The Xpert Xpress MVP test, performed on the GeneXpert Instrument Systems, is an automated qualitative in vitro diagnostic test for the detection of DNA targets from anaerobic bacteria associated with bacterial vaginosis (BV), Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis. The Xpert Xpress MVP test uses clinician-collected and self-collected vaginal swabs (collected in a clinical setting) from patients who are symptomatic for vaginitis/vaginosis. The Xpert Xpress MVP test utilizes real-time polymerase chain reaction (PCR) for the amplification of specific DNA targets and utilizes fluorogenic target-specific hybridization probes to detect and differentiate DNA from:

. Organisms associated with bacterial vaginosis (detected organisms not reported individually)
- o Atopobium spp. (Atopobium vaginae, Atopobium novel species CCUG 55226)
- Bacterial Vaginosis-Associated Bacterium 2 (BVAB2) o
- Megasphaera-1 o
Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis, species not differentiated)
Candida glabrata/Candida krusei (species not differentiated)
. Trichomonas vaginalis

The Xpert Xpress MVP test is intended to aid in the diagnosis of vaginal infections in women with a clinical presentation consistent with bacterial vaginosis, vulvovaginal candidiasis, or trichomoniasis.

Device Description

The Xpert® Xpress MVP test is an automated in vitro diagnostic test for qualitative detection of DNA targets from anaerobic bacteria associated with bacterial vaginosis, Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis, the agent of trichomoniasis. The Xpert Xpress MVP test is performed on GeneXpert Instrument Systems.

The GeneXpert Instrument Systems automate and integrate sample preparation, nucleic acid extraction and amplification, and detection of the target sequences in simple or complex samples using real-time PCR assays. The systems consist of an instrument, computer, and preloaded software for running tests and viewing the results. The systems require the use of single-use disposable cartridges that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained, cross-contamination between samples is minimized.

The Xpert Xpress MVP test includes reagents for the detection of DNA from BV organisms, Candida species, and Trichomonas vaginalis from vaginal swab samples. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are also included in the cartridge utilized by the GeneXpert System instrument. The SPC is present to control for adequate processing of the sample and to monitor for the presence of potential inhibitor(s) in the PCR reaction. The SPC also ensures that the PCR reaction conditions (temperature and time) are appropriate for the amplification reaction and that the PCR reagents are functional. The PCC verifies reagent rehydration, PCR tube filling, and confirms that all reaction components are present in the cartridge including monitoring for probe integrity and dye stability.

The Xpert Xpress MVP test is designed for use with the following specimens collected from symptomatic individuals: self-collected vaginal swabs (collected in a clinical setting) and clinician-collected vaginal swabs. The swab transport reagent included in the Xpert Swab Specimen Collection Kit is designed to collect and preserve patient specimens to allow transport to the laboratory prior to analysis with the Xpert Xpress MVP test.

AI/ML Overview

Here's an analysis of the acceptance criteria and study proving the device meets those criteria, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as distinct numerical targets for sensitivity, specificity, and agreement rates in the provided document. However, the performance outcomes of the Xpert Xpress MVP test are presented and can be interpreted as the device meeting the performance standards considered acceptable for its intended use, especially given the FDA's 510(k) clearance based on "substantial equivalence." The document compares the device's performance to an FDA-cleared predicate device.

For the purpose of this table, "Acceptance Criteria" will be inferred from the reported performance, as it highlights what the device achieved and what was deemed sufficient for clearance.

Test Parameter	Acceptance Criteria (Implied)	Reported Performance (Xpert Xpress MVP)	Sample Type	Comparator/Reference Method	Ground Truth Type
Bacterial Vaginosis (BV)	High PPA and NPA	PPA: 93.8% (531/566)	Clinician-collected (CVS)	FDA-cleared NAAT	NAAT results
		NPA: 93.8% (808/861)	Clinician-collected (CVS)	FDA-cleared NAAT	NAAT results
		PPA: 94.0% (533/567)	Self-collected (SVS)	FDA-cleared NAAT	NAAT results
		NPA: 92.9% (794/855)	Self-collected (SVS)	FDA-cleared NAAT	NAAT results
Candida group	High Sensitivity and Specificity	Sensitivity: 98.0% (396/404)	Clinician-collected (CVS)	Yeast culture + mass spectrometry	Culture + MS
		Specificity: 94.6% (984/1040)	Clinician-collected (CVS)	Yeast culture + mass spectrometry	Culture + MS
		Sensitivity: 97.5% (393/403)	Self-collected (SVS)	Yeast culture + mass spectrometry	Culture + MS
		Specificity: 92.1% (954/1036)	Self-collected (SVS)	Yeast culture + mass spectrometry	Culture + MS
Candida glabrata/krusei (C. glab-krus)	High Sensitivity and Specificity	Sensitivity: 93.6% (44/47)	Clinician-collected (CVS)	FDA-cleared NAAT (for discrepants)	Culture + MS (primary), NAAT (discrepant)
		Specificity: 99.6% (1392/1397)	Clinician-collected (CVS)	FDA-cleared NAAT (for discrepants)	Culture + MS (primary), NAAT (discrepant)
		Sensitivity: 97.8% (45/46)	Self-collected (SVS)	FDA-cleared NAAT (for discrepants)	Culture + MS (primary), NAAT (discrepant)
		Specificity: 99.4% (1384/1393)	Self-collected (SVS)	FDA-cleared NAAT (for discrepants)	Culture + MS (primary), NAAT (discrepant)
		Sensitivity (Contrived): 99.0% (98/99)	Clinician-collected (CVS)	Not specified (presumably internal reference)	Contrived specimens
		Specificity (Contrived): 96.4% (27/28)	Clinician-collected (CVS)	Not specified (presumably internal reference)	Contrived specimens
Trichomonas vaginalis (TV)	High PPA and NPA	PPA: 97.3% (73/75)	Clinician-collected (CVS)	Patient Infected Status (PIS) algorithm (FDA-cleared NAAT + TV culture)	PIS algorithm
		NPA: 99.6% (1332/1337)	Clinician-collected (CVS)	Patient Infected Status (PIS) algorithm (FDA-cleared NAAT + TV culture)	PIS algorithm
		PPA: 97.3% (72/74)	Self-collected (SVS)	Patient Infected Status (PIS) algorithm (FDA-cleared NAAT + TV culture)	PIS algorithm
		NPA: 99.8% (1330/1333)	Self-collected (SVS)	Patient Infected Status (PIS) algorithm (FDA-cleared NAAT + TV culture)	PIS algorithm

2. Sample Size Used for the Test Set and Data Provenance

Sample Size (Clinical Study/Test Set):
- Patients: 1,478 female patients (14 to ≥ 50 years of age).
- Vaginal Swabs Tested: 2,947 (one self-collected vaginal swab (SVS) and five clinician-collected vaginal swab (CVS) specimens per patient).
Data Provenance:
- Country of Origin of the Data: United States (multi-site clinical study with 12 sites from geographically diverse locations in the U.S.).
- Retrospective or Prospective: Prospective observational, method comparison clinical study.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

The document does not specify the number or qualifications of experts (e.g., radiologists, pathologists) used to establish the ground truth for the clinical test set. The ground truth for the clinical study was established by comparator methods (FDA-cleared NAATs, yeast culture followed by mass spectrometry, and a PIS algorithm). These methods are analytical laboratory tests, not dependent on expert visual review.

4. Adjudication Method for the Test Set

The document states: "When applicable, investigation of discrepant results was performed by testing specimens with another FDA-cleared NAAT."
This indicates a form of adjudication for discrepant results, where a third, independent, FDA-cleared NAAT was used to resolve disagreements between the Xpert Xpress MVP test and the initial comparator method. The specific rule (e.g., 2 out of 3 agreement) for this discrepancy resolution is not detailed, but the use of an independent NAAT as a tie-breaker or confirming tool is implied.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done.
This study evaluates an in vitro diagnostic (IVD) device that detects nucleic acid sequences from microorganisms using real-time PCR. It is not an imaging-based AI device that would typically involve human readers interpreting images. Therefore, the concept of human readers improving with AI vs. without AI assistance does not apply to this type of device.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, the primary performance evaluation of the Xpert Xpress MVP test in the clinical study was standalone.
The device is an automated, qualitative in vitro diagnostic test that performs sample preparation, nucleic acid extraction and amplification, and detection, and provides results "within 60 minutes." The clinical performance tables (Table 5-13) represent the direct output of the device compared to reference methods, without human interpretation of the device's signal directly impacting the final result reported by the device itself.
Human involvement is in specimen collection, loading the cartridge, and reviewing the system's final reported result for the pathogen. The device's diagnostic output for a given sample is fully automated.

7. The Type of Ground Truth Used

The ground truth varied by the target organism:

Bacterial Vaginosis (BV): An FDA-cleared nucleic acid amplification test (NAAT).
Candida group and Candida glabrata/krusei: Yeast culture followed by mass spectrometry for species identification. For Candida glabrata/krusei, there was also a "contrived" study, meaning the ground truth was based on known concentrations of the organisms.
Trichomonas vaginalis (TV): A Patient Infected Status (PIS) algorithm that included results from an FDA-cleared NAAT and TV culture.
Discrepancy Resolution: For all targets, a second FDA-cleared NAAT was used for investigation of discrepant results, effectively serving as an adjudication method to establish the clinical ground truth for those specific samples.

8. The Sample Size for the Training Set

The document describes the clinical study as a "performance evaluation" and "method comparison clinical study" used to demonstrate substantial equivalence. It does not explicitly reference or describe a separate "training set" for the device's algorithm in the context of machine learning, because this is a molecular diagnostic test based on PCR, not an adaptable AI algorithm that is trained on data in the traditional sense. The development of such a device involves assay design and optimization rather than machine learning training sets.

9. How the Ground Truth for the Training Set Was Established

Since there is no explicit mention of a "training set" in the context of an AI/ML algorithm for this PCR-based diagnostic device, the concept of establishing ground truth for a training set as typically described for AI/ML devices doesn't apply. The development and validation of the device would have involved extensive laboratory (non-clinical) studies, including analytical sensitivity (LoD), analytical reactivity (inclusivity), analytical specificity (exclusivity), microbial interference, competitive interference, interfering substances, and carry-over contamination studies (as described in Section 5.4), where the "ground truth" for these studies would be precisely controlled laboratory-prepared samples with known concentrations of target organisms and potential interferents.

