Predicate Devices

Reference Devices

AI/ML (Artificial Intelligence / Machine Learning)

No
The description focuses on real-time PCR technology and automated sample processing, with no mention of AI or ML algorithms for data analysis or interpretation.

Therapeutic

No
The device is described as a "qualitative in vitro real-time PCR test for the automated detection and differentiation of genomic DNA from Chlamvdia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) to aid in the diagnosis of chlamydial and gonorrheal disease". Its purpose is diagnostic, not therapeutic.

Diagnostic

Yes

The 'Intended Use / Indications for Use' section explicitly states that the test is used "to aid in the diagnosis of chlamydial and gonorrheal disease". Additionally, the 'Device Description' section also refers to it as an "automated in vitro diagnostic test".

SaMD (Software as a Medical Device)

No

The device description explicitly states that the system consists of an instrument, personal computer, and preloaded software, and requires the use of single-use disposable cartridges. It also describes the physical components of the GeneXpert Instrument Systems, including modules with syringe drives, ultrasonic horns, and thermocyclers. This indicates the device is a system that includes hardware components, not solely software.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use/Indications for Use: The description explicitly states it is a "qualitative in vitro real-time PCR test" and is used "to aid in the diagnosis of chlamydial and gonorrheal disease". This clearly indicates it is intended for use outside of the body to examine specimens for diagnostic purposes.
Device Description: The description further reinforces this by calling it an "automated in vitro diagnostic test". It describes the process of analyzing biological samples (DNA from Chlamydia trachomatis and Neisseria gonorrhoeae) using reagents and instrumentation.
Specimen Types: The test is designed to be performed on various biological specimens (urine, vaginal swabs, endocervical swabs, pharyngeal swabs, and rectal swabs), which are collected from the patient but analyzed in vitro.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / 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 Chlamvdia 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.

Product codes (comma separated list FDA assigned to the subject device)

QEP, MKZ, LSL, OOI, QBD

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 integrates sample purification, nucleic acid amplification and detection of the target sequences in simple or complex samples using real-time PCR. 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, crosscontamination 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.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

urogenital tract, extragenital sites (pharynx and rectum)

Indicated Patient Age Range

Not Found (Study participants were adults, range = 18 to 76 years)

Intended User / Care Setting

Not Found (Clinical setting - clinics focused on sexually transmitted diseases, women's health, student health and family planning, and LGBT health)

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Study participants included consenting adults seeking sexually transmitted disease (STD) testing at 9 US institutions. Both symptomatic and asymptomatic individuals were included. The study specimens consisted of prospectively collected rectal and pharyngeal swabs.
A total of 2767 study participants were enrolled.
2577 pharyngeal swab and 2538 rectal swab specimens were eligible for inclusion in the data analyses.
The anatomic site infected status (ASIS) algorithm was used as the reference, based on combined results from two NAAT tests, with a tiebreaker NAAT test if applicable. The anatomic site was considered infected if both reference test results were positive, and not infected if both were negative. If there was discordance between reference tests, an additional NAAT was used as a tiebreaker, with agreement of 2/3 NAATs determining the ASIS result. If two tests were equivocal or one equivocal and one not run, the third test result stood. If two tests were not run, ASIS was invalid. The tiebreaker was performed only for the organism with disagreement.

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

Non-Clinical Studies:

Analytical Sensitivity (LoD):
- Pooled Pharyngeal Swab Matrix:
  - CT serovar D: 161 EB/mL (95% positivity confirmed with >= 20 replicates)
  - CT serovar H: 225 EB/mL (95% positivity confirmed with >= 20 replicates)
  - NG ATCC 19424: 7.1 CFU/mL
  - NG ATCC 49226: 6.4 CFU/mL
- Pooled Rectal Swab Matrix:
  - CT serovar D: 88 EB/mL (95% positivity confirmed with >= 20 replicates)
  - CT serovar H: 161 EB/mL (95% positivity confirmed with >= 20 replicates)
  - NG ATCC 19424: 4.9 CFU/mL
  - NG ATCC 49226: 5.3 CFU/mL
Analytical Reactivity (Inclusivity):
- 14 CT serovars and 20 NG strains tested in pharyngeal and rectal swab matrices at levels near LoD. All were correctly reported.
Analytical Specificity (Cross-reactivity and Competitive Interference):
- 41 microorganisms (pharyngeal flora) and 43 microorganisms (rectal flora) tested in presence and absence of CT and NG at 2X LoD. No interference or cross-reactivity observed.
Interfering Substances:
- Various exogenous substances tested in pharyngeal and rectal swab matrices containing CT and NG at 3x LoD. No assay interference observed.

