Xpert Xpress MVP, GeneXpert Dx System, GeneXpert Infinity System

K221160 · Cepheid · PQA · Jun 7, 2022 · Microbiology

Device Facts

• Record ID: K221160
• Device Name: Xpert Xpress MVP, GeneXpert Dx System, GeneXpert Infinity System
• Applicant: Cepheid
• Product Code: PQA · Microbiology
• Decision Date: Jun 7, 2022
• Decision: SESE
• Submission Type: Special
• 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) o Atopobium spp. (Atopobium vaginae, Atopobium novel species CCUG 55226) Bacterial Vaginosis-Associated Bacterium 2 (BVAB2) O o 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

Xpert Xpress MVP is a multiplex nucleic acid amplification test for microorganisms associated with vaginitis and bacterial vaginosis. Operates on GeneXpert Dx and GeneXpert Infinity systems. Input: clinical samples; processing: automated nucleic acid extraction, amplification, and real-time detection via cartridge-based reagents; output: qualitative detection of target microorganisms. Used in clinical laboratory settings by trained personnel. Results assist clinicians in diagnosing vaginitis/bacterial vaginosis. Modification (K221160) involves cartridge reagent changes to extend shelf life and updated Assay Definition File commands.

Clinical Evidence

No clinical data provided. Substantial equivalence supported by design control activities, risk analysis, and verification/validation of reagent and software modifications.

Technological Characteristics

Real-time PCR assay; automated nucleic acid extraction/amplification. Disposable, single-use, multi-chambered fluidic cartridge. GeneXpert Instrument System (instrument, computer, preloaded software). Qualitative detection of DNA targets. Assay includes Sample Processing Control (SPC) and Probe Check Control (PCC).

Indications for Use

Indicated for symptomatic women (≥14 years) presenting with signs/symptoms of vaginitis/vaginosis (e.g., abnormal discharge, dysuria, itching, burning, irritation, pain, edema, or odor) to aid in the diagnosis of bacterial vaginosis, vulvovaginal candidiasis, or trichomoniasis 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 (K212536)

Submission Summary (Full Text)

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA) along with the Department of Health & Human Services. The FDA logo features a blue square with the letters "FDA" in white, followed by the words "U.S. FOOD & DRUG" in blue, and "ADMINISTRATION" in a smaller font size below. To the left of the FDA logo is the symbol of the Department of Health & Human Services, which consists of a stylized human figure.

June 7, 2022

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

Re: K221160

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, OOI Dated: April 20, 2022 Received: April 21, 2022

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 statutes and regulations administered by other Federal agencies. You must comply with all the Act's

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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 (OS) 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,

Noel J. Gerald, Ph.D. Chief 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 contains 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 or platforms. The registered trademark symbol is present after the word "Xpert".

# Section 5

# 510(k) Summary for Xpert Xpress MVP

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# 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 |
| |

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Image /page/5/Picture/0 description: The image shows the Cepheid logo, which includes a stylized blue wing-like design above the word "Cepheid." Below the logo, the text "Xpert® Xpress MVP" is displayed. The word "Xpert" has a registered trademark symbol next to it. The text is black and centered.

### 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: | April 20, 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 862.2570, Real Time Nucleic Acid Amplification<br>System, OOI |
| Classification<br>Advisory Panel | Microbiology (83) |
| Prescription Use | Yes |
| Predicate Device: | Xpert Xpress MVP (K212213) |

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Image /page/6/Picture/0 description: The image contains the Cepheid company logo, which features a stylized blue graphic resembling three curved lines above the company name. Below the logo, 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, and the "®" symbol denotes a registered trademark.

#### 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 vulyovaginal 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/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, indicating a specific product or service offered by Cepheid. The text is in a smaller, sans-serif font, with the "®" symbol indicating a registered trademark.

### 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
- o 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.

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Image /page/8/Picture/1 description: The image contains 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 Cepheid's diagnostic products or platforms.

#### 5.3 Substantial Equivalence

The new design of the Xpert Xpress MVP test is substantially equivalent to the original design of the Xpert Xpress MVP (K212213, the predicate device).