Summary

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February 9, 2022

Image /page/0/Picture/1 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which consists of the letters "FDA" in a blue square. To the right of the square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

Cepheid Wei Zhang Senior Regulatory Affairs Specialist 904 Caribbean Drive Sunnyvale, California 94089

Re: K212213

Trade/Device Name: Xpert Xpress MVP, GeneXpert Dx System, GeneXpert Infinity System Regulation Number: 21 CFR 866.3975 Regulation Name: Device That Detects Nucleic Acid Sequences From Microorganisms Associated With Vaginitis And Bacterial Vaginosis Regulatory Class: Class II Product Code: PQA, NSU Dated: July 14, 2021 Received: July 15, 2021

Dear Wei Zhang:

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

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

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

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statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Maria Ines Garcia Assistant Director Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known)

Device Name

Indications for Use (Describe)

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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Section 5 510(k) Summary for Xpert Xpress MVP

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5.0 510(k) Summary
5.1 Device Description
5.2 Device Intended Use
5.3 Substantial Equivalence
5.4 Non-Clinical Study
5.5 Clinical Studies
5.6 Conclusions

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5.0 510(k) Summary

As required by 21 CFR Section 807.92(c).

Submitted by:	Cepheid904 Caribbean DriveSunnyvale, CA 90489Phone number: (425) 420-8349Fax number: (408) 541-4192
Contact:	Wei Zhang, PhD RAC
Date of Preparation:	February 8, 2022
Device:
Trade name:	Xpert® Xpress MVP
Common name:	Xpert Xpress MVP
Type of Test:	Qualitative real-time polymerase chain reaction (PCR) anddetection test
Regulation number,Classification name,	21 CFR 866.3975, Vaginitis and Bacterial Vaginosis NucleicAcid Detection System, PQA
Product codeDefinition	21 CFR 866.3860, Trichomonas vaginalis Nucleic AcidAmplification Test System, OUY21 CFR 862.2570, Real Time Nucleic Acid AmplificationSystem, OOI
ClassificationAdvisory Panel	Microbiology (83)
Prescription Use	Yes
Predicate Device	BD MAX Vaginal Panel (K191957)

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5.1 Device Description

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5.2 Device Intended Use

. Organisms associated with bacterial vaginosis (detected organisms not reported individually)
- o Atopobium spp. (Atopobium vaginae, Atopobium novel species CCUG 55226)
- Bacterial Vaginosis-Associated Bacterium 2 (BVAB2) o
- Megasphaera-1 o
Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis, species not differentiated)
Candida glabrata/Candida krusei (species not differentiated)
. Trichomonas vaginalis

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5.3 Substantial Equivalence

The Xpert Xpress MVP test is substantially equivalent to the BD MAX Vaginal Panel [510(k) # K191957].

The following tables compare Xpert Xpress MVP to BD MAX Vaginal Panel (K191957). Table 5-1 shows similarities between the new device and the predicate.

Table 3-1: Similarities Between New Device and Predicate Device
Attribute	New DeviceXpert® Xpress MVP	Predicate DeviceBD MAX Vaginal Panel (K191957)
Regulation	Same	21CFR 866.3975Device that detects nucleic acid sequences from microorganisms associated with vaginitis and bacterial vaginosis
Product Code	Same	PQAVaginitis and bacterial vaginosis nucleic acid detection system
Device Class	Same	II
Intended Use	The Xpert® Xpress MVP test, performed on the GeneXpert® Instrument Systems, is an automated qualitative in vitro diagnostic test for the detection of DNA targets from anaerobic bacteria associated with bacterial vaginosis (BV), Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis . The Xpert Xpress MVP test uses clinician-collected and self-collected vaginal swabs (collected in a clinical setting) from patients who are symptomatic for vaginitis/vaginosis. The Xpert Xpress MVP test utilizes real-time polymerase chain reaction (PCR) for the amplification of specific DNA targets and utilizes fluorogenic target-specific hybridization probes to detect and differentiate DNA from:Organisms associated with bacterial vaginosis (detected organisms not reported individually) Atopobium spp. ( Atopobium vaginae, Atopobium novel species CCUG 55226) Bacterial Vaginosis-Associated Bacterium 2 (BVAB2)	The BD MAX Vaginal Panel performed on the BD MAX System is an automated qualitative in vitro diagnostic test for the direct detection of DNA targets from bacteria associated with bacterial vaginosis (qualitative results reported based on detection and quantitation of targeted organism markers), Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis from vaginal swabs in patients who are symptomatic for vaginitis/vaginosis. The test utilizes real-time polymerase chain reaction (PCR) for the amplification of specific DNA targets and utilizes fluorogenic target-specific hybridization probes to detect and differentiate DNA from:Bacterial vaginosis markers (Individual markers not reported) Lactobacillus spp. ( L. crispatus and L. jensenii ) Gardnerella vaginalis Atopobium vaginae
Comparison
Attribute	New DeviceXpert® Xpress MVP	Predicate DeviceBD MAX Vaginal Panel (K191957)
	○ Megasphaera-1• Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis, species not differentiated)• Candida glabrata/Candida krusei (species not differentiated)• Trichomonas vaginalisThe Xpert Xpress MVP test is intended to aid in the diagnosis of vaginal infections in women with a clinical presentation consistent with bacterial vaginosis, vulvovaginal candidiasis, or trichomoniasis.	○ Bacterial Vaginosis Associated Bacteria-2 (BVAB-2)○ Megasphaera-1• Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis)• Candida glabrata• Candida krusei• Trichomonas vaginalisThe BD MAX Vaginal Panel is intended to aid in the diagnosis of vaginal infections in women with a clinical presentation consistent with bacterial vaginosis, vulvovaginal candidiasis and trichomoniasis.
Laboratory Users	Same	CLIA Moderate Complexity
Specimen Type	Same	Clinician and patient-collected female vaginal swabs
Assay Technology	Same	Real-Time PCR
Single Use	Same	Yes
Automated Extraction, detection and result interpretation	Same	Yes
Assay Results	Same	Qualitative

Table 5-1: Similarities between New Device and Predicate Device

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Table 5-2 shows the differences between the new device and the predicate.

			Table 5-2: Differences between New Device and Predicate Device
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Comparison
Attribute	New Device	Predicate Device
	Xpert® Xpress MVP	BD MAX Vaginal Panel (K191957)
Organisms Detected	Organisms associated with bacterial vaginosis (detected organisms not reported individually) Atopobium spp. ( Atopobium vaginae , Atopobium novel species CCUG 55226) Bacterial Vaginosis-Associated Bacterium 2 (BVAB2)	Bacterial vaginosis markers (Individual markers not reported) Lactobacillus spp. ( L. crispatus and L. jensenii ) Gardnerella vaginalis Atopobium vaginae Bacterial Vaginosis Associated Bacteria-2 (BVAB-2)

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Comparison
Attribute	New DeviceXpert® Xpress MVP	Predicate DeviceBD MAX Vaginal Panel (K191957)
	Megasphaera-1 Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis, species not differentiated) Candida glabrata/Candida krusei (species not differentiated) Trichomonas vaginalis	Megasphaera-1 Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis) Candida glabrata Candida krusei Trichomonas vaginalis
Instrument Systems	Cepheid GeneXpert Instrument Systems	BD MAX System
Collection Device	Cepheid Xpert Swab Specimen Collection kit	MAX UVE Specimen Collection Kit
Time to Result	Single testWithin 60 minutes	Batch test~ 2-4 hours

The Xpert Xpress MVP test has the same general intended use as the predicate device and technological characteristics as the predicate device. The performance of the Xpert Xpress MVP test was evaluated in a multi-site clinical study. The results of the study demonstrated that the performance of the Xpert Xpress MVP test is substantially equivalent to the predicate device. The differences between the Xpert Xpress MVP test and the predicate device do not raise different questions of safety and effectiveness.

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5.4 Non-Clinical Study

Analytical Sensitivity

The analytical sensitivity (Limit of Detection, LoD) of the Xpert Xpress MVP test was determined by preparing dilutions for each of the target organisms detected by the test. The LoD is defined as the lowest concentration of organism sample that can be reproducibly distinguished from negative samples with 95% confidence. The near cut-off concentrations for the BV organisms were also determined. The near cut-off concentration for the BV organisms is defined as the lowest concentrations of Atopobium vaginae and Megasphaera-1, or A. vaginae and BVAB2. or A. vaginae and Megasphaera-1 and BVAB2. or A. vaginae in the absence of Megasphaera-1 and BVAB2 that result in BV POSITIVE test results and can be reproducibly distinguished from negative samples with a 95% confidence level. Positive samples were prepared by inoculating simulated vaginal swab matrix with each representative strain or quantified stock of plasmid DNA containing the cloned genomic target of BVAB2 or Megasphaera-1. Replicates of 20 were evaluated at a minimum of five concentrations for each of the target organisms. The LoD and/or near cut-off concentrations for the target organisms were estimated by probit analysis or by the classical approach using a 95% hit rate. The LoD for each Candida spp. and Trichomonas vaginalis strain was verified in natural clinical vaginal swab matrix and simulated vaginal swab matrix. The LoD and near cut-off concentrations for each BV organism were verified in simulated vaginal swab matrix. The verified LoD and near cut-off concentrations for Xpert Xpress MVP targets are presented in Table 5-3.

