Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description and performance studies focus on real-time PCR technology and standard analytical methods for detecting DNA. There is no mention of AI or ML in the summary.

Therapeutic

No.
The device is an in vitro diagnostic test designed to detect and differentiate genomic DNA from specific bacteria to aid in the diagnosis of chlamydial and gonorrheal urogenital disease. It does not provide therapy or treatment.

Diagnostic

Yes

The "Intended Use / Indications for Use" section explicitly states that the device is "to aid in the diagnosis of chlamydial and gonorrheal urogenital disease." Additionally, the "Device Description" calls it 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. This indicates the device is a hardware system with integrated software, not a software-only medical device.

IVD (In Vitro Diagnostic)

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

Here's why:

Intended Use/Indications for Use: The very first sentence explicitly states it 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 urogenital disease." The phrase "in vitro" and "to aid in the diagnosis" are key indicators of an IVD.
Device Description: The description further reinforces this by stating "The Xpert CT/NG Assay is an automated in vitro diagnostic test for qualitative detection and differentiation of DNA from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoege (NG)."
Specimen Types: The assay is designed to test human specimens (urine, endocervical swabs, vaginal swabs), which are typical for IVD tests.
Purpose: The purpose is to detect specific pathogens in these specimens to aid in the diagnosis of disease, which is the core function of an IVD.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The Xpert® CT/NG Assay, 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 urogenital disease. The assay may be used to test the following specimens from asymptomatic and symptomatic individuals: female and male urine, endocervical swab, and patient-collected vaginal swab (collected in a clinical setting).

Ancillary Collection Kits Indications for Use:

The Cepheid® Xpert® CT/NG Vaginal/Endocervical Specimen Collection Kit is designed to collect, preserve and transport patient Chiamydia trachomatis and Neisseria gonorrhoeae DNA in endocervical and vaginal specimens from symptomatic and asymptomatic individuals prior to analysis with the Cepheid Xpert CT/NG Assay.

The Cepheid® Xpert® CT/NG Urine Specimen Collection Kit is designed to preserve and transport Chlamydia trachomatis and Neisseria gonorrhoeae DNA in first-catch male and female urine specimens from symptomatic and asymptomatic individuals prior to analysis with the Cepheid Xpert CT/NG Assay.'

Product codes

MKZ, LSL, OOI

Device Description

The Xpert CT/NG Assay is an automated in vitro diagnostic test for qualitative detection and differentiation of DNA from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoege (NG). The assay is performed on the Cepheid GeneXpert Instrument Systems. The GeneXpert Instrument Systems automate and integrate sample purification, nucleic acid amplification, and detection of the target sequences in simple or complex samples using real-time PCR and RT-PCR assays. The systems consist of an instrument, personal computer, and preloaded software for running the tests on collected samples 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 selfcontained, cross-contamination between cartridges during the testing process is minimized.

The Xpert CT/NG Assay includes reagents for the 5' exonuclease real-time PCR detection and differentiation of CT and NG. Reagents for the detection of a Sample Processing Control (SPC), a Sample Adequacy Control (SAC), and a Probe Check Control (PCC) are also included in the cartridge. 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 DNA. The PCC verifies reagent rehydration. PCR tube filling in the cartridge, probe integrity, and dye stability. The primers and probes in the Xpert CT/NG Assay detect chromosomal sequences in the bacteria. One target is detected for CT (CT1) and two different targets are detected for NG (NG2 and NG4). Both NG targets need to be positive for the Xpert CT/NG Assay to return a positive NG result.

The GeneXpert Instrument Systems, comprised of the GeneXpert Dx Systems, the GeneXpert Infinity-48 System 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 Assay are the Cepheid® Xpert® CT/NG Vaginal/Endocervical Specimen Collection Kit and the Cepheid® Xpert® CTNG Urine Specimen Collection Kit.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Urogenital

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Clinical setting

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

A clinical study at thirty-six collection sites was conducted to compare Xpert CT/NG Assay performance relative to a patient infection status algorithm, based on results from the GEN-PROBE APTIMA Combo 2 Assay and Becton Dickenson ProbeTec ET Chlamydia trachomatis /Neisseria gonorrhoeae Amplified DNA Assay tests.
Study participants included consenting asymptomatic and symptomatic, sexually active males and females seen at locations including, but not limited to: OB/GYN, sexually transmitted disease (STD), teen, public health, and family planning clinics. The average age among female study participants was 30.3 years (range = 14 to 83 years); the average age among male study participants was 37.7 years (range = 17 to 74 years).

The study specimens consisted of prospectively collected male urine, female urine, endocervical swabs, urethral swabs and patient-collected vaginal swabs (collected in a clinical setting).

A female study participant was categorized as infected (I) by PIS for CT or NG if at least one positive result was reported from each reference NAAT test. If both NAAT tests resulted in equivocal results for both sample types (swab and urine) the PIS status was defined as equivocal (EQ). This is the only scenario for an overall PIS of EQ; no study participants fell into this category for this study. Female study participants with positive results on both reference urine specimens and negative results on both reference swab specimens were categorized as infected (I) for urine and not infected (NI) for the swab specimen. Any other combination of results was categorized as not infected (NI).

A male study participant was categorized as infected (I) by PIS for CT or NG if at least one positive result was reported from each reference NAAT test. If both NAAT tests resulted in equivocal results for both sample types (swab and urine) the PIS status was defined as equivocal (EQ). This is the only scenario for an overall PIS of EQ; no study participants fell into this category for this study. Any other combination of results was categorized as not infected (NI).

Summary of Performance Studies

A multi-site prospective investigational study at 36 US and UK institutions was conducted. The Xpert CT/NG Assay was compared to a patient infected status (PIS) algorithm based on combined results from two currently marketed NAAT tests (GEN-PROBE® APTIMA® Combo 2 Assay and Becton Dickenson ProbeTec™ ET Chlamydia trachomatis /Neisseria gonorrhoeae Amplified DNA Assay).

Total of 14,790 tests performed, with 416 (2.81%) retested due to ERROR, INVALID, or NO RESULT. The overall valid reporting rate was 99.6% (14,729/14,790).

Chlamydia trachomatis (CT) Performance:

Female PC-VS:
- Symptomatic (n=1294): Sensitivity 100% (95.4-100), Specificity 98.4% (97.5-99.0), PPV 79.8% (70.5-87.2), NPV 100% (99.7-100)
- Asymptomatic (n=2472): Sensitivity 99.2% (95.5-100), Specificity 99.5% (99.2-99.8), PPV 91.7% (85.6-95.8), NPV >99.9% (99.8-100)
- All (n=3766): Sensitivity 99.5% (97.3-100), Specificity 99.1% (98.8-99.4), PPV 86.6% (81.5-90.7), NPV >99.9% (99.8-100)
Female ES:
- Symptomatic (n=1293): Sensitivity 96.2% (89.3-99.2), Specificity 99.6% (99.0-99.9), PPV 93.8% (86.2-98.0), NPV 99.8% (99.3-99.9)
- Asymptomatic (n=2464): Sensitivity 95.9% (90.7-98.7), Specificity 99.5% (99.2-99.8), PPV 91.4% (85.1-95.6), NPV 99.8% (99.5-99.9)
- All (n=3757): Sensitivity 96.0% (92.3-98.3), Specificity 99.6% (99.3-99.7), PPV 92.3% (87.9-95.6), NPV 99.8% (99.6-99.9)
Female Urine:
- Symptomatic (n=1292): Sensitivity 98.8% (93.6-100), Specificity 99.7% (99.2-99.9), PPV 95.5% (88.8-98.7), NPV 99.9% (99.5-100)
- Asymptomatic (n=2475): Sensitivity 97.6% (93.2-99.5), Specificity 99.9% (99.7-100), PPV 98.4% (94.3-99.8), NPV 99.9% (99.6-100)
- All (n=3767): Sensitivity 98.1% (95.2-99.5), Specificity 99.8% (99.6-99.9), PPV 97.2% (94.0-99.0), NPV 99.9% (99.7-100)
Male Urine:
- Symptomatic (n=706): Sensitivity 97.6% (93.0-99.5), Specificity 99.7% (98.8-100), PPV 98.4% (94.2-99.8), NPV 99.5% (98.5-99.9)
- Asymptomatic (n=2730): Sensitivity 100.0% (95.1-100), Specificity 99.8% (99.6-99.9), PPV 93.6% (85.7-97.9), NPV 100% (99.9-100)
- All (n=3436): Sensitivity 98.5% (95.6-99.7), Specificity 99.8% (99.6-99.9), PPV 96.5% (92.9-98.6), NPV 99.9% (99.7-100)

Neisseria gonorrhoeae (NG) Performance:

Female PC-VS:
- Symptomatic (n=1294): Sensitivity 100% (87.2-100), Specificity 99.8% (99.4-100), PPV 93.1% (77.2-99.2), NPV 100% (99.7-100)
- Asymptomatic (n=2472): Sensitivity 100% (86.3-100), Specificity >99.9% (99.8-100), PPV 96.2% (80.4-99.9), NPV 100% (99.8-100)
- All (n=3766): Sensitivity 100% (93.2-100), Specificity 99.9% (99.8-100), PPV 94.5% (84.9-98.9), NPV 100% (99.9-100)
Female ES:
- Symptomatic (n=1293): Sensitivity 100% (87.2-100), Specificity 99.9% (99.6-100), PPV 96.4% (81.7-99.9), NPV 100% (99.7-100)
- Asymptomatic (n=2464): Sensitivity 100% (86.3-100), Specificity 100% (99.8-100), PPV 100% (86.3-100), NPV 100% (99.8-100)
- All (n=3757): Sensitivity 100% (93.2-100), Specificity >99.9% (99.8-100), PPV 98.1% (89.9-100), NPV 100% (99.9-100)
Female Urine:
- Symptomatic (n=1292): Sensitivity 96.6% (82.2-99.9), Specificity 100% (99.7-100), PPV 100% (87.7-100), NPV 99.9% (99.6-100)
- Asymptomatic (n=2475): Sensitivity 92.0% (74.0-99.0), Specificity >99.9% (99.8-100), PPV 95.8% (78.9-99.9), NPV 99.9% (99.7-100)
- All (n=3767): Sensitivity 94.4% (84.6-98.8), Specificity >99.9% (99.9-100), PPV 98.1% (89.7-100), NPV 99.9% (99.8-100)
Male Urine:
- Symptomatic (n=706): Sensitivity 99.1% (94.9-100), Specificity 100% (99.4-100), PPV 100% (96.5-100), NPV 99.8% (99.1-100)
- Asymptomatic (n=2730): Sensitivity 92.3% (64.0-99.8), Specificity 99.9% (99.7-100), PPV 80.0% (51.9-95.7), NPV >99.9% (99.8-100)
- All (n=3436): Sensitivity 98.3% (94.1-99.8), Specificity 99.9% (99.7-100), PPV 97.5% (92.9-99.5), NPV 99.9% (99.8-100)

Reproducibility: Evaluated at three sites (GeneXpert Dx, Infinity-80, Infinity-48) using spiked specimens at different LoD levels (1X, 2-3X, >20X) and negative samples. Generally high agreement with expected results. Confidence intervals for CT and NG agreement are provided in Tables 10 and 11.

Instrument System Precision: An in-house study compared GeneXpert Dx and Infinity-80 Instrument Systems. Specimens spiked at 0.25-0.5X LoD, 2-3X LoD, and >20X LoD, along with negative samples. Results are presented in Tables 15 and 16, with generally high agreement for higher concentrations and varying agreement for lower LoD concentrations (e.g., NG 0.25-0.5X LoD in swab matrix had 57.3% total agreement, CT 0.25-0.5X LoD in urine matrix had 42.2% total agreement).

Key Metrics

Sensitivity, Specificity, PPV (Positive Predictive Value), NPV (Negative Predictive Value).

Predicate Device(s)

K043224, K012351

Reference Device(s)

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information

Not Found

Regulation Number and Section

§ 866.3390

Neisseria spp. direct serological test reagents.(a)
Identification. Neisseria spp. direct serological test reagents are devices that consist of antigens and antisera used in serological tests to identifyNeisseria spp. from cultured isolates. Additionally, some of these reagents consist ofNeisseria spp. antisera conjugated with a fluorescent dye (immunofluorescent reagents) which may be used to detect the presence ofNeisseria spp. directly from clinical specimens. The identification aids in the diagnosis of disease caused by bacteria belonging to the genusNeisseria, such as epidemic cerebrospinal meningitis, meningococcal disease, and gonorrhea, and also provides epidemiological information on diseases caused by these microorganisms. The device does not include products for the detection of gonorrhea in humans by indirect methods, such as detection of antibodies or of oxidase produced by gonococcal organisms.(b)
Classification. Class II (performance standards).

