. Three replicates of each serovar/strain were tested for both pharyngeal and rectal swabs in Cepeid Xpert swab transport reagent (STR).
Table 5: Analytical Reactivity Results of Xpert CT/NG with CT Serovars in Rectal Swab Matrix
| C. trachomatis serovar | Concentration Tested in Rectal Swab Matrix | Test Result | |
| --- | --- | --- | --- |
| | | CT | NG |
| A | 1800 EB/mL | POS | NEG |
| B | 8.1 EB/mL | POS | NEG |
| Ba | 0.81 EB/mL | POS | NEG |
| C | 322 EB/mL | POS | NEG |
| E | 322 EB/mL | POS | NEG |
| E/SW2 | 0.81 IFU/mLa | POS | NEG |
| F | 322 EB/mL | POS | NEG |
| G | 644 EB/mL | POS | NEG |
| I | 0.16 EB/mL | POS | NEG |
| J | 644 EB/mL | POS | NEG |
| K | 644 EB/mL | POS | NEG |
| LGV I | 322 EB/mL | POS | NEG |
| LGV II | 322 EB/mL | POS | NEG |
| LGV III | 644 EB/mL | POS | NEG |
a IFU/mL = Infectious units per mL.
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Table 6: Analytical Reactivity Results of Xpert CT/NG with NG Strains in Rectal Swab Matrix
| N. gonorrhoeae Strain | Concentration Tested in Rectal Swab Matrix (CFU/mL) | Test Result | |
| --- | --- | --- | --- |
| | | CT | NG |
| 9793 | 10.6 | NEG | POS |
| 9830 | 10.6 | NEG | POS |
| 19999 | 10.6 | NEG | POS |
| 27629 | 10.6 | NEG | POS |
| 27630 | 10.6 | NEG | POS |
| 27631 | 10.6 | NEG | POS |
| 31148 | 10.6 | NEG | POS |
| 31397 | 10.6 | NEG | POS |
| 31399 | 10.6 | NEG | POS |
| 31400 | 10.6 | NEG | POS |
| 1170 | 42.4 | NEG | POS |
| 6395 | 10.6 | NEG | POS |
| 13281 | 10.6 | NEG | POS |
| 34447 | 10.6 | NEG | POS |
| 37541 | 10.6 | NEG | POS |
| 10226 | 10.6 | NEG | POS |
| 10227 | 10.6 | NEG | POS |
| 10932 | 10.6 | NEG | POS |
| 11472 | 10.6 | NEG | POS |
| 50348 | 10.6 | NEG | POS |
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Table 7: Analytical Reactivity Results of Xpert CT/NG with CT Serovars in Pharyngeal Swab Matrix
| C. trachomatis Serovar | Concentration Tested in Pharyngeal Swab Matrix | Test Result | |
| --- | --- | --- | --- |
| | | CT | NG |
| A | 1800 EB/mL | POS | NEG |
| B | 9 EB/mL | POS | NEG |
| Ba | 0.9 EB/mL | POS | NEG |
| C | 900 EB/mL | POS | NEG |
| E | 450 EB/mL | POS | NEG |
| E/SW2 | 0.9 IFU/mLa | POS | NEG |
| F | 450 EB/mL | POS | NEG |
| G | 900 EB/mL | POS | NEG |
| I | 0.18 EB/mL | POS | NEG |
| J | 900 EB/mL | POS | NEG |
| K | 900 EB/mL | POS | NEG |
| LGV I | 450 EB/mL | POS | NEG |
| LGV II | 450 EB/mL | POS | NEG |
| LGV III | 450 EB/mL | POS | NEG |
a IFU/mL = Infectious units per mL.
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Table 8: Analytical Reactivity Results of Xpert CT/NG with NG Strains in Pharyngeal Swab Matrix
| N. gonorrhoeae Strain | Concentration Tested in Pharyngeal Swab Matrix (CFU/mL) | Test Result | |
| --- | --- | --- | --- |
| | | CT | NG |
| 9793 | 14.2 | NEG | POS |
| 9830 | 14.2 | NEG | POS |
| 19999 | 14.2 | NEG | POS |
| 27629 | 14.2 | NEG | POS |
| 27630 | 14.2 | NEG | POS |
| 27631 | 14.2 | NEG | POS |
| 31148 | 14.2 | NEG | POS |
| 31397 | 14.2 | NEG | POS |
| 31399 | 14.2 | NEG | POS |
| 31400 | 14.2 | NEG | POS |
| 1170 | 14.2 | NEG | POS |
| 6395 | 14.2 | NEG | POS |
| 13281 | 14.2 | NEG | POS |
| 34447 | 14.2 | NEG | POS |
| 37541 | 14.2 | NEG | POS |
| 10226 | 14.2 | NEG | POS |
| 10227 | 14.2 | NEG | POS |
| 10932 | 14.2 | NEG | POS |
| 11472 | 14.2 | NEG | POS |
| 50348 | 14.2 | NEG | POS |
The Xpert CT/NG detected all 14 CT serovars and 20 NG strains in pharyngeal and rectal swab specimens.
# Cross-Reactivity
The cross-reactivity of the Xpert CT/NG test was evaluated in the presence of 43 microorganisms potentially present in rectal flora and 41 microorganisms potentially present in pharyngeal flora. Pooled negative clinical matrix was used for negative samples. Positive samples were made by spiking negative clinical matrix at $10^{6}$ CFU/ml for bacteria (except Entamoeba histolytica which was spiked at $10^{5}$ CFU/mL). Parasites were tested at $10^{6}$ cells/mL, and viruses were tested at $10^{5}$ TCID $_{50}$ /mL. Three replicates of each microorganism were tested in Cepeid Xpert swab transport reagent (STR).
