Xpert Xpress MVP, GeneXpert Dx System, GeneXpert Infinity System

K212213 · Cepheid · PQA · Feb 9, 2022 · Microbiology

Device Facts

• Record ID: K212213
• Device Name: Xpert Xpress MVP, GeneXpert Dx System, GeneXpert Infinity System
• Applicant: Cepheid
• Product Code: PQA · Microbiology
• Decision Date: Feb 9, 2022
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3975
• Device Class: Class 2

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) 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

Automated in vitro diagnostic test for qualitative detection of DNA targets from anaerobic bacteria associated with bacterial vaginosis, Candida species, and Trichomonas vaginalis. Input: vaginal swab specimens collected in Xpert Swab Specimen Collection Kit. Process: GeneXpert Instrument Systems automate sample preparation, nucleic acid extraction, real-time PCR amplification, and detection using fluorogenic hybridization probes. Output: qualitative results displayed in tabular/graphic formats within 60 minutes. Used in clinical settings by healthcare providers to aid diagnosis of vaginal infections. Results assist clinical decision-making for patients with symptoms of vaginitis/vaginosis, potentially benefiting patients through rapid, accurate identification of causative pathogens.

Clinical Evidence

Prospective blinded clinical study at 12 U.S. sites with 1,476 symptomatic female patients. Compared Xpert Xpress MVP to FDA-cleared NAATs and culture/mass spectrometry. CVS and SVS specimens tested. BV sensitivity 93.8%/94.0%, specificity 93.8%/92.9%. Candida group sensitivity 98.0%/97.5%, specificity 94.6%/92.1%. Candida glab-krus sensitivity 93.6%/97.8%, specificity 99.6%/99.3%. TV sensitivity 97.3%/97.3%, specificity 99.6%/99.8%. Contrived specimens used for lower prevalence analytes.

Technological Characteristics

Real-time PCR assay using fluorogenic target-specific hybridization probes. Automated extraction, amplification, and detection on GeneXpert Instrument Systems. Single-use disposable cartridges with integrated Sample Processing Control (SPC) and Probe Check Control (PCC). Connectivity: GeneXpert system with computer and preloaded software.

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- 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

• BD MAX Vaginal Panel (K191957)

Submission Summary (Full Text)

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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 ([e-mail]) or phone [phone] 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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Image /page/3/Picture/1 description: The image shows the logo for Cepheid. The logo consists of a blue graphic element resembling stylized wings or feathers above the word "Cepheid" in a simple, sans-serif font. Below the company name, the text "Xpert® Xpress MVP" is displayed, with the "®" symbol indicating a registered trademark.

# Section 5

# 510(k) Summary for Xpert Xpress MVP

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Image /page/4/Picture/0 description: The image shows the Cepheid logo and the text "Xpert® Xpress MVP" below it. The Cepheid logo consists of a stylized blue wing-like shape above the company name, which is written in a clean, sans-serif font. The "Xpert® Xpress MVP" text is written in a smaller, bolder font, with the "®" symbol indicating a registered trademark.

# Table of Contents

| 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<br> | |
| | |

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Image /page/5/Picture/0 description: The image shows the logo for Cepheid, a molecular diagnostics company. Below the company name is the text "Xpert® Xpress MVP". The Cepheid logo features a stylized graphic of blue curved lines above the company name.

# 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: | February 8, 2022 |
| Device: | |
| Trade name: | Xpert® Xpress MVP |
| Common name: | Xpert Xpress MVP |
| Type of Test: | Qualitative real-time polymerase chain reaction (PCR) and<br>detection test |
| Regulation number,<br>Classification name, | 21 CFR 866.3975, Vaginitis and Bacterial Vaginosis Nucleic<br>Acid Detection System, PQA |
| Product code<br>Definition | 21 CFR 866.3860, Trichomonas vaginalis Nucleic Acid<br>Amplification Test System, OUY<br>21 CFR 862.2570, Real Time Nucleic Acid Amplification<br>System, OOI |
| Classification<br>Advisory Panel | Microbiology (83) |
| Prescription Use | Yes |
| Predicate Device | BD MAX Vaginal Panel (K191957) |

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Image /page/6/Picture/1 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" in a smaller font. The logo is simple and modern, with a focus on the company name and product.

# 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, 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.

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Image /page/7/Picture/0 description: The image shows the text "Traditional 510(k) Submission" in a simple, sans-serif font. The text is horizontally oriented and appears to be the title or heading of a document. The words are stacked on a single line, with "Traditional" being the first word, followed by "510(k)", and then "Submission".