Summary

0

K121710

510(k) Summary

DEC 2 7 2012

::
:: : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : :

As required by 21 CFR Section 807.92(c).

Cepheid® .

904 Caribbean Drive

Submitted by:

| 904 Caribbean Drive
Sunnyvale, CA 90489
Phone number: (408) 400-8460

Fax number: (408) 541-6439
Contact:	Kerry J. Flom, Ph.D.
Date of Preparation:	December 26, 2012
Device:
Trade name:	Xpert® CT/NG
Common name:	Xpert CT/NG Assay
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:	866.3120/ Chlamydia serological reagents.
866.3390/ Neisseria spp. direct serological test reagents
Product code:	MKZ
LSL
Classification
Advisory Panel	Microbiology (83)
Predicate Devices -
Assay:	GEN-PROBE® APTIMA® Combo 2 Assay [510(k)
#K043224]
Becton Dickenson ProbeTec™ ET Chlamydia trachomatis
/Neisseria gonorrhoeae Amplified DNA Assay [510(k)
#K012351]
Predicate Devices –
Ancillary Specimen
Collection Kits:	GEN-PROBE® APTIMA® Combo 2 Assay [510(k)
#K043244] for use with:
GEN-PROBE® APTIMA® Unisex Swab Specimen Collection
Kit for Endocervical and Urethral Swab Specimens
GEN-PROBE® APTIMA® Urine Specimen Collection Kit for
Male and Female Urine
GEN-PROBE® APTIMA® Vaginal Swab Specimen
Collection Kit for Male and Female Urine

1

Device Description:

. The Xpert CT/NG Assay is an automated in vitro diagnostic test for qualitative detection 心: and differentiation of DNA from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoege (NG). The assay is performed on the Cepheid GeneXpert Instrument Systems. The GeneXpert Instrument Systems automate and integrate sample purification, nucleic acid amplification, and detection of the target sequences in simple or complex samples using real-time PCR and RT-PCR assays. The systems consist of an instrument, personal computer, and preloaded software for running the tests on collected samples 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 selfcontained, cross-contamination between cartridges during the testing process is minimized.

The Xpert CT/NG Assay includes reagents for the 5' exonuclease real-time PCR detection and differentiation of CT and NG. Reagents for the detection of a Sample Processing Control (SPC), a Sample Adequacy Control (SAC), and a Probe Check Control (PCC) are also included in the cartridge. 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 DNA. The PCC verifies reagent rehydration. PCR tube filling in the cartridge, probe integrity, and dye stability. The primers and probes in the Xpert CT/NG Assay detect chromosomal sequences in the bacteria. One target is detected for CT (CT1) and two different targets are detected for NG (NG2 and NG4). Both NG targets need to be positive for the Xpert CT/NG Assay to return a positive NG result.

The GeneXpert Instrument Systems, comprised of the GeneXpert Dx Systems, the GeneXpert Infinity-48 System 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 svringe 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 Assay are the Cepheid® Xpert® CT/NG Vaginal/Endocervical Specimen Collection Kit and the Cepheid® Xpert® CTNG Urine Specimen Collection Kit.

Device Intended Use:

Xpert CT/NG Assay:

The Xpert® CT/NG Assay, 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

2

aid in the diagnosis of chlamydial and gonorrheal urogenital disease. The assay may be used to test the following specimens from asymptomatic and symptomatic individuals: female and male urine, endocervical swab, and patient-collected vaginal swab (collected in a clinical setting).

Ancillary Collection Kits:

The Cepheid® Xpert® CT/NG Vaginal/Endocervical Specimen Collection Kit is designed to collect, preserve and transport patient Chlamydia trachomatis and Neisseria gonorrhoeae DNA in endocervical and vaginal specimens from symptomatic and asymptomatic individuals prior to analysis with the Cepheid Xpert CT/NG Assay.

The Cepheid Xpert CT/NG Vaginal/Endocervical Specimen Collection Kit has only been cleared for use with the Cepheid Xpert® CT/NG Assay.

The Cepheid® Xpert® CT/NG Urine Specimen Collection Kit is designed to preserve and transport Chlamydia trachomatis and Neisseria gonorrhoeae DNA in first-catch male and female urine specimens from symptomatic and asymptomatic individuals prior to analysis with the Cepheid Xpert CT/NG Assay.

Substantial Equivalence:

The Xpert CT/NG Assay is substantially equivalent to the following predicate assays:

K043224: GEN-PROBE® APTIMA® Combo 2 Assay, Gen-Probe Inc. .
K012351: Becton Dickenson ProbeTec™ ET Chlamydia trachomatis /Neisseria . gonorrhoeae Amplified DNA Assay, Becton Dickenson & Co.

Similarities and differences between the Cepheid Xpert CT/NG Assay and the predicate devices are shown in Table 1.

A clinical study at thirty-six collection sites was conducted to compare Xpert CT/NG Assay performance relative to a patient infection status algorithm, based on results from the GEN-PROBE APTIMA Combo 2 Assay and Becton Dickenson ProbeTec ET Chlamydia trachomatis /Neisseria gonorrhoeae Amplified DNA Assay tests.

3

	Device	Predicates
Item	Cepheid Xpert CT/NG
Assay	GEN-PROBE®
APTIMA® Combo 2
Assay	Becton Dickenson
ProbeTec™ ET
Chlamydia trachomatis
/Neisseria gonorrhoeae
Amplified DNA Assay
510(k) No.	To be assigned	K043224	K012351
Regulation	866.3120, 866.3390	866.3120, 866.3390	866.3120, 866.3390
Product Code	MKZ, LSL	MKZ, LSL	MKZ, LSL
Device Class	I, II	I, II	I, II
Technology/
Detection	Multiplex real-time
polymerase chain
reaction (PCR)	Multiplex transcription-
mediated amplification
(TMA)	Multiplex strand
displacement
amplification (SDA)
Intended Use	An automated, multiplex
real-time RT-PCR assay,
performed on the
GeneXpert Instrument
Systems, intended for the
in vitro qualitative and
differentiation of
genomic DNA from
Chlamydia trachomatis
(CT) and/or Neisseria
gonorrhoeae (NG) to aid
in the diagnosis of
chlamydial gonorrheal
urogenital disease. The
assay may be used to test
the following specimens
from asymptomatic and
symptomatic individuals:
female and male urine,
endocervical swab, and
patient-collected vaginal
swab (collected in a
clinical setting).	A target amplification
nucleic acid probe test
that utilizes target
capture for the in vitro
qualitative detection
and differentiation of
ribosomal RNA
(rRNA) from
Chlamydia trachomatis
(CT) and/or Neisseria
gonorrhoeae (GC) in
clinician-collected
endocervical, vaginal,
and male urethral swab
specimens, patient-
collected vaginal swab
specimens*, and female
and male
urine specimens. The
assay is also intended
for use with testing of
gynecological
specimens collected in
the PreservCyt Solution
and processed with the
Cytyc ThinPrep 2000
System. The assay may
be used to test
specimens from	Strand Displacement
Amplification (SDA)
technology for the
direct, qualitative
detection of
Chlamydia trachomatis
and Neisseria
gonorrhoeae DNA in
endocervical swabs,
male urethral swabs,
and in female and male
urine specimens as
evidence of
infection with C.
trachomatis, N.
gonorrhoeae, or of co-
infection with both
C. trachomatis and N.
gonorrhoeae.
Specimens may be
from symptomatic or
asymptomatic females
and males. A separate
Amplification Control
is an option for
inhibition testing
(BDProbeTec™ ET
CT/GC/AC Reagent
Pack).
	Device	Predicates
Item	Cepheid Xpert CT/NG
Assay	GEN-PROBE®
APTIMA® Combo 2
Assay	Becton Dickenson
ProbeTec™ ET
Chlamydia trachomatis
/Neisseria gonorrhoeae
Amplified DNA Assay
Indication for
Use	Asymptomatic and
symptomatic patients	symptomatic and
asymptomatic
individuals to aid in the
diagnosis of
gonococcal and/or
chlamydial urogenital
disease.
*Patient-collected
vaginal swab
specimens are an
option for screening
women when a pelvic
exam is not otherwise
indicated. The vaginal
swab specimen
collection kit is not for
home use.
Assay Targets	DNA from Chlamydia
trachomatis (CT) and/or
Neisseria gonorrhoeae
(NG)	Same	Same
Specimen
Types	Urine, endocervical
swab, and patient-
collected vaginal swab	ribosomal RNA
(rRNA) from
Chlamydia trachomatis
(CT) and/or Neisseria
gonorrhoeae (GC)	DNA from Chlamydia
trachomatis (CT) and
Neisseria gonorrhoeae
(NG)
CT Analyte
Targets	CT genomic DNA	Clinician-collected
endocervical, vaginal,
and male urethral
swab specimens,
patient-collected
vaginal swab
specimens, and female
and male
urine specimens	Endocervical swabs,
male urethral swabs,
and urine specimens for
females and males
NG Analyte
Targets	NG genomic DNA	CT ribosomal RNA	CT cryptic plasmid DNA
	Device		Predicates
Item	Cepheid Xpert CT/NG
Assay	GEN-PROBE®
APTIMA® Combo 2
Assay	Becton Dickenson
ProbeTec™ ET
Chlamydia trachomatis
/Neisseria gonorrhoeae
Amplified DNA Assay
Collection Kit	Urine collection kit
Swab collection kit	Urine collection kit
Swab collection kit	Urine collection kit
Swab collection kit
Technological
Principles	RT/PCR	TMA	SDA
Nucleic Acid
Extraction	Yes	Yes	Yes
Sample
Extraction	Self-contained and
automated after specimen
sample elution and two
single-dose reagent
additions.	Manual	Manual
Assay Results	Qualitative	Qualitative	Qualitative
Instrument
System	Cepheid GeneXpert
Instrument Systems	Gen-Probe Leader HC+
luminometer and Gen-
Probe Target Capture
System	ProbeTec™ ET System
Assay
Controls	Internal sample
processing control (SPC),
sample adequacy control
(SAC), and probe check
control (PCC).
External controls
available.	The Positive Control,
CT / Negative Control,
GC and the Positive
Control, GC / Negative
Control, CT act as
controls for the target
capture, amplification,
and detection steps of
the assay.	Amplification Control
(AC)
Rapid test
results	Approximately 90
minutes (1.5 hours) to
results.	Approximately 4.5
hours to results.	Approximately 3.5
hours to results.
Item	Device :
Cepheid Xpert CT/NG
Vaginal/Endocervical
Specimen Collection Kit	Predicate:
GEN-PROBE®
APTIMA® Unisex
Swab Specimen
Collection kit for
Endocervical and
Male Urethral Swab
Specimen	Predicate:
GEN-PROBE®
APTIMA® Vaginal
Swab Specimen
Collection kit
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 a Xpert
CT/NG 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 Endocervical
cleaning swab and an
individually-packaged
sterile specimen
collection swab that is
placed into the
Transport Tube after
swab sampling and is
used to stabilize the
nucleic acid until
sample preparation.	Contains an
individually
packaged sterile
specimen collection
swab that is placed
into the Transport
Tube after swab
sampling and is used
to stabilize the
nucleic acid until
sample preparation.

Table 1: Comparison of Similarities and Differences of the Xpert CT/NG Assay with the Predicate Devices

.

·

.

·

4

.

:

.

5

The Ancillary Specimen Collection Kits are substantially equivalent to the following predicate assays:

GEN-PROBE® APTIMA® Unisex Swab Specimen Collection Kit for o Endocervical and Urethral Swab Specimens [in 510(k) #K043144]
GEN-PROBE® APTIMA® Urine Specimen Collection Kit for Male and o Female Urine [in 510(k) #K043144]

6

GEN-PROBE® APTIMA® Vaginal Swab Specimen Collection Kit for o Male and Female Urine [in 510(k) #K043144] .
Similarities and differences between the Cepheid Collection Kits and the predicate Collection devices are shown in Table 2.

