Xpert® TV Assay on the Cepheid GeneXpert Instrument Systems (GeneXpert Dx, GeneXpert Infinity-48, GeneXpert Infinity-48s, and GeneXpertInfinity-80 systems), Xpert Vaginal/Endocervical Specimen Collection Kit, and Xpert Urine Specimen Collection Kit

K151565 · Cepheid · OUY · Oct 16, 2015 · Immunology

Device Facts

• Record ID: K151565
• Device Name: Xpert® TV Assay on the Cepheid GeneXpert Instrument Systems (GeneXpert Dx, GeneXpert Infinity-48, GeneXpert Infinity-48s, and GeneXpertInfinity-80 systems), Xpert Vaginal/Endocervical Specimen Collection Kit, and Xpert Urine Specimen Collection Kit
• Applicant: Cepheid
• Product Code: OUY · Immunology
• Decision Date: Oct 16, 2015
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3860
• Device Class: Class 2

Intended Use

The Cepheid Xpert TV Assay, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro diagnostic test for the detection of Trichomonas vaginalis genomic DNA. The test utilizes automated real-time polymerase chain reaction (PCR) to detect Trichomonas vaginalis genomic DNA. The Xpert TV Assay uses female urine specimens, endocervical swab specimens, or patient-collected vaginal swab specimens (collected in a clinical setting). The Xpert TV Assay is intended to aid in the diagnosis of trichomoniasis in symptomatic or asymptomatic individuals. Ancillary Collection Kits: Xpert Vaginal/Endocervical Specimen Collection Kit The Cepheid® Xpert® Vaginal/Endocervical Specimen Collection Kit is designed to collect, preserve, and transport Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis DNA in endocervical swab specimens (collected by a clinician) and patient-collected vaginal swab specimens (collected in a clinical setting) from symptomatic and asymptomatic women prior to analysis with the Xpert CT/NG Assay and the Xpert TV Assay. Xpert Urine Specimen Collection Kit The Cepheid® Xpert® Urine Specimen Collection Kit is designed to preserve and transport Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis DNA in first-catch urine specimens from symptomatic and asymptomatic individuals prior to analysis with the Xpert CT/NG Assay and the Xpert TV Assay. The Xpert Urine Specimen Collection Kit is intended for use with male (Xpert CT/NG Assay) and female (Xpert CT/NG Assay and Xpert TV Assay) urine.

Device Story

Automated in vitro diagnostic test for qualitative detection of Trichomonas vaginalis genomic DNA; utilizes real-time PCR. Input: female urine, endocervical swabs, or patient-collected vaginal swabs in transport reagent. Process: specimen transferred to self-contained disposable cartridge; GeneXpert Instrument System performs automated DNA extraction, amplification, and detection. Output: qualitative result (TV DETECTED/NOT DETECTED) generated by instrument software. Used in clinical settings (OB/GYN, STD, family planning clinics); operated by laboratory personnel. Provides rapid diagnostic aid for trichomoniasis; enables timely clinical decision-making and patient management.

Clinical Evidence

Multi-site prospective study (n=5391 tests) compared Xpert TV Assay to a patient infected status (PIS) algorithm (FDA-cleared NAAT + culture). Overall valid reporting rate 99.9%. Sensitivity and specificity were high across all specimen types: Endocervical swabs (Sens 98.9%, Spec 98.9%), Patient-collected vaginal swabs (Sens 96.4%, Spec 99.6%), and Urine (Sens 98.4%, Spec 99.7%).

Technological Characteristics

Real-time PCR assay; uses sequence-specific probes. Self-contained disposable cartridges. Internal controls: Sample Adequacy Control (SAC), Sample Processing Control (SPC), Probe Check Control (PCC). Instrument systems: GeneXpert Dx, Infinity-48, Infinity-48s, Infinity-80. Software-controlled automated processing.

Indications for Use

Indicated for the qualitative detection of Trichomonas vaginalis genomic DNA in female urine, endocervical swabs, and patient-collected vaginal swabs to aid in the diagnosis of trichomoniasis in symptomatic or asymptomatic individuals.

