Xpert TV, Xpert Urine Specimen Collection Kit, GeneXpert Dx Systems (GX-I, GX-II, GX-IV, GX-XVI), GeneXpert Infinity-48, Genxpert Infinity-48s and GeneXpert Infinity-80 Systems

K161619 · Cepheid · OUY · Aug 29, 2016 · Immunology

Device Facts

• Record ID: K161619
• Device Name: Xpert TV, Xpert Urine Specimen Collection Kit, GeneXpert Dx Systems (GX-I, GX-II, GX-IV, GX-XVI), GeneXpert Infinity-48, Genxpert Infinity-48s and GeneXpert Infinity-80 Systems
• Applicant: Cepheid
• Product Code: OUY · Immunology
• Decision Date: Aug 29, 2016
• 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 and male urine specimens, endocervical swab specimens, and 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 female and male urine specimens from symptomatic and asymptomatic individuals prior to analysis with the Xpert CT/NG Assay and the Xpert TV Assay.

Device Story

The Xpert TV Assay is an automated, qualitative in vitro diagnostic test for Trichomonas vaginalis genomic DNA. It uses single-use, multi-chambered fluidic cartridges containing PCR reagents. The user places a specimen (urine or swab) into the cartridge and inserts it into a GeneXpert Instrument System (GeneXpert Dx, Infinity-48, Infinity-48s, or Infinity-80). The system automates sample preparation, real-time PCR amplification, and detection within 70 minutes. The instrument uses an ultrasonic horn for cell lysis (though not used for this specific assay) and a proprietary I-CORE thermocycler. Results are automatically generated and displayed on the system interface. The device is used in clinical settings by laboratory personnel. It aids in the diagnosis of trichomoniasis, providing clinicians with rapid, automated molecular results to guide patient management.

Clinical Evidence

Prospective multicenter study of 4,611 eligible male subjects (symptomatic and asymptomatic). Performance evaluated against Patient Infected Status (PIS) using InPouch TV culture and bi-directional sequencing. Overall sensitivity 89.6% (95% CI: 83.0%-93.8%); overall specificity 99.3% (95% CI: 99.0%-99.5%). Assay success rate 99.7%.

Technological Characteristics

Real-time PCR assay; uses single-use, multi-chambered fluidic cartridges. Platform: GeneXpert Instrument Systems (GeneXpert Dx, Infinity-48, Infinity-48s, Infinity-80). Features: Sample Processing Control (SPC), Sample Adequacy Control (SAC), and Probe Check Control (PCC). Automated sample prep and thermocycling via I-CORE module. Connectivity: Standalone instrument system.

Indications for Use

Indicated for the detection of Trichomonas vaginalis genomic DNA in male and 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

• Cepheid Xpert TV assay (K151565)

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 and Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of three human profiles facing right, resembling a bird in flight.

August 29, 2016

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

Cepheid Scott Campbell, Ph.D., MBA Corporate Vice President and Chief Regulatory Officer 904 Caribbean Drive Sunnyvale, CA 94089-1189

Re: K161619

Trade/Device Name: Xpert® TV, 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, JSM Dated: June 10, 2016 Received: June 15, 2016

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,

# Steven R. Gitterman -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) K161619

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 and male urine specimens, endocervical swab specimens, and 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 female urine specimens from symptomatic and asymptomatic individuals prior to analysis with the Xpert CT/NG Assay and the Xpert TV Assay.

| Type of Use (Select one or both, as applicable) | |
|---------------------------------------------------------------------------------|--|
| <div> <span> ☑ Prescription Use (Part 21 CFR 801 Subpart D) </span> </div> | |
| <div> <span> ☐ Over-The-Counter Use (21 CFR 801 Subpart C) </span> </div> | |

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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, PhD, MBA |
| Date of Preparation: | July 13, 2016 |
| 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/ | 866.3860/ Trichomonas vaginalis nucleic acid amplification test<br>system /OUY |
| Product code: | 862.2570/Instrumentation for clinical multiplex test<br>systems/OOI |
| Classification<br>Advisory Panel | Microbiology (83) |
| Prescription Use | Yes |
| Predicate Device<br>Assay: | Cepheid Xpert TV Assay<br>[510(k) #K151565] |
| Predicate Device<br>Assay: | Xpert Urine Specimen Collection Kit<br>[510(k) #K151565] |

