(209 days)
Not Found
No
The description focuses on real-time PCR and hybridization probes for DNA detection, with no mention of AI or ML algorithms for data analysis or interpretation.
No
This device is an in vitro diagnostic test designed to detect DNA targets for diagnosis, not to provide therapy or treatment.
Yes
The "Intended Use / Indications for Use" section explicitly states that the Xpert Xpress MVP test is an "automated qualitative in vitro diagnostic test" and is "intended to aid in the diagnosis of vaginal infections."
No
The device is an in vitro diagnostic test that utilizes a physical instrument (GeneXpert Instrument Systems) and single-use disposable cartridges containing reagents to perform PCR and detect DNA targets. While it includes software for running tests and viewing results, it is fundamentally a hardware-based system with associated consumables.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states: "The Xpert Xpress MVP test... 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 "Device Description" section also begins by stating: "The Xpert® Xpress MVP test is an automated in vitro diagnostic test..."
These statements clearly identify the device as an in vitro diagnostic.
N/A
Intended Use / Indications for Use
The Xpert Xpress MVP test, performed on the GeneXpert Instrument Systems, is an automated qualitative in vitro diagnostic test for the detection of DNA targets from anaerobic bacteria associated with bacterial vaginosis (BV), Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis. The Xpert Xpress MVP test uses clinician-collected and self-collected vaginal swabs (collected in a clinical setting) from patients who are symptomatic for vaginitis/vaginosis. The Xpert Xpress MVP test utilizes real-time polymerase chain reaction (PCR) for the amplification of specific DNA targets and utilizes fluorogenic target-specific hybridization probes to detect and differentiate DNA from:
- . Organisms associated with bacterial vaginosis (detected organisms not reported individually)
- o Atopobium spp. (Atopobium vaginae, Atopobium novel species CCUG 55226)
- Bacterial Vaginosis-Associated Bacterium 2 (BVAB2) o
- Megasphaera-1 o
- Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis, species not differentiated)
- Candida glabrata/Candida krusei (species not differentiated)
- . Trichomonas vaginalis
The Xpert Xpress MVP test is intended to aid in the diagnosis of vaginal infections in women with a clinical presentation consistent with bacterial vaginosis, vulvovaginal candidiasis, or trichomoniasis.
Product codes
PQA, NSU
Device Description
The Xpert® Xpress MVP test is an automated in vitro diagnostic test for qualitative detection of DNA targets from anaerobic bacteria associated with bacterial vaginosis, Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis, the agent of trichomoniasis. The Xpert Xpress MVP test is performed on GeneXpert Instrument Systems.
The GeneXpert Instrument Systems automate and integrate sample preparation, nucleic acid extraction and amplification, and detection of the target sequences in simple or complex samples using real-time PCR assays. The systems consist of an instrument, computer, and preloaded software for running tests and viewing the results. The systems require the use of single-use disposable cartridges that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained, cross-contamination between samples is minimized.
The Xpert Xpress MVP test includes reagents for the detection of DNA from BV organisms, Candida species, and Trichomonas vaginalis from vaginal swab samples. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are also included in the cartridge utilized by the GeneXpert System instrument. The SPC is present to control for adequate processing of the sample and to monitor for the presence of potential inhibitor(s) in the PCR reaction. The SPC also ensures that the PCR reaction conditions (temperature and time) are appropriate for the amplification reaction and that the PCR reagents are functional. The PCC verifies reagent rehydration, PCR tube filling, and confirms that all reaction components are present in the cartridge including monitoring for probe integrity and dye stability.
The Xpert Xpress MVP test is designed for use with the following specimens collected from symptomatic individuals: self-collected vaginal swabs (collected in a clinical setting) and clinician-collected vaginal swabs. The swab transport reagent included in the Xpert Swab Specimen Collection Kit is designed to collect and preserve patient specimens to allow transport to the laboratory prior to analysis with the Xpert Xpress MVP test.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Vaginal
Indicated Patient Age Range
Female patients > 14 years of age
Intended User / Care Setting
Clinicians (collected in a clinical setting)
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
The clinical evaluation of the Xpert Xpress MVP test was a multi-site, prospective observational, method comparison clinical study that included twelve (12) sites from geographically diverse locations in the United States. Of the 12 sites, 10 participated in specimen collection and Xpert testing, 1 performed reference/comparator testing and specimen collection, and 1 site participated in specimen collection only.
All sites prospectively collected one (1) self-collected in a clinical setting, SVS) and five (5) clinician-collected vaginal swab (CVS) specimens from symptomatic patients, defined as female patients > 14 years of age who presented with signs and/or symptoms of vaginitis/vaginosis (including abnormal vaginal discharge; dysuria; vulvar/vaginal itching, burning, irritation, pain or vulvar edema; coital pain; or vaginal odor). The SVS specimen was always collected first. The study population comprised of 1,478 female patients 14 to ≥ 50 years of age. A total of 2,947 vaginal swabs were tested and were eligible for inclusion in the Xpert Xpress MVP study.
Performance of the Xpert Xpress MVP test in vaginal swab specimens was determined relative to comparator methods. Specifically, positive percent agreement (PPA)/negative percent agreement (NPA) for BV was assessed relative to an FDA-cleared nucleic acid amplification test (NAAT). Sensitivity and specificity for Candida group and Candida glabkrus targets were assessed relative to veast culture followed by mass spectrometry for species identification. PPA and NPA for TV were assessed relative to a patient infected status (PIS) algorithm that included results from an FDA-cleared NAAT and TV culture. When applicable, investigation of discrepant results was performed by testing specimens with another FDA-cleared NAAT.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
The performance of the Xpert Xpress MVP test was evaluated in a multi-site clinical study. The results of the study demonstrated that the performance of the Xpert Xpress MVP test is substantially equivalent to the predicate device.
Performance of the Xpert Xpress MVP test is presented in Table 5-13. The Xpert Xpress MVP test demonstrated PPA and NPA of 93.8% and 93.8% for BV detection in CVS specimens, respectively, and 94.0% and 92.9% in SVS specimens, respectively. For Candida group detection, the Xpert Xpress MVP test demonstrated sensitivity and specificity of 98.0% and 94.6% in CVS specimens, respectively, and 97.5% and 92.1% in SVS specimens, respectively. The Xpert Xpress MVP test demonstrated sensitivity and specificity of 93.6% and 99.6% for Candida glab-krus detection in CVS specimens, respectively, and 97.8% and 99.4% in SVS specimens, respectively. For TV detection, the Xpert Xpress MVP test demonstrated PPA and NPA of 97.3% and 99.6% in CVS specimens, respectively, and 97.3% and 99.8% in SVS specimens, respectively.
