Xpert Xpress MVP; GeneXpert Xpress System

K231381 · Cepheid · PQA · Oct 19, 2023 · Microbiology

Device Facts

• Record ID: K231381
• Device Name: Xpert Xpress MVP; GeneXpert Xpress System
• Applicant: Cepheid
• Product Code: PQA · Microbiology
• Decision Date: Oct 19, 2023
• Decision: SESE
• Submission Type: Dual Track
• Regulation: 21 CFR 866.3975
• Device Class: Class 2
• Attributes: Pediatric

Intended Use

The Xpert® Xpress MVP test, performed on the GeneXpert® Xpress System, 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) Megasphaera-1 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 Story

The Xpert Xpress MVP test is a qualitative, real-time PCR-based assay for the detection of vaginal pathogens. Input consists of clinician-collected or self-collected vaginal swabs in transport reagent. The operator transfers a liquid aliquot to a single-use disposable GeneXpert cartridge; the cartridge is loaded into the GeneXpert Xpress System. The system performs automated sample preparation (cell lysis, DNA extraction), nucleic acid amplification, and real-time fluorescent signal detection. The GeneXpert Hub (integrated computer/touchscreen) runs the software, which interprets fluorescent signals via embedded algorithms to report qualitative results for BV, Candida groups, and T. vaginalis within 60 minutes. The device is intended for use in CLIA-waived environments by untrained operators. Results aid clinicians in diagnosing bacterial vaginosis, vulvovaginal candidiasis, or trichomoniasis, facilitating targeted patient management.

Clinical Evidence

Prospective, blinded clinical study of 1,277 symptomatic subjects (≥14 years). Performance compared to reference methods (NAAT for BV, yeast culture/MALDI-TOF for Candida, PIS algorithm for TV). Sensitivity/Specificity: BV (92.9%/94.5% CVS; 93.5%/93.6% SVS), Candida group (98.1%/94.9% CVS; 97.8%/92.9% SVS), Candida glab-krus (94.1%/99.8% CVS; 100%/99.7% SVS), TV (98.0%/99.6% CVS; 97.9%/99.7% SVS). Reproducibility study at three CLIA-waived sites showed acceptable agreement across operators and sites.

Technological Characteristics

Real-time PCR-based nucleic acid amplification test. Uses single-use disposable GeneXpert cartridges with integrated sample processing, amplification, and detection. Includes internal Sample Processing Control (SPC) and Probe Check Control (PCC). Operates on the GeneXpert Xpress System (GeneXpert IV instrument + GeneXpert Hub).

Indications for Use

Indicated for symptomatic women (≥14 years) presenting with signs/symptoms of vaginitis/vaginosis. Detects DNA from BV-associated organisms (Atopobium spp., BVAB2, Megasphaera-1), Candida species (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis, C. glabrata, C. krusei), and Trichomonas vaginalis using clinician-collected or self-collected vaginal swabs.

Regulatory Classification

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.

Special Controls

*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.

Predicate Devices

• Xpert Xpress MVP, GeneXpert Dx System, GeneXpert Infinity System (K221160)

Submission Summary (Full Text)

{0}------------------------------------------------

Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: a symbol on the left and the text "FDA U.S. FOOD & DRUG ADMINISTRATION" on the right. The symbol on the left is a stylized image of a human figure, and the text on the right is in blue and white.

October 19, 2023

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

Re: K231381

Trade/Device Name: Xpert Xpress MVP; GeneXpert Xpress 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, OUY, OOI Dated: May 11, 2023 Received: May 12, 2023

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 (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 available 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.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device"

{1}------------------------------------------------

(https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30. Design controls; 21 CFR 820.90. Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review. the OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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 ([e-mail]) or phone [phone] or 301-796-7100).

> Sincerely. Noel J. Gerald -S

Noel J. Gerald, Ph.D. Branch Chief Bacterial Respiratory and Medical Countermeasures Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

{2}------------------------------------------------

# Indications for Use

510(k) Number (if known) K231381

Device Name Xpert Xpress MVP

#### Indications for Use (Describe)

The Xpert® Xpress MVP test, performed on the GeneXpert® Xpress System, 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) O
- 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.