Regulatory Classification

Identification

A Trichomonas vaginalis nucleic acid assay is a device that consists of primers, probes, enzymes, and controls for the amplification and detection of trichomonas nucleic acids in endocervical swabs, vaginal swabs, and female urine specimens, from women symptomatic for vaginitis, cervicitis, or urethritis and/or to aid in the diagnosis of trichomoniasis in asymptomatic women. The detection of trichomonas nucleic acids, in conjunction with other laboratory tests, aids in the clinical laboratory diagnosis of trichomoniasis caused by Trichomonas vaginalis.

Special Controls

*Classification.* Class II (special controls). The special controls are set forth in FDA's guideline document entitled: “Class II Special Controls Guideline: Nucleic Acid Amplification Assays for the Detection of*Trichomonas vaginalis;* Guideline for Industry and Food and Drug Administration Staff.” See § 866.1(e) for information on obtaining this document.

Predicate Devices

• Gen-Probe Aptima Trichomonas vaginalis Assay (K122062)
• Xpert CT/NG Vaginal/Endocervical Specimen Collection Kit (K121710)
• Xpert CT/NG Urine Specimen Collection Kit (K121710)

Submission Summary (Full Text)

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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized graphic of three human profiles facing right, stacked on top of each other. The graphic is surrounded by a circular border containing the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in all caps.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

October 16, 2015

Cepheid Scott Campbell, Ph.D., MBA Vice President, Clinical Affairs 904 Caribbean Drive Sunnyvale, CA 94089-1189

Re: K151565

Trade/Device Name: Xpert® TV Assay on the Cepheid GeneXpert Instrument Systems (GeneXpert Dx, GeneXpert Infinity-48, GeneXpert Infinity-48s, and GeneXpertInfinity-80 systems).

Xpert Vaginal/Endocervical Specimen Collection Kit, and Xpert Urine Specimen Collection Kit

Regulation Number: 21 CFR 866.3860 Regulation Name: Trichomonas vaginalis nucleic acid assay Regulatory Class: II Product Code: OUY, OOI Dated: September 11, 2015 Received: September 14, 2015

Dear Dr. Campbell:

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. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements

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as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. 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

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

# Tamara V. Feldblyum -S for

Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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## Indications for Use

510(k) Number (if known) K151565

Device Name Xpert® TV

#### Indications for Use (Describe)

The Cepheid Xpert TV Assay, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro diagnostic test for the detection of Trichomonas vaginalis genomic DNA. The test utilizes automated real-time polymerase chain reaction (PCR) to detect Trichomonas vaginalis genomic DNA. The Xpert TV Assay uses female urine specimens, endocervical swab specimens, or patient-collected vaginal swab specimens (collected in a clinical setting). The Xpert TV Assay is intended to aid in the diagnosis of trichomoniasis in symptomatic or asymptomatic individuals.

Ancillary Collection Kits:

Xpert Vaginal/Endocervical Specimen Collection Kit

The Cepheid® Xpert® Vaginal/Endocervical Specimen Collection Kit is designed to collect, preserve, and transport Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis DNA in endocervical swab specimens (collected by a clinician) and patient-collected vaginal swab specimens (collected in a clinical setting) from symptomatic and asymptomatic women prior to analysis with the Xpert CT/NG Assay and the Xpert TV Assay.

Xpert Urine Specimen Collection Kit

The Cepheid® Xpert® Urine Specimen Collection Kit is designed to preserve and transport Chlamydia trachomatis, Neisseria gonorthoeae, and Trichomonas vaginalis DNA in first-catch urine specimens from symptomatic and asymptomatic individuals prior to analysis with the Xpert CT/NG Assay and the Xpert TV Assay. The Xpert Urine Specimen Collection Kit is intended for use with male (Xpert CT/NG Assay) and female (Xpert CT/NG Assay and Xpert TV Assay) urine.

| Type of Use (Select one or both, as applicable) | |
|----------------------------------------------------------------------------------|----------------------------------------------------------------------|
| <input checked="" type="checkbox"/> Prescription Use (Part 21 CFR 801 Subpart D) | <input type="checkbox"/> Over-The-Counter Use (21 CFR 801 Subpart C) |

