cobas® liat CT/NG/MG nucleic acid test

K240197 · Roche Molecular Systems, Inc. · QEP · Jan 16, 2025 · Microbiology

Device Facts

• Record ID: K240197
• Device Name: cobas® liat CT/NG/MG nucleic acid test
• Applicant: Roche Molecular Systems, Inc.
• Product Code: QEP · Microbiology
• Decision Date: Jan 16, 2025
• Decision: SESE
• Submission Type: Dual Track
• Regulation: 21 CFR 866.3393
• Device Class: Class 2

Intended Use

The cobas liat CT/NG/MG nucleic acid test is an automated, qualitative in vitro nucleic acid diagnostic test that utilizes real-time polymerase chain reaction (PCR) for the direct detection of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Mycoplasma genitalium (MG) nucleic acid in male urine and vaginal swabs, all in cobas PCR Media (Roche Molecular Systems, Inc.). This test is intended as an aid in the diagnosis of urogenital infections in both symptomatic and asymptomatic individuals

Device Story

The cobas liat CT/NG/MG nucleic acid test is an automated, qualitative in vitro diagnostic test performed on the cobas liat analyzer. It utilizes real-time PCR to detect Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma genitalium nucleic acid in male urine and vaginal swabs collected in cobas PCR Media. The system integrates sample purification, nucleic acid amplification, and detection. An internal control is included to monitor sample processing and PCR inhibition. The device is used in clinical settings by operators, including CLIA-waived personnel. The analyzer provides qualitative results, which aid healthcare providers in diagnosing urogenital infections. By providing rapid, automated detection, the device facilitates timely clinical decision-making and patient management.

Clinical Evidence

Clinical performance was established in a multi-site, prospective study of 4,852 subjects. Results were compared to a Patient Infected Status (PIS) or Composite Comparator Algorithm (CCA) using FDA-cleared NAATs. Sensitivity for CT was 97.3% (male urine) and 98.2% (vaginal swabs); for NG, 100% (male urine) and 97.7% (vaginal swabs); for MG, 97.1% (male urine) and 95.2% (vaginal swabs). Specificity was >97% across all analytes and specimen types. Invalid rate was 0.1% after retesting.

Technological Characteristics

Automated, closed-tube real-time PCR system. Uses magnetic particles for nucleic acid purification. Assay tube contains pre-packed reagents separated by breakable seals. Analyte targets: CT (cryptic plasmid, 23S rRNA), NG (pivNG, NGR9), MG (mgpC, 23S rRNA). Includes internal control (armored RNA) for inhibition monitoring. Barcode-based specimen identification. Standalone analyzer with embedded microprocessor control. No calibration required by user.

Indications for Use

Indicated for the qualitative detection of Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma genitalium nucleic acid in male urine and vaginal swabs. Intended as an aid in the diagnosis of urogenital infections in both symptomatic and asymptomatic individuals.

Regulatory Classification

Identification

A device to detect nucleic acids from non-viral microorganism(s) causing sexually transmitted infections and associated resistance marker(s) is an in vitro diagnostic device intended for the detection and identification of nucleic acids from non-viral microorganism(s) and their associated resistance markers in clinical specimens collected from patients suspected of sexually transmitted infections. The device is intended to aid in the diagnosis of non-viral sexually transmitted infections in conjunction with other clinical and laboratory data. These devices do not provide confirmation of antibiotic susceptibility since mechanisms of resistance may exist that are not detected by the device.