Organism	Verified LoD
Atopobium vaginae	32 CFU/mL
BVAB2 (plasmid DNA)	50 copies/mL
Megasphaera-1 (plasmid DNA)	338 copies/mL
Candida albicans	30 CFU/mL
Candida tropicalis	750 CFU/mL
Candida parapsilosis	1,339 CFU/mL
Candida dubliniensis	1,316 CFU/mL
Candida glabrata	20 CFU/mL
Candida krusei	656 CFU/mL
Trichomonas vaginalis	5 cells/mL
BV Organism	Verified Near Cut-offConcentration
Atopobium vaginae(in the absence of Megasphaera-1 and BVAB2)	320,000 CFU/mL
Atopobium vaginae(in the presence of Megasphaera-1 and/or BVAB2)	2,750 CFU/mL
BVAB2 plasmid DNA	50 copies/mL
Megasphaera-1 plasmid DNA	390 copies/mL

Table 5-3: Verified LoD and Near Cut-off concentrations for Xpert Xpress MVP
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Image /page/12/Picture/0 description: The image shows the logo for Cepheid, a molecular diagnostics company. The logo features a stylized blue wing-like graphic above the company name, "Cepheid." Below the company name is the text "Xpert® Xpress MVP", which likely refers to one of Cepheid's diagnostic products or platforms.

Analytical Reactivity (Inclusivity)

The analytical reactivity of the Xpert Xpress MVP test was determined with 5 strains of Candida albicans, 5 strains of Candida dubliniensis, 5 strains of Candida tropicalis, 5 strains of Candida parapsilosis, 5 strains of Candida glabrata, 5 strains of Candida krusei, 11 strains of Atopobium spp. (Atopobium vaginae and/or Atopobium novel species CCUG 55226), and 10 strains of Trichomonas vaginalis that were diluted in simulated vaginal swab matrix at 3× LoD. Each Atopobium spp. strain was also evaluated at 3× near cut-off concentrations diluted in simulated vaginal swab matrix in the absence or presence of BVAB2 and/or Megasphaera-1 DNA to confirm the correct BV POSITIVE test results were reported.

The Xpert Xpress MVP test correctly identified 46 of 51 strains upon initial testing at 3× LoD. Two strains of Atopobium vaginae tested at 3× LoD and three strains of Candida albicans tested at 3× LoD were not detected and were tested at higher concentrations to determine the minimum concentration sufficient for detection. One Atopobium vaginae strain was detected at ~4× LoD and the other strain was detected at ~12× LoD. One Candida albicans strain was detected at ~4× LoD and the other two Candida albicans strains were detected at ~20× LoD.

For near cut-off concentration of Atopobium spp. in the absence of Megasphaera-1 and BVAB2, the Xpert Xpress MVP test correctly reported BV POSITIVE test result for 7 of the 11 strains upon initial testing at 3× near cut-off concentration. Four strains did not meet acceptance criteria and were further tested to determine the minimum concentration sufficient for reporting BV POSITIVE test result. One Atopobium spp. strain reported BV POSITIVE at ~4×, two strains at ~6×, and one strain at ~12× near cut-off concentration.

For the near cut-off concentration of Atopobium spp. in the presence of Megasphaera-1 and/or BVAB2, the Xpert Xpress MVP test correctly reported BV POSITIVE test result for 7 of the 11 strains upon initial testing at 3× near cut-off concentration. Four strains did not meet acceptance criteria and were further tested to determine the minimum concentration sufficient for reporting BV POSITIVE test result. Two Atopobium spp. strains reported BV POSITIVE at ~4x, one strain at ~6×, and one strain at ~7× near cut-off concentration. The analytical reactivity result summary is presented in Table 5-4.

Organism	Strain	Concentration	Result
			BV	Candidagroup	Candidaglab-krus	TV
	Negative Control		Negative	Not Detected	Not Detected	Not Detected
Atopobium spp.LoD(Below the nearcut-offconcentrations andnot generating BVPOSITIVE result) a	CCUG 39382	96 CFU/mL	pos a	Not Detected	Not Detected	Not Detected
	CCUG 42099	96 CFU/mL	pos a	Not Detected	Not Detected	Not Detected
	CCUG 43049	96 CFU/mL	pos a	Not Detected	Not Detected	Not Detected
	CCUG 44061	96 CFU/mL	pos a	Not Detected	Not Detected	Not Detected
	CCUG 44116	96 CFU/mL	pos a	Not Detected	Not Detected	Not Detected
	CCUG 44125	120 CFU/mL b	pos a	Not Detected	Not Detected	Not Detected
	CCUG 44156	96 CFU/mL	pos a	Not Detected	Not Detected	Not Detected

	CCUG 44258	96 CFU/mL	pos a	Not Detected	Not Detected	Not Detected
	CCUG 48515	400 CFU/mL c	pos a	Not Detected	Not Detected	Not Detected
	CCUG 55227	96 CFU/mL	pos a	Not Detected	Not Detected	Not Detected
	CCUG 55226	96 CFU/mL	pos a	Not Detected	Not Detected	Not Detected
	CCUG 39382	9.6×10⁵ CFU/mL	Positive	Not Detected	Not Detected	Not Detected
	CCUG 42099	9.6×10⁵ CFU/mL	Positive	Not Detected	Not Detected	Not Detected
	CCUG 43049	9.6×10⁵ CFU/mL	Positive	Not Detected	Not Detected	Not Detected
	CCUG 44061	9.6×10⁵ CFU/mL	Positive	Not Detected	Not Detected	Not Detected
Atopobium spp.	CCUG 44116	9.6×10⁵ CFU/mL	Positive	Not Detected	Not Detected	Not Detected
In the absence of	CCUG 44125	1.2×10⁶ CFU/mL d	Positive	Not Detected	Not Detected	Not Detected
Megasphaera-1	CCUG 44156	2.0×10⁶ CFU/mL e	Positive	Not Detected	Not Detected	Not Detected
and BVAB2	CCUG 44258	9.6×10⁵ CFU/mL	Positive	Not Detected	Not Detected	Not Detected
	CCUG 48515	4.0×10⁶ CFU/mL f	Positive	Not Detected	Not Detected	Not Detected
	CCUG 55227	9.6×10⁵ CFU/mL	Positive	Not Detected	Not Detected	Not Detected
	CCUG 55226	2.0×10⁶ CFU/mL g	Positive	Not Detected	Not Detected	Not Detected
	CCUG 39382	8,250 CFU/mL	Positive	Not Detected	Not Detected	Not Detected
	CCUG 42099	8,250 CFU/mL	Positive	Not Detected	Not Detected	Not Detected
	CCUG 43049	8,250 CFU/mL	Positive	Not Detected	Not Detected	Not Detected
	CCUG 44061	8,250 CFU/mL	Positive	Not Detected	Not Detected	Not Detected
Atopobium spp.	CCUG 44116	8,250 CFU/mL	Positive	Not Detected	Not Detected	Not Detected
	CCUG 44125	10,000 CFU/mL h	Positive	Not Detected	Not Detected	Not Detected
In the presence ofBVAB2	CCUG 44156	17,000 CFU/mL i	Positive	Not Detected	Not Detected	Not Detected
	CCUG 44258	8,250 CFU/mL	Positive	Not Detected	Not Detected	Not Detected
	CCUG 48515	17,000 CFU/mL J	Positive	Not Detected	Not Detected	Not Detected
	CCUG 55227	8,250 CFU/mL	Positive	Not Detected	Not Detected	Not Detected
	CCUG 55226	10,000 CFU/mL k	Positive	Not Detected	Not Detected	Not Detected
	CCUG 39382	8,250 CFU/mL	Positive	Not Detected	Not Detected	Not Detected
	CCUG 42099	8,250 CFU/mL	Positive	Not Detected	Not Detected	Not Detected
	CCUG 43049	8,250 CFU/mL	Positive	Not Detected	Not Detected	Not Detected
	CCUG 44061	8,250 CFU/mL	Positive	Not Detected	Not Detected	Not Detected
Atopobium spp.	CCUG 44116	8,250 CFU/mL	Positive	Not Detected	Not Detected	Not Detected
In the presence ofMegasphaera-1	CCUG 44125	10,000 CFU/mL h	Positive	Not Detected	Not Detected	Not Detected
	CCUG 44156	17,000 CFU/mL i	Positive	Not Detected	Not Detected	Not Detected
	CCUG 44258	8,250 CFU/mL	Positive	Not Detected	Not Detected	Not Detected
	CCUG 48515	20,000 CFU/mL j	Positive	Not Detected	Not Detected	Not Detected
	CCUG 55227	8,250 CFU/mL	Positive	Not Detected	Not Detected	Not Detected
	CCUG 55226	10,000 CFU/mL k	Positive	Not Detected	Not Detected	Not Detected
Atopobium spp.	CCUG 39382	8,250 CFU/mL	Positive	Not Detected	Not Detected	Not Detected
	CCUG 42099	8,250 CFU/mL	Positive	Not Detected	Not Detected	Not Detected
In the presence ofMegasphaera-1and BVAB2	CCUG 43049	8,250 CFU/mL	Positive	Not Detected	Not Detected	Not Detected
	CCUG 44061	8,250 CFU/mL	Positive	Not Detected	Not Detected	Not Detected
	CCUG 44116	8,250 CFU/mL	Positive	Not Detected	Not Detected	Not Detected
	CCUG 44125	10,000 CFU/mL h	Positive	Not Detected	Not Detected	Not Detected
	CCUG 44156	17,000 CFU/mL i	Positive	Not Detected	Not Detected	Not Detected
	CCUG 44258	8,250 CFU/mL	Positive	Not Detected	Not Detected	Not Detected
	CCUG 48515	17,000 CFU/mL j	Positive	Not Detected	Not Detected	Not Detected
	CCUG 55227	8,250 CFU/mL	Positive	Not Detected	Not Detected	Not Detected
	CCUG 55226	10,000 CFU/mL k	Positive	Not Detected	Not Detected	Not Detected
	ATCC 38289	120 CFU/mL l	Negative	Detected	Not Detected	Not Detected
	ATCC 62376	600 CFU/mL m	Negative	Detected	Not Detected	Not Detected
Candida albicans	ATCC 96113	90 CFU/mL	Negative	Detected	Not Detected	Not Detected
	ATCC 60193	90 CFU/mL	Negative	Detected	Not Detected	Not Detected
	ATCC 753	600 CFU/mL n	Negative	Detected	Not Detected	Not Detected
	ATCC MYA-179	3,948 CFU/mL	Negative	Detected	Not Detected	Not Detected
	ATCC MYA-577	3,948 CFU/mL	Negative	Detected	Not Detected	Not Detected
Candidadubliniensis	ATCC MYA-646	3,948 CFU/mL	Negative	Detected	Not Detected	Not Detected
	ATCC MYA-580	3,948 CFU/mL	Negative	Detected	Not Detected	Not Detected
	ATCC MYA-581	3,948 CFU/mL	Negative	Detected	Not Detected	Not Detected
	ATCC 34139	2,250 CFU/mL	Negative	Detected	Not Detected	Not Detected
	ATCC 90874	2,250 CFU/mL	Negative	Detected	Not Detected	Not Detected
Candida tropicalis	ATCC 204318	2,250 CFU/mL	Negative	Detected	Not Detected	Not Detected
	ATCC MYA-2733	2,250 CFU/mL	Negative	Detected	Not Detected	Not Detected
	ATCC MYA-277	2,250 CFU/mL	Negative	Detected	Not Detected	Not Detected
	ATCC 7330	4,017 CFU/mL	Negative	Detected	Not Detected	Not Detected
	ATCC 60548	4,017 CFU/mL	Negative	Detected	Not Detected	Not Detected
Candidaparapsilosis	ATCC 90875	4,017 CFU/mL	Negative	Detected	Not Detected	Not Detected
	ATCC 96139	4,017 CFU/mL	Negative	Detected	Not Detected	Not Detected
	ATCC 96140	4,017 CFU/mL	Negative	Detected	Not Detected	Not Detected
	ATCC 32312	60 CFU/mL	Negative	Not Detected	Detected	Not Detected
	ATCC 32554	60 CFU/mL	Negative	Not Detected	Detected	Not Detected
Candida glabrata	ATCC 15126	60 CFU/mL	Negative	Not Detected	Detected	Not Detected
	ATCC 2001	60 CFU/mL	Negative	Not Detected	Detected	Not Detected
	ATCC MYA-276	60 CFU/mL	Negative	Not Detected	Detected	Not Detected
	ATCC 28870	1,968 CFU/mL	Negative	Not Detected	Detected	Not Detected
	ATCC 32672	1,968 CFU/mL	Negative	Not Detected	Detected	Not Detected
Candida krusei	ATCC 90878	1,968 CFU/mL	Negative	Not Detected	Detected	Not Detected
	ATCC 200917	1,968 CFU/mL	Negative	Not Detected	Detected	Not Detected
	ATCC 201748	1,968 CFU/mL	Negative	Not Detected	Detected	Not Detected
	ATCC 30184	15 cells/mL	Negative	Not Detected	Not Detected	Detected
Trichomonas vaginalis	ATCC 30187	15 cells/mL	Negative	Not Detected	Not Detected	Detected
	ATCC 30238*	15 cells/mL	Negative	Not Detected	Not Detected	Detected
	ATCC 30240	15 cells/mL	Negative	Not Detected	Not Detected	Detected
	ATCC 30245	15 cells/mL	Negative	Not Detected	Not Detected	Detected
	ATCC 50139	15 cells/mL	Negative	Not Detected	Not Detected	Detected
	ATCC 50141	15 cells/mL	Negative	Not Detected	Not Detected	Detected
	ATCC 50167	15 cells/mL	Negative	Not Detected	Not Detected	Detected
	ATCC 50183	15 cells/mL	Negative	Not Detected	Not Detected	Detected
	ATCC PRA-95	15 cells/mL	Negative	Not Detected	Not Detected	Detected