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Table 9: Analytical Specificity Determination for Xpert CT/NG with Rectal Microorganisms
| Organism | Concentrationa (per cartridge) | CT | NG |
| --- | --- | --- | --- |
| No Template Control | N/A | Not Detected | Not Detected |
| Acinetobacter baumannii | 1.00E+06 | Not Detected | Not Detected |
| Anaerococcus tetradius | 1.00E+06 | Not Detected | Not Detected |
| Anaerococcus hydrogenalis | 1.00E+06 | Not Detected | Not Detected |
| Bacteroides fragilis | 1.00E+06 | Not Detected | Not Detected |
| Bifidobacterium adolescent | 1.00E+06 | Not Detected | Not Detected |
| Campylobacter jejuni | 1.00E+06 | Not Detected | Not Detected |
| Candida albicans | 1.00E+06 | Not Detected | Not Detected |
| Citrobacter freundii | 1.00E+06 | Not Detected | Not Detected |
| Clostridium difficile | 1.00E+06 | Not Detected | Not Detected |
| Entamoeba histolytica | 1.00E+05 | Not Detected | Not Detected |
| Enterobacter cloacae | 1.00E+06 | Not Detected | Not Detected |
| Enterococcus faecalis | 1.00E+06 | Not Detected | Not Detected |
| Enterococcus faecium | 1.00E+06 | Not Detected | Not Detected |
| Enterovirus | 1.00E+05 | Not Detected | Not Detected |
| Escherichia coli | 1.00E+06 | Not Detected | Not Detected |
| Fusobacterium necrophorum | 1.00E+06 | Not Detected | Not Detected |
| Fusobacterium nucleatum | 1.00E+06 | Not Detected | Not Detected |
| Giardia lamblia | 1.00E+06 | Not Detected | Not Detected |
| Helicobacter pylori | 1.00E+06 | Not Detected | Not Detected |
| Klebsiella oxytoca | 1.00E+06 | Not Detected | Not Detected |
| Lactobacillus acidophilus | 1.00E+06 | Not Detected | Not Detected |
| Lactobacillus delbrueckii | 1.00E+06 | Not Detected | Not Detected |
| Listeria monocytogenes | 1.00E+06 | Not Detected | Not Detected |
| Morganella morganii | 1.00E+06 | Not Detected | Not Detected |
| Norovirus | 1.00E+05 | Not Detected | Not Detected |
| Peptostreptococcus anaerobius | 1.00E+06 | Not Detected | Not Detected |
| Plesiomonas shigelloides | 1.00E+06 | Not Detected | Not Detected |
| Prevotella bivia | 1.00E+06 | Not Detected | Not Detected |
| Prevotella oralis | 1.00E+06 | Not Detected | Not Detected |
| Proteus mirabilis | 1.00E+06 | Not Detected | Not Detected |
| Providencia stuartii | 1.00E+06 | Not Detected | Not Detected |
| Pseudomonas aeruginosa | 1.00E+06 | Not Detected | Not Detected |
| Salmonella enterica sb enterica sv minnesota | 1.00E+06 | Not Detected | Not Detected |
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Table 10: Analytical Specificity Determination for Xpert CT/NG with Pharyngeal Microorganisms
| Organism | Concentrationa (per cartridge) | CT | NG |
| --- | --- | --- | --- |
| No Template Control | N/A | Not Detected | Not Detected |
| Actinobacillus actinomycetemcomitans | 1.00E+06 | Not Detected | Not Detected |
| Adenovirus | 1.00E+05 | Not Detected | Not Detected |
| Arcanobacterium haemolyticum | 1.00E+06 | Not Detected | Not Detected |
| Bordetella pertussis | 1.00E+06 | Not Detected | Not Detected |
| Campylobacter rectus | 1.00E+06 | Not Detected | Not Detected |
| Candida albicans | 1.00E+06 | Not Detected | Not Detected |
| Coronavirus | 1.00E+05 | Not Detected | Not Detected |
| Corynebacterium diphtheriae | 1.00E+06 | Not Detected | Not Detected |
| Fusobacterium necrophorum | 1.00E+06 | Not Detected | Not Detected |
| Haemophilus influenzae | 1.00E+06 | Not Detected | Not Detected |
| Herpes virus | 1.00E+05 | Not Detected | Not Detected |
| Human influenza virus A | 1.00E+05 | Not Detected | Not Detected |
| Human influenza virus B | 1.00E+05 | Not Detected | Not Detected |
| Human metapneumovirus | 1.00E+05 | Not Detected | Not Detected |
| Klebsiella pneumoniae | 1.00E+06 | Not Detected | Not Detected |
| Lactobacillus acidophilus | 1.00E+06 | Not Detected | Not Detected |
| Lactobacillus lactis | 1.00E+06 | Not Detected | Not Detected |
| Moraxella catarrhalis | 1.00E+06 | Not Detected | Not Detected |
| Mycoplasma pneumoniae | 1.00E+06 | Not Detected | Not Detected |
| Neisseria flavescens | 1.00E+06 | Not Detected | Not Detected |
| Oryza sativa | 1.00E+06 | Not Detected | Not Detected |
| Oryza sativa | 1.00E+06 | Not Detected | Not Detected |
| Oryza sativa | 1.00E+06 | Not Detected | Not Detected |
a Bacteria are enumerated in CFU/mL; Viruses in $\mathrm{TCID}_{50} / \mathrm{mL}$ or IFU/mL.