Clinical Performance Study:

Study Type: Multi-site prospective investigational study.
Sample Size: 2577 pharyngeal swab specimens, 2538 rectal swab specimens (eligible for analyses).
Overall Valid Reporting Rate: 99.1% (5116/5163).
Key Results (Sensitivity and Specificity vs. ASIS):
- Chlamydia trachomatis (CT) Detection:
  - Pharyngeal Swabs (PS):
    - Symptomatic: Sensitivity 100.0% (95 CI: 70.1-100.0), Specificity 100.0% (98.7-100.0)
    - Asymptomatic: Sensitivity 95.0% (95 CI: 83.5-98.6), Specificity 99.6% (99.3-99.8)
    - All: Sensitivity 95.9% (95 CI: 86.3-98.9), Specificity 99.7% (99.4-99.8)
  - Rectal Swabs (RS):
    - Symptomatic: Sensitivity 81.5% (95 CI: 63.3-91.8), Specificity 99.4% (96.6-99.9)
    - Asymptomatic: Sensitivity 86.6% (95 CI: 81.3-90.7), Specificity 99.4% (98.9-99.6)
    - All: Sensitivity 86.0% (95 CI: 80.9-89.9), Specificity 99.4% (98.9-99.6)
- Neisseria gonorrhoeae (NG) Detection:
  - Pharyngeal Swabs (PS):
    - Symptomatic: Sensitivity 92.9% (95 CI: 81.0-97.5), Specificity 98.9% (96.7-99.6)
    - Asymptomatic: Sensitivity 95.1% (95 CI: 90.7-97.5), Specificity 98.8% (98.2-99.2)
    - All: Sensitivity 94.7% (95 CI: 90.7-97.0), Specificity 98.8% (98.3-99.2)
  - Rectal Swabs (RS):
    - Symptomatic: Sensitivity 97.4% (95 CI: 86.8-99.6), Specificity 100.0% (97.5-100.0)
    - Asymptomatic: Sensitivity 89.8% (95 CI: 84.2-93.5), Specificity 99.6% (99.2-99.8)
    - All: Sensitivity 91.2% (95 CI: 86.6-94.4), Specificity 99.6% (99.3-99.8)

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

See "Summary of Performance Studies" section for Sensitivity and Specificity.
PPV, NPV are not explicitly listed but can be calculated from the provided TP, FP, TN, FN values.

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

Aptima Mycoplasma genitalium Assay [De Novo #DEN180047]

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

K173840, K043144

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

Regulation Number and Section

§ 866.3393 Device to detect nucleic acids from non-viral microorganism(s) causing sexually transmitted infections and associated resistance marker(s).

(a)
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.(b)
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.

Summary

0

Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the symbol of the Department of Health & Human Services on the left and the FDA acronym along with the full name of the agency on the right. The FDA part of the logo is in blue, with the acronym in a square and the full name written out next to it.

May 23, 2019

Cepheid Sudhakar Marla Senior Director, Regulatory Affairs 904 Caribbean Drive Sunnyvale, California 94089

Re: K190441

Trade/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 Regulation Number: 21 CFR 866.3393 Regulation Name: Device to detect nucleic acids from non-viral microorganism(s) causing sexually transmitted infections and associated resistance marker(s) Regulatory Class: Class II Product Code: QEP, MKZ, LSL, OOI, QBD Dated: February 22, 2019 Received: February 25, 2019

Dear Sudhakar Marla:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

1

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

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

Sincerely,

for

Uwe Scherf, Ph.D. Director Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

2

510(k) Summary

As required by 21 CFR Section 807.92(c).

| Submitted by: | Cepheid
904 Caribbean Drive
Sunnyvale, CA 90489
Phone number: (408) 548-8946
Fax number: (408) 541-4192 |
|---------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact: | Sudhakar Marla, Ph.D. |
| Date Submitted: | May 20, 2019 |
| Proprietary/Trade name: | Xpert® CT/NG |
| Common name: | Xpert CT/NG |
| 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). |
| Regulation Number
Classification Name: | 21 CFR 866.3393 Device to detect nucleic acids from non-viral
microorganism(s) causing sexually transmitted infections and
associated resistance marker(s) |
| Primary Product code: | QEP; Class II |
| Secondary Product code: | LSL, MKZ, OOI, QBD |
| Classification Advisory
Panel | Microbiology (83) |
| Prescription Use | Yes |
| Predicate Device -
Assay: | Aptima Mycoplasma genitalium Assay
[De Novo #DEN180047] |
| Predicate Devices -
Ancillary Specimen
Collection Kits: | Xpert Vaginal/Endocervical Specimen Collection Kit
[510(k) #K173840]
BD MAX UVE Specimen Collection Kit
[510(k) #K043144] |

3

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 integrates sample purification, nucleic acid amplification and detection of the target sequences in simple or complex samples using real-time PCR. 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, crosscontamination 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.

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 Chlamvdia 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,

4

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.