The following tables compare the new design of the Xpert Xpress MVP test to the original design of the Xpert Xpress MVP test (K212213). Table 5-1 shows similarities between the new design and the original design (K212213).

| Comparison | | |
|--------------------------------|----------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Attribute | New Device | Predicate Device |
| | Xpert Xpress MVP (New Design) | Xpert Xpress MVP (K212213) |
| Regulation | Same | 21CFR 866.3975<br>Device that detects nucleic acid sequences<br>from microorganisms associated with<br>vaginitis and bacterial vaginosis |
| Product Code | Same | PQA<br>Vaginitis and bacterial vaginosis nucleic acid<br>detection system |
| Device Class | Same | II |
| Intended Use | Same | The Xpert® Xpress MVP test, performed on<br>the GeneXpert® Instrument Systems, is an<br>automated qualitative <i>in vitro</i> diagnostic test<br>for the detection of DNA targets from<br>anaerobic bacteria associated with bacterial<br>vaginosis (BV), <i>Candida</i> species associated<br>with vulvovaginal candidiasis, and<br><i>Trichomonas vaginalis</i> . The Xpert Xpress<br>MVP test uses clinician-collected and self-<br>collected vaginal swabs (collected in a<br>clinical setting) from patients who are<br>symptomatic for vaginitis/ vaginosis. The<br>Xpert Xpress MVP test utilizes real-time<br>polymerase chain reaction (PCR) for the<br>amplification of specific DNA targets and<br>utilizes fluorogenic target-specific<br>hybridization probes to detect and<br>differentiate DNA from:<br>Organisms associated with bacterial<br>vaginosis (detected organisms not<br>reported individually) <i>Atopobium</i> spp. ( <i>Atopobium</i><br><i>vaginae</i> , <i>Atopobium</i> novel species<br>CCUG 55226)Bacterial Vaginosis-Associated<br>Bacterium 2 (BVAB2)Megasphaera-1 <i>Candida</i> spp. ( <i>C. albicans</i> , <i>C.</i><br><i>tropicalis</i> , <i>C. parapsilosis</i> , <i>C.</i> |
| | Comparison | |
| Attribute | New Device | Predicate Device |
| | Xpert Xpress MVP (New Design) | Xpert Xpress MVP (K212213) |
| | | • Candida glabrata/Candida krusei (species not differentiated)<br>• 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. |
| Laboratory Users | Same | CLIA Moderate Complexity |
| Specimen Type | Same | Clinician-collected and self-collected vaginal swabs (collected in a clinical setting) |
| Assay Technology | Same | Real-Time PCR |
| Organisms Detected | Same | • Organisms associated with bacterial vaginosis (detected organisms not reported individually)<br>• Atopobium spp. (Atopobium vaginae, Atopobium novel species CCUG 55226)<br>• Bacterial Vaginosis-Associated Bacterium 2 (BVAB2)<br>• 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 |
| Test Cartridge Technology | Same | Disposable single-use, multi-chambered fluidic cartridge |
| Sample Preparation | Same | Self-contained and automated after mixed specimen is added to cartridge. All other reagents are contained in the cartridge. |
| Assay Type | Same | Qualitative |
| Instrument Systems | Same | Cepheid GeneXpert Instrument Systems |
| Collection Device | Same | Cepheid Xpert Swab Specimen Collection kit |
| Time to Result | Same | Within 60 minutes |
| Comparison | | |
| Attribute | New Device | Predicate Device |
| | Xpert Xpress MVP (New Design) | Xpert Xpress MVP (K212213) |
| Reagents in<br>Cartridge | Cartridge Version 2<br>(Minor modifications to the reagents in the<br>self-contained, single-use disposable<br>cartridges) | Cartridge Version 1 |
| Assay Definition<br>File (ADF) | ADF Version 2<br>(Minor command modifications to<br>accommodate reagent changes) | ADF Version 1 |

#### 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 company logo. The logo consists of a blue graphic element resembling stylized wings or feathers, followed by the company name "Cepheid" in a clean, sans-serif font. Below the company name is the text "Xpert® Xpress MVP", with the "®" symbol indicating a registered trademark.