Table 2: Comparison of Similarities and Differences of the Xpert CT/NG Collection
Kits with the Predicate Device Collection Kits

| Item | Cepheid Xpert CT/NG
Urine Specimen Collection Kit | GEN-PROBE® APTIMA® Urine
Specimen Collection kit |
|-------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Description | Contains one individually packaged
sterile disposable transfer pipette and
one Xpert CT/NG Urine Transport
Reagent tube. Approximately 7 mL of
a first-catch urine specimen is
transferred to the Urine Transport
Reagent tube to preserve and transport
the specimen prior to analysis with the
Cepheid Xpert CT/NG Assay. | Contains a disposable transfer
pipette for adding approximately 2
mL of urine to a Specimen Transport
Tube containing 2.0 mL of
Transport Buffer. |

7

Non-Clinical Studies:

Analytical Sensitivity (Limit of Detection)

Studies were performed to determine the analytical limit of detection (LoD) of the Xpert CT/NG Assay with purified CT elementary bodies seeded into negative natural human pooled vaginal swab and pooled male urine matrices, and NG cells seeded into negative pooled simulated swab and pooled male urine matrices.

Pooled Vaginal Swab Matrix

Elementary bodies from two CT serovars, ATCC vr885 serovar D and ATCC vr879 serovar H. were purified by centrifugation through a 30% sucrose cushion and titered by enumeration of elementary bodies by transmission electron microscopy. Each serovar was diluted into pooled negative vaginal swab matrix and tested with the Xpert CTNG Assay. Replicates of 20 were evaluated at eight concentrations for CT serovar D and at seven concentrations 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 in vaginal swab matrix is 84 EB/mL. The claimed LoD for purified CT serovar H elementary bodies in vaginal swab matrix is 161 EB/mL (Table 3). In this study, LoDs for the remaining purified CT serovars (in EB/mL) are A (600), B (6), Ba (1900), C (34), E (6), F (202), G (96), I (21), J (150), K (117), LGV I (31), LGV II (20) and LGV III (210) EB/mL.

Organism	LoD
CT ATCC vr885 serovar D (EB/mL)	84
CT ATCC vr879 serovar H (EB/mL)	161

CT Serovar		LoD (GC/mL)
CT Serovar D		$1.0 x 10^3$
CT Serovar E		$1.0 x 10^3$

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

The LoD for NG, estimated by probit analysis, is 1.6 CFU/mL in a simulated swab matrix background (Table 4). An additional 30 NG strains were tested in a simulated matrix and the LoD was confirmed by testing replicates of three at or near the LoD.

Table 4: LoD of Two NG Strains in Pooled Vaginal Swab Matrix

Organism	LoD
NG ATCC19424 (CFU/mL)	1.5
NG ATCC49226 (CFU/mL)	1.6

Pooled Male Urine Matrix

Xpert CT/NG Assay 510(k) Summary

8

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 male urine. Replicates of 20 were evaluated at eight concentrations for CT serovar D and at seven concentrations 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 in male urine matrix is 75 EB/mL. The claimed LoD for purified CT serovar H elementary bodies in male urine matrix is 134 EB/mL (Table 5). In this study, LoDs for the remaining purified CT serovars (in EB/mL) are A (900), B (11), Ba (3037), C (34), E (12), F (151), G (48), I (43), J (112), K (88), LGV I (31), LGV II (40) and LGV III (157).

Table 5: LoD of Two CT Serovars in Pooled Male Urine Matrix

Organism	LoD
CT ATCC vr885 serovar D (EB/mL)	75
CT ATCC vr879 serovar H (EB/mL)	134

Two NG strains, ATCC 19424 and ATCC 49226, were tested in a sample matrix of negative pooled male urine. Replicates of 20 were evaluated at six concentrations. The LoD was estimated by probit analysis.

The LoD for NG, estimated by probit analysis, is 1.2 - 2. 7 CFU/mL in a male urine matrix background (Table 6). LoD for 30 additional NG strains was confirmed by testing replicates of three at or near the LoD.

Organism	LoD
NG ATCC19424 (CFU/mL)	2.7
NG ATCC49226 (CFU/mL)	1.2

Table 6: LoD of Two NG Strains in Pooled Male Urine Matrix

Analytical Specificity (Cross-reactivity)

One hundred and one (101) different microorganisms were tested at a concentration of at least 106 CFU/mL or 10 genome copies/mL in replicates of three (Table 7). All isolates were reported CT NOT DETECTED:NG NOT DETECTED; none of the organisms were detected by the Xpert CT/NG Assay. Positive and negative controls were included in the study. The analytical specificity was 100%.

Table 7: Analytical Specificity Determination for Xpert CT/NG Assay
---------------------------------------------------------------------	--	--	--	--	--

Acinetobacter calcoaceticus	Herpes simplex virus I'	Neisseria sicca (3)
Acinetobacter Iwoffi	Herpes simplex virus II'	Neisseria subflava (2)

9

Aerococcus viridans	Human papilloma virus1	Paracoccus denitrificans
Aeromonas hydrophila	Kingella denitrificans	Peptostreptococcus anaerobius
Alcaligenes faecalis	Kingella kingae	Plesiomonas shigelloides
Arcanobacterium pyogenes	Klebsiella oxytoca	Propionibacterium acnes
Bacteriodes fragilis	Klebsiella pneumoniae	Proteus mirabilis
Bifidobacterium adolescentis	Lactobacillus acidophilus	Proteus vulgaris
Branhamella catarrhalis	Lactobacillus brevis	Providencia stuartii
Brevibacterium linens	Lactobacillus jensonii	Pseudomonas aeruginosa
Candida albicans	Lactobacillus lactis	Pseudomonas fluorescens
Candida glabrata	Legionella pneumophila	Pseudomonas putida
Candida parapsilosis	Leuconostoc paramensenteroides	Rahnella aquatilis
Candida tropicalis	Listeria monocytogenes	Saccharomyces cerevisiae
Chlamydia pneumoniae	Micrococcus luteus	Salmonella minnesota
Chromobacterium violaceum	Moraxella lacunata	Salmonella typhimurium
Citrobacter freundii	Moraxella osloensis	Serratia marcescens
Clostridium perfringens	Morganella morganii	Staphylococcus aureus
Corynebacterium genitalium	Mycobacterium smegmatis	Staphylococcus epidermidis
Corynebacterium xerosis	N. meningiditis	Staphylococcus saprophyticus
Cryptococcus neoformans	N. meningitidis Serogroup A	Streptococcus agalactiae
Cytomegalovirus1	N. meningitidis Serogroup B	Streptococcus bovis
Eikenella corrodens	N. meningitidis Serogroup C	Streptococcus mitis
Enterococcus avium	N. meningitidis Serogroup D	Streptococcus mutans
Enterococcus faecalis	N. meningitidis Serogroup W135	Streptococcus pneumoniae
Enterococcus faecium	N. meningitidis Serogroup Y	Streptococcus pyogenes
Enterobacter aerogenes	Neisseria cinerea	Streptococcus salivarius
Enterobacter cloacae	Neisseria denitrificans	Streptococcus sanguis
Erysipelothrix rhusiopathiae	Neisseria elongata (3)	Streptococcus griseinus
Escherichia coli	Neisseria flava	Vibrio parahaemolyticus
Elizabethkingia meningoseptica2	Neisseria flavescens (2)	Yersinia enterocolitica
Fusobacterium nucleatum	Neisseria lactamica (5)
Gardnerella vaginalis	Neisseria mucosa (3)
Gemella haemolysans	Neisseria perflava
Haemophilus influenzae	Neisseria polysaccharea

.

Xpert CT/NG Assay 510(k) Summary

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י

10

(n) number of strains tested

Tested at 1 x 105 genome copies/mL

2 Previously known as Flavobacterium meningosepticum

Interfering Substances

Performance of the Xpert CT/NG Assay was evaluated in the presence of potentially interfering substances. The evaluated substances were diluted into vaginal/endocervical swab simulated matrix and urine matrix containing either 5x LoD CT serovar D and NG strain ATCC 49226 or x LoD CT serovar H and NG strain ATCC 19424.

There was no assay interference in the presence of the substances at the concentrations for vaginal/endocervical matrix (Table 8) and urine matrix (Table 9).

Substance	Concentration
Blood	1.0% v/v
Mucin	0.8% w/v
Seminal Fluid	5.0% v/v
Hormones	7 mg/mL Progesterone + 0.07
mg/mL Beta Estradiol
LGV II (CT EB)	106 EB/mL
Vagisil Anti Itch Cream	0.25% w/v
Clotrimazole Vaginal cream	0.25% w/v
Preparation H Hemorroidal cream	0.25% w/v
Miconazole 3	0.25% w/v
Monistat 1	0.25% w/v
Zovirax Cold Sore Cream	0.25% w/v
Vagisil Moisturizer	0.25% w/v
Vagi Gard Moisturizing Gel	0.25% w/v
KY Jelly Personal Lubricant	0.25% w/v

Table 8: Potentially Interfering Substances in Swab Matrix

11

Substance	Concentration
Yeast Gard Douche	0.25% w/v
Delfen Vaginal Contraceptive Foam	0.25% w/v
VH Essentials Povidone-Iodine
Medicated Douche	0.25% v/v
Leukocytes	106 cells/mL

Table 9: Potentially Interfering Substances in Urine Matrix

Substance	Concentration
Blood	0.3% v/v
Mucin	0.2% v/v
Seminal Fluid	5.0% v/v
Hormones	7 mg/mL Progesterone + 0.07
mg/mL Beta Estradiol
LGV II (CT EB)	106 EB/mL
Leukocytes	106 cells/mL
Norforms Deodorant Suppositories	0.25% w/v
BSA	10 mg/mL
Glucose	10 mg/mL
Bilirubin	0.2 mg/mL
Aspirin	40 mg/mL
Azithromycin	1.8 mg/mL
Doxycycline	3.6 mg/mL
Organisms - UTI Candida albicans/
Staphylococcus aureus/Escherichia coli	2.9 x 104 CFU/mL
Acetaminophen	3.2 mg/mL
Vagisil Feminine Powder	0.25% w/v
Acidic Urine	pH 4.0
Alkaline Urine	pH 9.0

Carry-Over Contamination Study

A study was conducted to demonstrate that single-use, self-contained GeneXpert cartridges prevent carry-over contamination in negative samples run following very high

12

positive samples in the same GeneXpert module. The study consisted of a negative sample processed in the same GeneXpert module immediately following a sample with high CT spike (1.9 x 104 EB/mL) and a high NG spike (5.2 x 105 CFU/mL). Two sample types were used for this testing: a) known pooled negative urine samples; and b) known pooled negative swab sample type was tested in each of four GeneXpert modules for a total of 44 runs for both swab and urine samples resulting in 20 positives and 24 negatives. All 40 positive samples were correctly reported as CT DETECTED:NG DETECTED. All 48 negative samples were correctly reported as CT NOT DETECTED;NG NOT DETECTED.

Clinical Performance Characteristics:

Reproducibility

Reproducibility of the Xpert CT/NG Assay was evaluated at three sites using specimens comprised of CT and NG organisms seeded into pooled, negative male urine (urine matrix) or in pooled, negative female vaginal swab samples (swab matrix). The specimens were prepared at concentration levels representing low positive (1X LoD), moderate positive (2-3X LoD), and high positive (>20X LoD) for each organism. Negative panel members were also included, and were comprised of pooled, negative male urine and pooled, negative vaginal swab samples. A panel of 22 specimens (11 in urine matrix and 11 in swab matrix) was tested on five different days by two different operators four times per day at three sites (22 specimens x 2 operators/day x 5 days x 4 replicates per day x 3 sites). Three lots of Xpert CT/NG reagents were included in the study, with two lots being tested at each site. Xpert CT/NG Assays were performed according to the Xpert CT/NG Assay procedure. The rate of agreement with expected results of CT and NG for each panel member is presented in Tables 10 and 11.

