(160 days)
Not Found
No
The summary describes a PCR-based diagnostic test and system, with no mention of AI or ML in the device description, intended use, or performance studies.
No
The device is an in vitro diagnostic test designed to detect DNA targets for conditions like bacterial vaginosis, vulvovaginal candidiasis, and trichomoniasis. It aids in diagnosis but does not directly treat or provide therapeutic benefit.
Yes
The "Intended Use / Indications for Use" section explicitly states "The Xpert Xpress MVP test is intended to aid in the diagnosis of vaginal infections". The "Device Description" also describes it as an "automated qualitative in vitro diagnostic test".
No
The device description explicitly states it includes hardware components: a GeneXpert IV instrument, a GeneXpert Hub with preloaded software, and single-use disposable GeneXpert cartridges.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use/Indications for Use: The very first sentence explicitly states it is an "automated qualitative in vitro diagnostic test". It also describes its purpose as detecting DNA targets from biological samples (vaginal swabs) to aid in the diagnosis of vaginal infections.
- Device Description: The description reiterates that it is an "automated in vitro diagnostic test". It details the components and process used to analyze the biological sample outside of the body.
- Mechanism: The test uses real-time PCR and hybridization probes to detect DNA in the sample, which is a common method for in vitro diagnostic tests.
- Sample Type: It analyzes biological specimens (vaginal swabs) collected from patients.
- Purpose: The results are intended to aid in the diagnosis of medical conditions (bacterial vaginosis, vulvovaginal candidiasis, or trichomoniasis).
All of these characteristics align with the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for 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) 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.
Product codes (comma separated list FDA assigned to the subject device)
PQA, OUY, OOI
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 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.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Vaginal
Indicated Patient Age Range
The study population comprised of 1,275 female patients 18 to ≥ 50 years of age. Additionally, two patients between 14-17 years of age were enrolled in the study.
Intended User / Care Setting
CLIA-waived environment
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Description of the test set: 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.
Sample size: Replicates of 20 were evaluated at a minimum of five concentrations for each of the target organisms.
Data source: 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.
Annotation protocol: 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 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.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Study type: Blinded clinical study
Sample size: 1,275 female patients 18 to ≥ 50 years of age. Additionally, two patients between 14-17 years of age. A total of 2,544 vaginal swabs were tested.
AUC: Not Found
MRMC: Not Found
Standalone performance: Not Found
Key results:
Performance of the Xpert Xpress MVP test is presented in Table 5-14. The Xpert Xpress MVP test demonstrated positive percent agreement (PPA) and negative percent agreement (NPA) of 92.9% and 94.5% for BV detection in CVS specimens, respectively, and 93.6% in SVS specimens, respectively. For Candida group detection, the Xpert Xpress MVP test demonstrated sensitivity and specificity of 98.1% and 94.9% in CVS specimens, respectively, and 97.8% and 92.9% in SVS specimens, respectively. The Xpert Xpress MVP test demonstrated sensitivity and specificity of 94.1% and 99.8% for Candida glab-krus detection in CVS specimens, respectively, and 100% and 99.7% in SVS specimens, respectively. For TV detection, the Xpert Xpress MVP test demonstrated PPA and NPA of 98.0% and 99.6% in CVS specimens, respectively, and 97.9% and 99.7% in SVS specimens, respectively.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
BV (CVS): PPA 92.9% (90.1% - 94.9%), NPA 94.5% (92.6% - 95.9%)
BV (SVS): PPA 93.5% (90.9% - 95.4%), NPA 93.6% (91.6% - 95.1%)
Candida group (CVS): Sensitivity 98.1% (96.1% - 99.1%), Specificity 94.9% (93.2% - 96.2%)
Candida group (SVS): Sensitivity 97.8% (95.8% - 98.9%), Specificity 92.9% (91.0% - 94.5%)
Candida glab-krus (CVS) Fresh Prospective: Sensitivity 94.1% (80.9% - 98.4%), Specificity 99.8% (99.4% - 99.9%)
Candida glab-krus (SVS) Fresh Prospective: Sensitivity 100% (89.6% - 100%), Specificity 99.7% (99.1% - 99.9%)
Candida glab-krus (Contrived): Sensitivity 99.0% (94.5%-99.8%), Specificity 96.4% (82.3%-99.4%)
TV (CVS) Fresh Prospective: PPA 98.0% (89.3% - 99.6%), NPA 99.6% (99.0% - 99.8%)
TV (SVS) Fresh Prospective: PPA 97.9% (89.1% - 99.6%), NPA 99.7% (99.2% - 99.9%)
TV (Contrived): PPA 94.4% (87.5%-97.6%), NPA 100% (88.3%-100%)
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
N/A
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 (DICE@fda.hhs.gov) or phone (1-800-638-2041 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) |
|---|
| ------------------------------------------------- |
| ☑ 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/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
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Table of Contents
| 5.0 510(k) Summary | 3 |
|---|---|
| 5.1 Device Description | 3 |
| 5.2 Device Intended Use | 4 |
| 5.3 Substantial Equivalence | 4 |
| 5.4 Non-Clinical Study | 7 |
| 5.5 Clinical Study | 22 |
| 5.6 Conclusions | 25 |
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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 |
| 904 Caribbean Drive | |
| Sunnyvale, CA 90489 | |
| Phone number: (425) 420-8349 | |
| Fax number: (408) 541-4192 | |
| 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 |
| (PCR) and detection test | |
| Regulation Number, | |
| Classification Name, | |
| Product Code | |
| Definition: | 21 CFR 866.3975, Vaginitis and Bacterial Vaginosis |
| Nucleic Acid Detection System, PQA | |
| 21 CFR 866.3860, Trichomonas vaginalis Nucleic | |
| Acid Amplification Test System, OUY | |
| 21 CFR 862.2570, Real Time Nucleic Acid | |
| Amplification System, OOI | |
| Classification | |
| 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
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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 | |
| GeneXpert Xpress System | Xpert® Xpress MVP, Performed on the | |
| GeneXpert Instrument Systems [K221160] | ||
| Regulation | Same | 21CFR 866.3975 |
| Device that detects nucleic acid sequences from | ||
| microorganisms associated with vaginitis and | ||
| bacterial vaginosis | ||
| Product Code | Same | PQA |
| Vaginitis and bacterial vaginosis nucleic acid | ||
| detection system | ||
| Device Class | Same | II |
| 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 | 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 | ||
| Comparison | ||
| Attribute | Subject Device | |
| Xpert® Xpress MVP, Performed on the | ||
| GeneXpert Xpress System | Predicate Device | |
| Xpert® Xpress MVP, Performed on the | ||
| 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) 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 | ||
| 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
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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 | ||
| GeneXpert Xpress System | Xpert® Xpress MVP, Performed on the | |
| 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.