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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 and male urine, endocervical swab and patientcollected 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

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

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into the GeneXpert instrument platform, which performs hands-off real-time, multiplex 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 and male urine specimens, endocervical swab specimens, and 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 female and male urine specimens from symptomatic and asymptomatic individuals prior to analysis with the Xpert CT/NG Assay and the Xpert TV Assay.

#### Substantial Equivalence:

The Xpert TV Assay is substantially equivalent to the cleared Cepheid Xpert TV Assay [510(k) #K151565]. The assays are identical in reagents and formulation and use the same real-time PCR technology and GeneXpert instruments. 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 | Current Cepheid<br>Xpert TV Assay |
| 510(k) Number | K161619 | K151565 |
| Regulation | Same | 866.3860 |
| Product Code | Same | 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>and male urine specimens,<br>endocervical swab specimens,<br>or patient-collected vaginal<br>swab specimens (collected in a<br>clinical setting). The Xpert<br>TV Assay is intended to aid in<br>the diagnosis of trichomoniasis<br>in symptomatic or<br>asymptomatic individuals. | 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<br>TV Assay is intended to aid in<br>the diagnosis of trichomoniasis<br>in symptomatic or<br>asymptomatic individuals. |
| Assay Targets | Same | T. vaginalis genomic DNA |
| Specimen Types | Endocervical Swabs<br>Vaginal Swabs<br>Female Urine<br>Male Urine | Endocervical Swabs<br>Vaginal Swabs<br>Female Urine |

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

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| Similarities | | |
|-------------------------------------|------------------------|---------------------------------------------------|
| Item | Device | Predicate Device |
| | Cepheid Xpert TV Assay | Current Cepheid<br>Xpert TV Assay |
| Nucleic Acid<br>Extraction | Yes | Yes |
| Assay Results | Same | Qualitative |
| Collection Kit | Same | Urine collection kit<br>Swab collection kit |
| Technology/<br>Detection | Same | Real-time polymerase chain<br>reaction (PCR) |
| Instrument System | Same | Cepheid GeneXpert<br>Instrument System |
| Laboratory Users | Same | Operators in Moderate and<br>High Complexity labs |
| Early assay<br>termination function | Same | Yes<br>(for positive samples) |

| Primary Differences | | |
|---------------------|-------------------------------------------------------------------|-----------------------------------------------------|
| | New Device | Predicate Device |
| Item | Cepheid Xpert TV Assay | Current Cepheid<br>Xpert TV Assay |
| Specimen Types | Endocervical Swabs<br>Vaginal Swabs<br>Female Urine<br>Male Urine | Endocervical Swabs<br>Vaginal Swabs<br>Female Urine |

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

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Ancillary Collection Kit:

## Xpert Urine Specimen Collection Kit

The predicate device for the Cepheid Xpert Urine Specimen Collection Kit is the current Cepheid Xpert Urine Specimen Collection Kit [510(k) # K151565]. The similarities and differences are shown in Table 5-2.

| Similarities | | |
|--------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Item | Device<br>Cepheid Xpert Urine<br>Specimen Collection Kit | Predicate<br>Current Cepheid Xpert Urine<br>Specimen Collection Kit |
| Intended Use<br>(Similarities) | The collection kit is designed<br>to preserve and transport<br><i>Chlamydia trachomatis</i> ,<br><i>Neisseria gonorrhoeae</i> and<br><i>Trichomonas vaginalis</i> DNA in<br>first-catch <b>male</b> and female<br>urine specimens from<br>symptomatic and<br>asymptomatic individuals prior<br>to analysis. | The collection kit is designed<br>to preserve and transport<br><i>Chlamydia trachomatis</i> and<br><i>Neisseria gonorrhoeae</i> and<br><i>Trichomonas vaginalis</i> DNA in<br>first-catch female urine<br>specimens from symptomatic<br>and 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 first-<br>catch urine specimen is<br>transferred to the Urine<br>Transport Reagent tube to<br>preserve and transport the<br>specimen prior to analysis with<br>the assay. |