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# 510(k) Summary

As required by 21 CFR Section 807.92(c).

| Submitted by: | Cepheid<br>904 Caribbean Drive<br>Sunnyvale, CA 90489<br>Phone number: [phone]<br>Fax number: [phone] |
|-------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact: | Scott A. Campbell, Ph.D, MBA |
| Date of Preparation: | October 12, 2015 |
| Device: | |
| Trade name: | Xpert® TV |
| Common name: | Xpert TV Assay |
| Type of Test: | Real-Time Polymerase Chain Reaction (PCR) for the detection<br>of Trichomonas vaginalis |
| Regulation number/<br>Classification name/<br>Product code: | 866.3860/ Trichomonas vaginalis nucleic acid amplification test<br>system /OUY<br>862.2570/Instrumentation for clinical multiplex test<br>systems/OOI |
| Classification<br>Advisory Panel | Microbiology (83) |
| Prescription Use | Yes |
| Predicate Device<br>Assay: | Gen-Probe® Aptima Trichomonas vaginalis Assay<br>[510(k) #K122062] |
| Predicate Device<br>Assay: | Xpert CT/NG Vaginal/Endocervical Specimen Collection Kit<br>[510(k) #K121710]<br>Xpert CT/NG Urine Specimen Collection Kit<br>[510(k) #K121710] |

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## Device Description:

The Xpert TV Assay is an automated real-time polymerase chain reaction (PCR) in vitro diagnostic test for qualitative detection of genomic DNA from Trichomonas vaginalis. The Xpert TV Assay is intended as an aid in the diagnosis of trichomoniasis.

The Xpert TV Assay is performed on the Cepheid GeneXpert® Instrument Systems (GeneXpert Dx., GeneXpert Infinity-48, GeneXpert Infinity-48s, and GeneXpert Infinity-80 systems). The GeneXpert Instrument System platform automates sample preparation, amplification and real-time detection.

The GeneXpert Instrument Systems require the use of single-use, disposable cartridges (the Xpert TV cartridges) that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained and specimens never come into contact with working parts of the instrument modules, cross-contamination between samples is minimized.

The Xpert TV Assay cartridges contain reagents for the detection of genomic DNA from T. vaginalis for use with the following specimens collected from symptomatic and asymptomatic individuals: female urine, endocervical swab and patient-collected vaginal swab (collected in a clinical setting). A Sample Processing Control (SPC). Sample Adequacy Control (SAC), and a Probe Check Control (PCC) are controls utilized by the GeneXpert Instrument System platform. The SPC, SAC, and PCC are controls utilized by the GeneXpert Instrument System platform. The SPC is present to control for adequate processing of the target trichomonads and to monitor the presence of inhibitors in the real-time PCR reaction to reduce the possibility of false negative results. The SAC reagents detect the presence of a single copy human gene and monitor whether the specimen contains human cells. The PCC verifies reagent rehydration, real-time PCR tube filling in the cartridge, probe integrity, and dye stability.

The single-use, multi-chambered fluidic cartridges are designed to complete sample preparation and real-time PCR for the detection of genomic DNA from T. vaginalis in 70 minutes or less. The GeneXpert Instrument Systems, comprised of the GeneXpert Dx Systems and the GeneXpert Infinity Systems, have 1 to 80 randomly accessible modules, depending upon the instrument, that are each capable of performing separate sample preparation and real-time PCR and RT-PCR tests. Each module contains a syringe drive for dispensing fluids (i.e., the syringe drive activates the plunger that works in concert with the rotary valve in the cartridge to move fluids between chambers), an ultrasonic horn for lysing cells or spores', and a proprietary I-CORE® thermocycler for performing real-time PCR and RT-PCR and detection.

The swab and/or urine specimens are collected from asymptomatic or symptomatic patients and placed into a specimen transport tube containing preservative. The specimen is transferred to the sample chamber of the disposable fluidic cartridge (the Xpert TV cartridge). The user initiates a test from the system user interface and places the cartridge into the GeneXpert instrument platform, which performs hands-off real-time, multiplex

¹ Although sonication is a fundamental capability of every GeneXpert module, sonication is not used in the Xpert TV Assay.