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| Peptostreptococcus micros | 1.00E+06 | Not Detected | Not Detected |
| --- | --- | --- | --- |
| Porphyromonas gingivalis | 1.00E+06 | Not Detected | Not Detected |
| Prevotella bivia | 1.00E+06 | Not Detected | Not Detected |
| Prevotella oralis^{b} | 1.00E+06 | Not Detected | Not Detected |
| Pseudomonas aeruginosa | 1.00E+06 | Not Detected | Not Detected |
| Respiratory syncytial virus | 1.00E+05 | Not Detected | Not Detected |
| Rhinovirus | 1.00E+05 | Not Detected | Not Detected |
| Saccharomyces cerevisiae | 1.00E+06 | Not Detected | Not Detected |
| Staphylococcus aureus | 1.00E+06 | Not Detected | Not Detected |
| Staphylococcus epidermidis | 1.00E+06 | Not Detected | Not Detected |
| Streptococcus anginosus | 1.00E+06 | Not Detected | Not Detected |
| Streptococcus dysgalactiae | 1.00E+06 | Not Detected | Not Detected |
| Streptococcus mitis | 1.00E+06 | Not Detected | Not Detected |
| Streptococcus mutans | 1.00E+06 | Not Detected | Not Detected |
| Streptococcus pneumoniae | 1.00E+06 | Not Detected | Not Detected |
| Streptococcus pyogenes | 1.00E+06 | Not Detected | Not Detected |
| Streptococcus salivarius | 1.00E+06 | Not Detected | Not Detected |
| Streptococcus sanguinis | 1.00E+06 | Not Detected | Not Detected |
| Tannerella forsythia^{c} | 4.44E+07 | Not Detected | Not Detected |
| Treponema denticola^{d} | 1.92E+06 | Not Detected | Not Detected |
| Veillonella parvula | 1.00E+06 | Not Detected | Not Detected |
a. Bacteria are enumerated in CFU/mL; Viruses in TCID50/mL or IFU/mL; genomic DNA in genome equivalents/mL.
b. Bacteroides oralis is Prevotella oralis.
c. Bacteriodes forsythus is Tannerella forsythia.
d. Genomic DNA tested.
Under the conditions of this study, all 43 microorganisms potentially encountered in the rectum were correctly reported as “CT NOT DETECTED; NG NOT DETECTED” by the Xpert CT/NG test. All 41 microorganisms potentially encountered in the pharyngeal specimens were correctly reported as “CT NOT DETECTED; NG NOT DETECTED” by the Xpert CT/NG test. Based on the results of this study, the analytical specificity of the Xpert CT/NG test with rectal and pharyngeal swab specimens is acceptable.
## Competitive Interference
Competitive interference of the Xpert CT/NG test was evaluated for positive CT and NG samples in the presence of 43 microorganisms potentially present in rectal flora and 41 microorganisms potentially present in pharyngeal flora. Positive CT and NG samples were generated in pooled negative clinical matrix spiked at 2 x LoD with CT serovar H and NG strain ATCC 19424. Test samples were then prepared by spiking
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CT and NG positive clinical matrix with other bacteria at $10^{6}$ CFU/ml, parasites at $10^{6}$ cells/mL (except Entamoeba histolytica at $10^{5}$ CFU/mL), or viruses at $10^{5}$ TCID $_{50}$ /mL. Three replicates of each microorganism were tested in Cepeid Xpert swab transport reagent (STR).
Table 11: Analytical Specificity Determination for Xpert CT/NG with Rectal Microorganisms
| Organism | Concentrationa (per cartridge) | CT | NG |
| --- | --- | --- | --- |
| Positive No Template Control | N/A | Detected | Detected |
| Negative No Template Control | N/A | Not Detected | Not Detected |
| Acinetobacter baumannii | 1.00E+06 | Detected | Detected |
| Anaerococcus tetradius | 1.00E+06 | Detected | Detected |
| Anaerococcus hydrogenalis | 1.00E+06 | Detected | Detected |
| Bacteroides fragilis | 1.00E+06 | Detected | Detected |
| Bifidobacterium adolescent | 1.00E+06 | Detected | Detected |
| Campylobacter jejuni | 1.00E+06 | Detected | Detected |
| Candida albicans | 1.00E+06 | Detected | Detected |
| Citrobacter freundii | 1.00E+06 | Detected | Detected |
| Clostridium difficile | 1.00E+06 | Detected | Detected |
| Entamoeba histolytica | 1.00E+05 | Detected | Detected |
| Enterobacter cloacae | 1.00E+06 | Detected | Detected |
| Enterococcus faecalis | 1.00E+06 | Detected | Detected |
| Enterococcus faecium | 1.00E+06 | Detected | Detected |
| Enterovirus | 1.00E+05 | Detected | Detected |
| Escherichia coli | 1.00E+06 | Detected | Detected |
| Fusobacterium necrophorum | 1.00E+06 | Detected | Detected |
| Fusobacterium nucleatum | 1.00E+06 | Detected | Detected |
| Giardia lamblia | 1.00E+06 | Detected | Detected |
| Helicobacter pylori | 1.00E+06 | Detected | Detected |
| Klebsiella oxytoca | 1.00E+06 | Detected | Detected |
| Lactobacillus acidophilus | 1.00E+06 | Detected | Detected |
| Lactobacillus delbreueckii | 1.00E+06 | Detected | Detected |
| Listeria monocytogenes | 1.00E+06 | Detected | Detected |
| Morganella morganii | 1.00E+06 | Detected | Detected |
| Norovirus | 1.00E+05 | Detected | Detected |
| Peptostreptococcus anaerobius | 1.00E+06 | Detected | Detected |
| Plesiomonas shigelloides | 1.00E+06 | Detected | Detected |
| Prevotella bivia | 1.00E+06 | Detected | Detected |
| Prevotella oralis | 1.00E+06 | Detected | Detected |
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Table 12: Analytical Specificity Determination for Xpert CT/NG with Pharyngeal Microorganisms
| Organism | Concentrationa (per cartridge) | CT | NG |
| --- | --- | --- | --- |
| No Template Control | N/A | Not Detected | Not Detected |
| Actinobacillus actinomycetemcomitans | 1.00E+06 | Detected | Detected |
| Adenovirus | 1.00E+05 | Detected | Detected |
| Arcanobacterium haemolyticum | 1.00E+06 | Detected | Detected |
| Bordetella pertussis | 1.00E+06 | Detected | Detected |
| Campylobacter rectus | 1.00E+06 | Detected | Detected |
| Candida albicans | 1.00E+06 | Detected | Detected |
| Coronavirus | 1.00E+05 | Detected | Detected |
| Corynebacterium diphtheriae | 1.00E+06 | Detected | Detected |
| Fusobacterium necrophorum | 1.00E+06 | Detected | Detected |
| Haemophilus influenzae | 1.00E+06 | Detected | Detected |
| Herpes virus | 1.00E+05 | Detected | Detected |
| Human influenza virus A | 1.00E+05 | Detected | Detected |
| Human influenza virus B | 1.00E+05 | Detected | Detected |
| Human metapneumovirus | 1.00E+05 | Detected | Detected |
| Klebsiella pneumoniae | 1.00E+06 | Detected | Detected |
| Lactobacillus acidophilus | 1.00E+06 | Detected | Detected |
| Lactobacillus acidophilus | 1.00E+06 | Detected | Detected |
| Lactobacillus acidophilus | 1.00E+06 | Detected | Detected |
| L. acidophilus | 1.00E+06 | Detected | Detected |
| L. acidophilus | 1.00E+06 | Detected | Detected |
| L. acidophilus | 1.00E+06 | Detected | Detected |
a Bacteria are enumerated in CFU/mL; Viruses in $\mathrm{TCID}_{50} / \mathrm{mL}$ or IFU/mL.