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

| <div> <span> <span style="font-size:100%;"> <span style="font-family:Arial;">☑ Prescription Use (Part 21 CFR 801 Subpart D)</span> </span> </span> </div> |
|-----------------------------------------------------------------------------------------------------------------------------------------------------------|
| <div> <span> <span style="font-size:100%;"> <span style="font-family:Arial;">☐ Over-The-Counter Use (21 CFR 801 Subpart C)</span> </span> </span> </div> |

#### CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

#### *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.*

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

> Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{3}------------------------------------------------

Image /page/3/Picture/0 description: The image contains the Cepheid company logo, which features a stylized blue wing-like design above the company name. Below the company name, the text "Xpert® Xpress MVP" is displayed, indicating a specific product or service offered by Cepheid. The text is in a simple, sans-serif font and is left-aligned.

# Section 5

# 510(k) Summary for Xpert Xpress MVP

{4}------------------------------------------------

Image /page/4/Picture/0 description: The image contains the Cepheid logo, which includes a stylized blue wing-like design above the company name. Below the company name, the text "Xpert® Xpress MVP" is displayed. The text is in a smaller font size than the company name, and the "Xpert" has a registered trademark symbol.

# Table of Contents

| <b>5.0 510(k) Summary</b> | 3 |
|------------------------------------|----|
| <b>5.1 Device Description</b> | 3 |
| <b>5.2 Device Intended Use</b> | 4 |
| <b>5.3 Substantial Equivalence</b> | 4 |
| <b>5.4 Non-Clinical Study</b> | 7 |
| <b>5.5 Clinical Study</b> | 22 |
| <b>5.6 Conclusions</b> | 25 |

{5}------------------------------------------------

Image /page/5/Picture/1 description: The image contains the Cepheid company logo, which features a stylized blue wing-like design above the company name in a serif font. Below the company name, the text "Xpert® Xpress MVP" is displayed, also in a serif font. The "Xpert" is followed by the registered trademark symbol.

#### 5.0 510(k) Summary

| As required by 21 CFR Section 807.92(c). | |
|---------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Submitted by: | Cepheid<br>904 Caribbean Drive<br>Sunnyvale, CA 90489<br>Phone number: [phone]<br>Fax number: [phone] |
| Contact: | Wei Zhang, PhD RAC |
| Date of Preparation: | October 3, 2023 |
| Device: | |
| Trade name: | Xpert® Xpress MVP |
| Common name: | Xpert Xpress MVP |
| Type of Test: | Qualitative real-time polymerase chain reaction<br>(PCR) and detection test |
| Regulation Number,<br>Classification Name,<br>Product Code<br>Definition: | 21 CFR 866.3975, Vaginitis and Bacterial Vaginosis<br>Nucleic Acid Detection System, PQA<br>21 CFR 866.3860, Trichomonas vaginalis Nucleic<br>Acid Amplification Test System, OUY<br>21 CFR 862.2570, Real Time Nucleic Acid<br>Amplification System, OOI |
| Classification<br>Advisory Panel: | Microbiology (83) |
| Prescription Use: | Yes |
| Predicate Device: | Xpert Xpress MVP (K221160) |

#### 5.1 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 (BV), Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis, the agent of trichomoniasis. In the CLIA-waived environment, the Xpert Xpress MVP test is performed on the GeneXpert® Xpress System.

The latest Hub configuration of the GeneXpert Xpress System consists of a GeneXpert IV instrument that executes sample preparation, nucleic acid amplification and real-time fluorescent signal detection for the tests, and a GeneXpert Hub with preloaded GeneXpert Xpress software for running the tests and viewing the test results. The GeneXpert Hub accessory integrates the computer, touchscreen monitor and barcode scanner. Each of the GeneXpert modules in the GeneXpert IV instrument can perform independent sample preparation and testing.

The Xpert Xpress MVP test is a PCR-based Nucleic Acid Amplification Test. Each test requires the use of a single-use disposable GeneXpert cartridge that contains all necessary reagents for the detection of DNA from BV organisms, Candida species, and Trichomonas vaginalis. A

{6}------------------------------------------------

Image /page/6/Picture/0 description: The image contains the Cepheid company logo, which features a stylized blue wing-like design above the company name in a simple, sans-serif font. Below the company name, the text "Xpert® Xpress MVP" is displayed, indicating a specific product or service offered by Cepheid. The text is in a smaller font size compared to the company name, with the "®" symbol indicating a registered trademark.

Sample Processing Control (SPC) and a Probe Check Control (PCC) are also included in the cartridge serving as internal controls. The SPC is present to control for adequate sample processing, to monitor PCR conditions, the presence of potential inhibitor(s) and possible reagent degradation. 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. Because the cartridges are self-contained, the risk of cross- contamination between samples is minimized.