Special Controls

A device to detect nucleic acids from non-viral microorganism(s) causing sexually transmitted infections and associated resistance marker(s) must comply with the following special controls: (1) The intended use for the 21 CFR 809.10 labeling must include a detailed description of targets the device detects, the results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended. (2) Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of specimen types claimed by this device: alternatively, the sample collection device must be cleared in a premarket submission as a part of this device. (3) The 21 CFR 809.10(b) labeling must include: (i) A detailed device description, including reagents, instruments, ancillary materials, all control elements, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens; (ii) Detailed discussion of the performance characteristics of the device for all claimed specimen types based on analytical studies, including, but not limited to. Limit of Detection, inclusivity, cross-reactivity, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, with-in lab precision, and reproducibility, as appropriate; (iii) Detailed descriptions of the test procedure, the interpretation of test results for clinical specimens, and acceptance criteria for any quality control testing. (iv) Limiting statements indicating that: (A)a negative test result does not preclude the possibility of infection; (B) the test results should be interpreted in conjunction with other clinical and laboratory data available to the clinician; (C) reliable results are dependent on adequate specimen collection, transport, storage, and processing. Failure to observe procedures in any one of these steps can lead to incorrect results; and (D)if appropriate (e.g., recommended by CDC, by current well-accepted clinical guidelines, or by published peer reviewed research), that the clinical performance is inferior in a specific clinical subpopulation or for a specific claimed specimen type. (v) If the device is intended to detect antimicrobial resistance markers, limiting statements, as appropriate, indicating that: (A)negative results for claimed resistance markers do not indicate susceptibility of detected microorganisms, as resistance markers not measured by the assay or other potential mechanisms of antibiotic resistance may be present; (B) detection of resistance markers cannot be definitively linked to specific microorganisms and the source of a detected resistance marker may be an organism not detected by the assay, including colonizing flora; (C) detection of antibiotic resistance markers may not correlate with phenotypic gene expression; and (D) therapeutic failure or success cannot be determined based on the assay results, since nucleic acid may persist following appropriate antimicrobial therapy. (4) Design verification and validation must include: (i) Detailed device description documentation, including, but not limited to, methodology from obtaining sample to result, design of primer/probe sequences, rationale for target sequence selection, and computational path from collected raw data to reported result (e.g., how collected raw signals are converted into a reported result). (ii) Detailed documentation of analytical studies including but not limited to, Limit of Detection, inclusivity, cross-reactivity, microbial interference, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, with-in lab precision, and reproducibility, as appropriate. (iii) Detailed documentation and performance results from a clinical study that includes prospective (sequential) samples for each claimed specimen type and, when determined to be appropriate by FDA, additional characterized clinical samples. The study must be performed on a study population consistent with the intended use population and compare the device performance to results obtained from FDA accepted comparator methods. Documentation from the clinical studies must include the clinical study protocol (including a predefined statistical analysis plan) study report, testing results, and results of all statistical analyses. (iv) A detailed description of the impact of any software, including, but not limited to, software applications and hardware-based devices that incorporate software, on the device's functions.

*Classification.* Class II (special controls). The special controls for this device are:(1) The intended use for the labeling required under § 809.10 of this chapter must include a detailed description of targets the device detects, the results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended. (2) Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of specimen types claimed by this device; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device. (3) The labeling required under § 809.10(b) of this chapter must include: (i) A detailed device description, including reagents, instruments, ancillary materials, all control elements, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens; (ii) Detailed discussion of the performance characteristics of the device for all claimed specimen types based on analytical studies, including Limit of Detection, inclusivity, cross-reactivity, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, within lab precision, and reproducibility, as appropriate; (iii) Detailed descriptions of the test procedure, the interpretation of test results for clinical specimens, and acceptance criteria for any quality control testing; (iv) Limiting statements indicating that: (A) A negative test result does not preclude the possibility of infection; (B) The test results should be interpreted in conjunction with other clinical and laboratory data available to the clinician; (C) Reliable results are dependent on adequate specimen collection, transport, storage, and processing. Failure to observe proper procedures in any one of these steps can lead to incorrect results; and (D) If appropriate ( *e.g.,* recommended by the Centers for Disease Control and Prevention, by current well-accepted clinical guidelines, or by published peer reviewed research), that the clinical performance is inferior in a specific clinical subpopulation or for a specific claimed specimen type; and(v) If the device is intended to detect antimicrobial resistance markers, limiting statements, as appropriate, indicating that: (A) Negative results for claimed resistance markers do not indicate susceptibility of detected microorganisms, as resistance markers not measured by the assay or other potential mechanisms of antibiotic resistance may be present; (B) Detection of resistance markers cannot be definitively linked to specific microorganisms and the source of a detected resistance marker may be an organism not detected by the assay, including colonizing flora; (C) Detection of antibiotic resistance markers may not correlate with phenotypic gene expression; and (D) Therapeutic failure or success cannot be determined based on the assay results, since nucleic acid may persist following appropriate antimicrobial therapy. (4) Design verification and validation must include: (i) Detailed device description documentation, including methodology from obtaining sample to result, design of primer/probe sequences, rationale for target sequence selection, and computational path from collected raw data to reported result ( *e.g.,* how collected raw signals are converted into a reported result).(ii) Detailed documentation of analytical studies, including, Limit of Detection, inclusivity, cross-reactivity, microbial interference, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, within lab precision, and reproducibility, as appropriate. (iii) Detailed documentation and performance results from a clinical study that includes prospective (sequential) samples for each claimed specimen type and, when determined to be appropriate by FDA, additional characterized clinical samples. The study must be performed on a study population consistent with the intended use population and compare the device performance to results obtained from FDA accepted comparator methods. Documentation from the clinical studies must include the clinical study protocol (including a predefined statistical analysis plan) study report, testing results, and results of all statistical analyses. (iv) A detailed description of the impact of any software, including software applications and hardware-based devices that incorporate software, on the device's functions.