Table 5-4: Analytical Reactivity of the Xpert Xpress MVP Test

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4 The LoD for Atopobium vaginae is for information only. All Atopobium spp. strains tested at ~3× LoD level reported BV NEGATIVE result calls as expected, as the concentration of Atopobium spp. strains tested was below the near cut-off concentration either in the presence or absence of Megal-BVAB2 target. Replicates reporting Atop gp Ct values of ≤ 40.0 was treated as positive (pos) when Atopobium spp. strains were tested at ~ 3× LoD.

b Atopobium vaginae CCUG 44125 was tested at ~ 4× LoD (120 CFU/mL) to obtain 3 of 3 Atop gp Ct values of ≤ 40.0 results.

6 Atopobium vaginae CCUG 48515 was tested at ~ 12× LoD (400 CFU/mL) to obtain 3 of 3 Atop gp Ct values of < 40.0 results.

d Atopobium vaginae CCUG 44125 was tested at ~ 4× near cut-off concentration (1.2×10° CFU/mL) in the absence of BVAD2 and Megasphaera-1 to obtain 3 of 3 BV POSITIVE result calls.
e Atopobium vaginae CCUG 44156 was tested at ~ 6× near cut-off concentration (2.0×10° CFU/mL) in the absence of BV AB2 and Megasphaera-1 to obtain 3 of 3 BV POSITIVE result calls.

1 Atopobium vaginae CCUG 48515 was tested at ~ 12× near cut-off concentration (4.0×10° CFU/mL) in the absence of BVAB2 and Megasphaera-1 to obtain 3 of 3 BV POSITIVE result calls.

8 Atopobium novel species CCUG 55226 was tested at ~ 6× near cut-off concentration (2.0×10° CFU/mL) in the absence of BVAB2 and Megasphaera-1 to obtain 3 of 3 BV POSITIVE result calls.

b Atopobium vaginae CCUG 44125 was tested at ~ 4× near cut-off concentration (10,000 CFU/mL) in the presence of BV AB2 and/or Megasphaera-1 to obtain 3 of 3 BV POSITIVE result calls.

1 Atopobium vaginae CCUG 44156 was tested at ~ 6× near cut-off concentration (17,000 CFU/mL) in the presence of BVAB2 and/or Megasphaera-1 to obtain 3 of 3 BV POSITIVE result calls.

i Atopobium vaginae CCUG 48515 was tested at ~ 6× (20.000 CFU/mL) near cut-off concentration in the presence of BVAB2 and/or Megasphaera-1 to obtain 3 of 3 BV POSITIVE result calls.

Atopobium novel species CCUG 55226 was tested at ~ 4× near cut-off concentration (10,000 CFU/mL) in the presence of BVAB2 and/or Megasphaera-1 to obtain 3 of 3 BV POSITIVE result calls.

1 Candida albicans ATCC 38289 was tested at ~ 4× LoD (120 CFU/mL) to obtain 3 of 3 Candida group DETECTED result calls.

™ Candida albicans ATCC 62376 was tested at ~ 20× LoD (600 CFU/mL) to obtain 3 of 3 Candida group DETECTED result calls.

" Candida albicans ATCC 753 was tested at ~ 20× LoD (600 CFU/mL) to obtain 3 of 3 Candida group DETECTED result calls.

metronidazole-resistant strain

Analytical Specificity (Exclusivity)

The analytical specificity of the Xpert Xpress MVP test was evaluated by testing a panel of 115 potentially cross-reactive microorganisms that are likely to be found in the vaginal flora/female genital tract. All strains were tested in triplicates in simulated vaginal swab matrix at a concentration of at least 10° CFU/mL, 10° cells/mL, 10° TCID50/mL, or 10° International Unit (IU)/mL. Three replicates were tested for each strain. No cross-reactivity

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was observed for all microorganisms tested with the Xpert Xpress MVP test at the concentrations listed in Table 5-5.