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 ancillary specimen collection kit for use with the Xpert Xpress MVP test is the Xpert Swab Specimen Collection Kit. The swab and the transport reagent included in the Xpert Swab Specimen Collection Kit are designed to collect and preserve patient specimens to allow transport to the testing site prior to analysis with the Xpert Xpress MVP test.

## 5.2 Device Intended Use

The Xpert® Xpress MVP test, performed on the GeneXpert® Xpress System, 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.

#### 5.3 Substantial Equivalence

The Xpert Xpress MVP test for use with the GeneXpert Xpress System is substantially equivalent to the same Xpert Xpress MVP test for use with the GeneXpert Instrument Systems [510(k) K221160]. The following tables compare the subject device to the previously cleared predicate device.

{7}------------------------------------------------

Table 5-1 shows similarities between the subject device and the predicate device.

| Comparison | | |
|-----------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | Subject Device | Predicate Device |
| Attribute | Xpert® Xpress MVP, Performed on the<br>GeneXpert Xpress System | Xpert® Xpress MVP, Performed on the<br>GeneXpert Instrument Systems [K221160] |
| Regulation | Same | 21CFR 866.3975<br>Device that detects nucleic acid sequences from<br>microorganisms associated with vaginitis and<br>bacterial vaginosis |
| Product Code | Same | PQA<br>Vaginitis and bacterial vaginosis nucleic acid<br>detection system |
| Device Class | Same | II |
| Intended Use | The Xpert® Xpress MVP test, performed on the<br>GeneXpert® Xpress System, is an automated<br>qualitative <i>in vitro</i> diagnostic test for the<br>detection of DNA targets from anaerobic bacteria<br>associated with bacterial vaginosis (BV),<br><i>Candida</i> species associated with vulvovaginal<br>candidiasis, and <i>Trichomonas vaginalis</i> . The<br>Xpert Xpress MVP test uses clinician-collected<br>and self-collected vaginal swabs (collected in a<br>clinical setting) from patients who are<br>symptomatic for vaginitis/vaginosis. The Xpert<br>Xpress MVP test utilizes real-time polymerase<br>chain reaction (PCR) for the amplification of<br>specific DNA targets and utilizes fluorogenic<br>target-specific hybridization probes to detect and<br>differentiate DNA from:<br>Organisms associated with bacterial vaginosis<br>(detected organisms not reported individually) <i>Atopobium</i> spp. ( <i>Atopobium vaginae,</i><br><i>Atopobium</i> novel species CCUG 55226) Bacterial Vaginosis-Associated Bacterium<br>2 (BVAB2) <i>Megasphaera</i> -1 <i>Candida</i> spp. ( <i>C. albicans, C. tropicalis, C.<br/>parapsilosis, C. dubliniensis</i> , species not<br>differentiated) <i>Candida glabrata/Candida krusei</i> (species not<br>differentiated) <i>Trichomonas vaginalis</i> The Xpert Xpress MVP test is intended to aid in<br>the diagnosis of vaginal infections in women with<br>a clinical presentation consistent with bacterial | The Xpert® Xpress MVP test, performed on the<br>GeneXpert® Instrument Systems, is an automated<br>qualitative <i>in vitro</i> diagnostic test for the<br>detection of DNA targets from anaerobic bacteria<br>associated with bacterial vaginosis (BV),<br><i>Candida</i> species associated with vulvovaginal<br>candidiasis, and <i>Trichomonas vaginalis</i> . The<br>Xpert Xpress MVP test uses clinician-collected<br>and self-collected vaginal swabs (collected in a<br>clinical setting) from patients who are<br>symptomatic for vaginitis/vaginosis. The Xpert<br>Xpress MVP test utilizes real-time polymerase<br>chain reaction (PCR) for the amplification of<br>specific DNA targets and utilizes fluorogenic<br>target-specific hybridization probes to detect and<br>differentiate DNA from:<br>Organisms associated with bacterial vaginosis<br>(detected organisms not reported individually) <i>Atopobium</i> spp. ( <i>Atopobium vaginae,</i><br><i>Atopobium</i> novel species CCUG 55226) Bacterial Vaginosis-Associated Bacterium<br>2 (BVAB2) <i>Megasphaera</i> -1 <i>Candida</i> spp. ( <i>C. albicans, C. tropicalis, C.<br/>parapsilosis, C. dubliniensis</i> , species not<br>differentiated) <i>Candida glabrata/Candida krusei</i> (species not<br>differentiated) <i>Trichomonas vaginalis</i> The Xpert Xpress MVP test is intended to aid in<br>the diagnosis of vaginal infections in women with<br>a clinical presentation consistent with bacterial |
| Comparison | | |
| Attribute | Subject Device<br>Xpert® Xpress MVP, Performed on the<br>GeneXpert Xpress System | Predicate Device<br>Xpert® Xpress MVP, Performed on the<br>GeneXpert Instrument Systems [K221160] |
| Specimen Type | Same | Clinician- and patient-collected vaginal swabs |
| Organisms Detected | Same | Organisms associated with bacterial vaginosis (detected organisms not reported individually) <i>Atopobium</i> spp. ( <i>Atopobium vaginae</i> ,<br><i>Atopobium</i> novel species CCUG 55226) Bacterial Vaginosis-Associated<br>Bacterium 2 (BVAB2) <i>Megasphaera</i> -1 <i>Candida</i> spp. ( <i>C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis</i> , species not differentiated) <i>Candida glabrata/Candida krusei</i> (species not differentiated) <i>Trichomonas vaginalis</i> |
| Assay Technology | Same | Real-Time PCR |
| Single Use | Same | Yes |
| Automated Extraction, Detection and Result Interpretation | Same | Yes |
| Assay Results | Same | Qualitative |
| Collection Device | Same | Cepheid Xpert Swab Specimen Collection Kit |
| Time to Result | Same | Within 60 minutes |