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Image /page/10/Picture/1 description: The image contains 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 Cepheid's diagnostic products.

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

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

The new design of the Xpert Xpress MVP test has the same intended use and the same technological characteristics as the original design (K212213, the predicate device). The differences between the new design of the Xpert Xpress MVP test and the original design include minor cartridge and ADF modifications, which do not raise different questions of safety and effectiveness. The risk analysis and equivalency study demonstrate that performance of the new design of Xpert Xpress MVP is acceptable for its intended use and is substantially equivalent to the original design of Xpert Xpress MVP (K212213) described above.

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Image /page/11/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.

#### 5.4 Non-Clinical Study Analytical Sensitivity

Refer to the previously FDA-cleared 510(k) Premarket Notification, K212213 for Analytical Sensitivity of the Xpert Xpress MVP test.

#### Analytical Sensitivity Equivalency Study

To determine if the analytical sensitivity of the new design was equivalent to that of the original design, an equivalency study was conducted comparing the limit of detection (LoD) and the near cut-off concentration of the original design (K212213) and the new design of the Xpert Xpress MVP 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 concentration for the BV targets 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.

For BV organisms, testing at LoD and near cut-off concentrations was performed in simulated vaginal swab matrix (SVM) only. For Candida group, Candida glab-krus and TV targets, testing was conducted with samples diluted in both SVM and pooled negative natural clinical vaginal swab matrix (VS) independently.

The analytical sensitivity of the two designs were deemed equivalent when both the original design (K212213) and the new design reported 19/20 or 20/20 POSITIVE/DETECTED results when tested at LoD/Near Cut-off concentration for each testing condition/target organism, and statistical analysis comparing the difference of mean Ct values of the original design (K212213) and the new design using a two-sample t-test with a marginal difference of 1.0 Ct value and the assumption of equal variances demonstrated that the results were not statistically different (p-value of > 0.05).

Results from the equivalency study at LoD concentrations are shown in Table 5-3. The number of positive results obtained out of the total number of replicates tested for each target at the LoD concentrations, the difference in the mean Cts between the two designs, and the ttest statistical analysis of the mean Ct values are presented.

| Table 5-3: Mean Ct Values and Differences Between the Two Designs of Xpert Xpress | | |
|-----------------------------------------------------------------------------------|--|--|
| MVP Test at LoD Concentrations | | |

| Organism | Concentration<br>Tested (1× LoD) | Matrix | Design | Replicates reported<br>positive results/<br>Total Replicates | Difference in<br>Mean Cts of<br>Two Designs | t-test<br><i>p</i> -value |
|------------------------------|----------------------------------|--------|---------------------------|--------------------------------------------------------------|---------------------------------------------|---------------------------|
| <i>Atopobium<br/>vaginae</i> | 32 CFU/mL | SVM | Original design (K212213) | 20/20 | 0.1 | >0.999 |
| | | | New design | 20/20 | | |
| <i>Megasphaera-1</i> | 338 copies/mL | SVM | Original design (K212213) | 19/20 | 0.1 | 0.999 |
| | | | New design | 19/20 | | |
| <i>BVAB2</i> | 50 copies/mL | SVM | Original design (K212213) | 19/20 | 0.6 | 0.916 |
| | | | New design | 19/20 | | |

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Image /page/12/Picture/0 description: The image shows the Cepheid logo. The logo consists of a blue graphic element resembling stylized wings or a swoosh above the word "Cepheid." Below "Cepheid" is the text "Xpert® Xpress MVP".