Xpert CT/NG Assay 510(k) Summary

13

| Sample | | Site 1
(GeneXpert Dx) | Site 2
(Infinity-80) | Site 3
(Infinity-48) | % Total
Agreement by
Sample |
|--------------|-----|-------------- | CT >20X LoD; | CT | 100% (40/40) | NG >20X LoD | NG | 100% (40/40) | CT >20X LoD; | CT | 100% (40/40) | NG 1X LoD | NG | 87.5% (35/40) | CT >20X LoD; | CT | 100% (40/40) | NG neg | NG | 100% (40/40) | CT 1X LoD: | CT | 90.0% (36/40) | NG >20X LoD | NG | 100% (40/40) | CT 1X LoD; | CT. | 97.5% (39/40) | NG 1X LoD | NG | 92.5% (37/40) | CT 1X LoD; | CT | 97.5% (39/40) | NG neg | NG | 100% (40/40) | CT 2-3X LoD; | CT | 100% (40/40) | NG neg | NG | 100% (40/40) | CT neg; | CT | 100% (40/40) | NG >20X LoD | NG | 100% (40/40) | CT neg; | CT | 100% (40/40) | NG IX LoD | NG | 100.0% (40/40) | CT neg; | СТ | 100% (40/40) | NG 2-3X LoD | NG | 97.5% (39/40) | CT neg; | CT | 100% (40/40) | NG neg | NG | 100% (40/40) ------------|-------------------------|-------------------------|-----------------------------------|
| 100% (40/40) | 100% (40/40) | 100% (120/120) |
| 100% (40/40) | 100% (40/40) | 100% (120/120) |
| 100% (40/40) | 100% (40/40) | 100% (120/120) |
| 97.5% (39/40) | 95.0% (38/40) | 93.3% (112/120) |
| 100% (40/40) | 100% (40/40) | 100% (120/120) |
| 100% (40/40) | 100% (40/40) | 100% (120/120) |
| 97.5% (39/40) | 95.0% (38/40) | 94.2% (113/120) |
| 100% (40/40) | 100% (40/40) | 100% (120/120) |
| 100% (40/40) | 100% (40/40) | 99.2% (119/120) |
| 90.0% (36/40) | 90.0% (36/40) | 90.8% (109/120) |
| 90.0% (36/40) | 90.0% (36/40) | 92.5% (111/120) |
| 100% (40/40) | 100% (40/40) | 100% (120/120) |
| 100% (40/40) | 100% (40/40) | 100% (120/120) |
| 100% (40/40) | 100% (40/40) | 100% (120/120) |
| 100% (40/40) | 100% (40/40) | 100% (120/120) |
| 100% (40/40) | 100% (40/40) | 100% (120/120) |
| 100% (40/40) | 100% (40/40) | 100% (120/120) |
| 97.5% (39/40) | 97.5% (39/40) | 98.3% (118/120) |
| 100% (40/40) | 100% (40/40) | 100% (120/120) |
| 100% (40/40) | 100% (40/40) | 99.2% (119/120) |
| 100% (40/40) | 100% (40/40) | 100% (120/120) |
| 100% (40/40) | 100% (40/40) | 100% (120/120) |

.

:

Table 10: Summary of Reproducibility Results by Study Site; Percent Agreement Swab Samples

:

.

14

| Sample | | Site 1
(GeneXpert Dx) | Site 2
(Infinity-80) | Site 3
(Infinity-48) | % Total
Agreement by
Sample | | | | | | Between-Site | | Between-Lot | | Between-Day | | Between-
Run¹ | | Within-Run | | Total | | |
|----------------------------|-----|--------------------------|-------------------------|-------------------------|-----------------------------------|-------|-------------|-------------|---------|--------------|--------------|------|-------------|------|-------------|------|------------------|------|------------|------|-----------|------|-----------|
| CT >20X LoD;
NG>20X LoD | CT | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) | Type | CT
(LoD) | NG
(LoD) | Agree/N | Agrmt
(%) | Mean
Ct | SD | CV
(%) | SD | CV
(%) | SD | CV
(%) | SD | CV
(%) | SD | CV
(%) | SD | CV
(%) |
| | NG | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) | Swab | >20X | >20X | 120/120 | 100 | 20.67 | 0.21 | 1.0 | 0.11 | 0.5 | 0.11 | 0.5 | 0.00 | 0.0 | 0.29 | 1.4 | 0.39 | 1.9 |
| CT >20X LoD;
NG 1X LoD | CT | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) | | >20X | 1X | 112/120 | 93.3 | 20.73 | 0.29 | 1.4 | 0.37 | 1.8 | 0.00 | 0.0 | 0.00 | 0.0 | 1.59 | 7.7 | 1.66 | 8.0 |
| | NG | 87.5% (35/40) | 97.5% (39/40) | 95.0% (38/40) | 93.3% (112/120) | | >20X | NEG | 120/120 | 100 | 20.59 | 0.00 | 0.0 | 0.21 | 1.0 | 0.06 | 0.3 | 0.08 | 0.4 | 0.26 | 1.3 | 0.35 | 1.7 |
| CT >20X LoD;
NG neg | CT | 100% (40/40) | 100% (40/40) | 100% (40/40) | .100% (120/120) | | 1X | >20X | 113/120 | 94.2 | 37.20 | 0.10 | 0.3 | 0.21 | 0.6 | 0.00 | 0.0 | 0.00 | 0.0 | 1.15 | 3.1 | 1.18 | 3.2 |
| | NG | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) | | 1X | 1X | 106/120 | 88.3 | 37.04 | 0.17 | 0.5 | 0.00 | 0.0 | 0.00 | 0.0 | 0.12 | 0.3 | 1.08 | 2.9 | 1.10 | 3.0 |
| CT 1X LoD;
NG >20X LoD | CT | 90.0% (36/40) | 97.5% (39/40) | 95.0% (38/40) | 94.2% (113/120) | | 1X | NEG | 111/120 | 92.5 | 37.04 | 0.06 | 0.2 | 0.00 | 0.0 | 0.00 | 0.0 | 0.00 | 0.0 | 1.12 | 3.0 | 1.12 | 3.0 |
| | NG | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) | | 2-3X | NEG | 120/120 | 100 | 35.63 | 0.13 | 0.4 | 0.00 | 0.0 | 0.15 | 0.4 | 0.10 | 0.3 | 0.77 | 2.2 | 0.80 | 2.3 |
| CT 1X LoD;
NG 1X LoD | CT | 97.5% (39/40) | 100% (40/40) | 100% (40/40) | 99.2% (119/120) | | NEG | >20X | 120/120 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | NG | 92.5% (37/40) | 90.0% (36/40) | 90.0% (36/40) | 90.8% (109/120) | | NEG | 1X | 118/120 | 98.3 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| CT 1X LoD;
NG neg | CT | 97.5% (39/40) | 90.0% (36/40) | 90.0% (36/40) | 92.5% (111/120) | | NEG | 2-3X | 119/120 | 99.2 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | NG | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) | | NEG | NEG | 120/120 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| CT 2-3X LoD;
NG neg | CT | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) | Urine | >20X | >20X | 120/120 | 100 | 21.46 | 0.23 | 1.0 | 0.00 | 0.0 | 0.12 | 0.5 | 0.02 | 0.1 | 0.31 | 1.4 | 0.40 | 1.9 |
| | NG | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) | | >20X | 1X | 115/120 | 95.8 | 21.33 | 0.13 | 0.6 | 0.05 | 0.2 | 0.13 | 0.6 | 0.00 | 0.0 | 0.43 | 2.0 | 0.47 | 2.2 |
| CT neg;
NG>20X LoD | CT | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) | | >20X | NEG | 120/120 | 100 | 21.36 | 0.19 | 0.9 | 0.00 | 0.0 | 0.12 | 0.6 | 0.02 | 0.1 | 0.47 | 2.2 | 0.52 | 2.4 |
| | NG | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) | | 1X | >20X | 111/120 | 92.5 | 37.24 | 0.36 | 1.0 | 0.00 | 0.0 | 0.00 | 0.0 | 0.00 | 0.0 | 1.33 | 3.6 | 1.38 | 3.7 |
| CT neg;
NG 1X LoD | CT | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) | | 1X | 1X | 97/120 | 80.8 | 37.15 | 0.40 | 1.1 | 0.18 | 0.5 | 0.17 | 0.4 | 0.00 | 0.0 | 1.02 | 2.8 | 1.13 | 3.0 |
| | NG | 100.0% (40/40) | 97.5% (39/40) | 97.5% (39/40) | 98.3% (118/120) | | 1X | NEG | 113/120 | 94.2 | 37.39 | 0.10 | 0.3 | 0.32 | 0.9 | 0.00 | 0.0 | 0.00 | 0.0 | 1.38 | 3.7 | 1.42 | 3.8 |
| CT neg;
NG 2-3X LoD | CT | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) | | 2-3X | NEG | 120/120 | 100 | 35.26 | 0.24 | 0.7 | 0.00 | 0.0 | 0.30 | 0.9 | 0.00 | 0.0 | 0.80 | 2.3 | 0.89 | 2.5 |
| | NG | 97.5% (39/40) | 100% (40/40) | 100% (40/40) | 99.2% (119/120) | | NEG | >20X | 119/120 | 99.2 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| CT neg;
NG neg | CT | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) | | NEG | 1X | 118/120 | 98.3 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | NG | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) | | NEG | 2-3X | 120/120 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | NEG | NEG | 119/120 | 99.2 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | | | | | | |

Table 11: Summary of Reproducibility Results by Study Site; Percent Agreement Urine Samples

The reproducibility of the Xpert CT/NG Assay was also evaluated in terms of the fluorescence signal expressed in Ct values for each target detected. The mean, standard deviation (SD), and coefficient of variation (CV) between-sites, between-lots, between-days, and between-runs for each panel member are presented in Tables 12 through 14.

15

Table 12: Summary of Reproducibility data for Swab and Urine Specimens – CT1 Target

ﺮ ﺍﻟﻤﺮﺍﺟﻊ ﺍﻟﻤﺴﺎﺣﺔ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍ Note: Vanability from some factors may be numerically negative, which can occur it the variability
measured with SD and CV is set to 0.
'A run is defined as the four samples

:

Xpert CT/NG Assay 510(k) Summary

:

. :

·

16

Table 13: Summary of Reproducibility data for Swab and Urine Specimens – NG2 Targe

| Type | Target Conc. | | Agree/N | Agrmt
(%) | Mean
Ct | Between-Site | | Between-Lot | | Between-
Run1 | | Within-Run | | Total | |
|-----------------------------------------------------------------------------------------------------------------------------------|--------------|-------------|---------|--------------|------------|--------------|-----------|-------------|-----------|------------------|-----------|------------|-----------|-------|-----------|
| | CT
(LoD) | NG
(LoD) | | | | SD | CV
(%) | SD | CV
(%) | SD | CV
(%) | SD | CV
(%) | SD | CV
(%) |
| Swab | >20X | >20X | 120/120 | 100 | 19.65 | 0.03 | 0.1 | 0.09 | 0.4 | 0.07 | 0.3 | 0.24 | 1.2 | 0.26 | 1.3 |
| | >20X | 1X | 112/120 | 93.3 | 35.38 | 0.22 | 0.6 | 0.00 | 0.0 | 0.00 | 0.0 | 1.98 | 5.6 | 1.99 | 5.6 |
| | >20X | NEG | 120/120 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | 1X | >20X | 113/120 | 94.2 | 19.69 | 0.12 | 0.6 | 0.00 | 0.0 | 0.19 | 1.0 | 0.43 | 2.2 | 0.49 | 2.5 |
| | 1X | 1X | 106/120 | 88.3 | 35.61 | 0.00 | 0.0 | 0.53 | 1.5 | 0.00 | 0.0 | 1.37 | 3.9 | 1.67 | 4.7 |
| | 1X | NEG | 111/120 | 92.5 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| Swab | 2-3X | NEG | 120/120 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | NEG | >20X | 120/120 | 100 | 19.60 | 0.10 | 0.5 | 0.07 | 0.4 | 0.00 | 0.0 | 0.20 | 1.0 | 0.25 | 1.3 |
| | NEG | 1X | 118/120 | 98.3 | 35.43 | 0.39 | 1.1 | 0.00 | 0.0 | 0.04 | 0.1 | 0.94 | 2.6 | 1.04 | 2.9 |
| | NEG | 2-3X | 119/120 | 99.2 | 33.97 | 0.00 | 0.0 | 0.15 | 0.4 | 0.00 | 0.0 | 0.71 | 2.1 | 0.74 | 2.2 |
| | NEG | NEG | 120/120 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | >20X | >20X | 120/120 | 100 | 20.34 | 0.06 | 0.3 | 0.09 | 0.4 | 0.00 | 0.0 | 0.23 | 1.1 | 0.26 | 1.3 |
| Urine | >20X' | 1X | 115/120 | 95.8 | 35.41 | 0.00 | 0.0 | 0.00 | 0.0 | 0.19 | 0.5 | 1.15 | 3.3 | 1.20 | 3.4 |
| | >20X | NEG | 120/120 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | 1X | >20X | 111/120 | 92.5 | 20.40 | 0.06 | 0.3 | 0.07 | 0.3 | 0.00 | 0.0 | 0.39 | 1.9 | 0.40 | 2.0 |
| | 1X | 1X | 97/120 | 80.8 | 35.57 | 0.20 | 0.6 | 0.00 | 0.0 | 0.13 | 0.4 | 1.28 | 3.6 | 1.31 | 3.7 |
| | 1X | NEG | 113/120 | 94.2 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | 2-3X | NEG | 120/120 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| Urine | NEG | >20X | 119/120 | 99.2 | 20.39 | 0.00 | 0.0 | 0.07 | 0.4 | 0.14 | 0.7 | 0.26 | 1.3 | 0.31 | 1.5 |
| | NEG | 1X | 118/120 | 98.3 | 35.35 | 0.00 | 0.0 | 0.11 | 0.3 | 0.00 | 0.0 | 0.92 | 2.6 | 0.99 | 2.8 |
| | NEG | 2-3X | 120/120 | 100 | 33.80 | 0.00 | 0.0 | 0.18 | 0.5 | 0.00 | 0.0 | 0.54 | 1.6 | 0.57 | 1.7 |
| | NEG | NEG | 119/120 | 99.2 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| 1Agrmt=Agreement, Conc=concentration, CV=coefficient of variation, N/A=Not Applicable for negative samples, SD=standard deviation | | | | | | | | | | | | | | | |