Predicate Devices

• cobas 6800/8800 CT/NG (K173887)
• cobas 6800/8800 TV/MG (K190433)

Submission Summary (Full Text)

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January 16th, 2025

Roche Molecular Systems, Inc. Deborah Leu Regulatory Affairs Project Manager 4300 Hacienda Drive Pleasanton, California 94588

Re: K240197

Trade/Device Name: cobas liat CT/NG/MG nucleic acid test Regulation Number: 21 CFR 866.3393 Regulation Name: Device To Detect Nucleic Acids From Non-Viral Microorganism(S) Causing Sexually Transmitted Infections And Associated Resistance Marker(S) Regulatory Class: Class II Product Code: OEP, LSL, MKZ Dated: January 24, 2024 Received: January 25, 2024

Dear Deborah Leu:

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 (the Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

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

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Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (OS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-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-regulatory

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assistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

# Himani Bisht -S

Himani Bisht, Ph.D. Assistant Director Viral Respiratory and HPV Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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# Indications for Use

510(k) Number (if known) K240197

Device Name cobas liat CT/NG/MG nucleic test

### Indications for Use (Describe)

The cobas liat CT/NG/MG nucleic acid test is an automated, qualitative in vitro nucleic acid diagnostic test that utilizes real-time polymerase chain reaction (PCR) for the direct detection of Chlamydia (CT). Neisseria gonorhoeae (NG), and Mycoplasma genitalium (MG) nucleic acid in male urine and vaginal swabs, all in cobas PCR Media (Roche Molecular Systems, Inc.).

This test is intended as an aid in the diagnosis of urogental infections in both symptomatic individuals.

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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# cobas® liat CT/NG/MG nucleic acid test 510(k) Summary

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.

| Submitter Name | Roche Molecular Systems, Inc. |
|----------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Address | 4300 Hacienda Drive,<br>Pleasanton, CA 94588-2722 |
| Contact | Deborah Leu<br>Phone: [phone]<br>Email: [e-mail] |
| Date Prepared | January 15, 2025 |
| Proprietary Name | cobas® liat CT/NG/MG nucleic acid test |
| Common Name | cobas® liat CT/NG/MG |
| Classification Name | Nucleic Acid Detection System For Non-Viral Microorganism(S) Causing<br>Sexually Transmitted Infections<br>DNA probe, Nucleic Acid Amplification, Chlamydia<br>Neisseria spp. direct serological test reagents |
| Product Codes | QEP<br>MKZ<br>LSL |
| Predicate Devices | cobas® 6800/8800 CT/NG, cobas® 6800/8800 TV/MG |
| Establishment Registration | Roche Molecular Systems, Inc. (2243471) |

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### DEVICE DESCRIPTION 1.

The test is performed on the cobas® liat analyzer which automates and integrates sample purification, nucleic acid amplification, and detection of the target sequence in biological samples using real-time PCR assays. The assay targets both the Cryptic plasmid and 23S rRNA of Chlamydia trachomatis, the pivNG and NGR9 of Neisseria gonorrhoeae, and the 23S rRNA and mgpC of Mycoplasma genitalium. An Internal Control (IC) is also included. The IC is present to control for adequate processing of the target bacteria through steps of sample purification, nucleic acid amplification, and to monitor the presence of inhibitors in the PCR processes.

### 2. INDICATIONS FOR USE

The cobas® liat CT/NG/MG nucleic acid test is an automated, qualitative in vitro nucleic acid diagnostic test that utilizes real-time polymerase chain reaction (PCR) for the direct detection of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Mycoplasma genitalium (MG) nucleic acid in male urine and vaginal swabs, all in cobas® PCR Media (Roche Molecular Systems, Inc.).

This test is intended as an aid in the diagnosis of urogenital infections in both symptomatic and asymptomatic individuals.

### TECHNOLOGICAL CHARACTERISTICS 3.

The primary technological characteristics and intended use of the RMS cobas® liat CT/NG/MG nucleic acid test are substantially equivalent to other legally marketed nucleic acid amplification tests intended for the qualitative detection of CT, NG, and MG.