| Organism | Concentration<br>Tested (1× LoD) | Matrix | Design | Replicates reported<br>positive results/<br>Total Replicates | Difference in<br>Mean Cts of<br>Two Designs | t-test<br>p-value |
|--------------------------|----------------------------------|--------|---------------------------|--------------------------------------------------------------|---------------------------------------------|-------------------|
| Candida<br>albicans | 30 CFU/mL | SVM | Original design (K212213) | 19/20 | 0.5 | 0.911 |
| | | | New design | 20/20 | | |
| | | VS | Original design (K212213) | 19/20 | 0.4 | 0.965 |
| | | | New design | 20/20 | | |
| Candida<br>dubliniensis | 1,316 CFU/mL | SVM | Original design (K212213) | 20/20 | 0.9 | 0.620 |
| | | | New design | 20/20 | | |
| | | VS | Original design (K212213) | 20/20 | 0.2 | >0.999 |
| | | | New design | 20/20 | | |
| Candida<br>tropicalis | 750 CFU/mL | SVM | Original design (K212213) | 19/20 | 0.7 | 0.826 |
| | | | New design | 20/20 | | |
| | | VS | Original design (K212213) | 20/20 | 0.1 | >0.999 |
| | | | New design | 20/20 | | |
| Candida<br>parapsilosis | 1,339 CFU/mL | SVM | Original design (K212213) | 20/20 | 0.3 | >0.999 |
| | | | New design | 20/20 | | |
| | | VS | Original design (K212213) | 20/20 | 0.0 | >0.999 |
| | | | New design | 20/20 | | |
| Candida<br>glabrata | 20 CFU/mL | SVM | Original design (K212213) | 20/20 | 0.3 | 0.936 |
| | | | New design | 20/20 | | |
| | | VS | Original design (K212213) | 20/20 | 0.3 | 0.999 |
| | | | New design | 20/20 | | |
| Candida krusei | 656 CFU/mL | SVM | Original design (K212213) | 20/20 | 0.3 | >0.999 |
| | | | New design | 20/20 | | |
| | | VS | Original design (K212213) | 20/20 | 0.2 | >0.999 |
| | | | New design | 20/20 | | |
| Trichomonas<br>vaginalis | 5 cells/mL | SVM | Original design (K212213) | 20/20 | 0.3 | 0.989 |
| | | | New design | 19/20 | | |
| | | VS | Original design (K212213) | 19/20 | 0.1 | 0.993 |
| | | | New design | 20/20 | | |

Results from the equivalency study at near cut-off concentrations are shown in Table 5-4. The number of positive results obtained out of the total number of replicates tested for each BV organism at the near cut-off concentrations, the difference in the mean Cts between the two designs, and the t-test statistical analysis of the mean Ct values are presented.

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Image /page/13/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." 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".

#### Table 5-4: Mean Ct Values and Differences Between the Two Designs of Xpert Xpress MVP at Near Cut-off Concentrations of BV Organisms

| Organism | Concentration<br>tested (1× near<br>Cut-off<br>Concentration) | Matrix | Design | Replicates<br>reported BV<br>positive results/<br>Total Replicates | Difference<br>in Mean<br>Atop gp Cts | t-test<br>p-value | Difference<br>in Mean<br>Mega1-<br>BVAB2 Cts | t-test<br>p-value |
|--------------------------------------------------------|---------------------------------------------------------------|--------|------------------------------|--------------------------------------------------------------------|--------------------------------------|-------------------|----------------------------------------------|-------------------|
| <i>A. vaginae</i> | $3.2×10^5$ CFU/mL | SVM | Original design<br>(K212213) | 19/20 | 0.1 | >0.999 | N/A | N/A |
| <i>A. vaginae</i> ;<br><i>Megasphaera</i> -1 | 2,750 CFU/mL;<br>390 copies/mL | SVM | Original design<br>(K212213) | 20/20 | 0.1 | >0.999 | 0.4 | 0.993 |
| <i>A. vaginae</i> ;<br>BVAB2 | 2,750 CFU/mL;<br>50 copies/mL | SVM | Original design<br>(K212213) | 20/20 | 0.1 | >0.999 | 0.4 | 0.999 |
| <i>A. vaginae</i> ;<br><i>Megasphaera</i> -1;<br>BVAB2 | 2,750 CFU/mL;<br>390 copies/mL;<br>50 copies/mL | SVM | Original design<br>(K212213) | 20/20 | 0.2 | >0.999 | 0.3 | 0.996 |
| <i>A. vaginae</i> | $3.2×10^5$ CFU/mL | SVM | New design | 20/20 | | | | |
| <i>A. vaginae</i> ;<br><i>Megasphaera</i> -1 | 2,750 CFU/mL;<br>390 copies/mL | SVM | New design | 19/20 | | | | |
| <i>A. vaginae</i> ;<br>BVAB2 | 2,750 CFU/mL;<br>50 copies/mL | SVM | New design | 20/20 | | | | |
| <i>A. vaginae</i> ;<br><i>Megasphaera</i> -1;<br>BVAB2 | 2,750 CFU/mL;<br>390 copies/mL;<br>50 copies/mL | SVM | New design | 20/20 | | | | |