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| Lactobacillus lactis | 1.00E+06 | Detected | Detected |
| --- | --- | --- | --- |
| Moraxella catarrhalis | 1.00E+06 | Detected | Detected |
| Mycoplasma pneumoniae | 1.00E+06 | Detected | Detected |
| Neisseria flavescens | 1.00E+06 | Detected | Detected |
| Peptostreptococcus micros | 1.00E+06 | Detected | Detected |
| Porphyromonas gingivalis | 1.00E+06 | Detected | Detected |
| Prevotella bivia | 1.00E+06 | Detected | Detected |
| Prevotella oralis^{b} | 1.00E+06 | Detected | Detected |
| Pseudomonas aeruginosa | 1.00E+06 | Detected | Detected |
| Respiratory syncytial virus | 1.00E+05 | Detected | Detected |
| Rhinovirus | 1.00E+05 | Detected | Detected |
| Saccharomyces cerevisiae | 1.00E+06 | Detected | Detected |
| Staphylococcus aureus | 1.00E+06 | Detected | Detected |
| Staphylococcus epidermidis | 1.00E+06 | Detected | Detected |
| Streptococcus anginosus | 1.00E+06 | Detected | Detected |
| Streptococcus dysgalactiae | 1.00E+06 | Detected | Detected |
| Streptococcus mitis | 1.00E+06 | Detected | Detected |
| Streptococcus mutans | 1.00E+06 | Detected | Detected |
| Streptococcus pneumoniae | 1.00E+06 | Detected | Detected |
| Streptococcus pyogenes | 1.00E+06 | Detected | Detected |
| Streptococcus salivarius | 1.00E+06 | Detected | Detected |
| Streptococcus sanguinis | 1.00E+06 | Detected | Detected |
| Tannerella forsythia^{c} | 4.44E+07 | Detected | Detected |
| Treponema denticola^{d} | 1.92E+06 | Detected | Detected |
| Veillonella parvula | 1.00E+06 | Detected | Detected |
a Bacteria are enumerated in CFU/mL; Viruses in TCID50/mL or IFU/mL; genomic DNA in genome equivalents/mL.
b Bacteroides oralis is Prevotella oralis.
c Bacteriodes forsythus is Tannerella forsythia.
d Genomic DNA tested.
Under the conditions of this study, in the presence of all 43 microorganisms potentially encountered in the rectum CT and NG were correctly reported as “CT DETECTED; NG DETECTED” by the Xpert CT/NG test. In the presence of all 41 microorganisms potentially encountered in the pharyngeal CT and NG were correctly reported as “CT DETECTED; NG DETECTED” by the Xpert CT/NG test. Based on the results of this study, the competitive interference of the Xpert CT/NG test with rectal and pharyngeal swab specimens is acceptable.
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# Interfering Substances
Interference of the Xpert CT/NG test by substances potentially found in the oralpharynx or rectum was evaluated for positive CT and NG samples. Positive CT and NG samples were generated in pooled negative pharyngeal or rectal clinical matrix spiked at $2 \times$ LoD with CT serovar D or H and NG strain ATCC 49226 or 19424, respectively. Test samples were then made by spiking CT and NG positive clinical matrix with the substances listed in the tables below. Eight positive and eight negative samples were tested per substance in Cepeid Xpert swab transport reagent (STR) using the Xpert CT/NG test.