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PCR for detection of DNA. The results are automatically generated at the end of the process in a report that can be viewed and printed.

The ancillary specimen collection kits for use with the Xpert TV Assay are the Cepheid Xpert Vaginal/Endocervical Specimen Collection Kit and the Cepheid Xpert Urine Specimen Collection Kit.

#### Device Intended Use:

The Cepheid Xpert TV Assay, performed on the GeneXpert Instrument Systems, is a qualitative in vitro diagnostic test for the detection of Trichomonas vaginalis genomic DNA. The test utilizes automated real-time polymerase chain reaction (PCR) to detect Trichomonas vaginalis genomic DNA. The Xpert TV Assay uses female urine specimens, endocervical swab specimens, or patient-collected vaginal swab specimens (collected in a clinical setting). The Xpert TV Assay is intended to aid in the diagnosis of trichomoniasis in symptomatic or asymptomatic individuals.

#### Ancillary Collection Kits:

#### Xpert Vaginal/Endocervical Specimen Collection Kit

The Cepheid® Xpert® Vaginal/Endocervical Specimen Collection Kit is designed to collect, preserve, and transport Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis DNA in endocervical swab specimens (collected by a clinician) and patient-collected vaginal swab specimens (collected in a clinical setting) from symptomatic and asymptomatic women prior to analysis with the Xpert CT/NG Assay and the Xpert TV Assay.

#### Xpert Urine Specimen Collection Kit

The Cepheid® Xpert® Urine Specimen Collection Kit is designed to preserve and transport Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis DNA in first-catch urine specimens from symptomatic and asymptomatic individuals prior to analysis with the Xpert CT/NG Assay and the Xpert TV Assay. The Xpert Urine Specimen Collection Kit is intended for use with male (Xpert CT/NG Assay) and female (Xpert CT/NG Assay and Xpert TV Assay) urine.

#### Substantial Equivalence:

The Xpert TV Assay is substantially equivalent to the Gen-Probe® Aptima Trichomonas vaginalis Assay [510(k) # K122062]. The Xpert TV Assay and the Gen-Probe Aptima Trichomonas vaginalis Assay both detect T. vaginalis from endocervical swab, patientcollected vaginal swab (collected in a clinical setting), and female urine specimens using nucleic acid-based technology. The performance of the Xpert TV Assay was evaluated in a multi-site clinical study in which the performance of the Xpert TV Assay was compared to a patient-infected status (PIS). The results of the study demonstrated that the performance of the Xpert TV Assay is substantially equivalent to the predicate device.

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Table 5-1 shows the similarities and differences between the Xpert TV Assay and the predicate device.