region of the come the country of council of the can occur it in ear occur if the variability due to those factors is very small. When this occurs, the variability as
measur

.

A run is defined as the four samples per panel member run by one operator at one site on one day

.

(pert CT/NG Assay 510(k) Summar

Page 17

.

17

Table 14: Summary of Reproducibility data for Swab and Urine Specimens – NG4 Targe

		Target Conc.					Between-Site		Between-Lot		Between-Day		Between-Run¹		Within-Run		Total
Type	CT
(LoD)	NG
(LoD)	Agree/N	Agrmt
(%)	Mean
Ct	SD	CV
(%)	SD	CV
(%)	SD	CV
(%)	SD	CV
(%)	SD	CV
(%)	SD	CV
(%)
Swab	>20X	>20X	120/120	100	19.34	0.00	0.0	0.12	0.6	0.11	0.6	0.00	0.0	0.39	2.0	0.42	2.2
	>20X	1X	112/120	93.3	35.00	0.41	1.2	0.00	0.0	0.00	0.0	0.32	0.9	1.89	5.4	1.96	5.6
	>20X	NEG	120/120	100	0	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
	1X	>20X	113/120	94.2	19.41	0.07	0.4	0.00	0.0	0.14	0.7	0.03	0.2	0.49	2.5	0.52	2.7
	1X	1X	106/120	88.3	35.47	0.32	0.9	0.00	0.0	0.00	0.0	0.70	2.0	0.90	2.5	1.19	3.3
	1X	NEG	111/120	92.5	0	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
	2-3X	NEG	120/120	100	0	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
	NEG	>20X	120/120	100	19.35	0.02	0.1	0.04	0.2	0.00	0.0	0.07	0.4	0.28	1.5	0.29	1.5
	NEG	1X	118/120	98.3	35.05	0.00	0.0	0.16	0.5	0.00	0.0	0.00	0.0	1.00	2.9	1.01	2.9
	NEG	2-3X	119/120	99.2	33.57	0.14	0.4	0.17	0.5	0.00	0.0	0.00	0.0	0.78	2.3	0.81	2.4
	NEG	NEG	120/120	100	0	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
	>20X	>20X	120/120	100	20.06	0.12	0.6	0.12	0.6	0.09	0.4	0.00	0.0	0.39	1.9	0.43	2.1
	>20X	1X	115/120	95.8	35.27	0.17	0.5	0.13	0.4	0.00	0.0	0.00	0.0	1.04	2.9	1.06	3.0
	>20X	NEG	120/120	100	0	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
Urine	1X	>20X	111/120	92.5	20.16	0.00	0.0	0.08	0.4	0.00	0.0	0.12	0.6	0.56	2.8	0.58	2.9
	1X	1X	97/120	80.8	35.25	0.00	0.0	0.00	0.0	0.41	1.2	0.00	0.0	1.17	3.3	1.24	3.5
	1X	NEG	113/120	94.2	0	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
	2-3X	NEG	120/120	100	0	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
	NEG	>20X	119/120	99.2	20.12	0.09	0.5	0.10	0.5	0.06	0.3	0.00	0.0	0.41	2.0	0.43	2.2
	NEG	1X	118/120	98.3	35.05	0.24	0.7	0.00	0.0	0.15	0.4	0.12	0.4	1.09	3.1	1.13	3.2
	NEG	2-3X	120/120	100	33.67	0.00	0.0	0.33	1.0	0.00	0.0	0.16	0.5	0.83	2.5	0.91	2.7
	NEG	NEG	119/120	99.2	0	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
Agrmt=Agreement, Conc=concentration, CV=coefficient of variation. N/A=Not Applicable for negative samples, SD=standard deviation

right Vigating Conce laction, or viction of the versear internationing de comes for samel in this occurs sers mail. When this occurs, the variability as and the variability o

.

Kpert CT/NG Assay 510(k) Summary

Page 18

18

Instrument System Precision

An in-house precision study was conducted to compare the performance of the GeneXpert Dx and the Infinity-80 Instrument Systems using specimens comprised of CT and NG organisms seeded into negative urine (urine matrix) or diluent for the Xpert CT/NG Assay (swab matrix). The specimens were prepared at concentration levels representing low positive (0.25-0.5X LoD), moderate positive (2-3X LoD), and high positive (>20X LoD) for each organism. Negative panel members were also included and were comprised of negative urine and negative diluent. A panel of 20 specimens (10 in urine matrix and 10 in swab matrix) was tested on 12 different days by two operators. Each operator conducted four runs of each panel specimen per day on each of the two instrument systems (20 specimens x 4 times/ day x 12 days x 2 operators x 2 instrument systems). One lot of Xpert CT/NG Assay was used for the study. Xpert CT/NG assays were performed according to the Xpert CT/NG Assay procedure. The rate of agreement with expected results of CT and NG for each panel member is presented by instrument in Tables 15 and 16.

| Sample | | GeneXpert Dx | Infinity-80 | % Total Agreement
by Sample |
|---------------------------------------|----|----------------|----------------|--------------------------------|
| CT>20X LoD; NG

20X LoD | CT | 100% (96/96) | 100% (95/95)a | 100% (191/191) |
| | NG | 100% (96/96) | 100% (95/95)a | 100% (191/191) |
| CT >20X LoD; NG
0.25-0.5X LoD | CT | 100% (96/96) | 100% (96/96) | 100% (192/192) |
| | NG | 62.5% (60/96) | 52.1% (50/96) | 57.3% (110/192) |
| CT >20X LoD; NG
neg | CT | 100% (96/96) | 100% (95/95)b | 100% (191/191) |
| | NG | 100% (96/96) | 100% (95/95)b | 100% (191/191) |
| CT 0.25-0.5X LoD;
NG>20X LoD | CT | 46.9% (45/96) | 42.7% (41/96) | 44.8% (86/192) |
| | NG | 100% (96/96) | 100% (96/96) | 100% (192/192) |
| CT 0.25-0.5X LoD;
NG 0.25-0.5X LoD | CT | 55.2% (53/96) | 60.4% (58/96) | 57.8% (111/192) |
| | NG | 50.0% (48/96) | 66.7% (64/96) | 58.3% (112/192) |
| CT 0.25-0.5X LoD;
NG neg | CT | 61.5% (59/96) | 62.1% (59/95)c | 61.8% (118/191) |
| | NG | 100% (96/96) | 100% (95/95)c | 100% (191/191) |
| CT 2-3X LoD; NG
2-3X LoD | CT | 100% (96/96) | 100% (96/96) | 100% (192/192) |
| | NG | 100% (96/96) | 100% (96/96) | 100% (192/192) |
| CT neg;
NG>20X LoD | CT | 100% (96/96) | 100% (96/96) | 100% (192/192) |
| | NG | 100% (96/96) | 100% (96/96) | 100% (192/192) |
| CT neg;
NG 0.25-0.5X LoD | CT | 100% (95/95)b | 100% (96/96) | 100% (191/191) |
| | NG | 58.9% (56/95)b | 62.5% (60/96) | 60.7% (116/191) |
| CT neg;
NG neg | CT | 100% (96/96) | 100% (96/96) | 100% (192/192) |
| | NG | 100% (96/96) | 100% (96/96) | 100% (192/192) |

Table 15: Summary of Instrument System Precision Results;
Percent Agreement Swab Matrix

4 One sample was indeterminate after initial and retest.

*One sample each of CT >20X LoD; NG neg sample and CT neg; NG 0.25-0.5.Y LoD resulted in ERROR on initial test and were not retested.

One sample mistakenly not tested.

19

| Sample | | GeneXpert Dx | Infinity-80 | % Total Agreement
by Sample |
|-------------------|----|---------------|---------------|--------------------------------|
| CT >20X LoD; NG | CT | 100% (96/96) | 100% (96/96) | 100% (192/192) |
| >20X LoD | NG | 100% (96/96) | 100% (96/96) | 100% (192/192) |
| CT >20X LoD; NG | CT | 100% (96/96) | 100% (96/96) | 100% (192/192) |
| 0.25-0.5X LoD | NG | 46.9% (45/96) | 49.0% (47/96) | 47.9% (92/192) |
| CT >20X LoD; NG | CT | 100% (96/96) | 100% (96/96) | 100% (192/192) |
| neg | NG | 100% (96/96) | 100% (96/96) | 100% (192/192) |
| CT 0.25-0.5X LoD; | CT | 50.0% (48/96) | 52.1% (50/96) | 51.0% (98/192) |
| NG >20X LoD | NG | 100% (96/96) | 100% (96/96) | 100% (192/192) |
| CT 0.25-0.5X LoD; | CT | 44.8% (43/96) | 39.6% (38/96) | 42.2% (81/192) |
| NG 0.25-0.5X LoD | NG | 62.5% (60/96) | 58.3% (56/96) | 60.4% (116/192) |
| CT 0.25-0.5X LoD; | CT | 46.9% (45/96) | 46.9% (45/96) | 46.9% (90/192) |
| NG neg | NG | 100% (96/96) | 100% (96/96) | 100% (192/192) |
| CT 2-3X LoD; NG | CT | 100% (96/96) | 100% (96/96) | 100% (192/192) |
| 2-3X LoD | NG | 100% (96/96) | 100% (96/96) | 100% (192/192) |
| CT neg; | CT | 100% (96/96) | 100% (96/96) | 100% (192/192) |
| NG >20X LoD | NG | 100% (96/96) | 100% (96/96) | 100% (192/192) |
| CT neg; | CT | 100% (96/96) | 100% (96/96) | 100% (192/192) |
| NG 0.25-0.5X LoD | NG | 36.5% (35/96) | 33.3% (32/96) | 34.9% (67/192) |
| CT neg; | CT | 100% (96/96) | 100% (96/96) | 100% (192/192) |
| NG neg | NG | 100% (96/96) | 100% (96/96) | 100% (192/192) |

Table 16: Summary of Instrument System Precision Results; Percent Agreement Urine Matrix

The reproducibility of the Xpert CT/NG Assay was also evaluated in terms of the fluorescence signal expressed in Ct values for each target detected. The mean, standard deviation (SD), and coefficient of variation (CV) between-instruments, between-days, and between-runs for each panel member are presented in Tables 17 through 19.

20

Table 17: Summary of Reproducibility data for Swab and Urine Specimens – CT1 Targer

.