Table 13: Potentially Interfering Substances Tested in Pharyngeal Swabs
| Potentially Interfering Substances to be Evaluated | Active Ingredient | Concentration Tested |
| --- | --- | --- |
| Control | N/A | N/A |
| Mucin (e.g., pig gastric mucin) | N/A | 25 mg/mL |
| Whole human blood | N/A | 5% v/v |
| Mouthwash (Cool Mint Listerine, antiseptic) | Eucalyptol 0.092% | 5% v/v |
| | Menthol 0.042% | |
| | Methyl salicylate 0.060% | |
| | Thymol 0.064% | |
| Cough Medicine (1) | Guaifenesin (Guaiacol glyceryl) | 5 mg/mL |
| Cough Medicine (2) | Dextromethorphan HBr | 100 μg/mL |
| Antibiotic (1) | Penicillin G | 1.2 mg/mL |
| Antibiotic (2) | Erythromycin | 15 μg/mL |
| Sugar-containing cold and flu remedies (e.g., syrup or lozenges, Tylenol Cold Sore Throat) | Acetaminophen | 5% v/v |
| Chloraseptic | Benzocaine | 5% v/v |
| Salt-modifying remedies (e.g., sodium chloride or sodium bicarbonate spray or rinse) | Sodium chloride | 50% v/v |
| Foods/drinks that increase salivary viscosity (e.g., bread, milk, xanthan gum) | Milk | 5% v/v |
| pH Modifying Remedies | Orange Juice | 5% v/v |
| Cold sore medication Abreva | Docosanol 10% | 5% v/v |
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Table 14: Potentially Interfering Substances Tested in Rectal Swabs
| Potentially Interfering Substances to be Evaluated | Active Ingredient | Concentration Tested |
| --- | --- | --- |
| Control | N/A | N/A |
| Barium sulfate | N/A | 0.25% w/v |
| Ciprofloxacin | N/A | 0.25% w/v |
| Condom (with spermicide) | Nonoxynol-9 | 1 condom (#) |
| Cortizone | Hydrocortisone | 0.25% w/v |
| ExLax | Sennosides | 0.25% w/v |
| Fecal fat | Stearic acid/ Palmitic acid/Cholesterol | 0.25% w/v |
| Imodium | Loperamide hydrochloride | 0.25% w/v |
| K-Y Jelly | N/A | 0.25% w/v |
| Milk of Magnesia | Calcium carbonate/ aluminum hydroxide/ magnesium hydroxide/ simethicone | 0.25% w/v |
| Mineral Oil | Mineral oil | 0.25% w/v |
| Neosporin | Polymixin B/ Neomycin/ Bacitracin | 0.25% w/v |
| Nystatin | Nystatin | 0.25% w/v |
| Pepcid | Famotidine | 0.25% w/v |
| Pepto-Bismol | Bismuth subsalicylate | 0.25% w/v |
| Preparation H | Phenylephrine | 0.25% w/v |
| Prilosec | Oemprazole | 0.25% w/v |
| Saline | Sodium chloride | 0.25% w/v |
| Tagamet | Cimetidine | 0.25% w/v |
| Vagisil | Benzocaine, resorcinol | 0.25% w/v |
Under the conditions of this study, all valid positive replicate samples were correctly identified using Xpert CT/NG when tested in the presence of all potentially interfering substances. All valid negative replicate samples were correctly identified using Xpert CT/NG in the presence of all interfering substances. Analysis of the cycle threshold (Ct value) demonstrated no clinically significant changes in Ct value for positive samples in
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the presence of any substance tested. Based on this study no new limitations for interference were added to the package insert.
f. Assay cut-off:
Please refer to submission K121710.
2. Comparison studies:
a. Method comparison with predicate device:
N/A
b. Matrix comparison:
N/A
3. Clinical studies:
a. Clinical Sensitivity and Specificity:
## Clinical Studies
Clinical evaluation of the Xpert CT/NG Assay to support throat and rectal swab specimen types was conducted in collaboration with the Antibacterial Resistance Leadership Group (ARLG) and funded by a grant from the National Institutes of Health (NIH) (Master GC, https://arlg.org/studies-in-progress; NCT02870101 https://clinicaltrials.gov/ct2/show/NCT02870101?term=NCT02870101&rank=1)
Performance characteristics of Xpert CT/NG were determined in a multi-site prospective investigational study, with samples collected at 9 US institutions, and tested at one of 2 reference laboratories. Xpert CT/NG was compared to an anatomic site infected status (ASIS) algorithm. The study was designed so that two comparator NAAT assays were run on every specimen.
The anatomic site was considered to be infected if both of the comparator test results were positive. The anatomic site was considered to be not infected when both reference test results were negative. If there was discordance between the two reference tests, an additional third NAAT was tested as a tiebreaker. As the tiebreaker test was not a combination test detecting both CT and NG, the tiebreaker assay was run only for the organism with a discordant result (e.g., if NG result disagreed between the two comparator tests and CT agreed, the tiebreaker was only run for NG). In this case, agreement of 2/3 comparatpr NAATs determined the ASIS result.
A detailed description of the ASIS for all possible outcomes was developed and applied to the study data. A summary of the ASIS result for all tested samples is presented in Tables 15-18.
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Table 15: Anatomic Site Infected Status – Pharyngeal CT
| ASIS^{a} | NAAT1 | NAAT2 | Tiebreaker NAAT | Xpert | Total |
| --- | --- | --- | --- | --- | --- |
| NI | - | - | NA^{b} | - | 2504 |
| NI | NR^{c} | - | - | - | 6 |
| NI | - | - | NA | + | 4 |
| NI | - | + | - | - | 5 |
| NI | + | - | - | - | 2 |
| NI | - | + | - | + | 1 |
| NI | + | - | - | + | 1 |
| NI | EQ^{d} | - | - | - | 1 |
| IND^{e} | + | - | EQ | + | 1 |
| IND | NR | - | + | + | 1 |
| Total Non Infected | | | | | 2526 |
| I | + | + | NA | + | 40 |
| I | - | + | + | + | 5 |
| I | + | - | + | + | 2 |
| I | + | + | NA | - | 1 |
| I | - | + | + | - | 1 |
| Total Infected | | | | | 49 |
a ASIS = Anatomic Site Infected Status: NI=Not Infected; I=Infected; IND=indeterminate, considered not infected.
b NA=Not applicable; both reference NAAT tests agreed.
c NR = Not run
d EQ=Equivocal
e IND=Indeterminate. Considered infected if Xpert Negative and not infected if Xpert positive to evaluate under worst-case scenario.
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Table 16: Anatomic Site Infected Status – Rectal CT
| ASIS^{a} | NAAT1 | NAAT2 | Tiebreaker NAAT | Xpert | Total |
| --- | --- | --- | --- | --- | --- |
| NI | - | - | NA^{b} | - | 2221 |
| NI | NR^{c} | - | - | - | 47 |
| NI | - | - | NA | + | 12 |
| NI | + | - | - | - | 11 |
| NI | - | + | - | - | 10 |
| NI | - | + | - | + | 2 |
| NI | - | EQ^{d} | - | - | 2 |
| IND^{e} | + | EQ | - | + | 1 |
| Total Non Infected | | | | | 2306 |
| I | + | + | NA | + | 172 |
| I | - | + | + | + | 14 |
| I | - | + | + | - | 11 |
| I | + | + | NA | - | 9 |
| I | + | - | + | + | 6 |
| I | + | - | + | - | 5 |
| I | + | EQ | + | + | 3 |
| I | - | EQ | + | - | 2 |
| I | NR | + | + | + | 2 |
| I | + | EQ | + | - | 1 |
| I | + | EQ | NR | - | 1 |
| I | NR | E | + | - | 1 |
| IND | - | NR | + | - | 1 |
| IND | + | - | NR | - | 1 |
| Total Infected | | | | | 229 |
a ASIS = Anatomic Site Infected Status: NI=Not Infected; I=Infected; IND=indeterminate, considered not infected.
b NA=Not applicable; both reference NAAT tests agreed.
c NR = Not run
d EQ=Equivocal
e IND=Indeterminate. Considered infected if Xpert negative and not infected if Xpert positive to evaluate under worst-case scenario.