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

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| Differences | | |
|-------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | Device | Predicate |
| Item | Cepheid Xpert Urine<br>Specimen Collection Kit | Current Cepheid Xpert Urine<br>Specimen Collection Kit |
| Intended Use<br>(differences) | Specimen storage and transport<br>when testing for the presence of<br><i>Chlamydia trachomatis</i> and<br><i>Neisseria gonorrhoeae</i> in first-<br>catch male and female urine<br>specimens and for the presence<br>of <i>Trichomonas vaginalis</i> in<br>first-catch female and male<br>urine specimens. | Specimen storage and transport<br>when testing for the presence of<br><i>Chlamydia trachomatis</i> and<br><i>Neisseria gonorrhoeae</i> in first-<br>catch male and female urine<br>specimens and for the presence<br>of <i>Trichomonas vaginalis</i> in<br>first-catch female 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"). The 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 x10+ cells/mL and stored at -20°C. Cells were thawed on ice for use in the study.

The 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 5-3). 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

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urine matrix is 2 cells/mL.

The LoD point estimates and confirmed LoD for each strain tested are summarized in Table 5-3.

| Trichomonas<br>vaginalis | LoD Estimates by<br>Probit Analysis<br>(cells/mL) | | Verified<br>LoD<br>(cells/mL) | Verification<br>(Positives/20) | Mean TV<br>Ct | Mean SAC<br>Ct | Mean SPC<br>Ct | LoD<br>Claim<br>(cells/mL) |
|-------------------------------|---------------------------------------------------|------------------|-------------------------------|--------------------------------|---------------|----------------|----------------|----------------------------|
| strain and matrix | Reagent<br>Lot 1 | Reagent<br>Lot 2 | | | | | | |
| 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 5-3: 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 10°CFU/mL or greater or at 1 x 10° genomes/mL. Viral strains were tested at 1 x 105 TCIDs0/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 105 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 10- 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 5-4 and Table 5-5 for urine and vaginal swab matrix, respectively.