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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 | ||||
|---|---|---|---|---|
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| BV Organism | Verified Near Cut-off
Concentration |
|----------------------------------------------------------------------|----------------------------------------|
| Atopobium vaginae
(in the absence of Megasphaera-1 and BVAB2) | 320,000 CFU/mL |
| Atopobium vaginae
(in the presence of Megasphaera-1 and/or BVAB2) | 2,750 CFU/mL |
| BVAB2 plasmid DNA | 50 copies/mL |
| Megasphaera-1 plasmid DNA | 390 copies/mL |
Table 5-4: 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 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 ~4×, one strain at ~6×, and one strain at ~7× near cut-off concentration. The analytical reactivity result summary is presented in Table 5-5.
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Image /page/11/Picture/0 description: The image shows the Cepheid company logo. The logo features a stylized blue wing-like design above the company name, "Cepheid," which is written in a bold, sans-serif font. Below the company name, the text "Xpert® Xpress MVP" is displayed in a smaller, sans-serif font, with the "®" symbol indicating a registered trademark.
Table 5-5: Analytical Reactivity of the Xpert Xpress MVP Test
| Result | ||||||
|---|---|---|---|---|---|---|
| Organism | ||||||
| Strain | Concentration | BV | Candida | |||
| group | Candida | |||||
| glab-krus | TV | |||||
| Negative Control | Negative | Not Detected | Not Detected | Not Detected | ||
| 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 | |
| Atopobium spp. | CCUG 44061 | 96 CFU/mL | pos a | Not Detected | Not Detected | Not Detected |
| LoD | ||||||
| (Below the near | CCUG 44116 | 96 CFU/mL | pos a | Not Detected | Not Detected | Not Detected |
| cut-off | CCUG 44125 | 120 CFU/mL b | pos a | Not Detected | Not Detected | Not Detected |
| concentrations and | CCUG 44156 | 96 CFU/mL | pos a | Not Detected | Not Detected | Not Detected |
| not generating BV | ||||||
| POSITIVE result) a | 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 | $9.6×10^5$ CFU/mL | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 42099 | $9.6×10^5$ CFU/mL | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 43049 | $9.6×10^5$ CFU/mL | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 44061 | $9.6×10^5$ CFU/mL | Positive | Not Detected | Not Detected | Not Detected | |
| Atopobium spp. | CCUG 44116 | $9.6×10^5$ CFU/mL | Positive | Not Detected | Not Detected | Not Detected |
| In the absence of | CCUG 44125 | $1.2×10^6$ CFU/mL d | Positive | Not Detected | Not Detected | Not Detected |
| Megasphaera-1 | CCUG 44156 | $2.0×10^6$ CFU/mL e | Positive | Not Detected | Not Detected | Not Detected |
| and BVAB2 | CCUG 44258 | $9.6×10^5$ CFU/mL | Positive | Not Detected | Not Detected | Not Detected |
| CCUG 48515 | $4.0×10^6$ CFU/mL f | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 55227 | $9.6×10^5$ CFU/mL | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 55226 | $2.0×10^6$ 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 | ||||||
| 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 | |
| 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 | |
| Result | ||||||
| Organism | Strain | Concentration | BV | Candida | ||
| group | Candida | |||||
| glab-krus | TV | |||||
| In the presence of | ||||||
| Megasphaera-1 | 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 | 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 | |
| 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 | |
| Atopobium spp. | 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 | |
| In the presence of | ||||||
| Megasphaera-1 | ||||||
| and BVAB2 | 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 | ||||||
| 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 | |
| Candida | ATCC 7330 | 4,017 CFU/mL | Negative | Detected | Not Detected | |
| parapsilosis | ATCC 60548 | 4,017 CFU/mL | Negative | Detected | Not Detected | |
| Organism | Strain | Concentration | Result | |||
| BV | Candida | |||||
| group | Candida | |||||
| glab-krus | TV | |||||
| ATCC 90875 | 4,017 CFU/mL | Negative | Detected | Not Detected | Not Detected | |
| ATCC 96139 | 4,017 CFU/mL | Negative | Detected | Not Detected | Not Detected | |
| ATCC 96140 | 4,017 CFU/mL | Negative | Detected | Not Detected | Not Detected | |
| ATCC 32312 | 60 CFU/mL | Negative | Not Detected | Detected | Not Detected | |
| ATCC 32554 | 60 CFU/mL | Negative | Not Detected | Detected | Not Detected | |
| Candida glabrata | ATCC 15126 | 60 CFU/mL | Negative | Not Detected | Detected | Not Detected |
| ATCC 2001 | 60 CFU/mL | Negative | Not Detected | Detected | Not Detected | |
| ATCC MYA-276 | 60 CFU/mL | Negative | Not Detected | Detected | Not Detected | |
| ATCC 28870 | 1,968 CFU/mL | Negative | Not Detected | Detected | Not Detected | |
| ATCC 32672 | 1,968 CFU/mL | Negative | Not Detected | Detected | Not Detected | |
| Candida krusei | ATCC 90878 | 1,968 CFU/mL | Negative | Not Detected | Detected | Not Detected |
| ATCC 200917 | 1,968 CFU/mL | Negative | Not Detected | Detected | Not Detected | |
| ATCC 201748 | 1,968 CFU/mL | Negative | Not Detected | Detected | Not Detected | |
| ATCC 30184 | 15 cells/mL | Negative | Not Detected | Not Detected | Detected | |
| ATCC 30187 | 15 cells/mL | Negative | Not Detected | Not Detected | Detected | |
| ATCC 30238* | 15 cells/mL | Negative | Not Detected | Not Detected | Detected | |
| Trichomonas | ||||||
| vaginalis | ATCC 30240 | 15 cells/mL | Negative | Not Detected | Not Detected | Detected |
| ATCC 30245 | 15 cells/mL | Negative | Not Detected | Not Detected | Detected | |
| ATCC 50139 | 15 cells/mL | Negative | Not Detected | Not Detected | Detected | |
| ATCC 50141 | 15 cells/mL | Negative | Not Detected | Not Detected | Detected | |
| ATCC 50167 | 15 cells/mL | Negative | Not Detected | Not Detected | Detected | |
| ATCC 50183 | 15 cells/mL | Negative | Not Detected | Not Detected | Detected | |
| ATCC PRA-95 | 15 cells/mL | Negative | Not Detected | Not Detected | Detected |
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Image /page/12/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 text is in a simple, sans-serif font and is horizontally aligned.