Organism	Concentration	Organism	Concentration
Bacteria		Bacteria
Acinetobacter baumannii	1×106 CFU/mL	Neisseria gonorrhoeae	1×106 CFU/mL
Acinetobacter calcoaceticus	1×106 CFU/mL	Olsenella uli	1×106 CFU/mL
Actinomyces israelii	1×106 CFU/mL	Pantoea agglomerans	1×106 CFU/mL
Actinomyces pyogenes	1×106 CFU/mL	Peptoniphilus asaccharolyticus	1×106 CFU/mL
Aerococcus viridans	1×106 CFU/mL	Peptoniphilus anaerobius	1×106 CFU/mL
Alcaligenes faecalis	1×106 CFU/mL	Peptostreptococcus anaerobius	1×106 CFU/mL
Anaerococcus tetradius	1×106 CFU/mL	Plesiomonas shigelloides	1×106 CFU/mL
Atopobium minutum	1×106 CFU/mL	Porphyromonasasaccharolytica	1×106 CFU/mL
Atopobium parvulum	1×106 CFU/mL	Prevotella bivia	1×106 CFU/mL
Atopobium rimae	1×106 CFU/mL	Prevotella melaninogenica	1×106 CFU/mL
Bacillus subtilis	1×106 CFU/mL	Prevotella oralis	1×106 CFU/mL
Bacteroides caccae	1×106 CFU/mL	Propionibacterium acnes	1×106 CFU/mL
Bacteroides fragilis	1×106 CFU/mL	Proteus mirabilis	1×106 CFU/mL
Bacteroides stercoris	1×106 CFU/mL	Providencia stuartii	1×106 CFU/mL
Bacteroides ureolyticus	1×106 CFU/mL	Pseudomonas aeruginosa	1×106 CFU/mL
Bifidobacterium adolescentis	1×106 CFU/mL	Salmonella typhimurium	1×106 CFU/mL
Bifidobacterium breve	1×106 CFU/mL	Serratia marcescens	1×106 CFU/mL
Bifidobacterium longum	1×106 CFU/mL	Shigella flexneri	1×106 CFU/mL
Brevibacterium linens	1×106 CFU/mL	Sneathia amnii	1×106 CFU/mL
Burkholderia cepacian	1×106 CFU/mL	Sneathia sanguinegens	1×106 CFU/mL
BVAB1	1×106 copies/mL	Staphylococcus aureus	1×106 CFU/mL
Campylobacter jejuni	1×106 CFU/mL	Staphylococcus epidermidis	1×106 CFU/mL
Chlamydia trachomatis	1×106 CFU/mL	Streptococcus agalactiae	1×106 CFU/mL
Citrobacter freundii	1×106 CFU/mL	Streptococcus mitis	1×106 CFU/mL
Clostridium perfringens	1×106 CFU/mL	Streptococcus mutans	1×106 CFU/mL
Corynebacterium genitalium	1×106 CFU/mL	Streptococcus salivarius	1×106 CFU/mL
Dialister micraerophilus	1×106 CFU/mL	Treponema pallidum	1×106 copies/mL
Eikenella corrodens	1×106 CFU/mL	Veillonella atypica	1×106 CFU/mL
Enterobacter aerogenes	1×106 CFU/mL	Veillonella parvula	1×106 CFU/mL
Enterococcus faecalis	1×106 CFU/mL	Vibrio parahaemolyticus	1×106 CFU/mL
Enterococcus faecium	1×106 CFU/mL	Yersinia enterocolitica	1×106 CFU/mL
Erysipelothrix rhusiopathiae	1×106 CFU/mL	Protozoans
Escherichia coli	1×106 CFU/mL	Pentatrichomonas hominis	5×104 cells/mL
Finegoldia magna	1×106 CFU/mL	Trichomonas tenax	10 cells/mL
Fusobacterium nucleatum	1×106 CFU/mL	Yeasts
Gardnerella vaginalis	1×106 CFU/mL	Candida catenulate	1×106 CFU/mL
Gemella haemolysans	1×106 CFU/mL	Candida famata	1×106 CFU/mL
Kingella denitrificans	1×106 CFU/mL	Candida haemulonii	1×106 CFU/mL
Klebsiella pneumoniae	1×106 CFU/mL	Candida inconspicua	1×106 CFU/mL
Kocuria rhizophila	1×106 CFU/mL	Candida intermedia	1×106 CFU/mL
Lactobacillus acidophilus	1×106 CFU/mL	Candida kefyr	1×106 CFU/mL
Lactobacillus crispatus	1×106 CFU/mL	Candida lusitaniae	1×106 CFU/mL
Lactobacillus gasseri	1×106 CFU/mL	Candida norvegica	1×106 CFU/mL
Lactobacillus helveticus	1×106 CFU/mL	Candida orthopsilosis	1×102 CFU/mL
Lactobacillus iners	1×106 CFU/mL	Candida rugosa	1×106 CFU/mL
Lactobacillus jensenii	1×106 CFU/mL	Candida utilis	1×106 CFU/mL
Lactobacillus johnsonii	1×106 CFU/mL	Kodamaea ohmerib	1×106 CFU/mL
Lactobacillus vaginalis	1×106 CFU/mL	Pichia fermentans	1×106 CFU/mL
Legionella pneumophila	1×106 CFU/mL	Pichia norvegensisc	1×106 CFU/mL
Mageeibacillus indolicusa	1×106 CFU/mL	Pichia occidentalisd	1×106 CFU/mL
Megasphaera-2	1×106 copies/mL	Saccharomyces cerevisiae	1×106 CFU/mL
Megasphaera elsdenii	1×106 CFU/mL	Viruses
Mobiluncus curtisii	1×106 CFU/mL	Hepatitis B virus	1×105 IU/mL
Mobiluncus mulieris	1×106 CFU/mL	Hepatitis C virus	1×105 IU/mL
Moraxella catarrhalis	1×106 CFU/mL	Herpes simplex virus I	1×105 TCID50/mL
Morganella morganii	1×106 CFU/mL	HIV-1	3×104 IU/mLe
Mycobacterium smegmatis	1×106 CFU/mL	Human herpesvirus 2	1×105 TCID50/mL
Mycoplasma genitalium	1×106 CFU/mL	Human papilloma virus	4.3×105 cells/mL
Mycoplasma hominis	1×106 CFU/mL	Varicella-zoster virus	1×105 copies/mL

Table 5-5: Organisms Tested for Analytical Specificity

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Traditional 510(k) Submission

ªMageeibacillus indolicus is formerly named BVAB3.

bKodamaea ohmeri is also reported as Pichia ohmeri and Candida guilliermondii.

º Pichia norvegensis is also reported as Candida norvegensis.

d Pichia occidentalis is also reported as Issatchenkia occidentalis and Candida sorbose Evaluated at highest concentration available

Microbial Interference

An interfering microorganism study was performed to assess the inhibitory effects of microorganisms that may be encountered in vaginal specimens on the performance of Xpert Xpress MVP. Thirteen microorganisms were tested for potential interference at ≥10° CFU/mL for bacteria and at ≥104 International Unit/mL or cells/mL for viruses (Table 5-6). Each of the microorganisms was tested in simulated vaginal swab matrix in the presence of a mixture of Atopobium vaginae at 3× near cut-off concentrations, Megasphaera-1 and BVAB2 targets each at ~1.5× near cut-off concentrations, and Candida albicans, Candida glabrata and Trichomonas vaginalis targets each at 3× LoD, in the absence of any Xpert

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Xpress MVP test targets. The results showed that the presence of the tested microorganisms did not interfere with the performance of the Xpert Xpress MVP test.

Microorganism
Dialister micraerophilus
Gardnerella vaginalis
Lactobacillus crispatus
Lactobacillus jensenii
Lactobacillus iners
Mageeibacillus indolicus
Mobiluncus curtisii
Porphyromonas asaccharolytica
Prevotella bivia
Sneathia amnii
Streptococcus agalactiae
HIV-1*
Human papilloma virus**

Table 5-6: Potentially Interfering Microorganisms Tested

*Evaluated at highest concentration available (3×104 IU/mL) **Evaluated at 1×104 cells/mL

Competitive Interference

Competitive interference between targets (BV, Candida group, Candida glab-krus and TV) of the Xpert Xpress MVP test caused by co-infections was evaluated by testing each target at low positive concentration in the presence of another target at high concentration in simulated vaginal swab matrix. Competitive inhibitory effects between the BV analytes (Atop gp and Megal-BVAB2) were also evaluated in simulated vaginal swab matrix. The conditions simulating co-infections were presented in Table 5-7. Under the conditions of this study, competitive inhibitory effects were not observed between MVP targets or between BV analytes with the Xpert Xpress MVP test.

	Testing Panel	Testing Target/Organisms(Low Positive)	CompetitiveTarget/Organisms(High Positive)
Competitive InterferenceEvaluation betweenMVP Targets	1	Atopobium vaginae(<3× near cut-off concentration) andBVAB2	Candida albicans(1×106 CFU/mL)
	2	(<3× near cut-off concentration)	Candida glabrata(1×106 CFU/mL)
	3	(<3× near cut-off concentration)	Trichomonas vaginalis(1×105 cells/mL)
Testing Panel	Testing Target/Organisms(Low Positive)	CompetitiveTarget/Organisms(High Positive)
4	Atopobium vaginae( $ < 3 \times $ near cut-off concentration) andMegasphaera-1	Candida albicans(1 $\times$ 10 $^6$ CFU/mL)
5	( $ < 3 \times $ near cut-off concentration)	Candida glabrata(1 $\times$ 10 $^6$ CFU/mL)
6	( $ < 3 \times $ near cut-off concentration)	Trichomonas vaginalis(1 $\times$ 10 $^5$ cells/mL)
7	Atopobium vaginae( $ < 3 \times $ near cut-off concentration),BVAB2	Candida albicans(1 $\times$ 10 $^6$ CFU/mL)
8	( $ < 1.5 \times $ near cut-off concentration) andMegasphaera-1	Candida glabrata(1 $\times$ 10 $^6$ CFU/mL)
9	( $ < 1.5 \times $ near cut-off concentration)	Trichomonas vaginalis(1 $\times$ 10 $^5$ cells/mL)
10	Atopobium vaginae	Candida albicans(1 $\times$ 10 $^6$ CFU/mL)
11	( $ < 3 \times $ near cut-off concentration)in the absence of BVAB2 andMegasphaera-1	Candida glabrata(1 $\times$ 10 $^6$ CFU/mL)
12		Trichomonas vaginalis(1 $\times$ 10 $^5$ cells/mL)
13		Atopobium vaginae(1 $\times$ 10 $^7$ CFU/mL),BVAB2(1 $\times$ 10 $^7$ copies/mL) andMegasphaera-1(1 $\times$ 10 $^7$ copies/mL)
14	Candida albicans( $ < 3 \times $ LoD)	Atopobium vaginae(1 $\times$ 10 $^7$ CFU/mL)in the absence of BVAB2and Megasphaera-1
15		Candida glabrata(1 $\times$ 10 $^6$ CFU/mL)
16		Trichomonas vaginalis(1 $\times$ 10 $^5$ cells/mL)
17		Atopobium vaginae(1 $\times$ 10 $^7$ CFU/mL),BVAB2(1 $\times$ 10 $^7$ copies/mL) andMegasphaera-1(1 $\times$ 10 $^7$ copies/mL)
18	Candida glabrata( $ < 3 \times $ LoD)	Atopobium vaginae(1 $\times$ 10 $^7$ CFU/mL)in the absence of BVAB2and Megasphaera-1
19		Candida albicans(1 $\times$ 10 $^6$ CFU/mL)
20		Trichomonas vaginalis(1 $\times$ 10 $^5$ cells/mL)
21	Trichomonas vaginalis( $ < 3 \times $ LoD)	Atopobium vaginae(1 $\times$ 10 $^7$ CFU/mL),BVAB2(1 $\times$ 10 $^7$ copies/mL) andMegasphaera-1
	Testing Panel	Testing Target/Organisms(Low Positive)	CompetitiveTarget/Organisms(High Positive)
	22		(1×107 copies/mL)
	23		Atopobium vaginae(1×107 CFU/mL)in the absence of BVAB2and Megasphaera-1
	24		Candida albicans(1×106 CFU/mL)
			Candida glabrata(1×106 CFU/mL)
Competitive InterferenceEvaluation between BVOrganisms	25	Atopobium vaginae(< 3× near cut-off concentration)	BVAB2(1×107 copies/mL) andMegasphaera-1(1×107 copies/mL)
	26	BVAB2(< 3× near cut-off concentration)	Atopobium vaginae(1×106 CFU/mL)
	27	Megasphaera-1(< 3× near cut-off concentration)	Atopobium vaginae(1×106 CFU/mL)
	28	BVAB2(< 1.5× near cut-off concentration) andMegasphaera-1(< 1.5× near cut-off concentration)	Atopobium vaginae(1×106 CFU/mL)

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Image /page/19/Picture/0 description: The image contains the logo for Cepheid, a molecular diagnostics company. The logo features a stylized blue graphic above the company name, "Cepheid," written in a clean, sans-serif font. Below the company name is the text "Xpert® Xpress MVP," indicating a specific product or service offered by Cepheid.