Substantial Equivalence:

The Xpert CT/NG is substantially equivalent to the predicate device, Aptima Mycoplasma genitalium Assay [De Novo #DEN180047: January 23, 2019].

Table 8-1 shows the similarities and differences between Xpert CT/NG and the predicate device.

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Similarities
	Device	Predicate Device
Item	Cepheid Xpert CT/NG	Aptima Mycoplasma
genitalium Assay
Nucleic Acid
Extraction	Yes	Yes
Assay Results	Same	Qualitative
Indication for Use	Same	Asymptomatic and
symptomatic patients

Table 8-1: Comparison of Similarities and Differences of Xpert CT/NG with the Predicate Device

Differences
Item	Device
Cepheid Xpert CT/NG	Predicate Device
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)
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	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
Differences
Item	Device
Cepheid Xpert CT/NG	Predicate Device
Aptima Mycoplasma
genitalium Assay
	(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.	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.
Differences
Item	Device
Cepheid Xpert CT/NG	Predicate Device
Aptima Mycoplasma
genitalium Assay
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.

6

7

The Xpert Swab Specimen Collection Kit is substantially equivalent to the following predicate devices:

. Cepheid Xpert Vaginal/Endocervical Specimen Collection Kit [510(k) #K173840]
Becton Dickinson BD MAX UVE Specimen Collection Kit [510(k) . #K043144]

Similarities and differences between the Cepheid Xpert Swab Specimen Collection Kit and the predicate collection devices are shown in Table 8-2.

8

Item	Device	Predicate Devices
	Cepheid Xpert Swab
Specimen Collection Kit	Cepheid Xpert
Vaginal/Endocervical
Specimen Collection Kit	BD MAX UVE Specimen
Collection Kit
510(k)
Number	K190441	K173840	K151589
Intended Use	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.	The Cepheid® Xpert®
Vaginal/Endocervical
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.	The BD MAX UVE
Specimen Collection Kit is
intended to be used in clinical
settings according to the
instructions provided for
collection and transport of
vaginal and endocervical
swab specimens, in addition
to the preservation of urine
from males and females.
This transport system is for
use for testing with the BD
MAX products.
Description	Contains an individually
packaged sterile large
cleaning swab (for
endocervical samples) and a
package containing an
individually packaged sterile
collection swab (for vaginal
and endocervical sampling)
and an Xpert Swab Transport
Reagent tube. The collection
swab is placed into the
Transport Reagent Tube after
swab sampling to stabilize
the nucleic acid until sample
preparation.	Contains an individually
packaged sterile large
cleaning swab (for
endocervical samples) and a
package containing an
individually packaged sterile
collection swab (for vaginal
and endocervical sampling)
and an Xpert Swab Transport
Reagent tube. The collection
swab is placed into the
Transport Reagent Tube after
swab sampling to stabilize the
nucleic acid until sample
preparation.	Contains a BD MAX
Specimen Collection Swab, a
graduated transfer pipette and
a
BD MAX UVE Sample
Buffer Tube. The BD MAX
Specimen Collection Swab is
a sterile polyester swab.
The swab is placed into the
BD MAX UVE Sample
Buffer Tube. For urine
specimens, a sample of urine
is transferred directly into the
BD MAX UVE Sample
Buffer Tube using the
graduated transfer pipette.

Table 8-2: Comparison of Similarities and Differences of the Xpert Swab Specimen Collection Kit with the Predicate Device Collection Kits

9

Non-Clinical Studies:

Analytical Sensitivity

Pooled Pharyngeal Swab Matrix

Purified and titered elementary bodies from two CT serovars. ATCC vr885 serovar D and ATCC vr879 serovar H. were each tested in a sample matrix of negative pooled clinical pharyngeal swab matrix. Replicates of 20 were evaluated at five concentrations for CT serovar D and for CT serovar H and LoDs were estimated by probit analysis. The claimed LoDs were confirmed by analyzing at least 20 replicate samples with elementary bodies diluted to the estimated LoD concentrations. For this study, the claimed LoD is defined as the lowest concentration at which 95% of at least 20 replicates are positive.

The claimed LoD for purified CT serovar D elementary bodies (EB) in pharvngeal swab matrix is 161 EB/mL (Table 8-3). The claimed LoD for purified CT serovar H elementary bodies in pharyngeal swab matrix is 225 EB/mL (Table 8-3).

Table 8-3: LoD of Two CT Serovars in Pooled Pharyngeal Swab Matrix

Organism	LoD
CT ATCC vr885 serovar D (EB/mL)	161
CT ATCC vr879 serovar H (EB/mL)	225

Two NG strains (ATCC 19424 and ATCC 49226) were tested. Replicates of 20 were evaluated at five concentrations. The LoD was estimated by probit analysis.

The LoD for NG, estimated by probit analysis, is 6.4 – 7.1 CFU/mL in a pooled pharyngeal swab matrix (Table 8-4).