BV
CVS: PPA 93.8% (531/566), NPA 93.8% (808/861)
SVS: PPA 94.0% (533/567), NPA 92.9% (794/855)
Candida group
CVS: Sensitivity 98.0% (396/404), Specificity 94.6% (984/1040)
SVS: Sensitivity 97.5% (393/403), Specificity 92.1% (954/1036)
Candida glab-krus (Fresh Prospective)
CVS: Sensitivity 93.6% (44/47), Specificity 99.6% (1392/1397)
SVS: Sensitivity 97.8% (45/46), Specificity 99.4% (1384/1393)
Candida glab-krus (Contrived)
CVS: Sensitivity 99.0% (98/99), Specificity 96.4% (27/28)
SVS: N/A
TV
CVS: PPA 97.3% (73/75), NPA 99.6% (1332/1337)
SVS: PPA 97.3% (72/74), NPA 99.8% (1330/1333)
Non-Determinate Rate
Initial non-determinate rate: 4.4% (130/2947)
Overall non-determinate rate (after retest): 0.7% (22/2947)
CVS initial non-determinate rate: 3.9% (58/1473)
CVS overall non-determinate rate: 0.5% (8/1473)
SVS initial non-determinate rate: 4.9% (72/1474)
SVS overall non-determinate rate: 0.9% (14/1474)
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
See "Summary of Performance Studies" section for PPA, NPA, Sensitivity, and Specificity values.
Predicate Device(s)
BD MAX Vaginal Panel (K191957)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
N/A
0
February 9, 2022
Image /page/0/Picture/1 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which consists of the letters "FDA" in a blue square. To the right of the square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
Cepheid Wei Zhang Senior Regulatory Affairs Specialist 904 Caribbean Drive Sunnyvale, California 94089
Re: K212213
Trade/Device Name: Xpert Xpress MVP, GeneXpert Dx System, GeneXpert Infinity System Regulation Number: 21 CFR 866.3975 Regulation Name: Device That Detects Nucleic Acid Sequences From Microorganisms Associated With Vaginitis And Bacterial Vaginosis Regulatory Class: Class II Product Code: PQA, NSU Dated: July 14, 2021 Received: July 15, 2021
Dear Wei Zhang:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal
1
statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Maria Ines Garcia Assistant Director Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known)
Device Name
Indications for Use (Describe)
| Type of Use (Select one or both, as applicable) | |
|---|---|
| ------------------------------------------------- | -- |
Prescription Use (Part 21 CFR 801 Subpart D)
| Over-The-Counter Use (21 CFR 801 Subpart C)
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Section 5
510(k) Summary for Xpert Xpress MVP
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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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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: | February 8, 2022 |
| Device: | |
| Trade name: | Xpert® Xpress MVP |
| Common name: | Xpert Xpress MVP |
| Type of Test: | Qualitative real-time polymerase chain reaction (PCR) and
detection test |
| Regulation number,
Classification name, | 21 CFR 866.3975, Vaginitis and Bacterial Vaginosis Nucleic
Acid Detection System, PQA |
| Product code
Definition | 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 | BD MAX Vaginal Panel (K191957) |
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5.1 Device Description
The Xpert® Xpress MVP test is an automated in vitro diagnostic test for qualitative detection of DNA targets from anaerobic bacteria associated with bacterial vaginosis, Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis, the agent of trichomoniasis. The Xpert Xpress MVP test is performed on GeneXpert Instrument Systems.
The GeneXpert Instrument Systems automate and integrate sample preparation, nucleic acid extraction and amplification, and detection of the target sequences in simple or complex samples using real-time PCR assays. The systems consist of an instrument, computer, and preloaded software for running tests and viewing the results. The systems require the use of single-use disposable cartridges that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained, cross-contamination between samples is minimized.
The Xpert Xpress MVP test includes reagents for the detection of DNA from BV organisms, Candida species, and Trichomonas vaginalis from vaginal swab samples. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are also included in the cartridge utilized by the GeneXpert System instrument. The SPC is present to control for adequate processing of the sample and to monitor for the presence of potential inhibitor(s) in the PCR reaction. The SPC also ensures that the PCR reaction conditions (temperature and time) are appropriate for the amplification reaction and that the PCR reagents are functional. The PCC verifies reagent rehydration, PCR tube filling, and confirms that all reaction components are present in the cartridge including monitoring for probe integrity and dye stability.
The Xpert Xpress MVP test is designed for use with the following specimens collected from symptomatic individuals: self-collected vaginal swabs (collected in a clinical setting) and clinician-collected vaginal swabs. The swab transport reagent included in the Xpert Swab Specimen Collection Kit is designed to collect and preserve patient specimens to allow transport to the laboratory prior to analysis with the Xpert Xpress MVP test.
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5.2 Device Intended Use
The Xpert Xpress MVP test, performed on the GeneXpert Instrument Systems, is an automated qualitative in vitro diagnostic test for the detection of DNA targets from anaerobic bacteria associated with bacterial vaginosis (BV), Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis. The Xpert Xpress MVP test uses clinician-collected and self-collected vaginal swabs (collected in a clinical setting) from patients who are symptomatic for vaginitis/vaginosis. The Xpert Xpress MVP test utilizes real-time polymerase chain reaction (PCR) for the amplification of specific DNA targets and utilizes fluorogenic target-specific hybridization probes to detect and differentiate DNA from:
- . Organisms associated with bacterial vaginosis (detected organisms not reported individually)
- o Atopobium spp. (Atopobium vaginae, Atopobium novel species CCUG 55226)
- Bacterial Vaginosis-Associated Bacterium 2 (BVAB2) o
- Megasphaera-1 o
- Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis, species not differentiated)
- Candida glabrata/Candida krusei (species not differentiated)
- . Trichomonas vaginalis
The Xpert Xpress MVP test is intended to aid in the diagnosis of vaginal infections in women with a clinical presentation consistent with bacterial vaginosis, vulvovaginal candidiasis, or trichomoniasis.
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Image /page/8/Picture/1 description: The image contains the Cepheid company logo. The logo consists of a blue graphic element resembling stylized wings or a swoosh above the company name "Cepheid." Below the company name, the text "Xpert® Xpress MVP" is displayed, indicating a specific product or service offered by Cepheid.
5.3 Substantial Equivalence
The Xpert Xpress MVP test is substantially equivalent to the BD MAX Vaginal Panel [510(k) # K191957].