Image /page/7/Picture/1 description: The image shows the logo for Cepheid, a molecular diagnostics company. Below the company name is the text "Xpert® Xpress MVP". The Cepheid logo features a stylized blue wing-like shape above the company name.

# 5.2 Device 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)
- 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.

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Image /page/8/Picture/1 description: The image contains the Cepheid company logo. The logo consists of a blue graphic element resembling stylized wings or a swoosh above the company name "Cepheid." Below the company name, the text "Xpert® Xpress MVP" is displayed, indicating a specific product or service offered by Cepheid.

# 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 Device<br>Xpert® Xpress MVP | Predicate Device<br>BD MAX Vaginal Panel (K191957) |
| Regulation | Same | 21CFR 866.3975<br>Device that detects nucleic acid sequences from microorganisms associated with vaginitis and bacterial vaginosis |
| Product Code | Same | PQA<br>Vaginitis 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 <i>in vitro</i> diagnostic test for the detection of DNA targets from anaerobic bacteria associated with bacterial vaginosis (BV), <i>Candida</i> species associated with vulvovaginal candidiasis, and <i>Trichomonas vaginalis</i> . 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:<br>Organisms associated with bacterial vaginosis (detected organisms not reported individually) Atopobium spp. ( <i>Atopobium vaginae, Atopobium</i> 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 <i>in vitro</i> 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), <i>Candida</i> species associated with vulvovaginal candidiasis, and <i>Trichomonas vaginalis</i> 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:<br>Bacterial vaginosis markers (Individual markers not reported) <i>Lactobacillus</i> spp. ( <i>L. crispatus</i> and <i>L. jensenii</i> ) <i>Gardnerella vaginalis Atopobium vaginae</i> |
| Comparison | | |
| Attribute | New Device<br>Xpert® Xpress MVP | Predicate Device<br>BD MAX Vaginal Panel (K191957) |
| | ○ Megasphaera-1<br>• Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis, species not differentiated)<br>• Candida glabrata/Candida krusei (species not differentiated)<br>• Trichomonas vaginalis<br>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. | ○ Bacterial Vaginosis Associated Bacteria-2 (BVAB-2)<br>○ Megasphaera-1<br>• Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis)<br>• Candida glabrata<br>• Candida krusei<br>• Trichomonas vaginalis<br>The 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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Image /page/9/Picture/0 description: The image contains the Cepheid logo, which features a stylized blue wing-like design above the company name. Below the company name, the text "Xpert® Xpress MVP" is displayed. The "Xpert" has a registered trademark symbol next to it.

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

| | | | Table 5-2: Differences between New Device and Predicate Device |
|--|--|--|----------------------------------------------------------------|
|--|--|--|----------------------------------------------------------------|

| 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. ( <i>Atopobium vaginae</i> , <i>Atopobium</i> novel species CCUG 55226) Bacterial Vaginosis-Associated Bacterium 2 (BVAB2) | Bacterial vaginosis markers (Individual markers not reported) <i>Lactobacillus</i> spp. ( <i>L. crispatus</i> and <i>L. jensenii</i> ) <i>Gardnerella vaginalis Atopobium vaginae</i> Bacterial Vaginosis Associated Bacteria-2 (BVAB-2) |

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Image /page/10/Picture/0 description: The image shows the Cepheid logo and product name. The logo features a stylized blue wing-like design above the word "Cepheid." Below the logo, the text "Xpert® Xpress MVP" is displayed, indicating the name of the product. The text is in a simple, sans-serif font.

| Comparison | | |
|--------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------|
| Attribute | New Device<br>Xpert® Xpress MVP | Predicate Device<br>BD 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 test<br>Within 60 minutes | Batch test<br>~ 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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Image /page/11/Picture/0 description: The image shows 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" in a smaller font size.

# 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-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 5-3: 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 | Candida<br>group | Candida<br>glab-krus | TV |
| | Negative Control | | Negative | Not Detected | Not Detected | Not Detected |
| Atopobium spp.<br>LoD<br>(Below the near<br>cut-off<br>concentrations and<br>not generating BV<br>POSITIVE 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 of<br>BVAB2 | 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 of<br>Megasphaera-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 of<br>Megasphaera-1<br>and 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 |
| Candida<br>dubliniensis | 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 |
| Candida<br>parapsilosis | 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 |
|…