Table 8-4: LoD of Two NG Strains in Pooled Pharyngeal Swab Matrix

Organism	LoD
NG ATCC 19424 (CFU/mL)	7.1
NG ATCC 49226 (CFU/mL)	6.4

10

Pooled Rectal Swab Matrix

Purified and titered elementary bodies from two CT serovars, ATCC vr885 serovar D and ATCC vr879 serovar H, were each tested in a sample matrix of negative pooled clinical rectal swab matrix. Replicates of 20 were evaluated at five concentrations for CT serovar D and for CT serovar H and LoDs were estimated by probit analysis. The claimed LoDs were confirmed by analyzing at least 20 replicate samples with elementary bodies diluted to the estimated LoD concentrations. For this study, the claimed LoD is defined as the lowest concentration at which 95% of at least 20 replicates are positive.

The claimed LoD for purified CT serovar D elementary bodies (EB) in rectal swab matrix is 88 EB/mL (Table 8-5). The claimed LoD for purified CT serovar H elementary bodies in rectal swab matrix is 161 EB/mL (Table 8-5).

Table 8-5: LoD of Two CT Serovars in Pooled Rectal Swab Matrix

Organism	LoD
CT ATCC vr885 serovar D (EB/mL)	88
CT ATCC vr879 serovar H (EB/mL)	161

Two NG strains (ATCC 19424 and ATCC 49226) were tested. Replicates of 20 were evaluated at five concentrations. The LoD was estimated by probit analysis.

The LoD for NG, estimated by probit analysis, is 4.9 - 5.3 CFU/mL in a pooled rectal swab matrix (Table 8-6).

Organism	LoD
NG ATCC 19424 (CFU/mL)	4.9
NG ATCC 49226 (CFU/mL)	5.3

Table 8-6: LoD of Two NG Strains in Pooled Rectal Swab Matrix

Analytical Reactivity (Inclusivity)

Fourteen CT serovars and twenty NG strains were tested in this study. Testing was performed using CT and NG cultures that were diluted in pooled clinical pharyngeal and pooled clinical rectal swab matrices at levels near the analytical LoD. Three replicates were tested for each strain. Results are shown in Table 8-8 for CT serovars and NG strains, respectively. All 14 CT serovars and all 20 NG strains were correctly reported using the Xpert CT/NG test.

11

| C. trachomatis | Concentration
Tested in Pharyngeal
Swab Matrix | Concentration
Tested in Rectal
Swab Matrix | Assay Result | |
|----------------|------------------------------------------------------|--------------------------------------------------|--------------|-----|
| serovar | | | CT | NG |
| A | 1800 EB/mL | 1800 EB/mL | POS | NEG |
| B | 9 EB/mL | 8.1 EB/mL | POS | NEG |
| Ba | 0.9 EB/mL | 0.81 EB/mL | POS | NEG |
| C | 900 EB/mL | 322 EB/mL | POS | NEG |
| E | 450 EB/mL | 322 EB/mL | POS | NEG |
| E/SW2 | 0.9 IFU/mLª | 0.81 IFU/mLª | POS | NEG |
| F | 450 EB/mL | 322 EB/mL | POS | NEG |
| G | 900 EB/mL | 644 EB/mL | POS | NEG |
| I | 0.18 EB/mL | 0.16 EB/mL | POS | NEG |
| J | 900 EB/mL | 644 EB/mL | POS | NEG |
| K | 900 EB/mL | 644 EB/mL | POS | NEG |
| LGV I | 450 EB/mL | 322 EB/mL | POS | NEG |
| LGV II | 450 EB/mL | 322 EB/mL | POS | NEG |
| LGV III | 450 EB/mL | 644 EB/mL | POS | NEG |

Table 8-7: Analytical Reactivity Results of the Xpert CT/NG Assay with CT Serovars in Pooled Pharyngeal and Rectal Swab Matrices

a. IFU/mL = Infectious units per mL.

Table 8-8: Analytical Reactivity Results of the Xpert CT/NG Assav with
NG Strains in Pharyngeal and Rectal Swab Matrices

| N. gonorrhoeae
Strain | Concentration
Tested in
Pharyngeal Swab
Matrix (CFU/mL) | Concentration
Tested in Rectal
Swab Matrix
(CFU/mL) | Assay Result | |
|---------------------------------|------------------------------------------------------------------|--------------------------------------------------------------|--------------|-----|
| 9793 | 14.2 | 10.6 | CT | NG |
| 9830 | 14.2 | 10.6 | NEG | POS |
| 19999 | 14.2 | 10.6 | NEG | POS |
| 27629 | 14.2 | 10.6 | NEG | POS |
| 27630 | 14.2 | 10.6 | NEG | POS |
| 27631 | 14.2 | 10.6 | NEG | POS |
| 31148 | 14.2 | 10.6 | NEG | POS |
| 31397 | 14.2 | 10.6 | NEG | POS |
| 31399 | 14.2 | 10.6 | NEG | POS |