The following tables compare Xpert Xpress MVP to BD MAX Vaginal Panel (K191957). Table 5-1 shows similarities between the new device and the predicate.
| Table 3-1: Similarities Between New Device and Predicate Device | ||
|---|---|---|
| Attribute | New Device | |
| Xpert® Xpress MVP | Predicate Device | |
| BD MAX Vaginal Panel (K191957) | ||
| 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® Instrument Systems, is an automated qualitative in vitro diagnostic test for the detection of DNA targets from anaerobic bacteria associated with bacterial vaginosis (BV), Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis . The Xpert Xpress MVP test uses clinician-collected and self-collected vaginal swabs (collected in a clinical setting) from patients who are symptomatic for vaginitis/vaginosis. The Xpert Xpress MVP test utilizes real-time polymerase chain reaction (PCR) for the amplification of specific DNA targets and utilizes fluorogenic target-specific hybridization probes to detect and differentiate DNA from: | |
| Organisms associated with bacterial vaginosis (detected organisms not reported individually) Atopobium spp. ( Atopobium vaginae, Atopobium novel species CCUG 55226) Bacterial Vaginosis-Associated Bacterium 2 (BVAB2) | The BD MAX Vaginal Panel performed on the BD MAX System is an automated qualitative in vitro diagnostic test for the direct detection of DNA targets from bacteria associated with bacterial vaginosis (qualitative results reported based on detection and quantitation of targeted organism markers), Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis from vaginal swabs in patients who are symptomatic for vaginitis/vaginosis. The test utilizes real-time polymerase chain reaction (PCR) for the amplification of specific DNA targets and utilizes fluorogenic target-specific hybridization probes to detect and differentiate DNA from: | |
| Bacterial vaginosis markers (Individual markers not reported) Lactobacillus spp. ( L. crispatus and L. jensenii ) Gardnerella vaginalis Atopobium vaginae | ||
| Comparison | ||
| Attribute | New Device | |
| Xpert® Xpress MVP | Predicate Device | |
| BD MAX Vaginal Panel (K191957) | ||
| ○ Megasphaera-1 | ||
| • Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis, species not differentiated) | ||
| • Candida glabrata/Candida krusei (species not differentiated) | ||
| • Trichomonas vaginalis | ||
| The Xpert Xpress MVP test is intended to aid in the diagnosis of vaginal infections in women with a clinical presentation consistent with bacterial vaginosis, vulvovaginal candidiasis, or trichomoniasis. | ○ Bacterial Vaginosis Associated Bacteria-2 (BVAB-2) | |
| ○ Megasphaera-1 | ||
| • Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis) | ||
| • Candida glabrata | ||
| • Candida krusei | ||
| • Trichomonas vaginalis | ||
| The BD MAX Vaginal Panel is intended to aid in the diagnosis of vaginal infections in women with a clinical presentation consistent with bacterial vaginosis, vulvovaginal candidiasis and trichomoniasis. | ||
| Laboratory Users | Same | CLIA Moderate Complexity |
| Specimen Type | Same | Clinician and patient-collected female vaginal swabs |
| Assay Technology | Same | Real-Time PCR |
| Single Use | Same | Yes |
| Automated Extraction, detection and result interpretation | Same | Yes |
| Assay Results | Same | Qualitative |
Table 5-1: Similarities between New Device and Predicate Device
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Table 5-2 shows the differences between the new device and the predicate.
| Table 5-2: Differences between New Device and Predicate Device | |||
|---|---|---|---|
| -- | -- | -- | ---------------------------------------------------------------- |
| Comparison | ||
|---|---|---|
| Attribute | New Device | Predicate Device |
| Xpert® Xpress MVP | BD MAX Vaginal Panel (K191957) | |
| Organisms Detected | Organisms associated with bacterial vaginosis (detected organisms not reported individually) Atopobium spp. ( Atopobium vaginae , Atopobium novel species CCUG 55226) Bacterial Vaginosis-Associated Bacterium 2 (BVAB2) | Bacterial vaginosis markers (Individual markers not reported) Lactobacillus spp. ( L. crispatus and L. jensenii ) Gardnerella vaginalis Atopobium vaginae Bacterial Vaginosis Associated Bacteria-2 (BVAB-2) |
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Image /page/10/Picture/0 description: The image shows the Cepheid logo and product name. The logo features a stylized blue wing-like design above the word "Cepheid." Below the logo, the text "Xpert® Xpress MVP" is displayed, indicating the name of the product. The text is in a simple, sans-serif font.
| Comparison | ||
|---|---|---|
| Attribute | New Device | |
| Xpert® Xpress MVP | Predicate Device | |
| BD MAX Vaginal Panel (K191957) | ||
| Megasphaera-1 Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis, species not differentiated) Candida glabrata/Candida krusei (species not differentiated) Trichomonas vaginalis | Megasphaera-1 Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis) Candida glabrata Candida krusei Trichomonas vaginalis | |
| Instrument Systems | Cepheid GeneXpert Instrument Systems | BD MAX System |
| Collection Device | Cepheid Xpert Swab Specimen Collection kit | MAX UVE Specimen Collection Kit |
| Time to Result | Single test | |
| Within 60 minutes | Batch test | |
| ~ 2-4 hours |
The Xpert Xpress MVP test has the same general intended use as the predicate device and technological characteristics as the predicate device. The performance of the Xpert Xpress MVP test was evaluated in a multi-site clinical study. The results of the study demonstrated that the performance of the Xpert Xpress MVP test is substantially equivalent to the predicate device. The differences between the Xpert Xpress MVP test and the predicate device do not raise different questions of safety and effectiveness.
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5.4 Non-Clinical Study
Analytical Sensitivity
The analytical sensitivity (Limit of Detection, LoD) of the Xpert Xpress MVP test was determined by preparing dilutions for each of the target organisms detected by the test. The LoD is defined as the lowest concentration of organism sample that can be reproducibly distinguished from negative samples with 95% confidence. The near cut-off concentrations for the BV organisms were also determined. The near cut-off concentration for the BV organisms is defined as the lowest concentrations of Atopobium vaginae and Megasphaera-1, or A. vaginae and BVAB2. or A. vaginae and Megasphaera-1 and BVAB2. or A. vaginae in the absence of Megasphaera-1 and BVAB2 that result in BV POSITIVE test results and can be reproducibly distinguished from negative samples with a 95% confidence level. Positive samples were prepared by inoculating simulated vaginal swab matrix with each representative strain or quantified stock of plasmid DNA containing the cloned genomic target of BVAB2 or Megasphaera-1. Replicates of 20 were evaluated at a minimum of five concentrations for each of the target organisms. The LoD and/or near cut-off concentrations for the target organisms were estimated by probit analysis or by the classical approach using a 95% hit rate. The LoD for each Candida spp. and Trichomonas vaginalis strain was verified in natural clinical vaginal swab matrix and simulated vaginal swab matrix. The LoD and near cut-off concentrations for each BV organism were verified in simulated vaginal swab matrix. The verified LoD and near cut-off concentrations for Xpert Xpress MVP targets are presented in Table 5-3.