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Image /page/20/Picture/0 description: The image shows the Cepheid logo. The logo consists of a blue graphic element resembling stylized wings or swooshes above the word "Cepheid." The words "Xpert® Xpress MVP" are printed below the logo. The text is in a simple, sans-serif font.

Interfering Substances

Twenty substances that may be present in the vaginal swab specimens with the potential to interfere with the performance of Xpert Xpress MVP test were evaluated. The potentially interfering substances included prescription and over-the-counter drugs, creams and/or gels, blood, hormones, semen and mucus. The substances, active ingredients, and concentrations tested are listed in Table 5-8. Potential interferents were tested in simulated vaginal swab matrix in the presence and absence of Xpert Xpress MVP targets at 3× LoD/3× near cut-off concentrations. With the exception of the 5.5% concentration of mucin (from porcine stomach), no clinically significant inhibitory effects from substances that may be encountered in vaginal specimens were observed on the performance of the Xpert Xpress MVP test. When mucin was tested at a concentration of 4.0%, no clinically significant inhibitory effect was observed on the performance of the Xpert Xpress MVP test.

Table 5-8: Potential Interfering Substances Tested

Substance/Class	Active Ingredient	Concentration Tested
Blood	Blood	5.0% v/v
Seminal Fluid	Semen	5.0% v/v
Mucus	Mucin (porcine stomach)	5.5% v/v (InterferenceObserved)4.0% v/v (Interference notObserved)
Leukocytes	Leukocytes	$10^5$ cells/mL

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Image /page/21/Picture/0 description: The image shows the Cepheid logo, which includes a stylized blue wing-like graphic above the company name. Below the company name, the text "Xpert® Xpress MVP" is displayed. The logo is clean and modern, with a focus on the company name and product.

Substance/Class	Active Ingredient	Concentration Tested
Intravaginal Hormones	Estradiol; Progesterone	7mg/mL Progesterone +0.07mg/mL Beta Estradiol
Over the counter (OTC)Vaginal Products;Contraceptives; Vaginaltreatments	Benzocaine 5%; Resorcinol 2%	0.25% w/v
	Clotrimazole 2%	0.25% w/v
	Miconazole Nitrate 4%	0.25% w/v
	Tioconazole 6.5%	0.25% w/v
	5% w/w acyclovir	0.25% w/v
	Glycerin, Propylene glycol	0.25% w/v
	Glycerin; carbomer	0.25% w/v
	Glycerin; sodium hydroxide; carbomer	0.25% w/v
	Glycerin, Hydroxyethyl cellulose	0.25% w/v
	Berberis Vulgaris 6X HPUS(Barberry), Borax 3X HPUS (SodiumBorate), Collinsonia Canadensis 3XHPUS (Stone Root), HamamelisVirginiana 6X HPUS (Witch Hazel),Bacillus coagulans (Lactospore®)	0.25% w/v
	Povidone-iodine 10% (topical)	0.25% v/v
	Povidone-iodine 0.3% (douche)	0.25% v/v
	Nonoxynol-9 12.5%	0.25% w/v
	Metronidazole 0.75%	0.25% w/v
Hemorrhoidal Cream	Glycerin 14%; Pramoxine HCl 1%	0.25% w/v

Carry-Over Contamination

A study was conducted to demonstrate that single-use, self-contained GeneXpert cartridges prevent specimen and amplicon carry-over contamination from very high titer positive samples into successively run negative samples when processed in the same GeneXpert module. The study consisted of a negative sample processed in the same GeneXpert module immediately after processing a very high BV positive sample (an A. vaginae strain at 2.8×10 CFU/mL and BVAB2 plasmid DNA at 5.0×10° copies/mL), a very high Candida group positive sample (a C. albicans strain at 3.0×106 CFU/mL), or a very high TV positive sample (a T. vaginalis strain at 5.0×10° cells/mL) in simulated vaginal swab matrix. The testing scheme was repeated 20 times in a single GeneXpert module for a total of 41 runs (20 high positive samples and 21 negative samples per module) across 3 GeneXpert modules. There was no evidence of any carry-over contamination. All 63 negative samples were correctly reported as negative/not detected. All 60 positive samples were correctly reported as positive/detected.

Time to Result

The time to result is defined as the time from the initiation of cartridge processing on the GeneXpert system to the time a result is displayed on the test screen. The time to result for the Xpert Xpress MVP test was determined by evaluating the test time of 50 random tests

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that were conducted as part of the clinical study. The Xpert Xpress MVP test has a turnaround time of within 60 minutes, and the data from this study is representative for the GeneXpert Instrument Systems.

Reproducibility and Precision

Reproducibility and precision of the Xpert Xpress MVP test was established through a multicenter (3 sites), blinded study utilizing a multi-factor nested design consisting of contrived panel members spanning the relevant limit of detection (LoD) spectrum (or, in the case of BV, the near cut-off concentration) for the 4 intended target types.

A panel of ten panel members with varying concentrations of the intended target types were tested by two operators in duplicate on six different days at three sites using three lots of Xpert Xpress MVP test cartridges. The total number of tests for each panel member was 144 (3 sites × 3 lots × 2 days × 2 operators × 2 runs × 2 replicates). The three concentrations for each intended target type included two positive levels (moderate positives at ~3× LoD/near cut-off concentration, low positives at ~1× LoD/near cut-off concentration) and one negative. For the BV target, a high negative level (<1× near the cut-off concentration) was also included.

Percent agreement for each panel member was analyzed across each of the 6 operators and across each of the 3 sites. Overall percent agreement for each panel member was calculated, as well as the Wilson Score 95% confidence interval for each proportion of concordance (Table 5-9).

Panel member	Site 01		Site 02		Site 03			Overall
	Op 1	Op 2	Subtotal	Op 1	Op 2	Subtotal	Op 1	Op 2	Subtotal	Agreement and95% CI
Negative	100%(24/24)	100%(24/24)	100%(48/48)	100%(24/24)	100%(24/24)	100%(48/48)	100%(24/24)	100%(24/24)	100%(48/48)	100%(144/144)97.4% - 100%
BV.High Neg	66.7%(16/24)	83.3%(20/24)	75.0%(36/48)	41.7%(10/24)	62.5%(15/24)	52.1%(25/48)	54.2%(13/24)	45.8%(11/24)	50.0%(24/48)	59.0%(85/144)50.9% - 66.7%
BV.Low Pos	91.7%(22/24)	100%(24/24)	95.8%(46/48)	95.8%(23/24)	95.8%(23/24)	95.8%(46/48)	100%(24/24)	100%(24/24)	100%(48/48)	97.2%(140/144)93.1% - 98.9%
BV.Mod Pos	100%(24/24)	100%(24/24)	100%(48/48)	100%(24/24)	100%(24/24)	100%(48/48)	100%(24/24)	100%(24/24)	100%(48/48)	100%(144/144)97.4% - 100%
C. albicans,Low Pos	95.8%(23/24)	100%(24/24)	97.9%(47/48)	100%(24/24)	100%(24/24)	100%(48/48)	100%(24/24)	100%(24/24)	100%(48/48)	99.3%(143/144)96.2% - 99.9%
C. albicans.Mod Pos	100%(24/24)	100%(24/24)	100%(48/48)	100%(24/24)	100%(24/24)	100%(48/48)	100%(24/24)	100%(24/24)	100%(48/48)	100%(144/144)97.4% - 100%

Table 5-9: Summary of Reproducibility and Precision Results

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Image /page/23/Picture/0 description: The image contains the Cepheid company logo. The logo consists of a blue graphic element resembling stylized wings or feathers, followed by the company name "Cepheid." Below the company name, the text "Xpert® Xpress MVP" is displayed, indicating a specific product or service offered by Cepheid.

Panel member	Site 01			Site 02			Site 03			OverallAgreement and95% CI
	Op 1	Op 2	Subtotal	Op 1	Op 2	Subtotal	Op 1	Op 2	Subtotal
C. glabrata,Low Pos	100%(24/24)	100%(24/24)	100%(48/48)	95.8%(23/24)	100%(24/24)	97.9%(47/48)	100%(24/24)	100%(24/24)	100%(48/48)	99.3%(143/144)96.2% - 99.9%
C. glabrata,Mod Pos	100%(24/24)	100%(24/24)	100%(48/48)	100%(24/24)	100%(24/24)	100%(48/48)	100%(24/24)	100%(24/24)	100%(48/48)	100%(144/144)97.4% - 100%
TV,Low Pos	95.8%(23/24)	95.8%(23/24)	95.8%(46/48)	91.7%(22/24)	95.8%(23/24)	93.8%(45/48)	87.5%(21/24)	100%(24/24)	93.8%(45/48)	94.4%(136/144)89.4% - 97.2%
TV,Mod Pos	100%(24/24)	100%(24/24)	100%(48/48)	100%(24/24)	100%(24/24)	100%(48/48)	100%(24/24)	100%(24/24)	100%(48/48)	100%(144/144)97.4% - 100%

Abbreviations: Mod, moderate; Neg, negative; Op, operator; Pos, positive

The reproducibility of the Xpert Xpress MVP test 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, between-operators, between-runs and within-run for each panel member are presented in Table 5-10.