12

| N. gonorrhoeae
Strain | Concentration
Tested in
Pharyngeal Swab
Matrix (CFU/mL) | Concentration
Tested in Rectal
Swab Matrix
(CFU/mL) | Assay Result | |
|---------------------------------|------------------------------------------------------------------|--------------------------------------------------------------|--------------|-----|
| | | | CT | NG |
| 31400 | 14.2 | 10.6 | NEG | POS |
| 1170 | 14.2 | 42.4 | NEG | POS |
| 6395 | 14.2 | 10.6 | NEG | POS |
| 13281 | 14.2 | 10.6 | NEG | POS |
| 34447 | 14.2 | 10.6 | NEG | POS |
| 37541 | 14.2 | 10.6 | NEG | POS |
| 10226 | 14.2 | 10.6 | NEG | POS |
| 10227 | 14.2 | 10.6 | NEG | POS |
| 10932 | 14.2 | 10.6 | NEG | POS |
| 11472 | 14.2 | 10.6 | NEG | POS |
| 50348 | 14.2 | 10.6 | NEG | POS |

Analytical Specificity (Cross-reactivity and Competitive Interference)

Forty-one microorganisms potentially present in pharyngeal flora (Table 8-9) and fortythree microorganisms potentially present in rectal flora (see Table 8-10) were tested using Xpert CT/NG. The microorganisms were tested in the presence (competitive interference) and absence (cross-reactivity) of 2X LoD CT (Serovar D) and NG (ATCC 49226) organisms and were diluted into pooled clinical negative pharyngeal swab matrix or pooled clinical negative rectal swab matrix for testing. Bacterial strains were tested in triplicate at a concentration of at least 10° CFU/mL except for Treponema denticola, which was tested at 1.92 x 106 genome equivalents/mL. Parasites were tested at 1 x 100 cells/mL except for Entamoeba histolytica, which was tested at 1 x 105 CFU/mL and viruses were tested at 1 x 105 TCID50/ml or 1 x 105 IFU/mL. Positive and negative controls were included in the study. All CT and NG positive samples remained positive and all CT and NG negative samples remained negative, indicating that there was no interference or cross-reactivity with the results of the Xpert CT/NG test for these microorganisms.

13

Pooled Pharyngeal Swab Matrix
Actinobacillus actinomycetemcomitans	Klebsiella pneumoniae	Staphylococcus aureus
Adenovirus	Lactobacillus
acidophilus	Staphylococcus
epidermidis
Arcanobacterium haemolyticum	Lactobacillus lactis	Streptococcus anginosus
Bordetella pertussis	Moraxella catarrhalis	Streptococcus
dysgalactiae
Campylobacter rectus	Mycoplasma pneumoniae	Streptococcus mitis
Candida albicans	Neisseria flavescens	Streptococcus mutans
Coronavirus	Peptostreptococcus
micros	Streptococcus
pneumoniae
Corynebacterium diphtheriae	Porphyromonas
gingivalis	Streptococcus pyogenes
Fusobacterium necrophorum	Prevotella bivia	Streptococcus salivarius
Haemophilus influenzae	Prevotella oralisa	Streptococcus sanguinis
Herpes virus	Pseudomonas
aeruginosa	Tannerella forsythiab
Human influenza virus A	Respiratory syncytial
virus	Treponema denticolac
Human influenza virus B	Rhinovirus	Veillonella parvula
Human metapneumovirus	Saccharomyces
cerevisiae

Table 8-9: Potential Cross-reacting/Competitive Interfering Microorganisms in Pooled Pharyngeal Swab Matrix

a. Bacteroides oralis is Prevotella oralis.

b. Bacteriodes forsythus is Tannerella forsythia.

c. Genomic DNA tested.

14

| Acinetobacter baumannii | Fusobacterium
necrophorum | Providencia stuartii |
|----------------------------|----------------------------------|---------------------------------------------------|
| Anaerococcus tetradius | Fusobacterium nucleatum | Pseudomonas aeruginosa |
| Anaerococcus hydrogenalis | Giardia lamblia | Salmonella enterica sb enterica sv
minnesota |
| Bacteroides fragilis | Helicobacter pylori | Salmonella enterica sb enterica sv
typhimurium |
| Bifidobacterium adolescent | Klebsiella oxytoca | Shigella flexneri |
| Campylobacter jejuni | Lactobacillus acidophilus | Shigella sonnei |
| Candida albicans | Lactobacillus delbreueckii | Staphylococcus aureus |
| Citrobacter freundii | Listeria monocytogenes | Staphylococcus epidermidis |
| Clostridium difficile | Morganella morganii | Streptococcus agalactiae |
| Entamoeba histolytica | Norovirus | Streptococcus dysgalactiae |
| Enterobacter cloacae | Peptostreptococcus
anaerobius | Vibrio cholerae |
| Enterococcus faecalis | Plesiomonas shigelloides | Vibrio parahaemolyticus |
| Enterococcus faecium | Prevotella bivia | Yersinia enterocolitica |
| Enterovirus | Prevotella oralis | |
| Escherichia coli | Proteus mirabilis | |