| Organism | Verified LoD |
|---|---|
| Atopobium vaginae | 32 CFU/mL |
| BVAB2 (plasmid DNA) | 50 copies/mL |
| Megasphaera-1 (plasmid DNA) | 338 copies/mL |
| Candida albicans | 30 CFU/mL |
| Candida tropicalis | 750 CFU/mL |
| Candida parapsilosis | 1,339 CFU/mL |
| Candida dubliniensis | 1,316 CFU/mL |
| Candida glabrata | 20 CFU/mL |
| Candida krusei | 656 CFU/mL |
| Trichomonas vaginalis | 5 cells/mL |
| BV Organism | Verified Near Cut-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 5-3: Verified LoD and Near Cut-off concentrations for Xpert Xpress MVP |
|---|
| ------------------------------------------------------------------------------ |
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Analytical Reactivity (Inclusivity)
The analytical reactivity of the Xpert Xpress MVP test was determined with 5 strains of Candida albicans, 5 strains of Candida dubliniensis, 5 strains of Candida tropicalis, 5 strains of Candida parapsilosis, 5 strains of Candida glabrata, 5 strains of Candida krusei, 11 strains of Atopobium spp. (Atopobium vaginae and/or Atopobium novel species CCUG 55226), and 10 strains of Trichomonas vaginalis that were diluted in simulated vaginal swab matrix at 3× LoD. Each Atopobium spp. strain was also evaluated at 3× near cut-off concentrations diluted in simulated vaginal swab matrix in the absence or presence of BVAB2 and/or Megasphaera-1 DNA to confirm the correct BV POSITIVE test results were reported.
The Xpert Xpress MVP test correctly identified 46 of 51 strains upon initial testing at 3× LoD. Two strains of Atopobium vaginae tested at 3× LoD and three strains of Candida albicans tested at 3× LoD were not detected and were tested at higher concentrations to determine the minimum concentration sufficient for detection. One Atopobium vaginae strain was detected at ~4× LoD and the other strain was detected at ~12× LoD. One Candida albicans strain was detected at ~4× LoD and the other two Candida albicans strains were detected at ~20× LoD.
For near cut-off concentration of Atopobium spp. in the absence of Megasphaera-1 and BVAB2, the Xpert Xpress MVP test correctly reported BV POSITIVE test result for 7 of the 11 strains upon initial testing at 3× near cut-off concentration. Four strains did not meet acceptance criteria and were further tested to determine the minimum concentration sufficient for reporting BV POSITIVE test result. One Atopobium spp. strain reported BV POSITIVE at ~4×, two strains at ~6×, and one strain at ~12× near cut-off concentration.
For the near cut-off concentration of Atopobium spp. in the presence of Megasphaera-1 and/or BVAB2, the Xpert Xpress MVP test correctly reported BV POSITIVE test result for 7 of the 11 strains upon initial testing at 3× near cut-off concentration. Four strains did not meet acceptance criteria and were further tested to determine the minimum concentration sufficient for reporting BV POSITIVE test result. Two Atopobium spp. strains reported BV POSITIVE at ~4x, one strain at ~6×, and one strain at ~7× near cut-off concentration. The analytical reactivity result summary is presented in Table 5-4.
| Organism | Strain | Concentration | Result | |||
|---|---|---|---|---|---|---|
| BV | Candida | |||||
| group | Candida | |||||
| glab-krus | TV | |||||
| Negative Control | Negative | Not Detected | Not Detected | Not Detected | ||
| Atopobium spp. | ||||||
| LoD | ||||||
| (Below the near | ||||||
| cut-off | ||||||
| concentrations and | ||||||
| not generating BV | ||||||
| POSITIVE result) a | CCUG 39382 | 96 CFU/mL | pos a | Not Detected | Not Detected | Not Detected |
| CCUG 42099 | 96 CFU/mL | pos a | Not Detected | Not Detected | Not Detected | |
| CCUG 43049 | 96 CFU/mL | pos a | Not Detected | Not Detected | Not Detected | |
| CCUG 44061 | 96 CFU/mL | pos a | Not Detected | Not Detected | Not Detected | |
| CCUG 44116 | 96 CFU/mL | pos a | Not Detected | Not Detected | Not Detected | |
| CCUG 44125 | 120 CFU/mL b | pos a | Not Detected | Not Detected | Not Detected | |
| CCUG 44156 | 96 CFU/mL | pos a | Not Detected | Not Detected | Not Detected | |
| CCUG 44258 | 96 CFU/mL | pos a | Not Detected | Not Detected | Not Detected | |
| CCUG 48515 | 400 CFU/mL c | pos a | Not Detected | Not Detected | Not Detected | |
| CCUG 55227 | 96 CFU/mL | pos a | Not Detected | Not Detected | Not Detected | |
| CCUG 55226 | 96 CFU/mL | pos a | Not Detected | Not Detected | Not Detected | |
| CCUG 39382 | 9.6×10⁵ CFU/mL | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 42099 | 9.6×10⁵ CFU/mL | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 43049 | 9.6×10⁵ CFU/mL | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 44061 | 9.6×10⁵ CFU/mL | Positive | Not Detected | Not Detected | Not Detected | |
| Atopobium spp. | CCUG 44116 | 9.6×10⁵ CFU/mL | Positive | Not Detected | Not Detected | Not Detected |
| In the absence of | CCUG 44125 | 1.2×10⁶ CFU/mL d | Positive | Not Detected | Not Detected | Not Detected |
| Megasphaera-1 | CCUG 44156 | 2.0×10⁶ CFU/mL e | Positive | Not Detected | Not Detected | Not Detected |
| and BVAB2 | CCUG 44258 | 9.6×10⁵ CFU/mL | Positive | Not Detected | Not Detected | Not Detected |
| CCUG 48515 | 4.0×10⁶ CFU/mL f | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 55227 | 9.6×10⁵ CFU/mL | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 55226 | 2.0×10⁶ CFU/mL g | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 39382 | 8,250 CFU/mL | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 42099 | 8,250 CFU/mL | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 43049 | 8,250 CFU/mL | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 44061 | 8,250 CFU/mL | Positive | Not Detected | Not Detected | Not Detected | |
| Atopobium spp. | CCUG 44116 | 8,250 CFU/mL | Positive | Not Detected | Not Detected | Not Detected |
| CCUG 44125 | 10,000 CFU/mL h | Positive | Not Detected | Not Detected | Not Detected | |
| In the presence of | ||||||
| BVAB2 | CCUG 44156 | 17,000 CFU/mL i | Positive | Not Detected | Not Detected | Not Detected |