As indicated in Table 1, the RMS cobas® liat CT/NG/MG nucleic acid test is substantially equivalent to significant characteristics of the identified predicate device, the currently cleared cobas® 6800/8800 CT/NG (K173887) and cobas® 6800/8800 TV/MG (K190433) for use on cobas® 6800/8800 Systems.

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### Comparison of the cobas® liat CT/NG/MG nucleic acid test and the Predicate Table 1: Device

| | Submitted Device:<br>cobas® liat CT/NG/MG<br>nucleic acid test | Predicate Device:<br>cobas® 6800/8800 CT/NG for<br>use on cobas® 6800/8800<br>Systems. | Predicate Device:<br>cobas® 6800/8800 TV/MG for<br>use on cobas® 6800/8800<br>Systems. |
|------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Regulation Name | 866.3393<br>866.3120<br>866.3390 | 866.3390<br>866.3120<br>862.2570 | 866.3393 |
| Product Code | QEP<br>MKZ<br>LSL | LSL<br>MKZ<br>OOI | QEP |
| | Submitted Device:<br>cobas® liat CT/NG/MG<br>nucleic acid test | Predicate Device:<br>cobas® 6800/8800 CT/NG for<br>use on cobas® 6800/8800<br>Systems. | Predicate Device:<br>cobas® 6800/8800 TV/MG for<br>use on cobas® 6800/8800<br>Systems. |
| Intended Use | The cobas® liat<br>CT/NG/MG nucleic acid<br>test is an automated,<br>qualitative in vitro nucleic<br>acid diagnostic test that<br>utilizes real-time<br>polymerase chain reaction<br>(PCR) for the direct<br>detection of Chlamydia<br>trachomatis (CT),<br>Neisseria gonorrhoeae<br>(NG), and Mycoplasma<br>genitalium (MG) nucleic<br>acid in male urine and<br>vaginal swabs, all in<br>cobas® PCR Media<br>(Roche Molecular<br>Systems, Inc.).<br>This test is intended as an<br>aid in the diagnosis of<br>urogenital infections in<br>both symptomatic and<br>asymptomatic individuals. | The cobas® CT/NG on the<br>cobas® 6800/8800 system is an<br>automated, qualitative in vitro<br>nucleic acid diagnostic test, that<br>utilizes real-time polymerase<br>chain reaction (PCR), for the<br>direct detection of Chlamydia<br>trachomatis (CT) and/or<br>Neisseria gonorrhoeae (NG)<br>DNA in male and female urine,<br>clinician-instructed self-collected<br>vaginal swab specimens<br>(collected in a clinical setting),<br>clinician-collected vaginal swab<br>specimens, and endocervical<br>swab specimens, all collected in<br>cobas® PCR Media (Roche<br>Molecular Systems, Inc.), and<br>cervical specimens collected in<br>PreservCyt® solution. This test<br>is intended as an aid in the<br>diagnosis of chlamydial and<br>gonococcal disease in both<br>symptomatic and asymptomatic<br>individuals. | cobas TV/MG on the cobas<br>6800/8800 Systems is an<br>automated, qualitative in vitro<br>nucleic acid diagnostic test that<br>utilizes real-time polymerase<br>chain reaction (PCR), for the<br>direct detection of Trichomonas<br>vaginalis (TV) and Mycoplasma<br>genitalium (MG) DNA in male or<br>female urine, self-collected<br>vaginal swab specimens<br>(collected in a clinical setting),<br>cliniciancollected vaginal swab<br>specimens, and endocervical<br>specimens, all collected in cobas<br>PCR Media (Roche Molecular<br>Systems, Inc.). cobas TV/MG<br>also detects TV DNA in cervical<br>specimens collected in<br>PreservCyt solution and MG DNA<br>in self-collected meatal swab<br>specimens (collected in a clinical<br>setting) and clinician collected<br>meatal swab specimens. This<br>test is intended as an aid in the<br>diagnosis of TV and MG<br>infections in individuals<br>suspected to have TV or MG<br>infection. A vaginal swab<br>(selfcollected or<br>cliniciancollected) is the preferred<br>specimen type for MG testing in<br>females due to higher sensitivity<br>compared to endocervical swabs<br>and urine. For males, urine is the<br>preferred specimen type due to<br>higher sensitivity compared to<br>meatal swabs. If vaginal swab or<br>male urine is not used and MG<br>testing is negative, further testing<br>with the preferred specimen type<br>may be indicated if M. genitalium<br>infection is strongly suspected. |
| | Submitted Device:<br>cobas® liat CT/NG/MG<br>nucleic acid test | Predicate Device:<br>cobas® 6800/8800 CT/NG for<br>use on cobas® 6800/8800<br>Systems. | Predicate Device:<br>cobas® 6800/8800 TV/MG for<br>use on cobas® 6800/8800<br>Systems. |
| Sample Type | Male urine,<br>vaginal swabs | Male and female urine,<br>Self-collected/clinician-collected<br>vaginal swab specimens in<br>cobas® PCR Media,<br>Endocervical swab specimens<br>in cobas® PCR Media,<br>Cervical specimens in<br>PreservCyt® solution. | TV and MG:<br>male and female urine, self-<br>collected vaginal swab<br>specimens (collected in a clinical<br>setting), clinician collected<br>vaginal swab specimens, and<br>endocervical swab specimens, all<br>collected in cobas PCR Media<br>TV only:<br>cervical specimens collected in<br>PreservCyt solution<br>MG only:<br>self-collected meatal swab<br>specimens (collected in a clinical<br>setting) and clinician collected<br>meatal swab specimens |
| Analyte Targets | Chlamydia trachomatis<br>(CT)<br>Neisseria gonorrhoeae<br>(NG)<br>Mycoplasma genitalium<br>(MG) | Chlamydia trachomatis (CT),<br>Neisseria gonorrhoeae (NG) | Trichomonas vaginalis (TV)<br>Mycoplasma genitalium (MG) |
| Ancillary<br>Collection Kits | cobas® PCR Urine Sample<br>Kit<br>cobas® PCR Media Uni<br>Swab Sample Kit | cobas® PCR Media Dual Swab<br>Sample Kit<br>cobas® PCR Media Uni Swab<br>Sample Kit<br>cobas® PCR Urine Sample Kit | cobas® PCR Media Dual Swab<br>Sample Kit<br>cobas® PCR Media Uni Swab<br>Sample Kit<br>cobas® PCR Urine Sample Kit |
| Sample<br>Preparation | Automated | Same | Same |
| Amplification<br>Technology | Real-time PCR | Same | Same |
| Detection<br>Chemistry | Assay using different<br>reporter dyes for target<br>and control | Paired reporter and quencher<br>fluorescence labeled probes<br>(TaqMan Technology) using<br>fluorescence resonance energy<br>transfer (FRET) | Paired reporter and quencher<br>fluorescence labeled probes<br>(TaqMan Technology) using<br>fluorescence resonance energy<br>transfer (FRET) |
| Controls Used | Sample processing control<br>(IC) Positive and negative<br>control | Same | Same |
| Results Analysis | PCR Cycle threshold<br>analysis | Same | Same |