Table 8-10: Potential Cross-reacting/Competitive Interfering Microorganisms in Pooled Rectal Swab Matrix

Interfering Substances

Potentially interfering exogenous substances were diluted in pooled clinical pharyngeal swab and pooled clinical rectal swab matrices containing two different mixtures of CT and NG cells. The first mixture contained 3x LoD CT serovar D and NG strain ATCC 49226. The second mixture contained 3x LoD CT serovar H and NG strain ATCC 19424.

There was no assay interference in the presence of the substances at the concentrations tested for pharyngeal swab matrix (Table 8-11) and rectal swab matrix (Table 8-12).

15

| Potentially Interfering Substances to be Evaluated | Concentration
Tested |
|--------------------------------------------------------|-------------------------|
| Mucin (pig gastric mucin) | 25 mg/mL |
| Whole human blood | 5% v/v |
| Mouthwash (Cool Mint Listerine, antiseptic) | 5% v/v |
| Cough Medicine Guaifenesin (Guaiacol glyceryl) | 5 mg/mL |
| Cough Medicine Dextromethorphan HBr | 100 µg/mL |
| Antibiotic (Penicillin G) | 1.2 mg/mL |
| Antibiotic (Erythromycin) | 15 µg/mL |
| Sugar-containing cold and flu remedies (Acetaminophen) | 5% v/v |
| Chloraseptic | 5% v/v |
| Salt-modifying remedy (sodium chloride) | 50% v/v |
| Foods/drinks that increase salivary viscosity (milk) | 5% v/v |
| pH Modifying Remedy (orange juice) | 5% v/v |
| Cold Sore medication Abreva | 5% v/v |
| Potentially Interfering Substances to be Evaluated | Concentration
Tested |
| Barium sulfate | 0.25% w/v |
| Ciprofloxacin | 0.25% w/v |
| Condom | 1 condom (#) |
| Cortizone | 0.25% w/v |
| ExLax | 0.25% w/v |
| Fecal fat (Stearic acid/Palmitic acid/Cholesterol) | 0.25% w/v |
| Imodium | 0.25% w/v |
| K-Y Jelly | 0.25% w/v |
| Milk of Magnesia | 0.25% w/v |
| Mineral Oil | 0.25% w/v |
| Neosporin
(Polymixin B/ Neomycin/Bacitracin) | 0.25% w/v |
| Nystatin | 0.25% w/v |
| Pepcid | 0.25% w/v |
| Pepto-Bismol | 0.25% w/v |
| Preparation H | 0.25% w/v |
| Prilosec | 0.25% w/v |
| Saline | 0.25% w/v |
| Tagamet | 0.25% w/v |
| Vagisil | 0.25% w/v |

Table 8-11: Potentially Interfering Substances Tested in Pooled Pharyngeal Swab Matrix

16

Table 8-12: Potentially Interfering Substances Tested in Pooled Rectal Swab Matrix

Carry-Over Contamination Study

Please refer to the previously FDA-cleared 510(k) #K121710 for additional information.

17

Linearity

Please refer to the previously FDA-cleared 510(k) #K121710 for additional information.

Clinical Performance Characteristics:

Reproducibility and Precision

Please refer to the previously FDA-cleared 510(k) #K121710 for additional information.

Clinical Performance Study

Performance characteristics of Xpert CT/NG were determined in a multi-site prospective investigational study at 9 US institutions by comparing Xpert CT/NG to the anatomic site infected status (ASIS) algorithm based on combined results from two NAAT tests, with a tiebreaker NAAT test if applicable.

The anatomic site was considered to be infected if both of the reference test results were positive. The anatomic site is considered to be not infected when both reference test results were negative. If there was discordance between the reference tests, an additional NAAT was tested as a tiebreaker. In this case, agreement of 2/3 of the reference NAATs determined the ASIS result. If two tests were equivocal or one equivocal and one not run, the third test result stood as the ASIS if positive or negative. If two tests were not run, the ASIS was considered invalid and excluded from the analysis. The tiebreaker test was run by the lab if any NAAT was not concordant with the others and interpreted only in the case of discordant results between the two planned reference tests for each assay. As the tiebreaker test was not a combination test, the tiebreaker was only run for the organism with disagreement (e.g., if NG disagrees and CT agrees, the tiebreaker was only run for NG).