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| Microorganism | Concentration<br>Testeda | 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 | TV DETECTED | |
| Brevibacterium linens | 7 x 106 | TV NOT DETECTED | TV DETECTED | |
| Campylobacter jejuni | 1 x 107 | TV NOT DETECTED | TV DETECTED | |
| Candida albicanse | 7 x 106 | TV NOT DETECTED | TV DETECTED | |
| Candida glabratae | 4 x 106 | TV NOT DETECTED | TV DETECTED | |
| Candida parapsilosie | 7 x 106 | TV NOT DETECTED | TV DETECTED | |
| Candida tropicalise | 6 x 106 | TV NOT DETECTED | TV DETECTED | |
| Chlamydia trachomatis | 2 x 106 | TV NOT DETECTED | TV DETECTED | |
| Chromobacterium violaceum | 7 x 106 | TV NOT DETECTED | TV DETECTED | |
| Citrobacter freundii | 1 x 106 | TV NOT DETECTED | TV DETECTED | |
| Clostridium difficileb | 4 x 106 | TV NOT DETECTED | TV DETECTED | |
| Clostridium perfringensb | 2 x 106 | TV NOT DETECTED | TV DETECTED | |
| Corynebacterium genitalium | 2 x 106 | TV NOT DETECTED | TV DETECTED | |
| Corynebacterium xerosis | 3 x 106 | TV NOT DETECTED | TV DETECTED | |
| Microorganism | Concentration<br>Testeda | Xpert TV Assay Result | | |
| | | Cross-Reactivity<br>(- T. vaginalis) | Competitive<br>Interference<br>(+ T. vaginalis) | |
| Cryptococcus neoformanse | 6 x 106 | TV NOT DETECTED | TV DETECTED | |
| Cryptosporidium parvumc | 1 x 105d | TV NOT DETECTED | TV DETECTED | |
| Cytomegalovirusf | 5 x 105 | TV NOT DETECTED | TV DETECTED | |
| Deinococcus radiodurans | 5 x 106 | TV NOT DETECTED | TV DETECTED | |
| Derxia gummosa | 1 x 105d | TV NOT DETECTED | TV DETECTED | |
| Eikenella corrodens | 5 x 106 | TV NOT DETECTED | TV DETECTED | |
| Entamoeba histolyticac | 1 x 105d | TV NOT DETECTED | TV DETECTED | |
| Enterobacter aerogenes | 1 x 106 | TV NOT DETECTED | TV DETECTED | |
| Enterobacter cloacae | 2 x 106 | TV NOT DETECTED | TV DETECTED | |
| Enterococcus avium | 7 x 106 | TV NOT DETECTED | TV DETECTED | |
| Enterococcus faecalis | 7 x 106 | TV NOT DETECTED | TV DETECTED | |
| Enterococcus faecium | 4 x 106 | TV NOT DETECTED | TV DETECTED | |
| Erysipelothrix rhusiopathiae | 1 x 107 | TV NOT DETECTED | TV DETECTED | |
| Escherichia coli | 1 x 107 | TV NOT DETECTED | TV DETECTED | |
| Flavobacterium meningosepticum | 1 x 107 | TV NOT DETECTED | TV DETECTED | |
| Fusobacterium nucleatumb | 4 x 106 | TV NOT DETECTED | TV DETECTED | |
| Gardnerella vaginalis | 2 x 106 | TV NOT DETECTED | TV DETECTED | |
| Gemella haemolysans | 6 x 106 | TV NOT DETECTED | TV DETECTED | |
| Giardia intestinalisc | 1 x 105d | TV NOT DETECTED | TV DETECTED | |
| Haemophilus ducreyi | 1 x 105d | TV NOT DETECTED | TV DETECTED | |
| Haemophilus influenzae | 3 x 106 | TV NOT DETECTED | TV DETECTED | |
| Herpes simplex virus If | 1 x 105 | TV NOT DETECTED | TV DETECTED | |
| Herpes simplex virus IIf | 1 x 105 | TV NOT DETECTED | TV DETECTED | |
| HIV-1f | 2 x 105 | TV NOT DETECTED | TV DETECTED | |
| Human papilloma virus 16f | 6 x 105 | TV NOT DETECTED | TV DETECTED | |
| Kingella dentrificans | 3 x 106 | TV NOT DETECTED | TV DETECTED | |
| Kingella kingae | 1 x 107 | TV NOT DETECTED | TV DETECTED | |
| Klebsiella oxytoca | 1 x 107 | TV NOT DETECTED | TV DETECTED | |
| Klebsiella pneumoniae | 7 x 106 | TV NOT DETECTED | TV DETECTED | |
| Lactobacillus acidophilus | 8 x 106 | TV NOT DETECTED | TV DETECTED | |
| Lactobacillus brevis | 7 x 106 | TV NOT DETECTED | TV DETECTED | |
| Lactobacillus crispatus | 2 x 106 | TV NOT DETECTED | TV DETECTED | |
| Microorganism | Concentration<br>Testeda | Xpert TV Assay Result | | |
| | | Cross-Reactivity<br>(- T. vaginalis) | Competitive<br>Interference<br>(+ T. vaginalis) | |
| Lactobacillus jensonii | 8 x 106 | TV NOT DETECTED | TV DETECTED | |
| Lactobacillus lactis | 7 x 106 | TV NOT DETECTED | TV DETECTED | |
| Lactobacillus vaginalis | 6 x 106 | TV NOT DETECTED | TV DETECTED | |
| Legionella pneumophila | 5 x 106 | TV NOT DETECTED | TV DETECTED | |
| Leuconostoc paramensenteroides | 7 x 106 | TV NOT DETECTED | TV DETECTED | |
| Listeria monocytogenes | 1 x 107 | TV NOT DETECTED | TV DETECTED | |
| Micrococcus luteus | 3 x 106 | TV NOT DETECTED | TV DETECTED | |
| Mobiluncus curtisiib | 3 x 106 | TV NOT DETECTED | TV DETECTED | |
| Moraxella lacunata | 6 x 106 | TV NOT DETECTED | TV DETECTED | |