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Image /page/13/Picture/0 description: The image shows the Cepheid logo, which includes a stylized blue wing-like graphic above the word "Cepheid." Below the logo, the text "Xpert® Xpress MVP" is displayed. The "Xpert" has a registered trademark symbol next to it.
a The LoD for Atopobium vaginae is for information only. All Atopobium spp. strains tested at ~3× LoD level reported BV NEGATIVE result calls as expected, as the concentration of Atopobium spp. strains tested was below the near cut-off concentration either in the presence of Megal-BVAB2 target. Replicates reporting Atop gp Ct values of ≤ 40.0 was treated as positive (pos) when Atopobium spp. strains were tested at ~ 3× LoD.
b Atopobium vaginae CCUG 44125 was tested at ~ 4× LoD (120 CFU/mL) to obtain 3 of 3 Atop gp Ct values of ≤ 40.0 results.
° Atopobium vaginae CCUG 48515 was tested at ~ 12× LoD (400 CFU/mL) to obtain 3 of 3 Atop gp Ct values of ≤ 40.0 results.
d Atopobium vaginae CCUG 44125 was tested at ~ 4× near cut-off concentration (1.2×10° CFU/mL) in the absence of BVAB2 and Megasphaera-1 to obtain 3 of 3 BV POSITIVE result calls.
° Atopobium vaginae CCUG 44156 was tested at ~ 6× near cut-off concentration (2.0×10° CFU/mL) in the absence of BVAB2 and Megasphaera-1 to obtain 3 of 3 BV POSITIVE result calls.
5 Atopobium vaginae CCUG 48515 was tested at ~ 12× near cut-off concentration (4.0×10° CFU/mL) in the absence of BVAB2 and Megasphaera-1 to obtain 3 of 3 BV POSITIVE result calls.
8 Atopobium novel species CCUG 55226 was tested at ~ 6× near cut-off concentration (2.0×10° CFU/mL) in the absence of BV AB2 and Megasphaera-1 to obtain 3 of 3 BV POSITIVE result calls.
h Atopobium vaginae CCUG 44125 was tested at ~ 4× near cut-off concentration (10,000 CFU/mL) in the presence of BVAB2 and/or Megasphaera-1 to obtain 3 of 3 BV POSITIVE result calls.
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Image /page/14/Picture/0 description: The image contains the Cepheid company logo, which features a stylized blue wing-like design. Below the logo, the text "Cepheid." is displayed in a simple font. Underneath "Cepheid.", the text "Xpert® Xpress MVP" is written, with the "®" symbol indicating a registered trademark.
1 Atopobium vaginae CCUG 44156 was tested at ~ 6× near cut-off concentration (17,000 CFU/mL) in the presence of BVAB2 and/or Megasphaera-1 to obtain 3 of 3 BV POSITIVE result calls.
- 1 Atopobium vaginae CCUG 48515 was tested at ~ 6× (17,000 CFU/mL) to ~ 7× (20,000 CFU/mL) near cut-off concentration in the presence of BVAB2 and/or Megasphaera-1 to obtain 3 of 3 BV POSITIVE result calls.
- k Atopobium novel species CCUG 55226 was tested at ~ 4× near cut-off concentration (10,000 CFU/mL) in the presence of BVAB2 and/or Megasphaera-1 to obtain 3 of 3 BV POSITIVE result calls.
- 1 Candida albicans ATCC 38289 was tested at ~ 4× LoD (120 CFUmL) to obtain 3 of 3 Candida group DETECTED result calls.
m Candida albicans ATCC 62376 was tested at ~ 20× LoD (600 CFU/mL) to obtain 3 of 3 Candida group DETECTED result calls.