Study participants included consenting 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, gav, 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. 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 pharvngeal 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 during shipment, 4 participants withdrew consent, 2 speciment errors, 2 post-swab collection

18

errors, 1 specimen not collected, 1 participant receiving antibiotics, and 13 specimens with Xpert results not available or non-determinate. 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 participants withdrew consent, 5 specimens shipment errors. 2 post-swab collection errors, 1 specimen not collected, 1 participant receiving antibiotics, and 46 specimens with Xpert results not available or non-determinate.

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 vielded valid results upon repeat assay (2 specimens were not retested). The overall valid reporting rate of the assay was 99.1% (5116/5163).

Chlamydia trachomatis Performance Results - Pharyngeal and Rectal Swabs Results from Xpert CT/NG were compared to the ASIS algorithm for determination of sensitivity and specificity. Results for CT by symptomatic status are shown in Table 8-13.

19

| Specimen | Status | n | TP | FP | TN | FN | Prev
% | Sensitivity %
(95 CI) | Specificity %
(95 CI) |
|----------|--------|------|-----|----|------|----|-----------|--------------------------|--------------------------|
| PS | Sym | 306 | 9 | 0 | 297 | 0 | 2.9 | 100.0%
(70.1-100.0) | 100.0%
(98.7%-100.0) |
| | Asym | 2269 | 38 | 8 | 2221 | 2 | 1.8 | 95.0%
(83.5-98.6) | 99.6%
(99.3-99.8) |
| | All | 2575 | 47 | 8 | 2518 | 2 | 1.9 | 95.9%
(86.3-98.9) | 99.7%
(99.4-99.8) |
| RS | Sym | 188 | 22 | 1 | 160 | 5 | 14.4 | 81.5%
(63.3-91.8) | 99.4%
(96.6-99.9) |
| | Asym | 2347 | 175 | 14 | 2131 | 27 | 8.6 | 86.6%
(81.3-90.7) | 99.4%
(98.9-99.6) |
| | All | 2535 | 197 | 15 | 2291 | 32 | 9.0 | 86.0%
(80.9-89.9) | 99.4%
(98.9-99.6) |

Table 8-13: Xpert CT/NG vs. ASIS for CT Detection by Symptomatic Status -Pharyngeal Swabs and Rectal Swabs

TP=true positive, FP=false positive, TN=true negative, PN=false negative, PS=pharyngeal swab

Neisseria gonorrhoeae Performance Results – Pharyngeal and Rectal Swabs

Results from Xpert CT/NG were compared to the ASIS algorithm for determination of sensitivity and specificity. Results for NG by symptomatic status are shown in Table 8-14.

Table 8-14: Xpert CT/NG vs. ASIS for NG Detection by Symptomatic Status -Pharyngeal Swabs and Rectal Swabs

| Specimen | Status | n | TP | FP | TN | FN | Prev % | Sensitivity %
(95 CI) | Specificity %
(95 CI) |
|----------|--------|------|-----|----|------|----|--------|--------------------------|--------------------------|
| PS | Sym | 306 | 39 | 3 | 261 | 3 | 13.7 | 92.9%
(81.0-97.5) | 98.9%
(96.7-99.6) |
| | Asym | 2269 | 156 | 26 | 2079 | 8 | 7.2 | 95.1%
(90.7-97.5) | 98.8%
(98.2-99.2) |
| | All | 2575 | 195 | 29 | 2340 | 11 | 8.0 | 94.7%
(90.7-97.0) | 98.8%
(98.3-99.2) |
| RS | Sym | 188 | 38 | 0 | 149 | 1 | 20.7 | 97.4%
(86.8-99.6) | 100.0%
(97.5-100.0) |
| | Asym | 2348 | 149 | 9 | 2173 | 17 | 7.1 | 89.8%
(84.2-93.5) | 99.6%
(99.2-99.8) |
| | All | 2536 | 187 | 9 | 2322 | 18 | 8.1 | 91.2%
(86.6-94.4) | 99.6%
(99.3-99.8) |

TP=true positive, FP=false positive, TN=true negative, PN=false negative, PS=pharyngeal swab, RS=rectal swab

20

Table 8-15 and Table 8-16 show the number of results designated as infected or not infected with CT based on the ASIS algorithm for pharyngeal and rectal specimens, respectively.

| ASISa | NAAT1 | NAAT2 | Tiebreaker
NAAT | Xpert | Total |
|--------------------|-------|-------|--------------------|-------|-------|
| NI | - | - | NAb | - | 2504 |
| NI | NRc | - | - | - | 6 |
| NI | - | - | NA | + | 4 |
| NI | - | + | - | - | 5 |
| NI | + | - | - | - | 2 |
| NI | - | + | - | + | 1 |
| NI | + | - | - | + | 1 |
| NI | EQd | - | - | - | 1 |
| INDe | + | - | EQ | + | 1 |
| IND | NR | - | + | + | 1 |
| Total Not Infected | | | | | 2526 |
| I | + | + | NA | + | 40 |
| I | - | + | + | + | 5 |
| I | + | - | + | + | 2 |
| I | + | + | NA | - | 1 |
| I | - | + | + | - | 1 |
| Total Infected | | | | | 49 |

Table 8-15: Anatomic Site Infected Status – Pharyngeal CT

ASIS = Anatomic Site Infected Status: NI=Not Infected; IND=indeterminate, considered not a. infected.

b. NA=Not applicable; both reference NAAT tests agreed.

c. NR = Not run

EQ=Equivocal d.