PanelMember	Analyte	Na	MeanCt	Site		Lot		Day		Operator		Between-Run		Within-run		Total
				SD	CV(%)	SD	CV(%)	SD	CV(%)	SD	CV(%)	SD	CV(%)	SD	CV(%)	SD	CV(%)
Negative	SPC	144	32.66	0.06	0.2	0.17	0.5	0	0	0.24	0.7	0	0	0.37	1.1	0.48	1.5
BV,High Neg		144	32.45	0.07	0.2	0.17	0.5	0	0	0.12	0.4	0.05	0.2	0.28	0.9	0.36	1.1
BV,Low Pos	Atop gp	144	31.95	0.03	0.1	0.19	0.6	0	0	0	0	0.27	0.8	0.51	1.6	0.61	1.9
BV,Mod Pos		144	30.56	0	0	0.2	0.7	0.13	0.4	0.1	0.3	0.14	0.4	0.3	1.0	0.42	1.4
BV,High Neg		111	41.08	0.26	0.6	0.27	0.7	0	0	0.35	0.9	0	0	1.28	3.1	1.38	3.4
BV,Low Pos	Megal-BVAB2	144	36.31	0	0	0.31	0.9	0	0	0	0	0.23	0.6	0.58	1.6	0.7	1.9
BV,Mod Pos		144	35.25	0.16	0.5	0.19	0.5	0.19	0.5	0	0	0	0	0.59	1.7	0.67	1.9
C. albicans,Low Pos	Cgroup	144	36.67	0	0	0.22	0.6	0	0	0.19	0.5	0.56	1.5	0.78	2.1	1.01	2.7

Table 5-10. Results of Reproducibility for the Xpert Xpress MVP Test

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Image /page/24/Picture/0 description: The image contains the logo for Cepheid, a molecular diagnostics company. The logo features a stylized blue wing-like graphic above the company name, "Cepheid.", written in a clean, sans-serif font. Below the company name is the text "Xpert® Xpress MVP", which likely refers to one of Cepheid's diagnostic products or platforms.

PanelMember	Analyte	Na	MeanCt	Site		Lot		Day		Operator		Between-Run		Within-run		Total
				SD	CV(%)	SD	CV(%)	SD	CV(%)	SD	CV(%)	SD	CV(%)	SD	CV(%)	SD	CV(%)
C. albicans,Mod Pos		144	35.00	0.27	0.8	0	0	0	0	0.6	1.7	0.45	1.3	0.55	1.6	0.96	2.8
C. glabrata,Low Pos	Cglab-krus	143	31.79	0	0	0.35	1.1	0	0	0	0	0.37	1.2	1.35	4.2	1.44	4.5
C. glabrata,Mod Pos	Cglab-krus	144	29.75	0.54	1.8	0.22	0.8	0.34	1.1	0.47	1.6	0.07	0.2	0.9	3.0	1.22	4.1
TV,Low Pos	TV	136	38.41	0.21	0.6	0.22	0.6	0	0	0.33	0.9	0	0	1.23	3.2	1.3	3.4
TV,Mod Pos	TV	144	35.97	0.15	0.4	0.09	0.3	0	0	0.07	0.2	0.23	0.6	0.5	1.4	0.58	1.6

Abbreviations: Atop gp, Atopobium group; Cglabrata/C, kruse; Cgroup, Candida spp; CV, coefficient of variance; Megal; Megasphaera-1; Mod, moderate; Neg, negative; Pos, positive; SD, standard deviation; SPC; sample processing control

4Number of samples with Ct values out of 144.

Note: The variance estimate from some factors may be numerically negative, which can occur if the variability due to those factors is very small. When this occurs, the variability as measured with SD and CV is set to 0.

Precision of the BV Target

Due to the diversity of organisms associated with the detection of BV, a separate single-site study was conducted to establish precision of the BV target. To establish the assay precision for the BV target in the Xpert Xpress MVP test, a single-center, blinded precision study was conducted utilizing samples with unique combinations of contrived BV organisms.

A panel of nine panel members were tested by two operators in duplicate on ten different days using one lot of Xpert Xpress MVP test cartridges. The total number of tests for each panel member was 80 (1 site × 1 lot × 10 days × 2 operators × 2 runs × 2 replicates). The panel included 1 negative panel member, a high negative level (<1× the near cut-off concentration), and two positive levels (low positives at ~1 × the near cut-off concentration, and moderate positives at ~3× the near cut-off concentration) utilizing unique combinations of the BV organisms (Atopobium vaginae, Megasphaera-1, and BVAB2). Table 5-11 presented agreement for each panel member, as well as the Wilson Score 95% confidence interval for each proportion of concordance.

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Image /page/25/Picture/0 description: The image contains the logo for Cepheid, a molecular diagnostics company. The logo features a stylized blue wing-like design above the company name, "Cepheid." Below the company name is the text "Xpert® Xpress MVP", which likely refers to one of Cepheid's diagnostic products or platforms. The registered trademark symbol is present after the word "Xpert".

Sample Type	OverallAgreement	95% CI
Negative	100% (80/80)	95.4% - 100%
A. vaginae, Low positive	97.5% (78/80)	91.3% - 99.3%
A. vaginae and BVAB2, High negative	66.3% (53/80)	55.4% - 75.7%
A. vaginae and BVAB2, Low positive	97.5% (78/80)	91.3% - 99.3%
A. vaginae and Megasphaera-1, High negative	23.8% (19/80)	15.8% - 34.1%
A. vaginae and Megasphaera-1, Low positive	95.0% (76/80)	87.8% - 98.0%
A. vaginae, BVAB2, and Megasphaera-1, High negative	53.8% (43/80)	42.9% - 64.3%
A. vaginae, BVAB2, and Megasphaera-1, Low positive	96.3% (77/80)	89.5% - 98.7%
A. vaginae, BVAB2, and Megasphaera-1, Moderate positive	100% (80/80)	95.4% - 100%

Table 5-11: Summary of Precision Results for the BV Target

Abbreviations: A. vaginae; Atopobium vaginae

Precision for BV targets was 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-days, between-operators, between-runs and within-run for each panel member are presented in Table 5-12.

		Na	MeanCt	Day		Operator		Between-Run		Within-run		Total
Panel member	Analyte			SD	CV (%)	SD	CV (%)	SD	CV (%)	SD	CV (%)	SD	CV (%)
Negative	SPC	80	32.84	0.00	0.0	0.49	1.5	0.22	0.7	0.90	2.7	1.05	3.2
A. vaginae , Low Pos	Atop gp	80	24.98	0.00	0.0	0.00	0.0	0.03	0.1	0.32	1.3	0.32	1.3
	SPC	80	32.64	0.17	0.5	0.17	0.5	0.12	0.4	0.37	1.1	0.46	1.4
A. vaginae andBVAB2, High Neg	Atop gp	80	32.35	0.00	0.0	0.16	0.5	0.00	0.0	0.20	0.6	0.26	0.8
	Megal-BVAB2b	75	41.30	0.37	0.9	0.00	0.0	0.26	0.6	1.15	2.8	1.24	3.0
	Atop gp	80	32.20	0.00	0.0	0.04	0.1	0.08	0.3	0.22	0.7	0.24	0.7
A. vaginae andBVAB2, Low Pos	Megal-BVAB2b	80	40.03	0.00	0.0	0.00	0.0	0.30	0.7	0.90	2.2	0.94	2.4
	SPC	80	32.63	0.11	0.3	0.17	0.5	0.00	0.0	0.39	1.2	0.44	1.3
A. vaginae andMega-1, High Neg	Atop gp	80	32.62	0.00	0.0	0.04	0.1	0.00	0.0	0.33	1.0	0.34	1.0
	Megal-BVAB2b	28	38.98	0.00	0.0	1.01	2.6	0.21	0.6	0.84	2.2	1.33	3.4
A. vaginae andMega-1, Low Pos	Atop gp	79	32.07	0.00	0.0	0.15	0.5	0.18	0.6	0.41	1.3	0.47	1.5
	Megal-BVAB2b	80	35.48	0.00	0.0	0.29	0.8	0.00	0.0	0.71	2.0	0.77	2.2

Table 5-12. Results of Precision for the BV Target

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Image /page/26/Picture/0 description: The image contains the logo for Cepheid, a molecular diagnostics company. The logo features a stylized blue graphic element resembling a wing or a series of curved lines above the company name, "Cepheid.", which is written in a serif font. Below the company name, the text "Xpert® Xpress MVP" is displayed, indicating a specific product or service offered by Cepheid.

Panel member	Analyte	Na	MeanCt	Day		Operator		Between-Run		Within-run		Total
				SD	CV(%)	SD	CV(%)	SD	CV(%)	SD	CV(%)	SD	CV(%)
A. vaginae, BVAB2,and Mega-1,High Neg	SPC	80	32.74	0.15	0.5	0.12	0.4	0.17	0.5	0.33	1.0	0.41	1.3
	Atop gp	80	32.53	0.00	0.0	0.15	0.5	0.00	0.0	0.22	0.7	0.27	0.8
	Mega1-BVAB2b	63	41.57	0.30	0.7	0.00	0.0	0.39	0.9	1.02	2.5	1.13	2.7
A. vaginae, BVAB2,and Mega-1,Low Pos	Atop gp	79	31.81	0.00	0.0	0.22	0.7	0.28	0.9	1.16	3.6	1.21	3.8
and Mega-1,Low Pos	Mega1-BVAB2b	80	36.25	0.15	0.4	0.00	0.0	0.10	0.3	0.69	1.9	0.71	2.0
A. vaginae, BVAB2,and Mega-1,Mod Pos	Atop gp	80	30.67	0.13	0.4	0.09	0.3	0.00	0.0	0.33	1.1	0.37	1.2
	Mega1-BVAB2b	80	35.64	0.00	0.0	0.26	0.7	0.00	0.0	0.48	1.3	0.54	1.5

Abbreviations: Atop gp, Atopobium group; CV, coefficient of variance; Megal , Mod; moderate; Neg, negative; Pos, positive; SD, standard deviation; SPC, sample processing control

a Number of samples with non-zero Ct values out of 80.

b Samples with Mega1-BVAB2 that did not generate a Ct value were excluded from analysis.

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Image /page/27/Picture/1 description: The image shows the Cepheid company logo and product name. The logo features a stylized blue wing-like design above the company name "Cepheid." Below the company name is the product name "Xpert® Xpress MVP," with the "®" symbol indicating a registered trademark.

5.5 Clinical Studies

The clinical evaluation of the Xpert Xpress MVP test was a multi-site, prospective observational, method comparison clinical study that included twelve (12) sites from geographically diverse locations in the United States. Of the 12 sites, 10 participated in specimen collection and Xpert testing, 1 performed reference/comparator testing and specimen collection, and 1 site participated in specimen collection only.