" Candida albicans ATCC 753 was tested at ~ 20× LoD (600 CFU/mL) to obtain 3 of 3 Candida group DETECTED result calls. * metronidazole-resistant strain
5.4.3 Analytical Specificity (Exclusivity)
The analytical specificity of the Xpert Xpress MVP test was evaluated by testing a panel of 115 potentially cross-reactive microorganisms that are likely to be found in the vaginal flora/female genital tract. All strains were tested in triplicates in simulated vaginal swab matrix at a concentration of at least 106 CFU/mL, 105 cells/mL, 105 TCID50/mL, or 104 International Unit (IU)/mL. No cross-reactivity was observed for all microorganisms tested with the Xpert Xpress MVP test at the concentrations listed in Table 5-6.
| Organism | Concentration | Organism | Concentration |
|---|---|---|---|
| Bacteria | Bacteria | ||
| Acinetobacter baumannii | 1×106 CFU/mL | Neisseria gonorrhoeae | 1×106 CFU/mL |
| Acinetobacter calcoaceticus | 1×106 CFU/mL | Olsenella uli | 1×106 CFU/mL |
| Actinomyces israelii | 1×106 CFU/mL | Pantoea agglomerans | 1×106 CFU/mL |
| Actinomyces pyogenes | 1×106 CFU/mL | Peptoniphilus asaccharolyticus | 1×106 CFU/mL |
| Aerococcus viridans | 1×106 CFU/mL | Peptoniphilus anaerobius | 1×106 CFU/mL |
| Alcaligenes faecalis | 1×106 CFU/mL | Peptostreptococcus anaerobius | 1×106 CFU/mL |
| Anaerococcus tetradius | 1×106 CFU/mL | Plesiomonas shigelloides | 1×106 CFU/mL |
| Atopobium minutum | 1×106 CFU/mL | Porphyromonas asaccharolytica | 1×106 CFU/mL |
| Atopobium parvulum | 1×106 CFU/mL | Prevotella bivia | 1×106 CFU/mL |
| Atopobium rimae | 1×106 CFU/mL | Prevotella melaninogenica | 1×106 CFU/mL |
| Bacillus subtilis | 1×106 CFU/mL | Prevotella oralis | 1×106 CFU/mL |
| Bacteroides caccae | 1×106 CFU/mL | Propionibacterium acnes | 1×106 CFU/mL |
| Bacteroides fragilis | 1×106 CFU/mL | Proteus mirabilis | 1×106 CFU/mL |
| Bacteroides stercoris | 1×106 CFU/mL | Providencia stuartii | 1×106 CFU/mL |
| Bacteroides ureolyticus | 1×106 CFU/mL | Pseudomonas aeruginosa | 1×106 CFU/mL |
| Bifidobacterium adolescentis | 1×106 CFU/mL | Salmonella typhimurium | 1×106 CFU/mL |
| Bifidobacterium breve | 1×106 CFU/mL | Serratia marcescens | 1×106 CFU/mL |
| Bifidobacterium longum | 1×106 CFU/mL | Shigella flexneri | 1×106 CFU/mL |
| Brevibacterium linens | 1×106 CFU/mL | Sneathia amnii | 1×106 CFU/mL |
| Organism | Concentration | Organism | Concentration |
| Burkholderia cepacian | 1×106 CFU/mL | Sneathia sanguinegens | 1×106 CFU/mL |
| BVAB1 | 1×106 copies/mL | Staphylococcus aureus | 1×106 CFU/mL |
| Campylobacter jejuni | 1×106 CFU/mL | Staphylococcus epidermidis | 1×106 CFU/mL |
| Chlamydia trachomatis | 1×106 CFU/mL | Streptococcus agalactiae | 1×106 CFU/mL |
| Citrobacter freundii | 1×106 CFU/mL | Streptococcus mitis | 1×106 CFU/mL |
| Clostridium perfringens | 1×106 CFU/mL | Streptococcus mutans | 1×106 CFU/mL |
| Corynebacterium genitalium | 1×106 CFU/mL | Streptococcus salivarius | 1×106 CFU/mL |
| Dialister micraerophilus | 1×106 CFU/mL | Treponema pallidum | 1×106 copies/mL |
| Eikenella corrodens | 1×106 CFU/mL | Veillonella atypica | 1×106 CFU/mL |
| Enterobacter aerogenes | 1×106 CFU/mL | Veillonella parvula | 1×106 CFU/mL |
| Enterococcus faecalis | 1×106 CFU/mL | Vibrio parahaemolyticus | 1×106 CFU/mL |
| Enterococcus faecium | 1×106 CFU/mL | Yersinia enterocolitica | 1×106 CFU/mL |
| Erysipelothrix rhusiopathiae | 1×106 CFU/mL | Protozoans | |
| Escherichia coli | 1×106 CFU/mL | Pentatrichomonas hominis | 5×104 cells/mL |
| Finegoldia magna | 1×106 CFU/mL | Trichomonas tenax | 10 cells/mL |
| Fusobacterium nucleatum | 1×106 CFU/mL | Yeasts | |
| Gardnerella vaginalis | 1×106 CFU/mL | Candida catenulate | 1×106 CFU/mL |
| Gemella haemolysans | 1×106 CFU/mL | Candida famata | 1×106 CFU/mL |
| Kingella denitrificans | 1×106 CFU/mL | Candida haemulonii | 1×106 CFU/mL |
| Klebsiella pneumoniae | 1×106 CFU/mL | Candida inconspicua | 1×106 CFU/mL |
| Kocuria rhizophila | 1×106 CFU/mL | Candida intermedia | 1×106 CFU/mL |
| Lactobacillus acidophilus | 1×106 CFU/mL | Candida kefyr | 1×106 CFU/mL |
| Lactobacillus crispatus | 1×106 CFU/mL | Candida lusitaniae | 1×106 CFU/mL |
| Lactobacillus gasseri | 1×106 CFU/mL | Candida norvegica | 1×106 CFU/mL |
| Lactobacillus helveticus | 1×106 CFU/mL | Candida orthopsilosis | 1×102 CFU/mL |
| Lactobacillus iners | 1×106 CFU/mL | Candida rugosa | 1×106 CFU/mL |
| Lactobacillus jensenii | 1×106 CFU/mL | Candida utilis | 1×106 CFU/mL |
| Lactobacillus johnsonii | 1×106 CFU/mL | Kodamaea ohmeri b | 1×106 CFU/mL |
| Lactobacillus vaginalis | 1×106 CFU/mL | Pichia fermentans | 1×106 CFU/mL |
| Legionella pneumophila | 1×106 CFU/mL | Pichia norvegensis c | 1×106 CFU/mL |
| Mageeibacillus indolicus a | 1×106 CFU/mL | Pichia occidentalis d | 1×106 CFU/mL |
| Megasphaera-2 | 1×106 copies/mL | Saccharomyces cerevisiae | 1×106 CFU/mL |
| Megasphaera elsdenii | 1×106 CFU/mL | Viruses | |
| Mobiluncus curtisii | 1×106 CFU/mL | Hepatitis B virus | 1×105 IU/mL |
| Mobiluncus mulieris | 1×106 CFU/mL | Hepatitis C virus | 1×105 IU/mL |
| Moraxella catarrhalis | 1×106 CFU/mL | Herpes simplex virus I | 1×105 TCID50/mL |
| Morganella morganii | 1×106 CFU/mL | HIV-1 | 3×104 IU/mL e |
| Mycobacterium smegmatis | 1×106 CFU/mL | Human herpesvirus 2 | 1×105 TCID50/mL |
| Organism | Concentration | Organism | Concentration |
| Mycoplasma genitalium | 1×106 CFU/mL | Human papilloma virus | 4.3×105 cells/mL |
| Mycoplasma hominis | 1×106 CFU/mL | Varicella-zoster virus | 1×105 copies/mL |
Table 5-6: Organisms Tested for Analytical Specificity
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Image /page/15/Picture/0 description: The image shows the logo for Cepheid, a molecular diagnostics company. The logo features a stylized blue graphic above the company name, "Cepheid." Below the company name is the text "Xpert® Xpress MVP", which likely refers to one of Cepheid's diagnostic products or platforms. The text is black and the background is white.