| CCUG 44258 | 8,250 CFU/mL | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 48515 | 17,000 CFU/mL J | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 55227 | 8,250 CFU/mL | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 55226 | 10,000 CFU/mL k | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 39382 | 8,250 CFU/mL | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 42099 | 8,250 CFU/mL | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 43049 | 8,250 CFU/mL | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 44061 | 8,250 CFU/mL | Positive | Not Detected | Not Detected | Not Detected | |
| Atopobium spp. | CCUG 44116 | 8,250 CFU/mL | Positive | Not Detected | Not Detected | Not Detected |
| In the presence of | ||||||
| Megasphaera-1 | CCUG 44125 | 10,000 CFU/mL h | Positive | Not Detected | Not Detected | Not Detected |
| CCUG 44156 | 17,000 CFU/mL i | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 44258 | 8,250 CFU/mL | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 48515 | 20,000 CFU/mL j | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 55227 | 8,250 CFU/mL | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 55226 | 10,000 CFU/mL k | Positive | Not Detected | Not Detected | Not Detected | |
| Atopobium spp. | CCUG 39382 | 8,250 CFU/mL | Positive | Not Detected | Not Detected | Not Detected |
| CCUG 42099 | 8,250 CFU/mL | Positive | Not Detected | Not Detected | Not Detected | |
| In the presence of | ||||||
| Megasphaera-1 | ||||||
| and BVAB2 | CCUG 43049 | 8,250 CFU/mL | Positive | Not Detected | Not Detected | Not Detected |
| CCUG 44061 | 8,250 CFU/mL | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 44116 | 8,250 CFU/mL | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 44125 | 10,000 CFU/mL h | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 44156 | 17,000 CFU/mL i | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 44258 | 8,250 CFU/mL | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 48515 | 17,000 CFU/mL j | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 55227 | 8,250 CFU/mL | Positive | Not Detected | Not Detected | Not Detected | |
| CCUG 55226 | 10,000 CFU/mL k | Positive | Not Detected | Not Detected | Not Detected | |
| ATCC 38289 | 120 CFU/mL l | Negative | Detected | Not Detected | Not Detected | |
| ATCC 62376 | 600 CFU/mL m | Negative | Detected | Not Detected | Not Detected | |
| Candida albicans | ATCC 96113 | 90 CFU/mL | Negative | Detected | Not Detected | Not Detected |
| ATCC 60193 | 90 CFU/mL | Negative | Detected | Not Detected | Not Detected | |
| ATCC 753 | 600 CFU/mL n | Negative | Detected | Not Detected | Not Detected | |
| ATCC MYA-179 | 3,948 CFU/mL | Negative | Detected | Not Detected | Not Detected | |
| ATCC MYA-577 | 3,948 CFU/mL | Negative | Detected | Not Detected | Not Detected | |
| Candida | ||||||
| dubliniensis | ATCC MYA-646 | 3,948 CFU/mL | Negative | Detected | Not Detected | Not Detected |
| ATCC MYA-580 | 3,948 CFU/mL | Negative | Detected | Not Detected | Not Detected | |
| ATCC MYA-581 | 3,948 CFU/mL | Negative | Detected | Not Detected | Not Detected | |
| ATCC 34139 | 2,250 CFU/mL | Negative | Detected | Not Detected | Not Detected | |
| ATCC 90874 | 2,250 CFU/mL | Negative | Detected | Not Detected | Not Detected | |
| Candida tropicalis | ATCC 204318 | 2,250 CFU/mL | Negative | Detected | Not Detected | Not Detected |
| ATCC MYA-2733 | 2,250 CFU/mL | Negative | Detected | Not Detected | Not Detected | |
| ATCC MYA-277 | 2,250 CFU/mL | Negative | Detected | Not Detected | Not Detected | |
| ATCC 7330 | 4,017 CFU/mL | Negative | Detected | Not Detected | Not Detected | |
| ATCC 60548 | 4,017 CFU/mL | Negative | Detected | Not Detected | Not Detected | |
| Candida | ||||||
| parapsilosis | ATCC 90875 | 4,017 CFU/mL | Negative | Detected | Not Detected | Not Detected |
| ATCC 96139 | 4,017 CFU/mL | Negative | Detected | Not Detected | Not Detected | |
| ATCC 96140 | 4,017 CFU/mL | Negative | Detected | Not Detected | Not Detected | |
| ATCC 32312 | 60 CFU/mL | Negative | Not Detected | Detected | Not Detected | |
| ATCC 32554 | 60 CFU/mL | Negative | Not Detected | Detected | Not Detected | |
| Candida glabrata | ATCC 15126 | 60 CFU/mL | Negative | Not Detected | Detected | Not Detected |
| ATCC 2001 | 60 CFU/mL | Negative | Not Detected | Detected | Not Detected | |
| ATCC MYA-276 | 60 CFU/mL | Negative | Not Detected | Detected | Not Detected | |
| ATCC 28870 | 1,968 CFU/mL | Negative | Not Detected | Detected | Not Detected | |
| ATCC 32672 | 1,968 CFU/mL | Negative | Not Detected | Detected | Not Detected | |
| Candida krusei | ATCC 90878 | 1,968 CFU/mL | Negative | Not Detected | Detected | Not Detected |
| ATCC 200917 | 1,968 CFU/mL | Negative | Not Detected | Detected | Not Detected | |
| ATCC 201748 | 1,968 CFU/mL | Negative | Not Detected | Detected | Not Detected | |
| ATCC 30184 | 15 cells/mL | Negative | Not Detected | Not Detected | Detected | |
| Trichomonas vaginalis | ATCC 30187 | 15 cells/mL | Negative | Not Detected | Not Detected | Detected |
| ATCC 30238* | 15 cells/mL | Negative | Not Detected | Not Detected | Detected | |
| ATCC 30240 | 15 cells/mL | Negative | Not Detected | Not Detected | Detected | |
| ATCC 30245 | 15 cells/mL | Negative | Not Detected | Not Detected | Detected | |
| ATCC 50139 | 15 cells/mL | Negative | Not Detected | Not Detected | Detected | |
| ATCC 50141 | 15 cells/mL | Negative | Not Detected | Not Detected | Detected | |
| ATCC 50167 | 15 cells/mL | Negative | Not Detected | Not Detected | Detected | |
| ATCC 50183 | 15 cells/mL | Negative | Not Detected | Not Detected | Detected | |
| ATCC PRA-95 | 15 cells/mL | Negative | Not Detected | Not Detected | Detected |
Table 5-4: Analytical Reactivity of the Xpert Xpress MVP Test
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4 The LoD for Atopobium vaginae is for information only. All Atopobium spp. strains tested at ~3× LoD level reported BV NEGATIVE result calls as expected, as the concentration of Atopobium spp. strains tested was below the near cut-off concentration either in the presence or absence of Megal-BVAB2 target. Replicates reporting Atop gp Ct values of ≤ 40.0 was treated as positive (pos) when Atopobium spp. strains were tested at ~ 3× LoD.