IND=Indeterminate. Considered if Xpert Negative and not infected if Xpert positive to evaluate e. under worst-case scenario.

21

| ASISa NAAT | Xpert | Total |
|--------------------|-- | NI | NI | NI | NI | NI | NI | NI | INDe | Total Not Infected | | I | I | I | I | I | I | I | I | I | I | I | I | IND | IND | Total Infected | | NAAT1 | NAAT2 | Tiebreaker
-----|-------|--------------------|-------|-------|
| - | - | NAb | - | 2221 |
| NRc | - | - | - | 47 |
| - | - | NA | + | 12 |
| + | - | - | - | 11 |
| - | + | - | - | 10 |
| - | + | - | + | 2 |
| - | EQd | - | - | 2 |
| + | EQ | - | + | 1 |
| | | | 2306 |
| + | + | NA | + | 172 |
| - | + | + | + | 14 |
| - | + | + | - | 11 |
| + | + | NA | - | 9 |
| + | - | + | + | 6 |
| + | - | + | - | 5 |
| + | EQ | + | + | 3 |
| - | EQ | + | - | 2 |
| NR | + | + | + | 2 |
| + | EQ | + | - | 1 |
| + | EQ | NR | - | 1 |
| NR | E | + | - | 1 |
| - | NR | + | - | 1 |
| + | - | NR | - | 1 |
| | | | 229 |

Table 8-16: Anatomic Site Infected Status – Rectal CT

ASIS = Anatomic Site Infected Status: NI=Not Infected; IND=indeterminate, considered not a. infected.

b. NA=Not applicable; both reference NAAT tests agreed.

C. NR = Not run

d. EQ=Equivocal

IND=Indeterminate. Considered if Xpert negative and not infected if Xpert positive to evaluate under e. worst-case scenario.

22

Table 8-17 and Table 8-18 show the number of results designated as infected or not infected with NG based on the ASIS algorithm for pharyngeal and rectal specimens, respectively.

| ASISa | NAAT1 | NAAT2 | Tiebreaker
NAAT | Xpert | Total |
|--------------------|-------|-------|--------------------|-------|-------|
| NI | - | - | NAb | - | 2317 |
| NI | - | - | NA | + | 19 |
| NI | - | + | - | - | 14 |
| NI | - | + | - | + | 4 |
| NI | + | - | - | - | 4 |
| NI | + | - | - | + | 4 |
| NI | NRc | - | - | - | 5 |
| NI | - | EQd | - | + | 1 |
| INDe | - | + | EQ | + | 1 |
| Total Not 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 | | | | |

Table 8-17: Anatomic Site Infected Status – Pharyngeal NG

-ASIS = Anatomic Site Infected Status: NI=Not Infected; IND=indeterminate, considered not a. infected.

b. NA=Not applicable; both reference NAAT tests agreed.

NR = Not run C.

EQ=Equivocal d.

IND=Indeterminate. Considered if Xpert negative and not infected if Xpert positive to evaluate under e. worst-case scenario.

23

| ASISa | NAAT1 | NAAT2 | Tiebreaker
NAAT | Xpert | Total |
|--------------------|-------|-------|--------------------|-------|-------|
| NI | - | - | NAb | - | 2261 |
| NI | NRc | - | - | - | 49 |
| NI | - | - | NA | + | 6 |
| NI | + | - | - | - | 5 |
| NI | - | + | - | - | 4 |
| NI | + | - | - | + | 2 |
| NI | - | EQd | - | - | 2 |
| NI | - | NR | - | - | 1 |
| INDe | + | EQ | - | + | 1 |
| Total Not 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 |

Table 8-18: Anatomic Site Infected Status - Rectal NG

ASIS = Anatomic Site Infected Status: NI=Not Infected; IND=indeterminate, considered not a. infected.

b. NA=Not applicable; both reference NAAT tests agreed.

с. NR = Not run

EQ=Equivocal d.

e. IND=Indeterminate. Considered if Xpert negative and not infected if Xpert positive to evaluate under worst-case scenario.

Conclusions

The results of the nonclinical analytical and clinical performance studies summarized above demonstrate that the Xpert CT/NG test performance is equivalent to the predicate.