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a Mageeibacillus indolicus is formerly named BVAB3.
b Kodamaea ohmeri is also reported as Pichia ohmeri and Candida guilliermondii.
& Pichia norvegensis is also reported as Candida norvegensis.
d Pichia occidentalis is also reported as Issatchenkia occidentalis and Candida sorbose.
e Evaluated at highest concentration available
5.4.4 Microbial Interference
An interfering microorganism study was performed to assess the inhibitory effects of microorganisms that may be encountered in vaginal specimens on the performance of Xpert Xpress MVP. Thirteen microorganisms were tested for potential interference at ≥10° CFU/mL for bacteria and at ≥104 International Unit/mL or cells/mL for viruses (Table 5-7). Each of the microorganisms was tested in simulated vaginal swab matrix in the presence of a mixture of Atopobium vaginae at 3× near cut-off concentrations, Megasphaera-1 and BVAB2 targets each at ~1.5× near cut-off concentrations, and Candida albicans, Candida glabrata and Trichomonas vaginalis targets each at 3× LoD, in the absence of any Xpert Xpress MVP test targets. The results showed that the presence of the tested microorganisms did not interfere with the performance of the Xpert Xpress MVP test.
| Microorganism |
|---|
| Dialister micraerophilus |
| Gardnerella vaginalis |
| Lactobacillus crispatus |
| Lactobacillus jensenii |
| Lactobacillus iners |
| Mageeibacillus indolicus |
| Mobiluncus curtisii |
| Porphyromonas asaccharolytica |
| Prevotella bivia |
| Sneathia amnii |
| Streptococcus agalactiae |
| HIV-1* |
| Human papilloma virus** |
Table 5-7: Potentially Interfering Microorganisms Tested
- Evaluated at highest concentration available (3×104 IU/mL)
** Evaluated at 1×104 cells/mL
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5.4.5 Competitive Interference
Competitive interference between targets (BV, Candida group, Candida glab-krus and TV) of the Xpert Xpress MVP test caused by co-infections was evaluated by testing each target at low positive concentration in the presence of another target at high concentration in simulated vaginal swab matrix. Competitive inhibitory effects between the BV analytes (Atop gp and Megal-BVAB2) were also evaluated in simulated vaginal swab matrix. The conditions simulating co-infections were presented in Table 5-8. Under the conditions of this study, competitive inhibitory effects were not observed between MVP targets or between BV analytes with the Xpert Xpress MVP test.
| | Testing Panel | Testing Target/Organisms
(Low Positive) | Competitive Target/Organisms
(High Positive) |
|----------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------|
| Competitive Interference
Evaluation between
MVP Targets | 1 | Atopobium vaginae
( $ Atopobium vaginae
( $1 \times 10^6$ CFU/mL) | |
Table 5-8: Competitive Interference Testing Conditions
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5.4.6 Interfering Substances
Twenty substances that may be present in the vaginal swab specimens with the potential to interfere with the performance of the Xpert Xpress MVP test were evaluated. The potentially interfering substances included prescription and over-the-counter drugs, creams and/or gels, blood, hormones, semen and mucus. The substances, active ingredients, and concentrations tested are listed in Table 5-9. Potential interferents were tested in simulated vaginal swab matrix in the presence and absence of Xpert Xpress MVP targets at 3× LoD/3× near cut-off concentrations. With the exception of the 5.5% concentration of mucin (from porcine stomach), no clinically significant inhibitory effects from substances that may be encountered in vaginal specimens were observed on the performance of the Xpert Xpress MVP test. When mucin was tested at a concentration of 4.0%, no clinically significant inhibitory effect was observed on the performance of the Xpert Xpress MVP test.