Type	CT	NG	Agree/N	Agrmt (%)	Mean Ct	SD	Between-Instrument CV (%)	SD	Between-Day CV (%)	SD	Between-Run' CV (%)	SD	Within-Run CV (%)	SD	Total CV (%)
Swab	>20X	>20X	191/191	100	23.52	0.05	0.2	0.02	0.1	0.00	0.0	0.25	1.1	0.26	1.1
	>20X	0.25-0.5X	110/192	57.3	23.52	0.00	0.0	0.00	0.0	0.08	0.3	0.18	0.7	0.19	0.8
	>20X	NEG	191/191	100	23.55	0.03	0.1	0.00	0.0	0.00	0.0	0.22	0.9	0.22	0.9
	0.25-0.5X	>20X	86/192	44.8	38.77	0.00	0.0	0.00	0.0	0.32	0.8	1.38	3.6	1.42	3.7
	0.25-0.5X	0.25-0.5X	59/192	30.7	38.46	0.00	0.0	0.30	0.8	0.00	0.0	1.35	3.5	1.39	3.6
	0.25-0.5X	NEG	118/191	61.8	38.05	0.08	0.2	0.00	0.0	0.00	0.0	1.26	3.3	1.26	3.3
	2-3X	2-3X	192/192	100	31.49	0.04	0.1	0.00	0.0	0.06	0.2	0.24	0.8	0.25	0.8
	NEG	>20X	192/192	100	0	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
	NEG	0.25-0.5X	116/191	60.7	0	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
	NEG	NEG	192/192	100	0	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
Urine	>20X	>20X	192/192	100	24.35	0.05	0.2	0.20	0.8	0.10	0.4	0.30	1.2	0.38	1.6
	>20X	0.25-0.5X	92/192	47.9	24.25	0.00	0.0	0.06	0.3	0.00	0.0	0.62	2.6	0.62	2.6
	>20X	NEG	192/192	100	24.12	0.00	0.0	0.15	0.6	0.19	0.8	0.34	1.4	0.41	1.7
	0.25-0.5X	>20X	98/192	51.0	38.33	0.12	0.3	0.00	0.0	0.84	2.2	1.03	2.7	1.33	3.5
	0.25-0.5X	0.25-0.5X	48/192	25.0	38.26	0.00	0.0	0.00	0.0	0.56	1.5	1.05	2.7	1.19	3.1
	0.25-0.5X	NEG	90/192	46.9	38.39	0.00	0.0	0.00	0.0	0.00	0.0	1.09	2.8	1.09	2.8
	2-3X	2-3X	192/192	100	31.85	0.00	0.0	0.11	0.4	0.18	0.6	0.32	1.0	0.39	1.2
	NEG	>20X	192/192	100	0	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
	NEG	0.25-0.5X	67/192	34.9	0	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
	NEG	NEG	192/192	100	0	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A

:

n "s ﺎ ﻓﻲ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ੰਡਿਕ ﺔ ofe. Variability from some ractors is

.

:

・

:

·

Xperi CT/NG Assay 510(k) Summary

Pagc 2 I

. .

21

| Table 18: Summary of Reproducibility data for

Swab and Urine Specimens – NG2 Target
Between-
Between-
Between-

.

Type	CT	NG	Agree/N	Agrmt (%)	Mean Ct	Between-Instrument SD	Between-Instrument CV (%)	Between-Day SD	Between-Day CV (%)	Between-Run' SD	Between-Run' CV (%)	Within-Run SD	Within-Run CV (%)	Total SD	Total CV (%)
Swab	>20X	>20X	191/191	100	19.03	0.01	0.0	0.02	0.1	0.00	0.0	0.21	1.1	0.21	1.1
	>20X	0.25-0.5X	110/192	57.3	37.63	0.07	0.2	0.46	1.2	0.00	0.0	1.55	4.1	1.62	4.3
	>20X	NEG	191/191	100	0	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
	0.25-0.5X	>20X	86/192	44.8	19.08	0.00	0.0	0.00	0.0	0.10	0.5	0.31	1.6	0.32	1.7
	0.25-0.5X	0.25-0.5X	59/192	30.7	36.78	0.00	0.0	0.24	0.6	0.00	0.0	1.47	4.0	1.49	4.0
	0.25-0.5X	NEG	118/191	61.8	0	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
	2-3X	2-3X	192/192	100	31.35	0.00	0.0	0.00	0.0	0.00	0.0	0.33	1.1	0.33	1.1
	NEG	>20X	192/192	100	19.02	0.00	0.0	0.00	0.0	0.07	0.4	0.22	1.2	0.23	1.2
Urine	NEG	0.25-0.5X	116/191	60.7	36.77	0.00	0.0	0.46	1.2	0.00	0.0	1.65	4.5	1.71	4.7
	NEG	NEG	192/192	100	0	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
	>20X	>20X	192/192	100	19.85	0.00	0.0	0.15	0.7	0.00	0.0	0.34	1.7	0.37	1.8
	>20X	0.25-0.5X	92/192	47.9	36.72	0.15	0.4	0.00	0	0.00	0.0	1.36	3.7	1.37	3.7
	>20X	NEG	192/192	100	0	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
	0.25-0.5X	>20X	98/192	51.0	19.51	0.00	0.0	0.00	0.0	0.00	0.0	1.20	6.1	1.20	6.1
	0.25-0.5X	0.25-0.5X	48/192	25.0	36.38	0.26	0.7	0.00	0.0	1.98	5.5	1.13	3.1	2.30	6.3
	0.25-0.5X	NEG	90/192	46.9	0	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
	2-3X	2-3X	192/192	100	31.53	0.00	0.0	0.09	0.3	0.16	0.5	0.42	1.3	0.46	1.4
	NEG	>20X	192/192	100	19.26	0.14	0.7	0.00	0.0	0.17	0.9	0.43	2.3	0.49	2.4
	NEG	0.25-0.5X	67/192	34.9	36.88	0.00	0.0	0.31	0.8	0.00	0	1.45	3.9	1.48	7.5
	NEG	NEG	192/192	100	0	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A

Note: Variability from some factors may be numcically negative, which can occur if the variability due to those factors is very small. When this ocurs, the
variability as me

Xpert CT/NG Assay 510(k) Summary

Page 22

·

22

Table 19: Summary of Reproducibility data for Swab and Urine Specimens – NG4 Targe

:

Type	Target Conc.		Between-Instrument	Between-Day	Between-Run'	Within-Run	Total
	CT	NG	Agree/N	Agrmt (%)	Mean Ct	SD	CV (%)	SD	CV (%)	SD	CV (%)	SD	CV (%)	SD	CV (%)
Swab	>20X	>20X	191/191	100	18.67	0.00	0.0	0.00	0.0	0.19	1.0	0.34	1.8	0.39	2.1
	>20X	0.25-0.5X	110/192	57.3	36.94	0.49	1.3	0.00	0.0	0.10	0.3	1.63	4.4	1.71	4.6
	>20X	NEG	191/191	100	0	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
	0.25-0.5X	>20X	86/192	44.8	18.72	0.06	0.3	0.00	0.0	0.21	1.1	0.41	2.2	0.46	2.5
	0.25-0.5X	0.25-0.5X	59/192	30.7	36.57	0.00	0.0	0.50	1.4	0.00	0.0	1.55	4.3	1.63	4.5
	0.25-0.5X	NEG	118/191	61.8	0	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
	2-3X	2-3X	192/192	100	31.06	0.00	0.0	0.05	0.2	0.00	0.0	0.42	1.4	0.43	1.4
	NEG	>20X	192/192	100	18.69	0.00	0.0	0.00	0.0	0.22	1.2	0.38	2.0	0.44	2.3
Urine	NEG	0.25-0.5X	116/191	60.7	36.31	0.08	0.2	0.13	0.4	0.00	0.0	1.24	3.4	1.25	3.4
	NEG	NEG	192/192	100	0	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
	>20X	>20X	192/192	100	19.44	0.01	0.1	0.10	0.5	0	0	0.45	2.3	0.46	2.4
	>20X	0.25-0.5X	92/192	47.9	36.31	0	0	0.04	0.1	0.17	0.5	1.18	3.2	1.19	6.1
	>20X	NEG	192/192	100	0	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
	0.25-0.5X	>20X	98/192	51.0	19.08	0	0	0	0	0	0	1.35	7.1	1.35	6.9
	0.25-0.5X	0.25-0.5X	48/192	25.0	36.16	0	0	0	0	0.24	0.7	0	0	1.98	5.5	2.00
	0.25-0.5X	NEG	90/192	46.9	0	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
	2-3X	2-3X	192/192	100	31.09	0	0	0.16	0.5	0.11	0.4	0.49	1.6	0.53	2.7
	NEG	>20X	192/192	100	18.80	0.04	0.2	0	0	0.14	0.7	0.47	2.5	0.50	2.6
	NEG	0.25-0.5X	67/192	34.9	36.58	0.18	0.5	0	0	0.74	2.0	1.40	3.8	1.60	8.2
	NEG	NEG	192/192	100	0	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A

Agrime agentent. Concection, C. (2) schient of variable for regarive sampes sommers and artition and other one of the variability as
Note: Variability form one lactors not

.

(pert CT/NG Assay 510(k) Summary

23

Clinical Performance Study

Performance characteristics of the Xpert CT/NG Assay were determined in a multi-site prospective investigational study at 36 US and UK institutions by comparing the Xpert CT/NG Assay to a patient infected status (PIS) algorithm based on combined results from two currently marketed NAAT tests.

Study participants included consenting asymptomatic and symptomatic, sexually active males and females seen at locations including, but not limited to: OB/GYN, sexually transmitted disease (STD), teen, public health, and family planning clinics. The average age among female study participants was 30.3 years (range = 14 to 83 years); the average age among male study participants was 37.7 years (range = 17 to 74 years).

The study specimens consisted of prospectively collected male urine, female urine, endocervical swabs, urethral swabs and patient-collected vaginal swabs (collected in a clinical setting).

A female study participant was categorized as infected (I) by PIS for CT or NG if at least one positive result was reported from each reference NAAT test. If both NAAT tests resulted in equivocal results for both sample types (swab and urine) the PIS status was defined as equivocal (EQ). This is the only scenario for an overall PIS of EQ; no study participants fell into this category for this study. Female study participants with positive results on both reference urine specimens and negative results on both reference swab specimens were categorized as infected (1) for urine and not infected (NI) for the swab specimen. Any other combination of results was categorized as not infected (NI).

A male study participant was categorized as infected (1) by PIS for CT or NG if at least one positive result was reported from each reference NAAT test. If both NAAT tests resulted in equivocal results for both sample types (swab and urine) the PIS status was defined as equivocal (EQ). This is the only scenario for an overall PIS of EQ; no study participants fell into this category for this study. Any other combination of results was categorized as not infected (NI).

Performance of the Xpert CT/NG Assay was calculated relative to the PIS for each of the three female sample types (endocervical swabs, self-collected vaginal swabs and urine), and male urine.

During the clinical evaluation of the Xpert CT/NG Assay, a total of 212 female subjects were infected with CT. Symptoms were reported in 41.0% (87/212) of infected and 34.1% (1221/3579) non-infected female subjects. A total of 54 female subjects were infected with NG. Symptoms were reported in 53.7% (29/54) of infected and 34.1% (1273/3729) non-infected female subjects. A total of 196 male subjects were infected with CT. Symptoms were reported in 62.8% (123/196) of infected and 18.0% (584/3248) non-infected male subjects. A total of 119 male subjects were infected with NG. Symptoms were reported in 89.1% (106/119) of infected and 18.1% (601/3325) noninfected male subjects.

24

Among the 14,790 tests performed, 416 had to be retested due to ERROR, INVALID or NO RESULT outcomes (2.81%, 95% CI 2.56-3.09). Of those, 355 specimens yielded valid results upon repeat assay (18 specimens were not retested). The overall valid reporting rate of the assay was 99.6% (14,729/14,790).