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#### NON-CLINICAL PERFORMANCE EVALUATION 4.

### Analytical sensitivity (Limit of Detection) 4.1.

Analytical sensitivity was determined by analyzing a dilution series of two representative strains/serovars of Chlamydia trachomatis (CT, Serovar D and I), Neisseria gonorrhoeae (NG, Strains 2948 and 891), and Mycoplasma genitalium (MG, Strains M30 and G37). The CT, NG, and MG cultures were diluted in pooled negative urine (UR) or pooled negative vaginal swab (VS) clinical specimens to 7 concentration levels. All levels were tested with at least 20 replicates per concentration tested across 3 unique lots of reagents. LoD for each specimen type is shown in Table 2, Table 3, and Table 4 for CT, NG, and MG, respectively as the target concentration which can be detected in ≥ 95% of the replicates for all lots.

CT concentration levels with at least 95% observed hit rate for all lots tested Table 2:

| Specimen Types | CT<br>Serovar D LoD<br>(EB/mL) | CT<br>Serovar D Mean<br>Ct Value | CT<br>Serovar I LoD<br>(EB/mL) | CT<br>Serovar I Mean Ct<br>Value |
|-------------------------------------|--------------------------------|----------------------------------|--------------------------------|----------------------------------|
| Urine in cobas® PCR Media | 0.085 | 36.2 | 0.784 | 36.0 |
| Vaginal Swab in cobas® PCR<br>Media | 0.170 | 35.3 | 0.784 | 35.7 |

EB = Elementary Bodies

| Table 3: NG concentration levels with at least 95% observed hit rate for all lots tested |
|------------------------------------------------------------------------------------------|
| |

| Specimen Types | NG<br>Strain 2948 LoD<br>(CFU/mL) | NG<br>Strain 2948 Mean<br>Ct Value | NG<br>Strain 891 LoD<br>(CFU/mL) | NG<br>Strain 891 Mean<br>Ct Value |
|-------------------------------------|-----------------------------------|------------------------------------|----------------------------------|-----------------------------------|
| Urine in cobas® PCR Media | 0.250 | 34.7 | 0.200 | 34.5 |
| Vaginal Swab in cobas® PCR<br>Media | 0.500 | 34.2 | 0.200 | 34.5 |

