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 individuals: female and male urine, endocervical swab, and patient-collected vaginal swab (collected in a clinical setting).

Ancillary Collection Kits:

Xpert Vaginal/Endocervical Specimen Collection Kit

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.

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.

Device Description

The Xpert CT/NG Assay is a rapid, automated in vitro diagnostic test for qualitative detection and differentiation of DNA from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG). The assay is performed on the Cepheid GeneXpert Instrument Systems. The Xpert CT/NG Assay 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 Assay 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 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® Vaginal/Endocervical Specimen Collection kit and the Cepheid® Xpert® Urine Specimen Collection kit.

AI/ML Overview

The provided text describes a 510(k) premarket notification for the Xpert CT/NG Assay, a qualitative in vitro real-time PCR test for the detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). This submission is primarily to support the removal of a limitation statement regarding the device's performance in pregnant women, building upon a previously cleared predicate device (K121710).

It's important to note that this document does not describe an AI/ML-based device. It is a molecular diagnostic test. Therefore, many of the requested criteria related to AI/ML device validation (e.g., number of experts for ground truth, MRMC study, training set details) are not applicable to this type of medical device submission.

However, I can extract the relevant information regarding performance criteria and the study conducted to support the change in the intended use.

Here's the breakdown based on the provided document:

Acceptance Criteria and Reported Device Performance

The "acceptance criteria" for this type of submission are typically demonstrating substantial equivalence to a predicate device and showing that the device performs as intended for its specified use. In this specific case, the main goal was to re-evaluate the device's performance in pregnant women to remove a previous limitation.

Since this is a diagnostic test and not an AI/ML device, the performance is typically measured by sensitivity and specificity against a confirmed ground truth, or by demonstrating equivalent performance to a legally marketed predicate device. The document refers back to the original 510(k) (K121710) for most of the detailed analytical and clinical performance characteristics, as the core technology of the device itself has not changed.

Table of Acceptance Criteria and Reported Device Performance (as inferred from the context of a 510(k) for a diagnostic test, particularly the focus within this document):

Criterion / Performance Metric	Acceptance Criteria (Implied)	Reported Device Performance (Summary within this document)
Clinical Performance (Pregnant Women)	Sufficient performance to support removal of the limitation statement for pregnant women.	Reanalysis of clinical data from K121710 supports removal of the limitation statement for pregnant women. (Specific sensitivity/specificity numbers are not detailed in this document but would be in K121710 report).
Similarities to Predicate	Device maintains essential technological characteristics, intended use, and performance as the predicate device.	The Xpert CT/NG Assay has the same intended use and fundamental scientific technology as the legally marketed predicate Xpert CT/NG Assay (K121710). Minimal differences (only a limitation statement changed).

Note: For a molecular diagnostic test like this, the "acceptance criteria" are usually based on assay validation metrics (e.g., LOD, inclusivity, exclusivity, clinical agreement with a reference method) that would have been established in the predicate device's clearance. This submission focuses on a specific clinical population.

Study Details:

Sample sizes used for the test set and the data provenance:
- Test Set Sample Size: The document states "Reanalysis of the clinical data from 510(k) #K121710 was performed for the specimens collected from women who were pregnant at the time of collection." The exact number of pregnant women's specimens re-analyzed is not provided in this document but would be found in the K121710 submission details.
- Data Provenance: The data comes from the original clinical study conducted for the predicate device (K121710). The document does not specify the country of origin, nor whether the original study was retrospective or prospective, but clinical studies for FDA clearance are typically prospective.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not Applicable in the traditional sense for a PCR test. Ground truth for diagnostic tests like this is typically established by:
  - Reference standard methods: Usually a combination of culture, a highly sensitive and specific laboratory-developed test (LDT), or another gold standard for detecting the bacterial DNA/organism.
  - Discrepancy resolution algorithms: In many PCR studies, samples that show discordant results between the investigational device and a comparator method are further tested by a third, highly reliable method (e.g., an in-house PCR with different targets, sequencing).
- The document does not specify the ground truth method or expert involvement in establishing it, as it refers back to the K121710 submission.
Adjudication method for the test set:
- Not Applicable in the traditional sense of human reader adjudication. For molecular diagnostic tests, ground truth is established by laboratory methods, not by human interpretation of images. Discrepancy resolution for discordant results between methods is a common practice, but it's not "adjudication" by experts in the context of image interpretation. The document doesn't detail this process for the K121710 data reanalysis.
If a multi-reader multi-case (MRMC) comparative effectiveness study was done, if so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- Not Applicable. This is a molecular diagnostic test (PCR), not an AI-assisted imaging device. Human readers are not involved in interpreting results in the way they would be with an AI device for radiology, for example.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Partially Applicable / This is a Standalone Device. The Xpert CT/NG Assay is a fully automated, standalone in vitro diagnostic device. It performs sample purification, nucleic acid amplification, and detection without human intervention in the assay process itself. The "performance" is the direct output of the instrument.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Likely a composite reference standard or culture/validated PCR. For sexually transmitted infections (STIs) detected via nucleic acid amplification tests (NAATs), the ground truth is typically established by using a combination of other highly sensitive and specific laboratory methods (e.g., another validated NAAT, potentially culture for NG, or a rigorous discrepancy resolution algorithm). The document refers to the original K121710 for details.
The sample size for the training set:
- Not Applicable / No separate "training set" for an AI/ML model. For a molecular diagnostic test, there isn't a "training set" in the sense of an AI model. The assay's performance characteristics (e.g., primer design, probe specificity, assay conditions) are optimized during development and then validated using analytical and clinical studies. The data from K121710 was likely used as a "test set" for performance evaluation, not for training a model.
How the ground truth for the training set was established:
- Not Applicable. (As there is no "training set" for an AI/ML model here). The ground truth for the clinical validation would have been established using the accepted reference methods for CT/NG detection, as described in point 6.