Chlamydia trachomatis Performance Results

Results from the Xpert CT/NG Assay were compared to the patient infected status (PIS) algorithm for determination of sensitivity, specificity, and predictive values. Sensitivity and specificity for CT by gender, specimen type, and symptom status are presented in Table 20.

| Specimen | | Sx
Status | n | TP | FP | TN | F
N | Prev
% | Sensitivity %
(95 CI) | Specificity %
(95 CI) | PPV %
(95 CI) | NPV %
(95 CI) |
|----------|-----------|--------------|------|-----|----|------|--------|-----------|--------------------------|--------------------------|---------------------|---------------------|
| | PC-
VS | Sym | 1294 | 79 | 20 | 1195 | 0 | 6.1 | 100
(95.4-100) | 98.4
(97.5-99.0) | 79.8
(70.5-87.2) | 100
(99.7-100) |
| | | Asym | 2472 | 121 | 11 | 2339 | 1 | 4.9 | 99.2
(95.5-100) | 99.5
(99.2-99.8) | 91.7
(85.6-95.8) | >99.9
(99.8-100) |
| | | All | 3766 | 200 | 31 | 3534 | 1 | 5.3 | 99.5
(97.3-100) | 99.1
(98.8-99.4) | 86.6
(81.5-90.7) | >99.9
(99.8-100) |
| Female | ES | Sym | 1293 | 76 | 5 | 1209 | 3 | 6.1 | 96.2
(89.3-99.2) | 99.6
(99.0-99.9) | 93.8
(86.2-98.0) | 99.8
(99.3-99.9) |
| | | Asym | 2464 | 117 | 11 | 2331 | 5 | 5.0 | 95.9
(90.7-98.7) | 99.5
(99.2-99.8) | 91.4
(85.1-95.6) | 99.8
(99.5-99.9) |
| | | All | 3757 | 193 | 16 | 3540 | 8 | 5.4 | 96.0
(92.3-98.3) | 99.6
(99.3-99.7) | 92.3
(87.9-95.6) | 99.8
(99.6-99.9) |
| | Urine | Sym | 1292 | 84 | 4 | 1203 | 1 | 6.6 | 98.8
(93.6-100) | 99.7
(99.2-99.9) | 95.5
(88.8-98.7) | 99.9
(99.5-100) |
| | | Asym | 2475 | 123 | 2 | 2347 | 3 | 5.1 | 97.6
(93.2-99.5) | 99.9
(99.7-100) | 98.4
(94.3-99.8) | 99.9
(99.6-100) |
| | | All | 3767 | 207 | 6 | 3550 | 4 | 5.6 | 98.1
(95.2-99.5) | 99.8
(99.6-99.9) | 97.2
(94.0-99.0) | 99.9
(99.7-100) |
| Male | Urine | Sym | 706 | 120 | 2 | 581 | 3 | 17.4 | 97.6
(93.0-99.5) | 99.7
(98.8-100) | 98.4
(94.2-99.8) | 99.5
(98.5-99.9) |
| | | Asym | 2730 | 73 | 5 | 2652 | 0 | 2.7 | 100.0
(95.1-100) | 99.8
(99.6-99.9) | 93.6
(85.7-97.9) | 100
(99.9-100) |
| | | All | 3436 | 193 | 7 | 3233 | 3 | 5.7 | 98.5
(95.6-99.7) | 99.8
(99.6-99.9) | 96.5
(92.9-98.6) | 99.9
(99.7-100) |

Table 20: Xpert CT/NG Assay vs. Patient Infected Status for CT Detection

TP=true positive. FP=false positive, TN=true negative, ES=endocervical swah, PC-VS=patient-collected vaginal swab

25

Neisseria gonorrhoeae Performance Results

Results from the Xpert CT/NG Assay were compared to the patient infected status (PIS) algorithm for determination of sensitivity, specificity, and predictive values. Sensitivity and specificity for NG by gender, specimen type, and symptom status are presented in Table 21.

Specimen	Sx Status	n	TP	FP	TN	FN	Prev %	Sensitivity % (95 CI)	Specificity % (95 CI)	PPV % (95 CI)	NPV % (95 CI)
PC-VS	Sym	1294	27	2	1265	0	2.1	100 (87.2-100)	99.8 (99.4-100)	93.1 (77.2-99.2)	100 (99.7-100)
	Asym	2472	25	1	2446	0	1.0	100 (86.3-100)	>99.9 (99.8-100)	96.2 (80.4-99.9)	100 (99.8-100)
	All	3766	52	3	3711	0	1.4	100 (93.2-100)	99.9 (99.8-100)	94.5 (84.9-98.9)	100 (99.9-100)
Female	ES	Sym	1293	27	1	1265	0	2.1	100 (87.2-100)	99.9 (99.6-100)	96.4 (81.7-99.9)	100 (99.7-100)	Asym	2464	25	0	2439	0	1.0	100 (86.3-100)	100 (99.8-100)	100 (86.3-100)	100 (99.8-100)	All	3757	52	1	3704	0	1.4	100 (93.2-100)	>99.9 (99.8-100)	98.1 (89.9-100)	100 (99.9-100)	Urine	Sym	1292	28	0	1263	1	2.2	96.6 (82.2-99.9)	100 (99.7-100)	100 (87.7-100)	99.9 (99.6-100)
		Female	ES	Sym	1293	27	1	1265	0	2.1	100 (87.2-100)	99.9 (99.6-100)	96.4 (81.7-99.9)	100 (99.7-100)	Asym	2464	25	0	2439	0	1.0	100 (86.3-100)	100 (99.8-100)	100 (86.3-100)	100 (99.8-100)
				Female	ES	Sym	1293	27	1	1265	0	2.1	100 (87.2-100)	99.9 (99.6-100)	96.4 (81.7-99.9)	100 (99.7-100)
Asym	2464					25	0	2439	0	1.0	100 (86.3-100)	100 (99.8-100)	100 (86.3-100)	100 (99.8-100)
All	3757	52	1			3704	0	1.4	100 (93.2-100)	>99.9 (99.8-100)	98.1 (89.9-100)	100 (99.9-100)
Urine	Sym	1292	28	0	1263	1	2.2	96.6 (82.2-99.9)	100 (99.7-100)	100 (87.7-100)	99.9 (99.6-100)
	Asym	2475	23	1	2449	2	1.0	92.0 (74.0-99.0)	>99.9 (99.8-100)	95.8 (78.9-99.9)	99.9 (99.7-100)
	All	3767	51	1	3712	3	1.4	94.4 (84.6-98.8)	>99.9 (99.9-100)	98.1 (89.7-100)	99.9 (99.8-100)
Male	Urine	Sym	706	105	0	600	1	15.0	99.1 (94.9-100)	100 (99.4-100)	100 (96.5-100)	99.8 (99.1-100)
		Asym	2730	12	3	2714	1	0.5	92.3 (64.0-99.8)	99.9 (99.7-100)	80.0 (51.9-95.7)	>99.9 (99.8-100)
		All	3436	117	3	3314	2	3.5	98.3 (94.1-99.8)	99.9 (99.7-100)	97.5 (92.9-99.5)	99.9 (99.8-100)

Table 21: Xpert CT/NG Assay vs. Patient Infected Status for NG Detection

TP=true positive, FP=false positive, TN=talse negalive, ES=endocervical swab, PC VS=patient-collected vaginal swab

Table 22 shows the number of results from symptomatic and asymptomatic females designated as infected or not infected with CT based on the PIS algorithm.

26

	NAAT1		NAAT2		Xpert			Symptom Status		Total
PISa	SWa	URa	SW	UR	PC-VSa	ESa	UR	Symp	Asymp
NIb	-	-	-	-	-	-	-	1160	2269	3429
NI	-	-	-	-	IND	-	-	6	8	14
NI	-	-	-	-	-	INDc	-	6	16	22
NI	-	-	-	-	-	-	IND	5	6	11
NI	-	-	-	-	+	+	-	0	1	1
NI	-	-	-	-	+	-	-	6	4	10
NI	-	-	-	-	-	+	-	3	5	8
NI	-	-	-	-	-	-	+	1	0	1
NI	-	-	-	EQd	-	-	-	6	20	26
NI	-	-	-	EQ	IND	IND	-	1	0	1
NI	-	-	EQ	EQ	-	-	-	3	4	7
NI	-	-	EQ	EQ	-	-	IND	1	0	1
NI	-	-	-	+	-	-	-	0	7	7
NI	-	-	+	-	-	-	-	3	0	3
NI	-	-	+	-	-	+	-	0	1	1
NIf	-	+	-	+	+	+	+	7	1	8
NIf	-	+	-	+	+	+	-	0	1	1
NIf	-	+	+	+	-	-	+	0	1	1
NI	-	+	-	-	-	-	-	1	0	1
NI	-	+	-	-	+	-	+	1	0	1
NI	+	-	-	-	-	-	-	4	8	12
NI	+	-	-	-	+	-	-	2	1	3
NI	+	-	-	-	+	+	-	1	2	3
NI	+	+	-	-	-	+	-	0	1	1
NI	+	+	-	-	-	-	-	1	0	1
NI	+	+	-	-	-	-	+	0	1	1
NI	+	+	-	-	+	+	+	1	1	2
NI	+	+	-	-	+	-	+	1	0	1
NI	+	+	-	-	+	-	-	1	0	1
Total Non-Infected								1221	2358	3579
Ie	+	+	+	+	+	+	+	65	104	169
I	+	+	+	+	IND	+	+	0	1	1
I	+	+	+	+	+	IND	+	0	1	1
I	+	+	+	+	+	+	IND	1	0	1
I	+	+	+	+	+	+	+	0	1	1
I	+	+	+	+	+	-	+	0	1	1
If	-	+	-	+	+	-	+	7	1	8
If	-	+	-	+	+	-	-	0	1	1
I	-	+	-	+	+	-	+	0	1	1
I	-	+	+	-	-	+	+	0	2	2
I	+	-	+	+	+	+	+	1	0	1
I	+	-	+	+	+	-	+	0	1	1
I	+	-	+	+	+	+	+	1	0	1
I	+	+	-	+	+	+	+	3	2	5

·

Table 22: Patient Infected Status – Female CT

・

, "

i

27

PISa	SWa	URa	SW	UR	PC-VSa	ESa	UR	Symp	Asymp	Total
I	+	+	+	-	+	+	+	3	4	7
I	+	+	+	-	+	+	-	1	1	2
I	+	+	+	-	+	-	+	0	1	1
I	+	-	+	-	+	+	+	1	0	1
I	+	-	EQ	+	+	+	+	0	1	1
Total Infected								87	125	212

| Total Infected

"PIS = Patient Infected Status; SW = Swab; UR = urine: PC-VS = Patient-collected Vaginal Swab; ES = Indocervical Swab °Ni = Non-infected

fIND = Indeceminate = ERROR, INVALID or NO RESULT by Xpert CT/NG Assay: specimens with IND results by Xpert are not included in the 2x2 tables for that specimen type.

"EQ = Equivocal result for this individual specimen type only; PIS status determined based on remaining specimens. °] = Infected

These samples are infected for urine and non-infected for swabs. In this table they appear twice.

Table 23 shows the number of results from symptomatic and asymptomatic females designated as infected or not infected with NG based on the PIS algorithm.

	NAAT1		NAAT2		Xpert			Symptom Status
PISa	SWa	URa	SW	UR	PC-VSa	ESa	UR	Symp	Asymp	Total
NIb	-	-	-	-	-	-	-	1229	2390	3619
NI	-	-	-	-	INDc	-	-	6	9	15
NI	-	-	-	-	-	IND	-	6	17	23
NI	-	-	-	-	-	-	IND	6	6	12
NI	-	-	-	-	+	-	+	0	1	1
NI	-	-	-	-	+	-	-	1	0	1
NI	-	-	EQd	-	-	-	-	2	5	7
NI	-	-	-	EQ	-	-	-	9	20	29
NI	-	-	-	+	-	-	-	1	3	4
NI	-	-	+	-	-	-	-	7	4	11
NIf	-	+	-	+	+	+	+	1	0	1
NIf	-	+	-	+	+	-	+	1	0	1
NI	-	+	+	-	-	-	-	1	0	1
NI	+	-	-	-	-	-	-	1	1	2
NI	-	-	EQ	-	-	-	IND	1	0	1
NI	-	-	-	EQ	-	IND	IND	1	0	1
Total Non-Infected
Ie	+	+	+	+	+	+	+	19	19	38
I	+	+	+	+	+	+	+	2	2	4
I	+	+	+	+	+	+	+	1	1	2
If	-	+	-	+	+	+	+	1	0	1
If	-	+	-	+	+	-	+	1	0	1
I	+	+	+	-	+	+	+	1	2	3
I	+	+	+	+	+	+	+	1	0	1
I	+	+	-	+	+	+	+	1	0	1
I	+	+	+	EQ	+	+	+	0	1	1
I	+	+	EQ	+	+	+	+	0	1	1

Table 23: Patient Infected Status - Female NG

:

28

PISa	NAAT1		NAAT2		Xpert		Symptom Status		Total
	SWa	URa	SW	UR	PC-VSa	ESa	UR	Symp	Asymp
1	+	EQ	+	-	+	+	+	1	0	1
Total Infected								29	25	54

4PIS = Patient Infected Status; SW = Swab; UR = urine; PC-VS = Patient-collected Vaginal Swab; ES = Endocervical Swab °NI = Non-infected

^IND = Indeterminate = ERROR, INVALID or NO RESULT by Xpert CT/NG Assay: specimens with INID results by Xpert are not included in the 2x2 tables for that specimen type.