b Atopobium vaginae CCUG 44125 was tested at ~ 4× LoD (120 CFU/mL) to obtain 3 of 3 Atop gp Ct values of ≤ 40.0 results.
6 Atopobium vaginae CCUG 48515 was tested at ~ 12× LoD (400 CFU/mL) to obtain 3 of 3 Atop gp Ct values of Atopobium vaginae
(Candida albicans
(1×106 CFU/mL) |
| | 2 | (Candida glabrata
(1×106 CFU/mL) |
| | 3 | (Trichomonas vaginalis
(1×105 cells/mL) |
| Testing Panel | Testing Target/Organisms
(Low Positive) | Competitive
Target/Organisms
(High Positive) | |
| 4 | Atopobium vaginae
( $ 5.5% v/v (Interference
Observed)
4.0% v/v (Interference not
Observed) |
| Leukocytes | Leukocytes | $10^5$ cells/mL |
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| Substance/Class | Active Ingredient | Concentration Tested |
|---|---|---|
| Intravaginal Hormones | Estradiol; Progesterone | 7mg/mL Progesterone + |
| 0.07mg/mL Beta Estradiol | ||
| Over the counter (OTC) | ||
| Vaginal Products; | ||
| Contraceptives; 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 | 0.25% w/v | |
| Berberis Vulgaris 6X HPUS | ||
| (Barberry), Borax 3X HPUS (Sodium | ||
| Borate), Collinsonia Canadensis 3X | ||
| HPUS (Stone Root), Hamamelis | ||
| Virginiana 6X HPUS (Witch Hazel), | ||
| Bacillus coagulans (Lactospore®) | 0.25% w/v | |
| Povidone-iodine 10% (topical) | 0.25% v/v | |
| Povidone-iodine 0.3% (douche) | 0.25% v/v | |
| Nonoxynol-9 12.5% | 0.25% w/v | |
| Metronidazole 0.75% | 0.25% w/v | |
| Hemorrhoidal Cream | Glycerin 14%; Pramoxine HCl 1% | 0.25% w/v |
Carry-Over Contamination
A study was conducted to demonstrate that single-use, self-contained GeneXpert cartridges prevent specimen and amplicon carry-over contamination from very high titer positive samples into successively run negative samples when processed in the same GeneXpert module. The study consisted of a negative sample processed in the same GeneXpert module immediately after processing a very high BV positive sample (an A. vaginae strain at 2.8×10 CFU/mL and BVAB2 plasmid DNA at 5.0×10° copies/mL), a very high Candida group positive sample (a C. albicans strain at 3.0×106 CFU/mL), or a very high TV positive sample (a T. vaginalis strain at 5.0×10° cells/mL) in simulated vaginal swab matrix. The testing scheme was repeated 20 times in a single GeneXpert module for a total of 41 runs (20 high positive samples and 21 negative samples per module) across 3 GeneXpert modules. There was no evidence of any carry-over contamination. All 63 negative samples were correctly reported as negative/not detected. All 60 positive samples were correctly reported as positive/detected.
Time to Result
The time to result is defined as the time from the initiation of cartridge processing on the GeneXpert system to the time a result is displayed on the test screen. The time to result for the Xpert Xpress MVP test was determined by evaluating the test time of 50 random tests
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that were conducted as part of the clinical study. The Xpert Xpress MVP test has a turnaround time of within 60 minutes, and the data from this study is representative for the GeneXpert Instrument Systems.
Reproducibility and Precision
Reproducibility and precision of the Xpert Xpress MVP test was established through a multicenter (3 sites), blinded study utilizing a multi-factor nested design consisting of contrived panel members spanning the relevant limit of detection (LoD) spectrum (or, in the case of BV, the near cut-off concentration) for the 4 intended target types.