| Similarities | | |
|----------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Item | Device | Predicate Device |
| | Cepheid Xpert TV Assay | Gen-Probe Aptima<br>Trichomonas vaginalis<br>Assay |
| 510(k) Number | K151565 | K122062 |
| Regulation | 866.3860 | 866.3860 |
| Product Code | OUY | OUY |
| Device Class | Same | II |
| Intended Use | The Cepheid Xpert TV Assay,<br>performed on the GeneXpert®<br>Instrument Systems, is a<br>qualitative in vitro diagnostic<br>test for the detection of<br>Trichomonas vaginalis<br>genomic DNA. The test<br>utilizes automated real-time<br>polymerase chain reaction<br>(PCR) to detect Trichomonas<br>vaginalis genomic DNA. The<br>Xpert TV Assay uses female<br>urine specimens, endocervical<br>swab specimens, or patient-<br>collected vaginal swab<br>specimens (collected in a<br>clinical setting). The Xpert TV<br>Assay is intended to aid in the<br>diagnosis of trichomoniasis in<br>symptomatic or asymptomatic<br>individuals.<br><br>Ancillary Collection Kits:<br><br>Xpert Vaginal/Endocervical<br>Specimen Collection Kit<br><br>The Cepheid® Xpert® | The APTIMA Trichomonas<br>vaginalis Assay is an in vitro<br>qualitative nucleic acid<br>amplification test (NAAT) for<br>the detection of ribosomal<br>RNA (rRNA) from<br>Trichomonas vaginalis to aid<br>in the diagnosis of<br>trichomoniasis using the<br>TIGRIS DTS System. The<br>assay may be used to test the<br>following specimens from<br>symptomatic or asymptomatic<br>women: clinician-collected<br>endocervical swabs, clinician-<br>collected vaginal swabs,<br>female urine specimens, and<br>specimens collected in<br>PreservCyt Solution. |
| Similarities | | |
| Item | Device | Predicate Device |
| | Cepheid Xpert TV Assay | Gen-Probe Aptima<br>Trichomonas vaginalis<br>Assay |
| | Vaginal/Endocervical<br>Specimen Collection Kit is<br>designed to collect, preserve,<br>and transport Chlamydia<br>trachomatis, Neisseria<br>gonorrhoeae, and<br>Trichomonas vaginalis DNA<br>in endocervical swab<br>specimens (collected by a<br>clinician) and patient-collected<br>vaginal swab specimens<br>(collected in a clinical setting)<br>from symptomatic and<br>asymptomatic women prior to<br>analysis with the Xpert CT/NG<br>Assay and the Xpert TV<br>Assay.<br><br>Xpert Urine Specimen<br>Collection Kit<br><br>The Cepheid® Xpert® Urine<br>Specimen Collection Kit is<br>designed to preserve and<br>transport Chlamydia<br>trachomatis, Neisseria<br>gonorrhoeae, and<br>Trichomonas vaginalis DNA<br>in first-catch urine specimens<br>from symptomatic and<br>asymptomatic individuals prior<br>to analysis with the Xpert<br>CT/NG Assay and the Xpert<br>TV Assay. The Xpert Urine<br>Specimen Collection Kit is<br>intended for use with male<br>(Xpert CT/NG Assay) and<br>female (Xpert CT/NG Assay<br>and Xpert TV Assay) urine. | |
| Assay Targets | <i>T. vaginalis</i> genomic DNA | <i>T. vaginalis</i> ribosomal RNA |
| Similarities | | |
| Item | Device | Predicate Device |
| | Cepheid Xpert TV Assay | Gen-Probe Aptima<br>Trichomonas vaginalis<br>Assay |
| Specimen Types | Endocervical Swabs<br>Vaginal Swabs<br>Female Urine | Endocervical Swabs<br>Vaginal Swabs<br>Female Urine |
| Nucleic Acid<br>Extraction | Yes | Yes |
| Assay Results | Same | Qualitative |
| Collection Kit | Same | Urine collection kit<br>Swab collection kit |

#### Table 5-1: Comparison of Similarities and Differences of the Xpert TV Assay with the Predicate Device

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| Primary Differences | | | |
|-------------------------------------|-----------------------------------------------------------|-----------------------------------------------------|--|
| | New Device | Predicate Device | |
| Item | Cepheid Xpert TV Assay | Gen-Probe Aptima<br>Trichomonas vaginalis Assay | |
| Technology/<br>Detection | Multiplex real-time<br>polymerase chain reaction<br>(PCR) | Transcription-mediated<br>amplification (TMA) | |
| Specimen Types | Endocervical Swabs<br>Vaginal Swabs<br>Female Urine | Endocervical Swabs<br>Vaginal Swabs<br>Female Urine | |
| Instrument System | Cepheid GeneXpert<br>Instrument System | TIGRIS DTS System | |
| Laboratory Users | Operators in Moderate and<br>High Complexity labs | CLIA High Complexity | |
| Early assay<br>termination function | Yes<br>(for positive samples) | No | |

The Xpert TV Assay has the same general intended use as the predicate device and has the same technological characteristics as the predicate device. The differences between the Xpert TV Assay and the predicate device do not raise different questions of safety and effectiveness. The clinical study demonstrates that the Xpert TV Assay is acceptable

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for its intended use with inexperienced lab users and is substantially equivalent to the predicate device described above.