All sites prospectively collected one (1) self-collected in a clinical setting, SVS) and five (5) clinician-collected vaginal swab (CVS) specimens from symptomatic patients, defined as female patients > 14 years of age who presented with signs and/or symptoms of vaginitis/vaginosis (including abnormal vaginal discharge; dysuria; vulvar/vaginal itching, burning, irritation, pain or vulvar edema; coital pain; or vaginal odor). The SVS specimen was always collected first. The study population comprised of 1,478 female patients 14 to ≥ 50 years of age. A total of 2,947 vaginal swabs were tested and were eligible for inclusion in the Xpert Xpress MVP study.

Performance of the Xpert Xpress MVP test in vaginal swab specimens was determined relative to comparator methods. Specifically, positive percent agreement (PPA)/negative percent agreement (NPA) for BV was assessed relative to an FDA-cleared nucleic acid amplification test (NAAT). Sensitivity and specificity for Candida group and Candida glabkrus targets were assessed relative to veast culture followed by mass spectrometry for species identification. PPA and NPA for TV were assessed relative to a patient infected status (PIS) algorithm that included results from an FDA-cleared NAAT and TV culture. When applicable, investigation of discrepant results was performed by testing specimens with another FDA-cleared NAAT.

Performance of the Xpert Xpress MVP test is presented in Table 5-13. The Xpert Xpress MVP test demonstrated PPA and NPA of 93.8% and 93.8% for BV detection in CVS specimens, respectively, and 94.0% and 92.9% in SVS specimens, respectively. For Candida group detection, the Xpert Xpress MVP test demonstrated sensitivity and specificity of 98.0% and 94.6% in CVS specimens, respectively, and 97.5% and 92.1% in SVS specimens, respectively. The Xpert Xpress MVP test demonstrated sensitivity and specificity of 93.6% and 99.6% for Candida glab-krus detection in CVS specimens, respectively, and 97.8% and 99.4% in SVS specimens, respectively. For TV detection, the Xpert Xpress MVP test demonstrated PPA and NPA of 97.3% and 99.6% in CVS specimens, respectively, and 97.3% and 99.8% in SVS specimens, respectively.

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	Clinician-collected (CVS)		Self-collected (SVS)
	Sensitivity/PPA(95% CI)	Specificity/NPA(95% CI)	Sensitivity/PPA(95% CI)	Specificity/NPA(95% CI)
BV	93.8%531/566 a(91.5% - 95.5%)	93.8%808/861 b(92.0% - 95.3%)	94.0%533/567 c(91.7% - 95.7%)	92.9%794/855 d(90.9% - 94.4%)
Candida group*	98.0%396/404 e(96.1% - 99.0%)	94.6%984/1040 f(93.1% - 95.8%)	97.5%393/403 g(95.5% - 98.7%)	92.1%954/1036 h(90.3% - 93.6%)
Candida glab-krusFresh Prospective	93.6%44/47 i(82.8% - 97.8%)	99.6%1392/1397 j(99.2% - 99.9%)	97.8%45/46 k(88.7% - 99.6%)	99.4%1384/1393 l(98.8% - 99.7%)
Candida glab-krusContrived**	99.0%98/99(94.5% - 99.8%)	96.4%27/28(82.3% - 99.4%)	N/A	N/A
TV	97.3%73/75 m(90.8% - 99.3%)	99.6%1332/1337 n(99.1% - 99.8%)	97.3%72/74 o(90.7% - 99.3%)	99.8%1330/1333 p(99.3% - 99.9%)

Table 5-13: Overall Performance of the Xpert Xpress MVP Test

*Target includes C. albicans, C. tropicalis, C. parapsilosis, and C. dubliniensis

**Contrived specimens were prepared using individual negative clinical CVS and SVS specimens.

a Testing results with a second FDA-cleared NAAT: 14 were also negative and 21 were positive.

b Testing results with a second FDA-cleared NAAT: 25 were also positive and 28 were negative.

C Testing results with a second FDA-cleared NAAT: 12 were also negative and 22 were positive.

d Testing results with a second FDA-cleared NAAT: 23 were also positive and 38 were negative.

6 Testing results with an FDA-cleared NAAT: 5 were also negative and 3 were positive.

f Testing results with an FDA-cleared NAAT: 31 were also positive and 24 were negative and 1 had no result.

8 Testing results with an FDA-cleared NAAT: 5 were also negative and 5 were positive.

h Testing results with an FDA-cleared NAAT: 38 were also positive and 43 were negative and 1 had no result.

i Testing results with an FDA-cleared NAAT: 2 were also negative and 1 was positive.

i Testing results with an FDA-cleared NAAT: 5 were negative.

k Testing results with an FDA-cleared NAAT: 1 was also negative.

1 Testing results with an FDA-cleared NAAT: 9 were negative.

m Testing results a second FDA-cleared NAAT: 1 was also negative and 1 was positive.

n Testing results a second FDA-cleared NAAT: 4 were also positive and 1 had no result.

0 Testing results a second FDA-cleared NAAT: 1 was also negative and 1 was positive.

P Testing results a second FDA-cleared NAAT: 3 were also positive.

Asymptomatic Population

Although the Xpert Xpress MVP test is not intended for use in an asymptomatic patient population, positivity rates were calculated from CVS and SVS specimens collected from asymptomatic patients to assess how often patients who, despite being asymptomatic, harbored microbial flora associated with vaginosis and candidiasis that could be detected by the Xpert Xpress MVP test. Positivity rates are presented by target and by race/ethnicity in Table 5-14.

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Image /page/29/Picture/1 description: The image contains the logo for Cepheid. The logo consists of a blue graphic element resembling stylized wings or a swoosh above the word "Cepheid." in a serif font. Below the company name is the text "Xpert® Xpress MVP", with the "®" symbol indicating a registered trademark.

	Target	Overall	Black /AfricanAmerican^	Hispanic/Latino	Not Hispanic/Latino	Others*
CVS	BV	32.9%	51.0%	25.5%	19.5%	36.4%
		(52/158)	(26/51)	(14/55)	(8/41)	(4/11)
	Candida group	17.1%	25.5%	16.4%	7.3%	18.2%
		(27/158)	(13/51)	(9/55)	(3/41)	(2/11)
	Candida glab-krus	4.4%	2.0%	5.5%	4.9%	9.1%
		(7/158)	(1/51)	(3/55)	(2/41)	(1/11)
SVS	BV	31.5%	49.1%	24.1%	16.3%	41.7%
		(51/162)	(26/53)	(13/54)	(7/43)	(5/12)
	Candida group	19.1%	28.3%	18.5%	7.0%	25.0%
		(31/162)	(15/53)	(10/54)	(3/43)	(3/12)
	Candida glab-krus	4.9%	1.9%	7.4%	4.7%	8.3%
		(8/162)	(1/53)	(4/54)	(2/43)	(1/12)

Table 5-14: Positivity Rates in Asymptomatic Patients According to the Xpert Xpress MVP Test

*Including: American Indian or Alaska Native, Asian, Mixed/Unknown

^Includes one Black/African American who was of Hispanic or Latino descent for CVS specimens: includes two Black/African American who was of Hispanic or Latino descent for SVS specimens.

Non-Determinate Rate

Of the 2,947 Xpert Xpress MVP runs performed in the clinical study, 130 resulted in nondeterminate ("Error", "Invalid" or "No Results") results on first attempt. Upon retest of these 130 specimens, 22 remained non-determinate. The initial non-determinate rate was 4.4% (130/2947) and the overall non-determinate rate was 0.7% (22/2947).

The initial non-determinate rate for CVS specimens was 3.9% (58/1473) and the overall nondeterminate rate was 0.5% (8/1473). The initial non-determinate rate for SVS specimens was 4.9% (72/1474) and the overall non-determinate rate was 0.9% (14/1474).

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Image /page/30/Picture/0 description: The image shows the logo for Cepheid, a molecular diagnostics company. The logo features a stylized blue graphic above the company name, "Cepheid." Below the company name is the text "Xpert® Xpress MVP", which likely refers to one of their diagnostic products. The logo is simple and professional, conveying a sense of innovation and expertise in the field of molecular diagnostics.

5.6 Conclusions

The results of the non-clinical analytical and clinical performance studies summarized above demonstrated that the Xpert Xpress MVP test is substantially equivalent to the predicate device.

Regulation Number and Section

§ 866.3975 Device that detects nucleic acid sequences from microorganisms associated with vaginitis and bacterial vaginosis.

(a)
Identification. A device that detects nucleic acid sequences from microorganisms associated with vaginitis and bacterial vaginosis is a qualitative in vitro diagnostic device intended for the detection of microbial nucleic acid sequences in vaginal specimens collected from patients with signs and symptoms of vaginitis or bacterial vaginosis. This device is intended to aid in the diagnosis of vaginitis or bacterial vaginosis when used in conjunction with clinical signs and symptoms and other laboratory findings.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Design verification and validation must include:
(i) Documentation with a detailed device description of device components; ancillary reagents required but not provided; and explanation of the methodology including primer/probe sequence, design, and rationale for sequence selection.
(ii) Documentation with information that demonstrates the performance characteristics of the device, including:
(A) Limit of Detection;
(B) Precision (reproductivity);
(C) Analytical specificity;
(D) Analytical reactivity (inclusivity);
(E) Specimen stability; and
(F) Effects of interfering substances.
(iii) Detailed documentation from a prospective clinical study. As appropriate to the intended use, the prospective clinical study must be performed on an appropriate study population, including women of various ages and ethnicities. The prospective clinical study must compare the device performance to results obtained from well-accepted comparator methods.
(iv) Detailed documentation for device software, including software applications and hardware-based devices that incorporate software.
(2) The labeling required under § 809.10(b) of this chapter must include:
(i) A detailed explanation of the interpretation of results and acceptance criteria;
(ii) For devices with an intended use that includes detection of nucleic acid sequences from bacteria associated with bacterial vaginosis, clinical performance stratified by patient demographics such as race, ethnicity, age, and pregnancy status.
(iii) For devices with an intended use that includes detection of nucleic acid sequences from bacteria associated with bacterial vaginosis, a summary of device results in an asymptomatic population with demographic characteristics appropriate to the intended use population.
(iv) For devices with an intended use that includes detection of either Candida species or bacteria associated with bacterial vaginosis, a limitation that
Candida species and bacterial compositions associated with bacterial vaginosis can be present as part of normal vaginal flora and results should be considered in conjunction with available clinical information.