CFU = Colony Forming Units

| Table 4: | MG concentration levels with at least 95% observed hit rate for all lots tested. |
|----------|----------------------------------------------------------------------------------|
|----------|----------------------------------------------------------------------------------|

| Specimen Types | MG<br>M30 LoD (cp/mL) | MG<br>M30 Mean Ct<br>Value | MG<br>G37 LoD (cp/mL) | MG<br>G37 Mean Ct<br>Value |
|---------------------------|-----------------------|----------------------------|-----------------------|----------------------------|
| Urine in cobas® PCR Media | 0.250 | 35.2 | 0.500 | 33.7 |

{10}------------------------------------------------

| Specimen Types | MG<br>M30 LoD (cp/mL) | MG<br>M30 Mean Ct<br>Value | MG<br>G37 LoD (cp/mL) | MG<br>G37 Mean Ct<br>Value |
|-------------------------------------|-----------------------|----------------------------|-----------------------|----------------------------|
| Vaginal Swab in cobas® PCR<br>Media | 0.250 | 34.4 | 0.250 | 33.9 |

cp = copies

### 4.2. Inclusivity

Inclusivity was performed for an additional 15 CT serovars, 43 NG strains, and 6 MG strains using one lot of reagents. Testing was performed using CT, NG, and MG cultures that were spiked into pools of negative clinical specimens. Three replicates per dilution level were tested for each subtype per specimen type. The lowest level at which all three replicates tested as positive are reported in Table 5, Table 6, and Table 7 for CT, NG, and MG, respectively.

| Serovar Type or Variant | Urine Specimens (EB/mL) | Vaginal Swab Specimens (EB/mL) |
|-------------------------|-------------------------|--------------------------------|
| A | 0.1 | 0.2 |
| B | 0.4 | 0.2 |
| Ba | 0.4 | 1 |
| C | 0.7 | 0.7 |
| E | 2 | 36 |
| F | 0.4 | 0.04 |
| G | 0.4 | 0.4 |
| H | 0.4 | 3 |
| J | 0.1 | 0.2 |
| K | 0.1 | 0.04 |
| LGV Type 1 | 0.1 | 0.04 |
| LGV Type 2 | 1600 | 200 |
| LGV Type 3 | 0.1 | 0.7 |
| nvCT | 0.1 | 0.7 |
| Finnish-nvCT | 1:100 of Patient Sample | 1:100 of Patient Sample |