Ancillary Collection Kits:

Xpert Vaginal/Endocervical Specimen Collection Kit and Xpert Urine Specimen Collection Kit

The predicate devices for the ancillary specimen collection kits, the Cepheid Xpert® Vaginal/Endocervical Specimen Collection Kit and Cepheid Xpert Urine Specimen Collection Kit, are the Cepheid Xpert CT/NG Vaginal/Endocervical Specimen Collection Kit and the Cepheid Xpert CT/NG Urine Specimen Collection Kit [510(k) #K121710]. The similarities and differences are shown in Tables 5-2 and 5-3.

| Similarities | | |
|--------------------------------|------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | Device | Predicate |
| Item | Cepheid Xpert<br>Vaginal/Endocervical<br>Specimen Collection Kit | Cepheid Xpert CT/NG<br>Vaginal/Endocervical<br>Specimen Collection Kit |
| Intended Use<br>(Similarities) | Same | The collection kit is used for<br>the collection of endocervical<br>swab specimens (collected by a<br>clinician) and patient-collected<br>vaginal swab specimens<br>(collected in a clinical setting)<br>and is designed to collect,<br>preserve and transport patient<br>Chlamydia trachomatis and<br>Neisseria gonorrhoeae DNA in<br>endocervical and vaginal<br>specimens. |
| Single-use Device | Yes | Yes |
| Transport Medium<br>pH | Same | 8.15-8.55 |

## Table 5-2: Comparison of Similarities and Differences of the Xpert Vaginal/Endocervical Specimen Collection Kit with the Predicate Device

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| Similarities | | |
|--------------|------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | Device | Predicate |
| Item | Cepheid Xpert<br>Vaginal/Endocervical<br>Specimen Collection Kit | Cepheid Xpert CT/NG<br>Vaginal/Endocervical<br>Specimen Collection Kit |
| Description | Same | Contains an individually<br>packaged sterile large cleaning<br>swab (for endocervical<br>samples) and a package<br>containing an individually<br>packaged sterile collection<br>swab (for vaginal and<br>endocervical sampling) and a<br>swab transport reagent tube.<br>The collection swab is placed<br>into the transport reagent tube<br>after swab sampling to stabilize<br>the nucleic acid until sample<br>preparation. |

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| Differences | | |
|-------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Item | Device | Predicate |
| Intended Use<br>(differences) | Specimen storage<br>and transport when testing for<br>the presence of <i>Chlamydia</i><br><i>trachomatis</i> , <i>Neisseria</i><br><i>gonorrhoeae</i> , and<br><i>Trichomonas vaginalis</i> in<br>vaginal and endocervical swab<br>specimens. | Specimen storage<br>and transport when testing for<br>the presence of <i>Chlamydia</i><br><i>trachomatis</i> and <i>Neisseria</i><br><i>gonorrhoeae</i> in vaginal and<br>endocervical swab specimens. |

| Table 5-3: Comparison of Similarities and Differences of the Xpert Urine Specimen |
|-----------------------------------------------------------------------------------|
| Collection Kit with the Predicate Device |

| Similarities | | |
|--------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | Device | Predicate |
| Item | Cepheid Xpert Urine<br>Specimen Collection Kit | Cepheid Xpert CT/NG Urine<br>Specimen Collection Kit |
| Intended Use<br>(Similarities) | The collection kit is designed to<br>preserve and transport<br>Chlamydia trachomatis and<br>Neisseria gonorrhoeae DNA in<br>first-catch female urine<br>specimens from symptomatic<br>and asymptomatic individuals<br>prior to analysis. | The collection kit is designed<br>to preserve and transport<br>Chlamydia trachomatis and<br>Neisseria gonorrhoeae DNA<br>in first-catch male and female<br>urine specimens from<br>symptomatic and<br>asymptomatic individuals<br>prior to analysis. |
| Single-use Device | Yes | Yes |
| Transport Medium<br>pH | Same | 7.95 – 8.35 |
| Description | Same | Contains one individually<br>packaged sterile disposable<br>transfer pipette and one urine<br>transport reagent tube.<br>Approximately 7 mL of a<br>first-catch urine specimen is<br>transferred to the Urine<br>Transport Reagent tube to<br>preserve and transport the<br>specimen prior to analysis<br>with the assay. |