# Table 5-1: Similarities between Subject Device and Predicate Device

{8}------------------------------------------------

Image /page/8/Picture/0 description: The image shows the Cepheid logo with the text "Xpert® Xpress MVP" below it. The Cepheid logo consists of a stylized blue graphic above the word "Cepheid." The graphic appears to be a series of curved lines or strokes, resembling a stylized wing or a burst of energy. The text "Xpert® Xpress MVP" is written in a simple, sans-serif font.

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

#### Table 5-2: Differences between Subject Device and Predicate Device

| Comparison | | |
|-----------------|----------------------------------------------------------------|-------------------------------------------------------------------------------|
| Attribute | Subject Device | Predicate Device |
| | Xpert® Xpress MVP, Performed on the<br>GeneXpert Xpress System | Xpert® Xpress MVP, Performed on the<br>GeneXpert Instrument Systems [K221160] |
| Instrumentation | Cepheid GeneXpert Xpress System | Cepheid GeneXpert Instrument Systems |

The Xpert Xpress MVP test, performed on the GeneXpert Xpress System, has the same general intended use and the same technological characteristics as the predicate device. The differences between the subject device and the predicate device do not raise different questions of safety and effectiveness. The clinical study demonstrates that performance of the subject device is acceptable for its intended use and is substantially equivalent to the predicate device described above.

{9}------------------------------------------------

Image /page/9/Picture/0 description: The image shows the Cepheid company logo, which includes a stylized blue wing-like design above the company name in a serif font. Below the company name, the text "Xpert® Xpress MVP" is displayed, indicating a specific product or service offered by Cepheid. The registered trademark symbol is present after the word "Xpert".

The information provided in this submission including the clinical performance and comparison of the test results to comparators in this premarket notification is complete and supports a substantial equivalence decision for the Xpert Xpress MVP test.

#### 5.4 Non-Clinical Study

Analytical study data were generated using the GeneXpert Instrument Systems (GeneXpert Dx running GeneXpert Dx software version 4.7b or higher or GeneXpert Infinity-80 running Xpertise software version 6.4b or higher). The data were re-analyzed with GeneXpert Xpress software version 6.4a and demonstrated acceptable results.

## 5.4.1 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 and Table 5-4 below.

| 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 |

| | | Table 5-3: Verified LoD and Near Cut-off concentrations for Xpert Xpress MVP | | |
|--|--|------------------------------------------------------------------------------|--|--|
| | | | | |

{10}------------------------------------------------

| BV Organism | Verified Near Cut-off<br>Concentration |
|----------------------------------------------------------------------|----------------------------------------|
| Atopobium vaginae<br>(in the absence of Megasphaera-1 and BVAB2) | 320,000 CFU/mL |
| Atopobium vaginae<br>(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 5-4: Verified LoD and Near Cut-off concentrations for Xpert Xpress MVP

# 5.4.2 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…