The Xpert Xpress MVP original design (K212213) and new design both verified the LoD and near cut-off concentrations with at least 19 of 20 replicates reported POSITIVE/DETECTED results in the head to-head testing. In addition, the differences in mean target Cts were within the marginal difference of 1.0 Ct value, and no statistically significant differences in the mean Ct values were observed for all test targets between the two designs, demonstrating that the analytical sensitivity of the two designs of Xpert Xpress MVP is equivalent.

#### Equivalencv Study using Clinical Specimens

A study using prospectively collected clinician-collected vaginal swab specimens was performed to demonstrate equivalence in performance of the Xpert Xpress MVP test between the original design (K212213) and the new design. The positive percent agreement (PPA) and negative percent agreement (NPA) of the new design of Xpert Xpress MVP for Bacterial Vaginosis (BV), Candida group, Candida glabrata/Candida krusei and Trichomonas vaginalis (TV) targets were determined relative to the original design (K212213) using clinical specimens to further support the equivalency claim for the two designs of the Xpert Xpress MVP test. Three sites in the United States participated in the prospective specimen collection, and one clinician-collected vaginal swab was collected from each symptomatic patient, 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; or vaginal odor). The specimens were transported to Cepheid (Sunnyvale, CA) and all testing was performed by a trained operator at Cepheid.

A total of 174 participants were enrolled and provided 174 clinician-collected vaginal swabs (VS) for this study. Two VS specimens were not tested, as there was not enough volume in the specimen tubes upon receipt of the specimens to support testing with both the original design (K212213) and the new design of the Xpert Xpress MVP test. After initial testing,

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Image /page/14/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. Below the company name is the text "Xpert® Xpress MVP", which likely refers to one of Cepheid's diagnostic products or platforms.

three runs provided non-determinate results (2 INVALID and 1 ERROR). One specimen could not be retested as there was insufficient specimen volume remained. One run still resulted in a non-determinate result (INVALID) upon retesting. After retesting, one run vielded a valid result and was included in the final data analysis. The first two specimens could not be included in the final data analysis, as there were no valid results from both the original design (K212213) and the new design of the test for comparison. Therefore, a total of 170 prospectively collected ("fresh") VS specimens was included in the final data analysis for all targets. In addition, there were 20 contrived C. glabrata and C. krusei specimens for the Candida glab-krus target, and 20 contrived T. vaginalis specimens for the TV target.

As an attempt to further investigate specimens with discordant results (i.e. difference in test results between Xpert Xpress MVP original design (K212213) and new design), specimens were retested with both the original design (K212213) and the new design if enough specimen volume remained. The retest results were for information only and were not included in the final data analysis.

The overall performance of the Xpert Xpress MVP new design relative to the original design (K212213) is presented in Table 5-5. The results of the repeat testing are provided as footnotes to the table.

| | PPA<br>(95% CI) | NPA<br>(95% CI) |
|---------------------------|-------------------------------------|---------------------------------------|
| BV | 98.3%<br>56/57 a<br>(90.6% - 100%) | 99.1%<br>112/113 b<br>(95.2% - 100%) |
| Candida group | 97.4%<br>38/39 c<br>(86.5% - 99.9%) | 98.5%<br>129/131 d<br>(94.6% - 99.8%) |
| Candida glab-krus Overall | 100%<br>31/31<br>(90.8% - 100%) | 100%<br>159/159<br>(98.1% - 100%) |
| Fresh | 100%<br>11/11<br>(76.2% - 100%) | 100%<br>159/159<br>(98.1% - 100%) |
| Contrived | 100%<br>20/20<br>(86.1% - 100%) | N/A |
| TV Overall | 100%<br>32/32<br>(91.1% - 100%) | 100%<br>158/158<br>(98.1% - 100%) |
| Fresh | 100%<br>12/12<br>(77.9% - 100%)) | 100%<br>158/158<br>(98.1% - 100%) |