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Table 17: Anatomic Site Infected Status – Pharyngeal NG
| ASIS^{a} | NAAT1 | NAAT2 | Tiebreaker
NAAT | Xpert | Total |
| --- | --- | --- | --- | --- | --- |
| NI | - | - | NA^{b} | - | 2317 |
| NI | - | - | NA | + | 19 |
| NI | - | + | - | - | 14 |
| NI | - | + | - | + | 4 |
| NI | + | - | - | - | 4 |
| NI | + | - | - | + | 4 |
| NI | NR^{c} | - | - | - | 5 |
| NI | - | EQ^{d} | - | + | 1 |
| IND^{e} | - | + | EQ | + | 1 |
| Total Non Infected | | | | | 2369 |
| I | + | + | NA | + | 175 |
| I | + | + | NA | - | 4 |
| I | - | + | + | + | 16 |
| I | - | + | + | - | 5 |
| I | + | - | + | + | 2 |
| I | NR | + | + | + | 2 |
| IND | + | EQ | - | - | 1 |
| IND | - | EQ | + | - | 1 |
| Total Infected | | | | | 206 |
a. ASIS = Anatomic Site Infected Status: NI=Not Infected; I=Infected; IND=indeterminate, considered not infected.
b. NA=Not applicable; both reference NAAT tests agreed.
c. NR = Not run
d. EQ=Equivocal
e. IND=Indeterminate. Considered infected if Xpert negative and not infected if Xpert positive to evaluate under worst-case scenario.
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Table 18: Anatomic Site Infected Status – Rectal NG
| ASIS^{a} | NAAT1 | NAAT2 | Tiebreaker
NAAT | Xpert | Total |
| --- | --- | --- | --- | --- | --- |
| NI | - | - | NA^{b} | - | 2261 |
| NI | NR^{c} | - | - | - | 49 |
| NI | - | - | NA | + | 6 |
| NI | + | - | - | - | 5 |
| NI | - | + | - | - | 4 |
| NI | + | - | - | + | 2 |
| NI | - | EQ^{d} | - | - | 2 |
| NI | - | NR | - | - | 1 |
| IND^{e} | + | EQ | - | + | 1 |
| Total Non Infected | | | | | 2331 |
| I | + | + | NA | + | 172 |
| I | - | + | + | + | 13 |
| I | + | + | NA | - | 8 |
| I | - | + | + | - | 8 |
| I | + | - | + | + | 1 |
| I | + | EQ | + | + | 1 |
| I | NR | + | + | - | 1 |
| IND | - | EQ | + | - | 1 |
| Total Infected | | | | | 205 |
a ASIS = Anatomic Site Infected Status: NI=Not Infected; I=Infected; IND=indeterminate, considered not infected.
b NA=Not applicable; both reference NAAT tests agreed.
c NR = Not run
d EQ=Equivocal
e IND=Indeterminate. Considered infected if Xpert negative and not infected if Xpert positive to evaluate under worst-case scenario.
Study participants included adults seeking sexually transmitted disease (STD) testing at the participating clinics, which included clinics focused on sexually transmitted diseases, women’s health, student health and family planning, as well as clinics specializing in lesbian, gay, bisexual, and transgender (LGBT) health. Potential subjects were identified, assessed for eligibility and approached for informed consent. Both symptomatic and asymptomatic individuals were included in the study population following informed consent. The study specimens consisted of prospectively collected rectal and pharyngeal swabs. Performance of Xpert CT/NG was calculated relative to the ASIS for each of the two sample types.
A total of 2767 study participants were enrolled in the study, of which 2577 pharyngeal swab and 2538 rectal swab specimens were eligible for inclusion in the data analyses. One hundred and ninety (190) pharyngeal specimens were excluded from the data analyses due to the following reasons: 167 for temperature excursions
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during shipment, 4 specimens from participants who withdrew consent, 2 specimens that had shipment errors, 2 post-swab collection errors, 1 specimen not collected, 1 specimen from a participant receiving antibiotics, and 13 specimens with Xpert results that were either not available or indeterminate. Two hundred and twenty-nine (229) rectal specimens were excluded from the data analyses due to the following reasons: 167 for temperature excursions during shipment, 6 specimens from participants who withdrew consent, 5 specimens that had shipment errors, 2 post-swab collection errors, 1 specimen not collected, 1 specimen from a participant receiving antibiotics, and 46 specimens with Xpert results that were either not available or indeterminate.
Among the study participants included in the data analyses for pharyngeal swab performance 20.8% were female at birth and 79.2% were male at birth. The average age was 33.8 years (range = 18 to 76 years).
Among the study participants included in the data analyses for rectal swab performance 20.9% were female at birth and 79.1% were male at birth. The average age was 33.7 years (range = 18 to 76 years).
Of the 2572 study participants eligible for inclusion in the pharyngeal and rectal swab analyses for CT detection, 0.9% (22/2572) were positive for CT by pharyngeal swab and rectal swab by ASIS. Of the 2573 study participants eligible for inclusion in the pharyngeal and rectal swab analyses for NG detection, 3.7% (95/2573) were positive for NG by pharyngeal swab and rectal swab.