#### Table 5: Inclusivity testing for CT serovars

{11}------------------------------------------------

| Strain ID | Urine Specimens (CFU/mL) | Vaginal Swab Specimens (CFU/mL) |
|------------------------------------------------------------------------------|--------------------------|---------------------------------|
| ATCC 27633 | 0.2 | 0.5 |
| ATCC 49226 | 1 | 0.006 |
| ATCC 700825 | 0.01 | 0.001 |
| Clinical Isolate SS169 | 0.06 | 0.02 |
| NBL 1606 | 0.3 | 0.08 |
| NBL 1952 | 0.2 | 0.1 |
| NBL 2012 | 0.2 | 0.3 |
| NRL 1977 | 0.02 | 0.02 |
| NRL 8042 - Belgium | 0.02 | 0.02 |
| NRL 13477 | 0.09 | 0.1 |
| NRL 13819 | 0.006 | 0.004 |
| NRL 33155 - Atlanta | 0.09 | 0.001 |
| NRL 33641 | 0.01 | 0.07 |
| NRL 35495 | 0.01 | 0.07 |
| NRL DAN 09612 | 0.02 | 0.03 |
| NRL DN 7896 - DENMARK | 0.9 | 0.3 |
| NRL DN 7901 - DENMARK | 0.02 | 0.02 |
| NRL DOM 362 - Dominican Republic | 0.09 | 0.09 |
| NRL DOM 1271 - Dominican Republic | 0.4 | 0.1 |
| NRL KPO 1148 - KENYA (KPO) | 0.2 | 0.07 |
| NRL KPO 1161 - KENYA (KPO) | 0.02 | 0.02 |
| NRL Peru 33 | 0.07 | 0.07 |
| NRL Peru 83 | 0.02 | 0.02 |
| NRL PITT 94-4833 - PITTSBURGH<br>(PITT) | 0.02 | 0.02 |
| NRL PITT 94-8561 - PITTSBURGH<br>(PITT) | 0.09 | 0.1 |
| NRL PP 132 - PHILLIPINES | 0.09 | 0.1 |
| NRL SEN 97 P-292 - SENEGAL (SEN) | 0.006 | 0.02 |
| NRL SEN 97 P-301 - SENEGAL (SEN) | 0.006 | 0.07 |
| Roche Diagnostics K.K.,Japan<br>RDN001-00193 | 0.02 | 0.03 |
| Roche Diagnostics, Australia 04D125:<br>Darwin Northern Territory, Australia | 0.09 | 0.1 |
| Roche Diagnostics, Australia 04D127:<br>Darwin Northern Territory, Australia | 0.09 | 0.1 |
| Strain ID | Urine Specimens (CFU/mL) | Vaginal Swab Specimens (CFU/mL) |
| Roche Diagnostics, Australia 04D129:<br>Darwin Northern Territory, Australia | 0.09 | 0.1 |
| Roche Diagnostics, Australia 04D130:<br>Darwin Northern Territory, Australia | 0.4 | 0.1 |
| Roche Diagnostics, Australia 04D132:<br>Darwin Northern Territory, Australia | 0.09 | 0.09 |
| Roche Diagnostics, Australia 05D003:<br>Darwin Northern Territory, Australia | 0.02 | 0.03 |
| Roche Diagnostics, Australia 05D004:<br>Darwin Northern Territory, Australia | 0.006 | 0.004 |
| Roche Diagnostics, Australia 4551 -<br>Western Australia | 0.02 | 0.02 |
| Statens Serum Institut 223/06 | 0.006 | 0.006 |
| Statens Serum Institut 1498/46 | 0.02 | 0.02 |
| Statens Serum Institut 2170/46 | 0.02 | 0.02 |
| Statens Serum Institut 2222/46 | 0.4 | 0.09 |
| Statens Serum Institut 6973/45 | 0.09 | 0.09 |
| UCSF58 | 0.06 | 0.07 |

### Table 6: Inclusivity testing for NG strains

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

#### Table 7: Inclusivity testing for MG strains

| Strain ID | MG (copies/mL) | |
|-----------|-----------------|------------------------|
| | Urine Specimens | Vaginal Swab Specimens |
| M2288 | 2 | 1 |
| M2300 | 0.8 | 0.3 |
| M2341 | 0.8 | 1 |
| SEA-1 | 8 | 33 |
| M2321 | 0.8 | 0.3 |
| TW 10-5G | 0.08 | 0.08 |

### 4.3. Analytical specificity/cross reactivity

A panel of 181 strains of bacteria, fungi and viruses, including those commonly found in patient specimens, 52 representative strains of non-gonorrhoeae Neisseria species and other phylogenetically unrelated organisms, were tested to assess analytical specificity. The organisms listed in Table 8 were spiked at concentrations of ≥1 x 106 units/mL* for bacteria or fungi and ≥1 x 105 units/mL for viruses into pools of negative vaginal swab specimens collected in cobas®

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

PCR Media and negative urine specimens stabilized in cobas® PCR Media. Testing was performed with each potential interfering organism in the absence of, as well as mixed with, CT, NG, and MG cultures at ~3x LoD. Results indicated that 180 of the non-target organisms tested did not generate any false positive or false negative results due to cross-reactivity or interference. One strain of Neisseria lactamica (CCUG 26479), at concentrations greater than 1 x 10ª CFU/mL, interfered with detection of NG at ~3x LoD. At 1 x 104 CFU/mL, this N. lactamica strain did not interfere with detection of NG at ~3x LoD, nor did 8 additional strains of N. lactamica when tested at concentrations ≥1 x 106 CFU/mL.

*Four bacteria could only be tested at a concentration below 1 x 106 units/mL and above 7 x 104 units/mL due to low stock titers.