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| Similarities | | |
|-------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------|
| Item | Device | Predicate |
| | Cepheid Xpert Urine<br>Specimen Collection Kit | Cepheid Xpert CT/NG Urine<br>Specimen Collection Kit |
| Differences | | |
| Item | Device | Predicate |
| Intended Use<br>(differences) | Specimen storage and transport<br>when testing for the presence of<br>Chlamydia trachomatis,<br>Neisseria gonorrhoeae, and<br>Trichomonas vaginalis in urine<br>specimens. | Specimen storage and transport<br>when testing for the presence of<br>Chlamydia trachomatis and<br>Neisseria gonorrhoeae in urine<br>specimens. |

## Non-Clinical Studies:

## Analytical Sensitivity (Limit of Detection)

The analytical sensitivity or limit of detection (LoD) of the Xpert TV Assay was assessed using two Trichomonas vaginalis strains, one metronidazole susceptible (T. vaginalis ATCC® 30001™), and one metronidazole resistant (T. vaginalis ATCC® 30238™). Both strains were tested individually in clinical T. vaginalis-negative pooled urine matrix in Cepheid Xpert Urine Transport Reagent and clinical T. vaginalisnegative pooled vaginal swab matrix (VS) in Cepheid Xpert Swab Transport Reagent.

T. vaginalis was cultured and incubated at 35°C. Visual examination of the cultures for white precipitate (indicating growth) was conducted every 24 hours for 3 to 5 days. Cell pellets were resuspended in growth medium and enumerated visually using light microscopy. The concentration of isolates was expressed as the number of cells per milliliter (cells/mL). Cultures were diluted in culture medium to 1 x 10 cells/mL and stored at -20°C. Cells were thawed on ice for use in the study.

The limit of detection (LoD) was estimated by testing replicates of 20 at five concentrations for each strain and sample type over three days. The LoD for each strain was estimated by probit analysis. The claimed LoDs were confirmed by analyzing at least 20 replicates with T. vaginalis cells diluted to the estimated LoD concentrations. The LoD is defined as the lowest number of cells/mL that can be reproducibly distinguished from negative samples with 95% confidence or the lowest concentration at which 19 of 20 replicates were positive. The study was performed with two different lots of Xpert TV reagents and the claimed LoD for each strain is the higher of the two determinations (Table 5-4). The claimed LoD for T. vaginalis strains ATCC 30001 and ATCC 30238 in vaginal swab matrix is 2 cells/mL. The claimed LoD for T. vaginalis strain ATCC 30001 in urine matrix is 3 cells/mL. The claimed LoD for T. vaginalis strain ATCC 30238 in urine matrix is 2 cells/mL.

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The LoD point estimates and confirmed LoD for each genogroup tested are summarized in Table 5-4.

| Trichomonas<br>vaginalis | LoD Estimates by<br>Probit Analysis<br>(cells/mL) | | Verified<br>LoD | Verification<br>(Positives/20) | Mean TV<br>Ct | Mean SAC<br>Ct | Mean SPC<br>Ct | LoD<br>Claim |
|-------------------------------|---------------------------------------------------|------------------|-----------------|--------------------------------|---------------|----------------|----------------|--------------|
| strain and matrix | Reagent<br>Lot 1 | Reagent<br>Lot 2 | (cells/mL) | | | | | (cells/mL) |
| ATCC 30001 in<br>Vaginal Swab | 2.0 | 1.6 | 2.0 | 20/20 | 39.1 | 21.4 | 33.9 | 2 |
| ATCC 30238 in<br>Vaginal Swab | 1.7 | 2.1 | 2.1 | 20/20 | 37.5 | 21.4 | 33.7 | 2 |
| ATCC 30001 in<br>Urine | 2.2 | 2.5 | 2.5 | 20/20 | 38.2 | 29.3 | 34.1 | 3 |
| ATCC 30238 in<br>Urine | 2.1 | 1.7 | 2.1 | 20/20 | 38.2 | 29.2 | 33.8 | 2 |