#### Table 5-5: Overall Performance of Xpert Xpress MVP New Design relative to the Original Design (K212213)

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Image /page/15/Picture/0 description: The image shows the Cepheid company logo along with the product name Xpert Xpress MVP. The Cepheid logo features a stylized blue wing-like design above the company name, which is written in a clean, sans-serif font. Below the company name, the product name "Xpert Xpress MVP" is displayed, with the "R" in "Xpert" enclosed in a circle, indicating a registered trademark.

| Contrived | 100%<br>20/20<br>(86.1% - 100%) | N/A |
|-----------|---------------------------------|-----|
|-----------|---------------------------------|-----|

N/A: Not Applicable

a There was one specimen that reported BV NEGATIVE test result with Xpert Xpress MVP new design but was BV POSITIVE with Xpert Xpress MVP original design (K212213). Upon retesting of this specimen, both the original design (K212213) and the new design reported BV POSITIVE test results.

b There was one specimen that reported BV POSITIVE test result with Xpert Xpress MVP new design but was BV NEGATIVE with Xpert Xpress MVP original design (K212213). Upon retesting of this specimen, the original design (K212213) reported BV POSITIVE test result and the new design reported BV NEGATIVE test result.

C There was one specimen that reported Candida group NOT DETECTED test result with Xpert Xpress MVP new design but was Candida group DETECTED with Xpert Xpress MVP original design (K212213). Upon retesting of this specimen, both the original design and the new design reported Candida group NOT DETECTED test results.

d There were two specimens that reported Candida group DETECTED test results with Xpert Xpress MVP new design but were Candida group NOT DETECTED with Xpert Xpress MVP original design (K212213). Upon retesting, both the original design (K212213) and the new design reported Candida group NOT DETECTED test results for these two specimens.

The investigation of both the false positive and false negative results showed that these specimens had Ct values close to the assay cut-off. This suggested that the discrepancies were most likely due to specimens which were near LoD or sub-LoD levels.

Of the 456 runs in this study (including external controls), four runs (4/456, 0.88%) provided non-determinate GeneXpert results (3 INVALID, 1 ERROR). Of these four non-determinates (ND), one run was from the 236 runs of the original design (K212213) and the overall nondeterminate rate was 0.42% (1/236); three runs were from the 220 runs of the new design and the overall non-determinate rate was 1.4% (3/220).

#### Analytical Reactivity (Inclusivity)

Refer to the previously FDA-cleared 510(k) Premarket Notification, K212213 for Analytical Reactivity (Inclusivity) of the Xpert Xpress MVP test. No additional testing was conducted.

#### Analytical Specificity (Exclusivity)

Refer to the previously FDA-cleared 510(k) Premarket Notification, K212213 for Analytical Specificity (Exclusivity) of the Xpert Xpress MVP test. No additional testing was conducted.

#### Microbial Interference

Refer to the previously FDA-cleared 510(k) Premarket Notification, K212213 for Microbial Interference of the Xpert Xpress MVP test. No additional testing was conducted.

#### Competitive Interference

Refer to the previously FDA-cleared 510(k) Premarket Notification, K212213 for Competitive Interference of the Xpert Xpress MVP test. No additional testing was conducted.

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Image /page/16/Picture/0 description: The image contains the Cepheid company logo, which features a stylized blue wave-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.

#### Interfering Substances

The potentially inhibitory effects of substances encountered in vaginal specimens on the performance of the original design of the Xpert Xpress MVP test were evaluated in the absence or presence of MVP targets. Among all potentially interfering substances tested. clinically significant inhibitory effects were previously observed in the positive samples containing mucin at a concentration of 5.5% when tested with the ori…