| Acholeplasma laidlawii | Eikenella corrodens | Mobiluncus curtisii | Peptostreptococcus<br>anaerobius |
|-----------------------------------------------------------|--------------------------------------------------------------------------|-------------------------------------------------------|---------------------------------------------------------|
| Acholeplasma oculi a,c | Enterobacter aerogenes<br>(Klebsiella aerogenes) | Moraxella catarrhalis | Plesiomonas shigelloides |
| Acinetobacter calcoaceticus | Enterobacter cloacae | Moraxella lacunata | Prevotella bivia |
| Acinetobacter Iwoffii | Enterococcus avium | Moraxella osloensis | Cutibacterium acnes |
| Actinomyces israelii a,c | Enterococcus faecalis (2<br>strains) | Morganella morganii | Proteus mirabilis |
| Actinomyces pyogenes<br>(Trueperella pyogenes) | Enterococcus faecium (2<br>strains) | Mycobacterium smegmatis | Proteus vulgaris |
| Aerococcus viridans | Erwinia herbicola<br>(Pantoea agglomerans) | Mycoplasma faucium a,c | Providencia stuartii |
| Aeromonas hydrophila | Erysipelothrix rhusiopathiae | Mycoplasma fermentans | Pseudomonas aeruginosa |
| Alcaligenes faecalis | Escherichia coli | Mycoplasma hominis | Pseudomonas fluorescens |
| Atopobium vaginae<br>(Fannyhessea vaginae) | Flavobacterium<br>meningosepticum<br>(Elizabethkingia<br>meningoseptica) | Mycoplasma orale | Pseudomonas putida |
| Bacillus subtilis | Fusobacterium nucleatum | Mycoplasma penetrans | Rahnella aquatilis |
| Bacteroides fragilis | Gardnerella vaginalis | Mycoplasma pirum | Rhizobium radiobacter<br>(Agrobacterium<br>tumefaciens) |
| Bacteroides ureolyticus<br>(Campylobacter<br>ureolyticus) | Gemella haemolysans | Mycoplasma pneumoniae | Rhodospirillum rubrum |
| Bifidobacterium<br>adolescentis | Giardia Intestinalis | Mycoplasma primatum | Saccharomyces cerevisiae |
| Bifidobacterium breve | Haemophilus ducreyi | Mycoplasma salivarium | Salmonella minnesota |
| Blautia producta | Haemophilus influenzae | Mycoplasma<br>spermatophilum | Salmonella typhimurium |
| Brevibacterium linens | Herpes simplex virus I | Neisseria cinerea (4<br>strains) | Serratia marcescens |
| Campylobacter jejuni | Herpes simplex virus II | Neisseria denitrificans<br>(Bergeriella denitrifican) | Staphylococcus aureus |
| Candida albicans (2 strains) | HIV-1 | Neisseria elongata (3<br>strains) | Staphylococcus epidermidis |
| Candida glabrata<br>(Nakaseomyces glabratus) | Human papilloma virus 16<br>(CaSki cells) | Neisseria flava | Staphylococcus<br>saprophyticus |
| Candida parapsilosis | Kingella denitrificans | Neisseria flavescens (2<br>strains) | Streptococcus agalactiae |
| Candida tropicalis | Kingella kingae | Neisseria lactamica (9<br>strains)b | Streptococcus bovis |
| Chlamydia pneumoniae | Klebsiella oxytoca | Neisseria macacae | Streptococcus mitis |
| Chlamydia psittaci | Klebsiella pneumoniae | Neisseria meningitidis<br>Serogroup A | Streptococcus mutans |
| Chromobacterium<br>violaceum | Lactobacillus acidophilus | Neisseria meningitidis<br>Serogroup B | Streptococcus pneumoniae |
| Citrobacter braakii | Lactobacillus brevis<br>(Levilactobacillus brevis) | Neisseria meningitidis<br>Serogroup C<br>(4 strains) | Streptococcus pyogenes |
| Citrobacter freundii | Lactobacillus crispatus | Neisseria meningitidis<br>Serogroup D | Streptococcus salivarius |
| Clostridium difficile<br>(Clostridioides difficile) | Lactobacillus jensenii | Neisseria meningitidis<br>Serogroup W135 | Streptococcus sanguinis |
| Clostridium perfringens | Lactobacillus lactis | Neisseria meningitidis<br>Serogroup Y | Streptomyces griseinus |
| Corynebacterium<br>genitalium | Lactobacillus vaginalis<br>(Limosilactobacillus<br>vaginalis) | Neisseria mucosa (3<br>strains) | Trichomonas tenax |
| Corynebacterium xerosis | Legionella pneumophila (2<br>strains) | Neisseria perflava | Ureaplasma parvum |
| Cryptococcus neoformans | Leptotrichia buccalis | Neisseria polysaccharea | Ureaplasma urealyticum a,c |
| Cytomegalovirus | Leuconostoc<br>mesenteroides | Neisseria sicca (3 strains) | Veillonella parvula |
| Deinococcus radiodurans | Leuconostoc<br>paramesenteroides<br>(Weissella<br>paramesenteroides) | Neisseria subflava (14<br>strains) | Vibrio parahaemolyticus |
| Derxia gummosa | Listeria monocytogenes | Paracoccus denitrificans…