| Substance/Class | Active Ingredient | Concentration Tested |
|---|---|---|
| Blood | Blood | 5.0% v/v |
| Seminal Fluid | Semen | 5.0% v/v |
| Mucus | Mucin (porcine stomach) | 5.5% v/v (Interference Observed) |
| 4.0% v/v (Interference not Observed) | ||
| Leukocytes | Leukocytes | 105 cells/mL |
| Intravaginal Hormones | Estradiol; Progesterone | 7mg/mL Progesterone + 0.07mg/mL Beta Estradiol |
| Over the counter (OTC) | ||
| Vaginal Products; | ||
| Contraceptives; Vaginal | ||
| treatments | Benzocaine 5%; Resorcinol 2% | 0.25% w/v |
| Clotrimazole 2% | 0.25% w/v | |
| Miconazole Nitrate 4% | 0.25% w/v | |
| Tioconazole 6.5% | 0.25% w/v | |
| 5% w/w acyclovir | 0.25% w/v | |
| Glycerin, Propylene glycol | 0.25% w/v | |
| Glycerin; carbomer | 0.25% w/v | |
| Glycerin; sodium hydroxide; carbomer | 0.25% w/v | |
| Glycerin, Hydroxyethyl cellulose | ||
| Berberis Vulgaris 6X HPUS (Barberry), Borax 3X HPUS (Sodium Borate), Collinsonia Canadensis 3X HPUS (Stone Root), Hamamelis | 0.25% w/v |
Table 5-9: Potential Interfering Substances Tested
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| Substance/Class | Active Ingredient | Concentration Tested |
|---|---|---|
| Virginiana 6X HPUS (Witch Hazel), | ||
| Bacillus coagulans (Lactospore®) | ||
| Povidone-iodine 10% (topical) | 0.25% v/v | |
| Povidone-iodine 0.3% (douche) | 0.25% v/v | |
| Nonoxynol-9 12.5% | 0.25% w/v | |
| Metronidazole 0.75% | 0.25% w/v | |
| Hemorrhoidal Cream | Glycerin 14%; Pramoxine HCl 1% | 0.25% w/v |
5.4.7 Carry-Over Contamination
A study was conducted to demonstrate that single-use, self-contained GeneXpert cartridges prevent specimen and amplicon carry-over contamination from very high titer positive samples into successively run negative samples when processed in the same GeneXpert module. The study consisted of a negative sample processed in the same GeneXpert module immediately after processing a very high BV positive sample (an A. vaginge strain at 2.8×107 CFU/mL and BVAB2 plasmid DNA at 5.0×10° copies/mL), a very high Candida group positive sample (a C. albicans strain at 3.0×10€ CFU/mL), or a very high TV positive sample (a T. vaginalis strain at 5.0×106 cells/mL) in simulated vaginal swab matrix. The testing scheme was repeated 20 times in a single GeneXpert module for a total of 41 runs (20 high positive samples and 21 negative samples per module) across 3 GeneXpert modules. There was no evidence of any carry-over contamination. All 63 negative samples were correctly reported as negative/not detected. All 60 positive samples were correctly reported as positive/detected.
5.4.8 Time to Result
The time to result is defined as the time from the initiation of cartridge processing on the GeneXpert Xpress System to the time a result is displayed on the test screen. The time to result for the Xpert Xpress MVP test was determined by evaluating the test time of 50 random tests that were conducted as part of an analytical study. The Xpert Xpress MVP test has a turnaround time of within 60 minutes.
5.4.9 Reproducibility and Precision
Reproducibility and precision of the Xpert Xpress MVP test was established by untrained users through a multicenter (3 sites) representative of a CLIA-waived environment, blinded study utilizing a multi-factor nested design consisting of contrived panel members spanning the relevant limit of detection (LoD) spectrum (or, in the case of BV, the near cut-off concentration) for the 4 intended target types.
A panel of ten panel members with varying concentrations of the intended target types were tested by three operators in duplicate on five different days at three sites using one lot of Xpert Xpress MVP test cartridges. The total number of tests for each panel member was 90 (3 sites × 5 days × 3 operators × 1 run × 2 replicates). The three concentrations for each intended target type included two positive levels (moderate positives at ~3× LoD/near cut-off concentration, low positives at ~1× LoD/near cut-off concentration) and one negative. For the BV target, a high negative level (A. vaginae , Low Pos | Atop gp | 80 | 24.98 | 0.00 | 0.0 | 0.00 | 0.0 | 0.03 | 0.1 | 0.32 | 1.3 | 0.32 | 1.3 |
| A. vaginae and
BVAB2, High Neg | SPC | 80 | 32.64 | 0.17 | 0.5 | 0.17 | 0.5 | 0.12 | 0.4 | 0.37 | 1.1 | 0.46 | 1.4 |
| | Atop gp | 80 | 32.35 | 0.00 | 0.0 | 0.16 | 0.5 | 0.00 | 0.0 | 0.20 | 0.6 | 0.26 | 0.8 |
| | Mega1-
BVAB2b | 75 | 41.30 | 0.37 | 0.9 | 0.00 | 0.0 | 0.26 | 0.6 | 1.15 | 2.8 | 1.24 | 3.0 |
Table 5-13: Results of Precision for the BV Target
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| Panel member | Analyte | N a | Mean
Ct | Day | | Operator | | Between-Run | | Within-run | | Total | |
|-----------------------------------------------|-------------------|-----|------------|------|-----------|----------|-----------|-------------|-----------|------------|-----------|-------|-----------|
| | | | | SD | CV
(%) | SD | CV
(%) | SD | CV
(%) | SD | CV
(%) | SD | CV
(%) |
| A. vaginae and
BVAB2, Low Pos | Atop gp | 80 | 32.20 | 0.00 | 0.0 | 0.04 | 0.1 | 0.08 | 0.3 | 0.22 | 0.7 | 0.24 | 0.7 |
| | Megal-
BVAB2 b | 80 | 40.03 | 0.00 | 0.0 | 0.00 | 0.0 | 0.30 | 0.7 | 0.90 | 2.2 | 0.94 | 2.4 |
| A. vaginae and
Mega-1, High Neg | SPC | 80 | 32.63 | 0.11 | 0.3 | 0.17 | 0.5 | 0.00 | 0.0 | 0.39 | 1.2 | 0.44 | 1.3 |
| | Atop gp | 80 | 32.62 | 0.00 | 0.0 | 0.04 | 0.1 | 0.00 | 0.0 | 0.33 | 1.0 | 0.34 | 1.0 |
| | Megal-
BVAB2 b | 28 | 38.98 | 0.00 | 0.0 | 1.01 | 2.6 | 0.21 | 0.6 | 0.84 | 2.2 | 1.33 | 3.4 |
| A. vaginae and
Mega-1, Low Pos | Atop gp | 79 | 32.07 | 0.00 | 0.0 | 0.15 | 0.5 | 0.18 | 0.6 | 0.41 | 1.3 | 0.47 | 1.5 |
| | Megal-
BVAB2 b | 80 | 35.48 | 0.00 | 0.0 | 0.29 | 0.8 | 0.00 | 0.0 | 0.71 | 2.0 | 0.77 | 2.2 |
| A. vaginae, BVAB2,
and Mega-1,
High Neg | SPC | 80 | 32.74 | 0.15 | 0.5 | 0.12 | 0.4 | 0.17 | 0.5 | 0.33 | 1.0 | 0.41 | 1.3 |
| | Atop gp | 80 | 32.53 | 0.00 | 0.0 | 0.15 | 0.5 | 0.00 | 0.0 | 0.22 | 0.7 | 0.27 | 0.8 |
| | Megal-
BVAB2 b | 63 | 41.57 | 0.30 | 0.7 | 0.00 | 0.0 | 0.39 | 0.9 | 1.02 | 2.5 | 1.13 | 2.7 |
| A. vaginae, BVAB2.