4EQ = Equivocal result for this individual specimen type only: PIS status determined based on remaining specimens. ೪ = Infected

These samples are infected for urine and non-infected for swabs. In this table they appear twice.

Table 24 shows the number of results from symptomatic and asymptomatic males designated as infected or not infected with CT based on the PIS algorithm.

PISa	NAAT1		NAAT2		GX	Symptom Status		Total
	SWa	URa	SW	UR	UR	Symp	Asymp
NIb	-	-	-	-	-	568	2621	3189
NI	-	-	-	EQc	-	0	19	19
NI	-	-	+	-	-	2	1	3
NI	+	-	-	-	-	6	1	7
NI	+	+	-	-	-	1	1	2
NI	-	-	-	+	-	2	7	9
NI	-	+	-	-	-	2	1	3
NI	-	-	EQ	-	-	0	1	1
NI	+	+	-	-	+	2	4	6
NI	-	-	-	-	+	0	1	1
NI	-	-	-	-	INDd	1	6	7
NI	-	-	EQ	IND	IND	0	1	1
Total Non-Infected
						584	2664	3248
Ie	+	+	+	+	+	104	50	154
I	+	+	-	+	+	8	10	18
I	+	+	-	+	+	4	7	11
I	+	+	+	-	+	2	2	4
I	+	-	+	-	+	1	0	1
I	+	-	-	+	+	1	0	1
I	-	+	+	+	+	0	1	1
I	+	+	+	EQ	+	0	2	2
I	EQ	+	-	+	+	0	1	1
I	+	-	+	-	-	2	0	2
I	+	+	+	-	-	1	0	1
Total Infected						123	73	196

Table 24: Patient Infected Status - Male CT

aPIS = Patient Infected Status; SW = Swab; UR = urine.

°NI = Non-infected

"EQ = Equivocal result for this individual specimen type only; PIS status determined based on remaining specimens. 4!ND = Indeterninate = ERROR, INVALID or NO RESULT by Xpert CT/NG Assay; specimens with IND results by Xpert are not included in the 2x2 tables for that specimen type.

೪ = Infected

29

Table 25 shows the number of results from symptomatic and asymptomatic males designated as infected or not infected with NG based on the PIS algorithm

	NAAT1		NAAT2		GX	Symptom Status	Total
bla"	SW"	UR*	SW	UR	UR	Symp	Asymp
NIb	t	-	-	-	-	રતે રહ્યું રહ્યું રહ્યું રહ્યું રહ્યું રહ્યું રહ્યું રહ્યું રહ્યું રહ્માન સાય સાય સાય સાય સાય તેમને સાથે સાથે સાથે સાથે સાથે સાથે સાથે સાથે સાથે છે. આ ગામના પાસની તેમની સાથે	2680	3277
NI	-		-	EO°	-	0	21	2 I
NI		-	EQ	-		0	1	1
NI	EQ	EQ	-	-	ﺖ	l	0	1
NI	-	:	+	-	ﮯ	0	3	3
NI	-	-	-	+-	-	0	3	3
NI	ﮯ	+	-	-	=	0	1	1
NI	+			-	-	2	5	7
NI	-	EQ		-	+	0	1	1
NI	EO	ﮯ	+	-	-f-	0	1
NI	-	•		ー	+	0	. 1
NI	-	ﺳ		-	INDa	l	6	7
NI			-	EQ	IND	0	1	l
	Total Non-Infected					60 I	2724	3325
le	+	-+-	+	-+-	-+-	। ()રે	1 1	।। ୧
I	+	+-	್ಕೆ	-	+	0	1.	1
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------	+	-	+	ー	-	0	1	1
	+		제	-f-		l	0	1
	Total Infected			1 06	13	। 19

Table 25: Patient Infected Status - Male NG

*PIS = Patient Infected Status; SW = Swab; UR = urine.

"N1 = Non-infected

EQ = Equivocal result for this individual specimen type only: PIS status determined based on remaining specimens. 41ND = Indeterminate = ERROR, INVALID or.NO RESULT by Xpert CT/NG Assay, specimens with IND results by Xpert are not included in the 2x2 tables for that specimen type.

°I = Infected

Hypothetical estimated positive and negative predictive values (PPV and NPV) for different prevalence rates using Xpert CT/NG Assay are shown in Tables 26 through 29 below. These calculations are based on a hypothetical prevalence and the overall sensitivity and specificity (compared to the patient infected status) observed during the Xpert CT/NG for a multi-center clinical study (Tables 20 and 21).

In patient-collected vaginal swab specimens, the overall sensitivity and specificity for CT were 99.5% and 99.1%, respectively (Table 20). The overall sensitivity and specificity for NG were 100% and 99.9%, respectively (Table 21). The following table shows PPV and NPV for patient-collected vaginal swab specimens using hypothetical prevalence rates.

30

| Prevalence

Rate (%)	CT				NG
	Sensitivity
(%)	Specificity
(%)	PPV
(%)	NPV
(%)	Sensitivity
(%)	Specificity
(%)	PPV
(%)	NPV
(%)
1	99.5	99.1	53.6	100	100	99.9	92.6	100
2	99.5	99.1	70.0	100	100	99.9	96.2	100
5	99.5	99.1	85.8	100	100	99.9	98.5	100
10	99.5	99.1	92.7	99.9	100	99.9	99.3	100
15	99.5	99.1	95.3	99.9	100	99.9	99.5	100
20	99.5	99.1	96.6	99.9	100	99.9	99.7	100
25	99.5	99.1	97.4	99.8	100	99.9	99.8	100
30	99.5	99.1	98.0	99.8	100	99.9	99.8	100
50	99.5	99.1	99.1	99.5	100	99.9	99.9	100

Table 26: Hypothetical PPV and NPV- Patient-collected Vaginal Swabs

In endocervical swab specimens, the overall sensitivity and specificity for CT were 96.0% and 99.6%, respectively (Table 20). The overall sensitivity and specificity for NG were 100% and >99.9%, respectively (Table 21). The following table shows PPV and NPV for endocervical swab specimens using hypothetical prevalence rates.

CT					NG
Prevalence Rate (%)	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)
1	96.0	99.6	68.3	100	100	>99.9	97.4	100
2	96.0	99.6	81.3	99.9	100	>99.9	98.7	100
5	96.0	99.6	91.8	99.8	100	>99.9	99.5	100
10	96.0	99.6	96.0	99.6	100	>99.9	99.8	100
15	96.0	99.6	97.4	99.3	100	>99.9	99.8	100
20	96.0	99.6	98.2	99.0	100	>99.9	99.9	100
25	96.0	99.6	98.6	98.7	100	>99.9	99.9	100
30	96.0	99.6	98.9	98.3	100	>99.9	99.9	100
50	96.0	99.6	99.5	96.2	100	>99.9	100	100

Table 27: Hypothetical PPV and NPV- Endocervical Swabs

In female urine specimens, the overall sensitivity and specificity for CT were 98.1% and 99.8%, respectively (Table 20). The overall sensitivity and specificity for NG were 94.4% and >99.9%, respectively (Table 21). The following table shows PPV and NPV for female urine specimens using hypothetical prevalence rates.

Table 28: Hypothetical PPV and NPV- Female Urine

	CT				NG
Prevalence
Rate (%)	Sensitivity
(%)	Specificity
(%)	PPV
(%)	NPV
(%)	Sensitivity
(%)	Specificity
(%)	PPV
(%)	NPV
(%)
1	98.1	99.8	85.5	100	94.4	>99.9	97.3	99.9
2	98.1	99.8	92.2	100	94.4	>99.9	98.6	99.9
5	98.1	99.8	96.8	99.9	94.4	>99.9	99.5	99.7
10	98.1	99.8	98.5	99.8	94.4	>99.9	99.7	99.4
15	98.1	99.8	99.0	99.7	94.4	>99.9	99.8	99.0
20	98.1	99.8	99.3	99.5	94.4	>99.9	99.9	98.6
25	98.1	99.8	99.5	99.4	94.4	>99.9	99.9	98.2
30	98.1	99.8	99.6	99.2	94.4	>99.9	99.9	97.7
50	98.1	99.8	99.8	98.1	94.4	>99.9	100	94.7

Xpert CT/NG Assay 510(k) Summary

31

In male urine specimens, the overall sensitivity and specificity for CT were 98.5% and 99.8%, respectively (Table 20). The overall sensitivity and specificity for NG were 98.3% and 99.9%, respectively (Table 21). The following table shows PPV and NPV for male urine specimens using hypothetical prevalence rates.

	CT				NG
Prevalence
Rate (%)	Sensitivity
(%)	Specificity
(%)	PPV
(%)	NPV
(%)	Sensitivity
(%)	Specificity
(%)	PPV
(%)	NPV
(%)
1	98.5	99.8	82.2	100	98.3	99.9	91.7	100
2	98.5	99.8	90.3	100	98.3	99.9	95.7	100
5	98.5	99.8	96.0	99.9	98.3	99.9	98.3	99.9
10	98.5	99.8	98.1	99.8	98.3	99.9	99.2	99.8
15	98.5	99.8	98.8	99.7	98.3	99.9	99.5	99.7
20	98.5	99.8	99.1	99.6	98.3	99.9	99.6	99.6
25	98.5	99.8	99.3	99.5	98.3	99.9	99.7	99.4
30	98.5	99.8	99.5	99.3	98.3	99.9	99.8	99.3
50	98.5	99.8	99.8	98.5	98.3	99.9	99.9	98.3

Table 29: Hypothetical PPV and NPV- Male Urine

Conclusions

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

32

DEPARTMENT OF HEALTH & HUMAN SERVICES

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-002

DEC 2 7 2012

Cepheid® c/o Kerry Flom, Ph.D. Senior Vice President. Clinical Affairs and Regulatory Submissions 904 Caribbean Drive Sunnyvale, CA 90489

Re: K121710

Xpert® CT/NG Regulation Number: 21 CFR 866.3390 Regulation Name: Neisseria spp. direct serological test reagents Regulatory Class: Class II Product Code: LSL, MKZ, OOI Dated: December 10, 2012 Received: December 11, 2012

Dear Dr. Flom:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

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

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set

33

Page 2 - Kerry Flom

forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostics and Radiological Health at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Sally A. Hojvat

Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

34

4.0 Indications for Use Statement

Indications for Use Form

510(k) Number (if known): _ K12|710

Device Name: Xpert® CT/NG

Indications for Use:

The Xpert® CT/NG Assay, 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 urogenital disease. The assay may be used to test the following specimens from asymptomatic and symptomatic individuals: female and male urine, endocervical swab, and patient-collected vaginal swab (collected in a clinical setting).

Ancillary Collection Kits Indications for Use:

The Cepheid® Xpert® CT/NG Vaginal/Endocervical Specimen Collection Kit is designed to collect, preserve and transport patient Chiamydia trachomatis and Neisseria gonorrhoeae DNA in endocervical and vaginal specimens from symptomatic and asymptomatic individuals prior to analysis with the Cepheid Xpert CT/NG Assay.

The Cepheid® Xpert® CT/NG Urine Specimen Collection Kit is designed to preserve and transport Chlamydia trachomatis and Neisseria gonorrhoeae DNA in first-catch male and female urine specimens from symptomatic and asymptomatic individuals prior to analysis with the Cepheid Xpert CT/NG Assay.'

| Prescription Use
(Part 21 CFR 801 Subpart D)
X | AND/OR Over-The-Counter Use
(21 CFR 801 Subpart C) |

------------------------------------------------------	-------------------------------------------------------

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

35

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Sak am
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

从121710 510(k)_