A panel of ten panel members with varying concentrations of the intended target types were tested by two operators in duplicate on six different days at three sites using three lots of Xpert Xpress MVP test cartridges. The total number of tests for each panel member was 144 (3 sites × 3 lots × 2 days × 2 operators × 2 runs × 2 replicates). The three concentrations for each intended target type included two positive levels (moderate positives at ~3× LoD/near cut-off concentration, low positives at ~1× LoD/near cut-off concentration) and one negative. For the BV target, a high negative level (A. vaginae , Low Pos | Atop gp | 80 | 24.98 | 0.00 | 0.0 | 0.00 | 0.0 | 0.03 | 0.1 | 0.32 | 1.3 | 0.32 | 1.3 |
| | SPC | 80 | 32.64 | 0.17 | 0.5 | 0.17 | 0.5 | 0.12 | 0.4 | 0.37 | 1.1 | 0.46 | 1.4 |
| A. vaginae and
BVAB2, High Neg | Atop gp | 80 | 32.35 | 0.00 | 0.0 | 0.16 | 0.5 | 0.00 | 0.0 | 0.20 | 0.6 | 0.26 | 0.8 |
| | Megal-
BVAB2b | 75 | 41.30 | 0.37 | 0.9 | 0.00 | 0.0 | 0.26 | 0.6 | 1.15 | 2.8 | 1.24 | 3.0 |
| | Atop gp | 80 | 32.20 | 0.00 | 0.0 | 0.04 | 0.1 | 0.08 | 0.3 | 0.22 | 0.7 | 0.24 | 0.7 |
| A. vaginae and
BVAB2, Low Pos | Megal-
BVAB2b | 80 | 40.03 | 0.00 | 0.0 | 0.00 | 0.0 | 0.30 | 0.7 | 0.90 | 2.2 | 0.94 | 2.4 |
| | SPC | 80 | 32.63 | 0.11 | 0.3 | 0.17 | 0.5 | 0.00 | 0.0 | 0.39 | 1.2 | 0.44 | 1.3 |
| A. vaginae and
Mega-1, High Neg | Atop gp | 80 | 32.62 | 0.00 | 0.0 | 0.04 | 0.1 | 0.00 | 0.0 | 0.33 | 1.0 | 0.34 | 1.0 |
| | Megal-
BVAB2b | 28 | 38.98 | 0.00 | 0.0 | 1.01 | 2.6 | 0.21 | 0.6 | 0.84 | 2.2 | 1.33 | 3.4 |
| A. vaginae 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-
BVAB2b | 80 | 35.48 | 0.00 | 0.0 | 0.29 | 0.8 | 0.00 | 0.0 | 0.71 | 2.0 | 0.77 | 2.2 |
Table 5-12. Results of Precision for the BV Target
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| Panel member | Analyte | Na | Mean
Ct | Day | | Operator | | Between-Run | | Within-run | | Total | |
|-----------------------------------------------|--------------|----|------------|------|-----------|----------|-----------|-------------|-----------|------------|-----------|-------|-----------|
| | | | | SD | CV
(%) | SD | CV
(%) | SD | CV
(%) | SD | CV
(%) | SD | CV
(%) |
| A. vaginae, BVAB2,
and Mega-1,
High Neg | SPC | 80 | 32.74 | 0.15 | 0.5 | 0.12 | 0.4 | 0.17 | 0.5 | 0.33 | 1.0 | 0.41 | 1.3 |
| | Atop gp | 80 | 32.53 | 0.00 | 0.0 | 0.15 | 0.5 | 0.00 | 0.0 | 0.22 | 0.7 | 0.27 | 0.8 |
| | Mega1-BVAB2b | 63 | 41.57 | 0.30 | 0.7 | 0.00 | 0.0 | 0.39 | 0.9 | 1.02 | 2.5 | 1.13 | 2.7 |
| A. vaginae, BVAB2,
and Mega-1,
Low Pos | Atop gp | 79 | 31.81 | 0.00 | 0.0 | 0.22 | 0.7 | 0.28 | 0.9 | 1.16 | 3.6 | 1.21 | 3.8 |
| and Mega-1,
Low Pos | Mega1-BVAB2b | 80 | 36.25 | 0.15 | 0.4 | 0.00 | 0.0 | 0.10 | 0.3 | 0.69 | 1.9 | 0.71 | 2.0 |
| A. vaginae, BVAB2,
and Mega-1,
Mod Pos | Atop gp | 80 | 30.67 | 0.13 | 0.4 | 0.09 | 0.3 | 0.00 | 0.0 | 0.33 | 1.1 | 0.37 | 1.2 |
| | Mega1-BVAB2b | 80 | 35.64 | 0.00 | 0.0 | 0.26 | 0.7 | 0.00 | 0.0 | 0.48 | 1.3 | 0.54 | 1.5 |
Abbreviations: Atop gp, Atopobium group; CV, coefficient of variance; Megal , Mod; moderate; Neg, negative; Pos, positive; SD, standard deviation; SPC, sample processing control
a Number of samples with non-zero Ct values out of 80.
b Samples with Mega1-BVAB2 that did not generate a Ct value were excluded from analysis.
Note: The variance estimate from some factors may be numerically negative, which can occur if the variability due to those factors is very small. When this occurs, the variability as measured with SD and CV is set to 0.
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5.5 Clinical Studies
The clinical evaluation of the Xpert Xpress MVP test was a multi-site, prospective observational, method comparison clinical study that included twelve (12) sites from geographically diverse locations in the United States. Of the 12 sites, 10 participated in specimen collection and Xpert testing, 1 performed reference/comparator testing and specimen collection, and 1 site participated in specimen collection only.
All sites prospectively collected one (1) self-collected in a clinical setting, SVS) and five (5) clinician-collected vaginal swab (CVS) specimens from symptomatic patients, defined as female patients > 14 years of age who presented with signs and/or symptoms of vaginitis/vaginosis (including abnormal vaginal discharge; dysuria; vulvar/vaginal itching, burning, irritation, pain or vulvar edema; coital pain; or vaginal odor). The SVS specimen was always collected first. The study population comprised of 1,478 female patients 14 to ≥ 50 years of age. A total of 2,947 vaginal swabs were tested and were eligible for inclusion in the Xpert Xpress MVP study.
Performance of the Xpert Xpress MVP test in vaginal swab specimens was determined relative to comparator methods. Specifically, positive percent agreement (PPA)/negative percent agreement (NPA) for BV was assessed relative to an FDA-cleared nucleic acid amplification test (NAAT). Sensitivity and specificity for Candida group and Candida glabkrus targets were assessed relative to veast culture followed by mass spectrometry for species identification. PPA and NPA for TV were assessed relative to a patient infected status (PIS) algorithm that included results from an FDA-cleared NAAT and TV culture. When applicable, investigation of discrepant results was performed by testing specimens with another FDA-cleared NAAT.
Performance of the Xpert Xpress MVP test is presented in Table 5-13. The Xpert Xpress MVP test demonstrated PPA and NPA of 93.8% and 93.8% for BV detection in CVS specimens, respectively, and 94.0% and 92.9% in SVS specimens, respectively. For Candida group detection, the Xpert Xpress MVP test demonstrated sensitivity and specificity of 98.0% and 94.6% in CVS specimens, respectively, and 97.5% and 92.1% in SVS specimens, respectively. The Xpert Xpress MVP test demonstrated sensitivity and specificity of 93.6% and 99.6% for Candida glab-krus detection in CVS specimens, respectively, and 97.8% and 99.4% in SVS specimens, respectively. For TV detection, the Xpert Xpress MVP test demonstrated PPA and NPA of 97.3% and 99.6% in CVS specimens, respectively, and 97.3% and 99.8% in SVS specimens, respectively.