Among the 5163 tests performed, 198 (3.8%) had to be retested due to ERROR, INVALID or NO RESULT outcomes. Of those, 151 specimens yielded valid results upon repeat assay (2 specimens were not retested). The overall valid reporting rate of the assay was 99.1% (5116/5163).
The clinical performance for the Xpert CT/NG assay is shown below in Tables 19-31.
Table 19: Clinical Performance for CT Detection of the Xpert CT/NG for Pharyngeal Swabs
| CT Detection
Pharyngeal Swabs (2575 specimens) | ASIS for CT Detection Result | | |
| --- | --- | --- | --- |
| | | Positive | Negative |
| Xpert CT/NG | Positive | 47 | 8 |
| | Negative | 2 | 2518 |
| Total | | 49 | 2526 |
| Sensitivity: 95.9% (47/49); 95% CI: (83.6% - 98.9%) | | | |
| Specificity: 99.7% (2518/2526); 95% CI: (99.4% - 99.8%) | | | |
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Table 20: Clinical Performance for CT Detection of the Xpert CT/NG for Pharyngeal Swabs for Symptomatic Subjects
| CT Detection Symptomatic Pharyngeal Swabs (306 specimens) | ASIS for CT Detection Result | | |
| --- | --- | --- | --- |
| | | Positive | Negative |
| Xpert CT/NG | Positive | 9 | 0 |
| | Negative | 0 | 297 |
| Total | | 9 | 297 |
| Sensitivity: 100.0% (9/9); 95% CI: (70.1% - 100.0%) | | | |
| Specificity: 100.0% (297/297); 95% CI: (98.7% - 100.0%) | | | |
Table 21: Clinical Performance for CT Detection of the Xpert CT/NG for Pharyngeal Swabs for Asymptomatic Subjects
| CT Detection Asymptomatic Pharyngeal Swabs (2269 specimens) | ASIS for CT Detection Result | | |
| --- | --- | --- | --- |
| | | Positive | Negative |
| Xpert CT/NG | Positive | 38 | 8 |
| | Negative | 2 | 2221 |
| Total | | 40 | 2229 |
| Sensitivity: 95.0% (38/40); 95% CI: (83.5% - 98.6%) | | | |
| Specificity: 99.6% (2221/2229); 95% CI: (99.3% - 99.8%) | | | |
Table 22: Clinical Performance for CT Detection of the Xpert CT/NG for Rectal Swabs
| CT Detection Rectal Swabs (2535 specimens) | ASIS for CT Detection Result | | |
| --- | --- | --- | --- |
| | | Positive | Negative |
| Xpert CT/NG | Positive | 197 | 15 |
| | Negative | 32 | 2291 |
| Total | | 229 | 2306 |
| Sensitivity: 86.0% (197/229); 95% CI: (80.9% - 89.9%) | | | |
| Specificity: 99.4% (2291/2306); 95% CI: (98.9% - 99.6%) | | | |
Table 23 Clinical Performance for CT Detection of the Xpert CT/NG for Rectal Swabs for Symptomatic Subjects
| CT Detection Symptomatic Rectal Swabs (188 specimens) | ASIS for CT Detection Result | | |
| --- | --- | --- | --- |
| | | Positive | Negative |
| Xpert CT/NG | Positive | 22 | 1 |
| | Negative | 5 | 160 |
| Total | | 27 | 161 |
| Sensitivity: 81.5% (22/27); 95% CI: (63.3% - 91.8%) | | | |
| Specificity: 99.4% (160/161); 95% CI: (96.6% - 99.9%) | | | |
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Table 24 Clinical Performance for CT Detection of the Xpert CT/NG for Rectal Swabs for Asymptomatic Subjects
| CT Detection Asymptomatic Rectal Swabs (2347 specimens) | ASIS for CT Detection Result | | |
| --- | --- | --- | --- |
| | | Positive | Negative |
| Xpert CT/NG | Positive | 175 | 14 |
| | Negative | 27 | 2131 |
| Total | | 202 | 2145 |
| Sensitivity: 86.6% (175/202); 95% CI: (81.3% - 90.7%) | | | |
| Specificity: 99.4% (2131/2145); 95% CI: (98.9% - 99.6%) | | | |
Table 25: Clinical Performance for NG Detection of the Xpert CT/NG for Pharyngeal Swabs
| NG Detection Pharyngeal Swabs (2575 specimens) | ASIS for NG Detection Result | | |
| --- | --- | --- | --- |
| | | Positive | Negative |
| Xpert CT/NG | Positive | 195 | 29 |
| | Negative | 11 | 2340 |
| Total | | 206 | 2369 |
| Sensitivity: 94.7% (195/206); 95% CI: (90.7% - 97.0%) | | | |
| Specificity: 98.8% (2340/2369); 95% CI: (98.3% - 99.2%) | | | |
Table 26: Clinical Performance for NG Detection of the Xpert CT/NG for Pharyngeal Swabs for Symptomatic Subjects
| NG Detection Symptomatic Pharyngeal Swabs (306 specimens) | ASIS for NG Detection Result | | |
| --- | --- | --- | --- |
| | | Positive | Negative |
| Xpert CT/NG | Positive | 39 | 3 |
| | Negative | 3 | 261 |
| Total | | 42 | 264 |
| Sensitivity: 92.9% (39/42); 95% CI: (81.0% - 97.5%) | | | |
| Specificity: 98.9% (261/264); 95% CI: (96.7% - 99.6%) | | | |
Table 27: Clinical Performance for NG Detection of the Xpert CT/NG for Pharyngeal Swabs for Asymptomatic Subjects
| NG Detection Asymptomatic Pharyngeal Swabs (2269 specimens) | ASIS for NG Detection Result | | |
| --- | --- | --- | --- |
| | | Positive | Negative |
| Xpert CT/NG | Positive | 156 | 26 |
| | Negative | 8 | 2079 |
| Total | | 164 | 2105 |
| Sensitivity: 95.1% (156/164); 95% CI: (90.7% - 97.5%) | | | |
| Specificity: 98.8% (2079/2105); 95% CI: (98.2% - 99.2%) | | | |
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Table 28: Clinical Performance for NG Detection of the Xpert CT/NG for Rectal Swabs
| NG Detection Rectal Swabs (2536 specimens) | ASIS for NG Detection Result | | |