Table 5-4: LoD of Two T. vaginalis Strains in Pooled Vaginal Swab Matrix and Urine Matrix

## Analytical Specificity (Cross-reactivity and Competitive Interference)

A panel of 124 microorganisms, including bacteria, fungi, and viruses commonly found in the urogenital tract, as well as other protozoans closely related to T. vaginalis were tested with the Xpert TV Assay. The microorganisms were tested in the presence (competitive interference) and absence (cross-reactivity) of 3X LoD T. vaginalis ATCC 30001 cells. The microorganisms were seeded into either pooled Trichomonas vaginalis-negative urine matrix (patient urine added to Cepheid Urine Transport Reagent) or pooled Trichomonas vaginalis-negative vaginal swab matrix (vaginal swabs collected into Cepheid Swab Transport Reagent).

Each bacterial or fungal strain was tested at 1 x 106 CFU/mL or greater or at 1 x 10° genomes/mL. Viral strains were tested at 1 x 105 U/mL or 105 genomes/mL or greater. Protozoans were cultured in growth media, visually enumerated by light microscopy and tested at 1 x 105 cells/mL or greater or 106 genomes/mL. All microorganisms were tested in triplicate. Positive and negative controls were included in the study. One organism, Trichomonas tenax, demonstrated cross-reactivity (result of TV DETECTED in the absence of TV) at 1 x 10 cells/mL for the urine and vaginal swab matrix samples. Trichomonas tenax was subjected to repeat analysis at various other concentrations until a result of TV NOT DETECTED was obtained (at 1 x 102 cells/mL). This is addressed in Limitations in the package insert. For the other 123 microorganisms, all TV positive samples remained positive and all TV negative samples remained negative, indicating that there was no interference or cross-reactivity with the results of the Xpert TV Assay for these microorganisms. Results are shown in Table 5-5 and Table 5-6 for urine and vaginal swab matrix, respectively.

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| Microorganism | Concentration<br>Testeda | Xpert TV Assay Result | | | | | | |
|---------------------------------------|--------------------------------|--------------------------------------------------------------------------------------------------------------|-------------------------------------------------|-----------------------------|-----------------------|--|-------------|--|
| | | Cross-Reactivity<br>(- T. vaginalis) | Competitive<br>Interference<br>(+ T. vaginalis) | | | | | |
| Achromobacter xerosis | 8 x 106 | TV NOT DETECTED | TV DETECTED | | | | | |
| Acinetobacter calcoaceticus | 3 x 106 | TV NOT DETECTED | TV DETECTED | | | | | |
| Acinetobacter lwoffii | 6 x 106 | TV NOT DETECTED | TV DETECTED | | | | | |
| Actinomyces israeliib | 2 x 106 | TV NOT DETECTED | TV DETECTED | | | | | |
| Actinomyces pyogenes | 8 x 106 | TV NOT DETECTED | TV DETECTED | | | | | |
| Aerococcus viridans | 5 x 106 | TV NOT DETECTED | TV DETECTED | | | | | |
| Aeromonas hydrophila | 1 x 107 | TV NOT DETECTED | TV DETECTED | | | | | |
| Alcaligenes faecalis | 1 x 107 | TV NOT DETECTED | TV DETECTED | | | | | |
| Atopobium vaginaeb | 2 x 106 | TV NOT DETECTED | TV DETECTED | | | | | |
| Bacillus subtilis | 6 x 106 | TV NOT DETECTED | TV DETECTED | | | | | |
| Bacteroides fragilisb | 5 x 106 | TV NOT DETECTED | TV DETECTED | | | | | |
| Bacteroides ureolyticusb | 1 x 106 | TV NOT DETECTED | TV DETECTED | | | | | |
| Bifidobacterium adolescentisb | 6 x 106 | TV NOT DETECTED | TV DETECTED | | | | | |
| Bifidobacterium brevi (breve)b | 9 x 106 | TV NOT DETECTED | TV DETECTED | | | | | |
| Blastocystis hominisc | 1 x 105d | TV NOT DETECTED | TV DETECTED | | | | | |
| Branhamella catarrhalis | 1 x 107 | TV NOT DETECTED…