| Moraxella osloensis | 5 x 106 | TV NOT DETECTED | TV DETECTED | |
| Morganella morganii | 1 x 107 | TV NOT DETECTED | TV DETECTED | |
| Mycobacterium smegmatis | 7 x 106 | TV NOT DETECTED | TV DETECTED | |
| Mycoplasma genitalium | 1 x 106d | TV NOT DETECTED | TV DETECTED | |
| Mycoplasma hominis | 1 x 106d | TV NOT DETECTED | TV DETECTED | |
| Neisseria cinerea | 1 x 106 | TV NOT DETECTED | TV DETECTED | |
| Neisseria dentrificans | 2 x 106 | TV NOT DETECTED | TV DETECTED | |
| Neisseria elongata | 7 x 106 | TV NOT DETECTED | TV DETECTED | |
| Neisseria flava | 9 x 106 | TV NOT DETECTED | TV DETECTED | |
| Neisseria flavescens | 8 x 106 | TV NOT DETECTED | TV DETECTED | |
| Neisseria gonorrhoeae | 6 x 106 | TV NOT DETECTED | TV DETECTED | |
| Neisseria lactamica | 3 x 106 | TV NOT DETECTED | TV DETECTED | |
| Neisseria mucosa | 9 x 106 | TV NOT DETECTED | TV DETECTED | |
| Neisseria perflava | 3 x 106 | TV NOT DETECTED | TV DETECTED | |
| Neisseria polysaccharea | 4 x 106 | TV NOT DETECTED | TV DETECTED | |
| Neisseria sicca | 8 x 106 | TV NOT DETECTED | TV DETECTED | |
| Neisseria subflava | 9 x 106 | TV NOT DETECTED | TV DETECTED | |
| Pantoea agglomerans | 4 x 106 | TV NOT DETECTED | TV DETECTED | |
| Paracoccus denitrificans | 8 x 106 | TV NOT DETECTED | TV DETECTED | |
| Pentatrichomonis hominisc | 1 x 106 | TV NOT DETECTED | TV DETECTED | |
| Peptostreptococcus anaerobiusb | 4 x 106 | TV NOT DETECTED | TV DETECTED | |
| Peptostreptococcus productusb | 2 x 106 | TV NOT DETECTED | TV DETECTED | |
| Plesiomonas shigelloides | 4 x 106 | TV NOT DETECTED | TV DETECTED | |
| Microorganism | Concentration<br>Testeda | Xpert TV Assay Result | | |
| | | Cross-Reactivity<br>(- T. vaginalis) | Competitive<br>Interference<br>(+ T. vaginalis) | |
| Prevotella biviab | 1 x 106 | TV NOT DETECTED | TV DETECTED | |
| Propionibacterium acnesb | 3 x 106 | TV NOT DETECTED | TV DETECTED | |
| Proteus mirabilis | 1 x 107 | TV NOT DETECTED | TV DETECTED | |
| Proteus vulgaris | 1 x 107 | TV NOT DETECTED | TV DETECTED | |
| Providencia stuartii | 1 x 107 | TV NOT DETECTED | TV DETECTED | |
| Pseudomonas aeruginosa | 8 x 106 | TV NOT DETECTED | TV DETECTED | |
| Pseudomonas fluorescens | 8 x 106 | TV NOT DETECTED | TV DETECTED | |
| Pseudomonas putida | 7 x 106 | TV NOT DETECTED | TV DETECTED | |
| Rahnella aquatilis | 1 x 107 | TV NOT DETECTED | TV DETECTED | |
| Rhodospirillum rubrum | 1 x 106d | TV NOT DETECTED | TV DETECTED | |
| Saccharomyces cerevisiaee | 6 x 106 | TV NOT DETECTED | TV DETECTED | |
| Salmonella minnesota | 1 x 106 | TV NOT DETECTED | TV DETECTED | |
| Salmonella typhimurium | 1 x 107 | TV NOT DETECTED | TV DETECTED | |
| Serratia marcescens | 2 x 106 | TV NOT DETECTED | TV DETECTED | |
| Staphylococcus aureus | 9 x 106 | TV NOT DETECTED | TV DETECTED | |
| Staphylococcus epidermidis | 7 x 106 | TV NOT DETECTED | TV DETECTED | |
| Staphylococcus saprophyticus | 8 x 106 | TV NOT DETECTED | TV DETECTED | |
| Streptococcus agalactiae | 1 x 107 | TV NOT DETECTED | TV DETECTED | |
| Streptococcus bovis | 8 x 106 | TV NOT DETECTED | TV DETECTED | |
| Streptococcus mitis | 2 x 106 | TV NOT DETECTED | TV DETECTED | |
| Streptococcus mutans | 2 x 107 | TV NOT DETECTED | TV DETECTED | |
| Streptococcus pneumoniae | 1 x 106 | TV NOT DETECTED | TV DETECTED | |
| Streptococcus pyogenes | 2 x 106 | TV NOT DETECTED | TV DETECTED | |
| Streptococcus salivarius | 9 x 106 | TV NOT DETECTED | TV DETECTED | |
| Streptococcus sanguis | 5 x 106 | TV NOT DETECTED | TV DETECTED | |
| Streptomyces griseinus | 6 x 106 | TV NOT DETECTED | TV DETECTED | |
| Trichomonas tenaxc | 1 x 105 | TV DETECTED | TV DETECTED | |
| Trichomonas tenaxc | 1 x 103 | TV DETECTED | TV DETECTED | |
| Trichomonas tenaxc | 1 x 102 | TV NOT DETECTED | TV DETECTED | |
| Ureaplasma parvum | 1 x 106d | TV NOT DETECTED | TV DETECTED | |
| Ureaplasma urealyticum | 1 x 106 | TV NOT DETECTED | TV DETECTED | |
| Vibrio parahaemolyticus | 9 x 106 | TV NOT DETECTED | TV DETECTED | |
| | Microorganism | Concentration<br>Testeda | Xpert TV Assay Result | |
| | | | Cross-Reactivity<br>(- <i>T. vaginalis</i> ) | Competitive<br>Interference<br>(+ <i>T. vaginalis</i> ) |
| | <i>Yersinia enterocolitica</i> | 8 x 106 | TV NOT DETECTED | TV DETECTED |