28
| Clinician-collected (CVS) | Self-collected (SVS) | ||||
|---|---|---|---|---|---|
| Sensitivity/PPA | |||||
| (95% CI) | Specificity/NPA | ||||
| (95% CI) | Sensitivity/PPA | ||||
| (95% CI) | Specificity/NPA | ||||
| (95% CI) | |||||
| BV | 93.8% | ||||
| 531/566 a | |||||
| (91.5% - 95.5%) | 93.8% | ||||
| 808/861 b | |||||
| (92.0% - 95.3%) | 94.0% | ||||
| 533/567 c | |||||
| (91.7% - 95.7%) | 92.9% | ||||
| 794/855 d | |||||
| (90.9% - 94.4%) | |||||
| Candida group* | 98.0% | ||||
| 396/404 e | |||||
| (96.1% - 99.0%) | 94.6% | ||||
| 984/1040 f | |||||
| (93.1% - 95.8%) | 97.5% | ||||
| 393/403 g | |||||
| (95.5% - 98.7%) | 92.1% | ||||
| 954/1036 h | |||||
| (90.3% - 93.6%) | |||||
| Candida glab-krus | |||||
| Fresh Prospective | 93.6% | ||||
| 44/47 i | |||||
| (82.8% - 97.8%) | 99.6% | ||||
| 1392/1397 j | |||||
| (99.2% - 99.9%) | 97.8% | ||||
| 45/46 k | |||||
| (88.7% - 99.6%) | 99.4% | ||||
| 1384/1393 l | |||||
| (98.8% - 99.7%) | |||||
| Candida glab-krus | |||||
| Contrived** | 99.0% | ||||
| 98/99 | |||||
| (94.5% - 99.8%) | 96.4% | ||||
| 27/28 | |||||
| (82.3% - 99.4%) | N/A | N/A | |||
| TV | 97.3% | ||||
| 73/75 m | |||||
| (90.8% - 99.3%) | 99.6% | ||||
| 1332/1337 n | |||||
| (99.1% - 99.8%) | 97.3% | ||||
| 72/74 o | |||||
| (90.7% - 99.3%) | 99.8% | ||||
| 1330/1333 p | |||||
| (99.3% - 99.9%) |
Table 5-13: Overall Performance of the Xpert Xpress MVP Test
*Target includes C. albicans, C. tropicalis, C. parapsilosis, and C. dubliniensis
**Contrived specimens were prepared using individual negative clinical CVS and SVS specimens.
a Testing results with a second FDA-cleared NAAT: 14 were also negative and 21 were positive.
b Testing results with a second FDA-cleared NAAT: 25 were also positive and 28 were negative.
C Testing results with a second FDA-cleared NAAT: 12 were also negative and 22 were positive.
d Testing results with a second FDA-cleared NAAT: 23 were also positive and 38 were negative.
6 Testing results with an FDA-cleared NAAT: 5 were also negative and 3 were positive.
f Testing results with an FDA-cleared NAAT: 31 were also positive and 24 were negative and 1 had no result.
8 Testing results with an FDA-cleared NAAT: 5 were also negative and 5 were positive.
h Testing results with an FDA-cleared NAAT: 38 were also positive and 43 were negative and 1 had no result.
i Testing results with an FDA-cleared NAAT: 2 were also negative and 1 was positive.
i Testing results with an FDA-cleared NAAT: 5 were negative.
k Testing results with an FDA-cleared NAAT: 1 was also negative.
1 Testing results with an FDA-cleared NAAT: 9 were negative.
m Testing results a second FDA-cleared NAAT: 1 was also negative and 1 was positive.
n Testing results a second FDA-cleared NAAT: 4 were also positive and 1 had no result.
0 Testing results a second FDA-cleared NAAT: 1 was also negative and 1 was positive.
P Testing results a second FDA-cleared NAAT: 3 were also positive.
Asymptomatic Population
Although the Xpert Xpress MVP test is not intended for use in an asymptomatic patient population, positivity rates were calculated from CVS and SVS specimens collected from asymptomatic patients to assess how often patients who, despite being asymptomatic, harbored microbial flora associated with vaginosis and candidiasis that could be detected by the Xpert Xpress MVP test. Positivity rates are presented by target and by race/ethnicity in Table 5-14.
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Image /page/29/Picture/1 description: The image contains the logo for Cepheid. The logo consists of a blue graphic element resembling stylized wings or a swoosh above the word "Cepheid." in a serif font. Below the company name is the text "Xpert® Xpress MVP", with the "®" symbol indicating a registered trademark.
| | Target | Overall | Black /African
American^ | Hispanic/Latino | Not Hispanic/Latino | Others* |
|-----|-----------------------|----------|-----------------------------|-----------------|---------------------|---------|
| CVS | BV | 32.9% | 51.0% | 25.5% | 19.5% | 36.4% |
| | | (52/158) | (26/51) | (14/55) | (8/41) | (4/11) |
| | Candida group | 17.1% | 25.5% | 16.4% | 7.3% | 18.2% |
| | | (27/158) | (13/51) | (9/55) | (3/41) | (2/11) |
| | Candida glab-
krus | 4.4% | 2.0% | 5.5% | 4.9% | 9.1% |
| | | (7/158) | (1/51) | (3/55) | (2/41) | (1/11) |
| SVS | BV | 31.5% | 49.1% | 24.1% | 16.3% | 41.7% |
| | | (51/162) | (26/53) | (13/54) | (7/43) | (5/12) |
| | Candida group | 19.1% | 28.3% | 18.5% | 7.0% | 25.0% |
| | | (31/162) | (15/53) | (10/54) | (3/43) | (3/12) |
| | Candida glab-
krus | 4.9% | 1.9% | 7.4% | 4.7% | 8.3% |
| | | (8/162) | (1/53) | (4/54) | (2/43) | (1/12) |
Table 5-14: Positivity Rates in Asymptomatic Patients According to the Xpert Xpress MVP Test
*Including: American Indian or Alaska Native, Asian, Mixed/Unknown
^Includes one Black/African American who was of Hispanic or Latino descent for CVS specimens: includes two Black/African American who was of Hispanic or Latino descent for SVS specimens.
Non-Determinate Rate
Of the 2,947 Xpert Xpress MVP runs performed in the clinical study, 130 resulted in nondeterminate ("Error", "Invalid" or "No Results") results on first attempt. Upon retest of these 130 specimens, 22 remained non-determinate. The initial non-determinate rate was 4.4% (130/2947) and the overall non-determinate rate was 0.7% (22/2947).
The initial non-determinate rate for CVS specimens was 3.9% (58/1473) and the overall nondeterminate rate was 0.5% (8/1473). The initial non-determinate rate for SVS specimens was 4.9% (72/1474) and the overall non-determinate rate was 0.9% (14/1474).
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Image /page/30/Picture/0 description: The image shows the logo for Cepheid, a molecular diagnostics company. The logo features a stylized blue graphic above the company name, "Cepheid." Below the company name is the text "Xpert® Xpress MVP", which likely refers to one of their diagnostic products. The logo is simple and professional, conveying a sense of innovation and expertise in the field of molecular diagnostics.
5.6 Conclusions
The results of the non-clinical analytical and clinical performance studies summarized above demonstrated that the Xpert Xpress MVP test is substantially equivalent to the predicate device.