and Mega-1,
Low Pos | Atop gp | 79 | 31.81 | 0.00 | 0.0 | 0.22 | 0.7 | 0.28 | 0.9 | 1.16 | 3.6 | 1.21 | 3.8 |
| | Megal-
BVAB2 b | 80 | 36.25 | 0.15 | 0.4 | 0.00 | 0.0 | 0.10 | 0.3 | 0.69 | 1.9 | 0.71 | 2.0 |
| A. vaginae, BVAB2,
and Mega-1,
Mod Pos | Atop gp | 80 | 30.67 | 0.13 | 0.4 | 0.09 | 0.3 | 0.00 | 0.0 | 0.33 | 1.1 | 0.37 | 1.2 |
| | Megal-
BVAB2 b | 80 | 35.64 | 0.00 | 0.0 | 0.26 | 0.7 | 0.00 | 0.0 | 0.48 | 1.3 | 0.54 | 1.5 |
Abbreviations: Atop gp, Atopobium group; CV, coefficient of variation; Mega1; Mod; moderate; Neg, negative; Pos, positive; SD, standard deviation; SPC, sample processing control
" Number of samples with non-zero Ct values out of 80.
b Samples with Mega1-BVAB2 that did not generate a Ct value were excluded from analysis.
Note: The variance estimate from some be numerically negative, which can occur if the variability due to those factors is very small. When this occurs, the variability as measured with SD and CV is set to 0.
5.5 Clinical Study
A blinded clinical study was conducted to evaluate the performance of the Xpert Xpress MVP test at 9 geographically diverse sites in the U.S. Subjects included female patients > 14 years of age who presented with signs and/or symptoms of vaginosis/vaginitis. For eligible subjects, one (1) self-collected (collected in a clinical setting, SVS) and five (5) clinician-collected vaginal swab (CVS) specimens were obtained for testing with the Xpert Xpress MVP test and reference/comparator testing. Patient management continued at the site per the standard practice, independent of investigational test results.
Performance of the Xpert Xpress MVP test in vaginal swab specimens was determined relative to reference/comparator methods. Specifically, positive percent agreement (PPA)/negative percent agreement (NPA) for BV was assessed relative to an FDA-cleared nucleic acid amplification test (NAAT). Sensitivity and specificity for Candida group and Candida glab-krus targets were assessed relative to yeast culture followed by mass spectrometry for species
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identification. PPA and NPA for TV were assessed relative to a patient infected status (PIS) algorithm that included results from an FDA-cleared NAAT and TV culture. When applicable, investigation of discrepant results was performed by testing specimens with another FDAcleared NAAT.
The study population comprised of 1,275 female patients 18 to ≥ 50 years of age. Additionally, two patients between 14-17 years of age were enrolled in the study. A total of 2,544 vaginal swabs were tested and were eligible for inclusion in the Xpert Xpress MVP study.
Performance of the Xpert Xpress MVP test is presented in Table 5-14. The Xpert Xpress MVP test demonstrated positive percent agreement (PPA) and negative percent agreement (NPA) of 92.9% and 94.5% for BV detection in CVS specimens, respectively, and 93.6% in SVS specimens, respectively. For Candida group detection, the Xpert Xpress MVP test demonstrated sensitivity and specificity of 98.1% and 94.9% in CVS specimens, respectively, and 97.8% and 92.9% in SVS specimens, respectively. The Xpert Xpress MVP test demonstrated sensitivity and specificity of 94.1% and 99.8% for Candida glab-krus detection in CVS specimens, respectively, and 100% and 99.7% in SVS specimens, respectively. For TV detection, the Xpert Xpress MVP test demonstrated PPA and NPA of 98.0% and 99.6% in CVS specimens, respectively, and 97.9% and 99.7% in SVS specimens, respectively.