| --- | --- | --- | --- |
| | | Positive | Negative |
| Xpert CT/NG | Positive | 187 | 9 |
| | Negative | 18 | 2322 |
| Total | | 205 | 2331 |
| Sensitivity: 91.2% (187/205); 95% CI: (86.6% - 94.4%) | | | |
| Specificity: 99.6% (2322/2331); 95% CI: (99.3% - 99.8%) | | | |
Table 29: Clinical Performance for NG Detection of the Xpert CT/NG for Rectal Swab for Symptomatic Subjects
| NG Detection Symptomatic Rectal Swabs (188 specimens) | ASIS for NG Detection Result | | |
| --- | --- | --- | --- |
| | | Positive | Negative |
| Xpert CT/NG | Positive | 38 | 0 |
| | Negative | 1 | 149 |
| Total | | 39 | 149 |
| Sensitivity: 97.4% (38/39); 95% CI: (86.% - 99.6%) | | | |
| Specificity: 100.0% (149/149); 95% CI: (97.5% - 100.0%) | | | |
Table 30: Clinical Performance for NG Detection of the Xpert CT/NG for Rectal Swab for Asymptomatic Subjects
| NG Detection Asymptomatic Rectal Swabs (2348 specimens) | ASIS for NG Detection Result | | |
| --- | --- | --- | --- |
| | | Positive | Negative |
| Xpert CT/NG | Positive | 149 | 9 |
| | Negative | 17 | 2173 |
| Total | | 166 | 2182 |
| Sensitivity: 89.8% (149/166); 95% CI: (84.2% - 93.5%) | | | |
| Specificity: 99.6% (2173/2182); 95% CI: (99.2% - 99.8%) | | | |
4. Clinical cut-off: N/A
5. Expected values/Reference range:
Prevalence was calculated for valid Xpert CT/NG samples using ASIS positive samples for each organism and anatomical site. Prevalence rates for each are listed below by site (9 sites) and combined overall. The nine sites included both low and high prevalence sites.
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Table 31: Prevalence of CT and NG in oral and rectal swabs
| Organism and Anatomical Site | Clinical Site Number | Number of Specimens Collected at Each site | Prevalence |
| --- | --- | --- | --- |
| CT, Oral | 15 | 143 | 2.80% |
| | 93 | 225 | 0.40% |
| | 106 | 359 | 0.80% |
| | 226 | 112 | 0.00% |
| | 351 | 334 | 1.50% |
| | 431 | 393 | 1.50% |
| | 609 | 288 | 2.40% |
| | 625 | 367 | 4.40% |
| | 637 | 354 | 2.00% |
| | All Sites | 2575 | 1.90% |
| NG, Oral | 15 | 143 | 9.10% |
| | 93 | 225 | 0.90% |
| | 106 | 359 | 5.60% |
| | 226 | 112 | 1.80% |
| | 351 | 334 | 4.80% |
| | 431 | 393 | 7.10% |
| | 609 | 288 | 9.70% |
| | 625 | 367 | 10.40% |
| | 637 | 354 | 16.70% |
| | All Sites | 2575 | 8.00% |
| CT, Rectal | 15 | 142 | 12.70% |
| | 93 | 221 | 7.20% |
| | 106 | 355 | 10.40% |
| | 226 | 108 | 1.90% |
| | 351 | 330 | 7.30% |
| | 431 | 385 | 2.90% |
| | 609 | 279 | 9.70% |
| | 625 | 363 | 12.70% |
| | 637 | 352 | 13.60% |
| | All Sites | 2535 | 9.03% |
| NG, Rectal | 15 | 143 | 8.40% |
| | 93 | 221 | 1.80% |
| | 106 | 355 | 7.90% |
| | 226 | 108 | 0.90% |
| | 351 | 330 | 5.80% |
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| | 431 | 385 | 6.80% |
| --- | --- | --- | --- |
| | 609 | 280 | 9.30% |
| | 625 | 363 | 7.70% |
| | 637 | 351 | 17.40% |
| | All Sites | 2536 | 8.08% |
N. Instrument Name:
This assay can be run on the following GeneXpert instruments: Dx R1, Dx R2, Infinity-48, and Infinity G2 (includes the Infinity-80 and Infinity 48s). Dx R1 is a family of instruments composed of the GX-I, GX-IV, and GX-XVI. The Dx R2 family currently consists only of the GX-II instrument.
O. System Descriptions:
1. Instrument Name:
Instrument software for the GeneXpert Instrument Systems is associated with currently cleared devices as follows:
- GeneXpert Dx instruments utilize GeneXpert Dx software v5.1 (last reviewed by FDA¹ was Dx v4.8);
- Infinity-48 utilizes Xpertise v4.6a;
- Infinity G2 instruments utilize Xpertise v6.5. The current submission contains review documentation for the use of Dx software version 6.0 and Xpertise software version 6.6 (for the G2 Instruments).
- Generation 1 Instrument Infinity-48 is not currently intended for software upgrade beyond the already reviewed version 4.6a.
2. System Description:
The GeneXpert Instrument System family (GeneXpert Dx and Infinity Systems) automates and integrates sample purification, nucleic acid amplification and detection of target sequences within compatible, assay-specific, single-use cartridges. The instrument systems each contain a computer and preloaded software for running tests and viewing the results.
3. Software:
FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types.
Yes ☐ X ☐ or No ☐
4. Level of Concern
Moderate
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5. Software Description
See software consult(s) for previously cleared Xpert Xpress assays (e.g. K162456 and K171552).
P. Other Supportive Instrument Performance Characteristics Data Not Covered In The "Performance Characteristics" Section above:
Not Applicable
Q. Proposed Labeling:
The labeling supports the finding of substantial equivalence for this device.
R. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