Table 5-4: Analytical Specificity/Competitive Interference Determination for Xpert TV Assay in Urine Matrix

{12}------------------------------------------------

{13}------------------------------------------------

{14}------------------------------------------------

{15}------------------------------------------------

a. Tests run ≥ 10° CFU/mL for bacteria and fungi, ≥10° genomes/mL for yeast, ≥10° TCIDsy/mL or ≥10° genomes/mL for viruses and ≥105 cells/mL for protozoans.

b. Anaerobic organism

c. Protozoan

d. Genome equivalents tested (DNA)

e. Fungal organism

f. Virus

| Table 5-5: Analytical Specificity/Competitive Interference Determination for |
|------------------------------------------------------------------------------|
| Xpert TV Assav in Vaginal Swab Matrix |

| Microorganism | Concentration<br>Testeda | Xpert TV Assay Result | |
|-----------------------------------|--------------------------|--------------------------------------|-------------------------------------------------|
| | | Cross-Reactivity<br>(- T. vaginalis) | Competitive<br>Interference<br>(+ T. vaginalis) |
| Achromobacter xerosis | 1 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 | 5 x 106 | TV NOT DETECTED | TV DETECTED |
| Alcaligenes faecalis | 5 x 106 | 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 105 d | TV NOT DETECTED | TV DETECTED |
| Branhamella catarrhalis | 3 x 106 | TV NOT DETECTED | TV DETECTED |
| Brevibacterium linens | 8 x 106 | TV NOT DETECTED | TV DETECTED |
| Campylo…