Summary

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April 27, 2018

Cepheid Jim Kelly, Ph.D. Executive Director, Regulatory Affairs 904 Caribbean Drive Sunnyvale, California 94089

Re: K173840

Trade/Device Name: 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, LIO Dated: December 15, 2017 Received: December 18, 2017

Dear Jim Kelly:

This letter corrects our substantially equivalent letter of March 16, 2018.

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. 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.

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); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR

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Part 820); 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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

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, Uwe Scherf -S

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

Enclosure

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Indications for Use

510(k) Number (if known) K173840

Device Name Xpert CT/NG

Indications for Use (Describe)

Ancillary Collection Kits:

Xpert Vaginal/Endocervical Specimen Collection Kit

Xpert Urine Specimen Collection Kit

Type of Use (Select one or both, as applicable)
-------------------------------------------------

	Prescription Use (Part 21 CFR 801 Subpart D)
	Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) Summary

As required by 21 CFR Section 807.92(c).

Submitted by:	Cepheid904 Caribbean DriveSunnyvale, CA 90489Phone number: (847) 228-3299Fax number: (847) 890-6589
Contact:	Jim Kelly, Ph.D.
Date Submitted:	February 13, 2017
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 anddifferentiation of DNA from Chlamydia trachomatis (CT)and/or Neisseria gonorrhoeae (NG).
Regulation NumberClassification Name:	21 CFR 866.3390 Neisseria spp. direct serological test reagents21 CFR 866.3120 Chlamydia serological reagents21 CFR 862.2570 Instrumentation for clinical multiplex systems21 CFR 866.2900 Microbiological specimen collection andtransport device
RegulatoryClassification	II
Product code:	LSL: DNA-Reagents, NeisseriaMKZ: DNA Probe, Nucleic Acid Amplification, ChlamydiaOOI: Real Time Nucleic Acid Amplification SystemLIO: Device, Specimen Collection
ClassificationAdvisory Panel	Microbiology (83)
Prescription Use	Yes
Predicate Device:	Xpert® CT/NG[510(k) #K121710]

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Device Description:

Device Intended 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).

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Ancillary Collection Kits:

Xpert Vaginal/Endocervical Specimen Collection Kit

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.

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.

Substantial Equivalence:

The Xpert CT/NG Assay is substantially equivalent to the predicate device, Cepheid Xpert CT/NG Assay [510(k) # K121710, cleared on December 27, 2012].

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

Similarities
Item	Device	Predicate Device
	Cepheid Xpert CT/NG Assay	Cepheid Xpert CT/NG Assay
510(k) Number	To be assigned	K121710
Regulation	Same	866.3390, 866.3120
Product Code	Same	LSL, MKZ
Device Class	Same	II
Technology/Detection	Same	Multiplex real-timepolymerase chain reaction(PCR)
Intended Use	Same	The Xpert® CT/NG Assay,performed on the GeneXpert®Instrument Systems, is aqualitative in vitro real-timePCR test for the automated
Similarities
Item	Device	Predicate Device
	Cepheid Xpert CT/NG Assay	Cepheid Xpert CT/NG Assaydetection and differentiation of genomic DNA fromChlamydia 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: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 Cepheid® Xpert® Urine Specimen Collection Kit is designed to preserve and

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

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Similarities
Item	Device	Predicate Device
	Cepheid Xpert CT/NG Assay	Cepheid Xpert CT/NG Assay
		gonorrhoeae, andTrichomonas vaginalis DNAin first-catch female and maleurine specimens fromsymptomatic andasymptomatic individuals priorto analysis with the XpertCT/NG Assay and the XpertTV Assay.
Indication for Use	Same	Asymptomatic andsymptomatic patients
Assay Targets	Same	DNA from Chlamydiatrachomatis (CT) and/orNeisseria gonorrhoeae (NG)
Specimen Type	Same	Urine, endocervical swab, andpatient-collected vaginal swab(collected in a clinical setting)
CT Analyte Targets	Same	CT genomic DNA
NG Analyte Targets	Same	NG genomic DNA
Collection Kit	Same	Urine collection kitSwab collection kit
Nucleic AcidExtraction	Yes	Yes
Assay Results	Same	Qualitative
Instrument System	Same	Cepheid GeneXpertInstrument System
Assay Controls	Same	Internal sample processingcontrol (SPC), sampleadequacy control (SAC), andprobe check control (PCC).External controls available.
Time to obtain testresults	Same	Approximately 90 minutes (1.5hours) to results.

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Primary Differences
	Device	Predicate Device
Item	Cepheid Xpert CT/NG Assay	Cepheid Xpert CT/NG Assay
Limitation	Xpert CT/NG Assayperformance has not beenevaluated in patients with ahistory of hysterectomy.	Xpert CT/NG Assayperformance has not beenevaluated in pregnant women,or in patients with a history ofhysterectomy.

The Xpert CT/NG Assay has the same intended use as the predicate device and has the same technological characteristics as the predicate device.

Non-Clinical Studies:

Analytical Sensitivity