| Clinician-collected (CVS) | Self-collected (SVS) | |||
|---|---|---|---|---|
| Sensitivity/PPA | ||||
| (95% CI) | Specificity/NPA | |||
| (95% CI) | Sensitivity/PPA | |||
| (95% CI) | Specificity/NPA | |||
| (95% CI) | ||||
| BV | 92.9% | |||
| 429/462 a | ||||
| (90.1% - 94.9%) | 94.5% | |||
| 719/761 b | ||||
| (92.6% - 95.9%) | 93.5% | |||
| 434/464 c | ||||
| (90.9% - 95.4%) | 93.6% | |||
| 711/760 d | ||||
| (91.6% - 95.1%) | ||||
| Candida group* | 98.1% | |||
| 360/367 e | ||||
| (96.1% - 99.1%) | 94.9% | |||
| 820/864 f | ||||
| (93.2% - 96.2%) | 97.8% | |||
| 359/367 g | ||||
| (95.8% - 98.9%) | 92.9% | |||
| 804/865 h | ||||
| (91.0% - 94.5%) | ||||
| Candida glab-krus | ||||
| Fresh Prospective | 94.1% | |||
| 32/34 i | ||||
| (80.9% - 98.4%) | 99.8% | |||
| 1195/1197 j | ||||
| (99.4% - 99.9%) | 100% | |||
| 33/33 | ||||
| (89.6% - 100%) | 99.7% | |||
| 1195/1199 k | ||||
| (99.1% - 99.9%) | ||||
| Candida glab-krus | ||||
| Contrived** | 99.0% | |||
| 98/99 | ||||
| (94.5%-99.8%) | 96.4% | |||
| 27/28 | ||||
| (82.3%-99.4%) | N/A | N/A | ||
| TV | ||||
| Fresh Prospective | 98.0% | |||
| 48/49 l | ||||
| (89.3% - 99.6%) | 99.6% | |||
| 1155/1160 m | ||||
| (99.0% - 99.8%) | 97.9% | |||
| 47/48 n | ||||
| (89.1% - 99.6%) | 99.7% | |||
| 1159/1162 o | ||||
| (99.2% - 99.9%) | ||||
| TV | ||||
| Contrived** | 94.4% | |||
| 84/89 | ||||
| (87.5%-97.6%) | 100% | |||
| 29/29 | ||||
| (88.3%-100%) | N/A | N/A |
Table 5-14: Overall Performance of the Xpert Xpress MVP Test
- Target includes C. albicans, C. tropicalis, C. parapsilosis, and C. dubliniensis
** Contrived specimens were prepared using individual negative clinical CVS and SVS specimens.
a Testing results with a second FDA-cleared NAAT: 15 were also negative and 18 were positive.
b Testing results with a second FDA-cleared NAAT: 21 were also positive and 21 were negative.
6 Testing results with a second FDA-cleared NAAT: 9 were also negative and 21 were positive.
d Testing results with a second FDA-cleared NAAT: 20 were also positive and 29 were negative.
e Testing results with an FDA-cleared NAAT: 5 were also negative and 2 were positive.
f Testing results with an FDA-cleared NAAT: 25 were also positive and 19 were negative.
8 Testing results with an FDA-cleared NAAT: 4 were also negative and 4 were positive.
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Xpert® Xpress MVP
h Testing results with an FDA-cleared NAAT: 30 were also positive and 31 were negative.
i Testing results with an FDA-cleared NAAT: 1 was also negative and 1 was positive.
- J Testing results with an FDA-cleared NAAT: 2 were negative.
- k Testing results with an FDA-cleared NAAT: 4 were negative.
- 1 Testing results with a second FDA-cleared NAAT: 1 was positive.
- m Testing results with a second FDA-cleared NAAT: 4 were also positive and 1 had no result.
- n Testing results with a second FDA-cleared NAAT: 1 was positive.
º Testing results with a second FDA-cleared NAAT: 3 were also positive
5.5.1 Asymptomatic Population
Although the Xpert Xpress MVP test is not intended for use in an asymptomatic patient population, positivity rates were calculated from CVS and SVS specimens collected from asymptomatic patients to assess how often patients who, despite being asymptomatic, harbored microbial flora associated with vaginosis and candidiasis that could be detected by the Xpert Xpress MVP test. Positivity rates are presented by target and by race/ethnicity in Table 5-15.
Table 5-15: Positivity Rates in Asymptomatic Patients According to the Xpert Xpress MVP Test
| | Target | Overall | Black /African
American^ | White | | Other* |
|-----|-----------------------|-------------------|-----------------------------|---------------------|-------------------------|-----------------|
| CVS | BV | 32.9%
(52/158) | 51.0%
(26/51) | Hispanic/
Latino | Not Hispanic
/Latino | 36.4%
(4/11) |
| CVS | Candida
group | 17.1%
(27/158) | 25.5%
(13/51) | 16.4%
(9/55) | 7.3%
(3/41) | 18.2%
(2/11) |
| CVS | Candida glab-
krus | 4.4%
(7/158) | 2.0%
(1/51) | 5.5%
(3/55) | 4.9%
(2/41) | 9.1%
(1/11) |
| SVS | BV | 31.5%
(51/162) | 49.1%
(26/53) | 24.1%
(13/54) | 16.3%
(7/43) | 41.7%
(5/12) |
| SVS | Candida
group | 19.1%
(31/162) | 28.3%
(15/53) | 18.5%
(10/54) | 7.0%
(3/43) | 25.0%
(3/12) |
| SVS | Candida glab-
krus | 4.9%
(8/162) | 1.9%
(1/53) | 7.4%
(4/54) | 4.7%
(2/43) | 8.3%
(1/12) |
^Includes one Black/African American who was of Hispanic or Latino descent for CVS specimens; includes two Black/African Americans who were of Hispanic or Latino descent for SVS specimens. *Including: American Indian or Alaska Native, Asian, Mixed/Unknown
5.5.2 Non-Determinate Rate
Of the 2,544 Xpert Xpress MVP runs performed in the clinical study, 126 resulted in nondeterminate ("INSTRUMENT ERROR" or "NO RESULT - REPEAT TEST") results on first attempt. Upon retest of these 126 specimens, 21 remained non-determinate. The initial nondeterminate rate was 5.0% (126/2544) and the overall non-determinate rate was 0.8% (21/2544). The initial non-determinate rate for CVS specimens was 4.6% (59/1269) and the overall nondeterminate rate was 0.6% (8/1269). The initial non-determinate rate for SVS specimens was 5.3% (67/1275) and the overall non-determinate rate was 1.0% (13/1275).
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5.6 Conclusions
The results of the non-clinical analytical and clinical performance studies summarized above demonstrated that the Xpert Xpress MVP test for use with GeneXpert Xpress System is substantially equivalent to the predicate device.