Predicate Devices

cobas® 6800/8800 CT/NG, cobas® 6800/8800 TV/MG

Reference Devices

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes a real-time PCR assay and analyzer. There is no mention of AI or ML in the device description, intended use, or performance studies. The analysis relies on detecting specific nucleic acid sequences and comparing results to a composite comparator algorithm, not on AI/ML-based interpretation.

Therapeutic

No.
The device is an in vitro diagnostic test intended to aid in the diagnosis of urogenital infections by detecting specific nucleic acids, not to provide therapy or treatment.

Diagnostic

Yes

The "Intended Use / Indications for Use" section explicitly states that the test is "an automated, qualitative in vitro nucleic acid diagnostic test" and is "intended as an aid in the diagnosis of urogenital infections."

SaMD (Software as a Medical Device)

No

The device is a nucleic acid diagnostic test performed on a physical analyzer (cobas® liat analyzer) that automates sample processing, amplification, and detection. It is not solely software.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use: The "Intended Use / Indications for Use" section explicitly states that the device is an "in vitro nucleic acid diagnostic test."
Sample Type: The test is performed on biological samples (male urine and vaginal swabs) which are collected from the human body but tested outside of it.
Purpose: The test is intended as an "aid in the diagnosis of urogenital infections." This is a diagnostic purpose.
Method: It utilizes real-time polymerase chain reaction (PCR) for the direct detection of nucleic acid, which is a common method for in vitro diagnostic tests.

All of these points align with the definition of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / 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.

Product codes (comma separated list FDA assigned to the subject device)

OEP, MKZ, LSL

Device Description

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.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Urogenital

Indicated Patient Age Range

Not Found

Intended User / Care Setting

CLIA-waived sites; moderate complexity laboratory

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

A total of 4852 subjects (2512 females and 2340 males) were enrolled in the study and provided specimens for collection. Of these subjects, 72 were non-evaluable due to protocol deviations and incidents (18), invalid cobas and/or final comparator result (45), or sample collection incidents (9). Of the evaluable subjects, 2304 male subjects provided 2302 male urine specimens (2 subjects provided vaginal swab specimens) and 2476 females provided 1240 clinician-collected vaginal swabs and 1236 self-collected vaginal swabs for evaluation in the clinical study.

Prospectively enrolled female subjects provided 4 vaginal swab specimens, three for comparator tests and one for the cobas liat CT/NG/MG nucleic acid test. Vaginal swab specimen for the cobas® liat CT/NG/MG nucleic acid test was either collected by clinician or self-collected.

Prospectively enrolled male subjects provided a urine specimen that was aliquoted into the respective manufacturers' collection devices and cobas® PCR Media.

Specimens were tested for CT, NG, and MG using cobas® liat CT/NG/MG and the comparator NAATs. All tests were run according to the respective IFU.

The clinical performance of cobas® liat CT/NG/MG was evaluated by comparing the results from collected specimen types to a pre-specified PIS/CCA result. The PIS/CCA result for each analyte was derived from a combination of 3 comparator NAATs (NAAT1, NAAT2, and NAAT3). If NAAT1 and NAAT2 are concordant, then the final PIS/CCA result for the respective analyte is the concordant result obtained from NAAT1 and NAAT2. If NAAT1 and NAAT2 are discordant, then NAAT3 is performed to be the tiebreaker between the first 2 discordant results.

Supplementation with archived specimens was included in this study due to the expected low NG prevalence for male urine and vaginal swabs. The archived specimens were prospectively collected samples from a prior clinical trial study (K173887).

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Non-Clinical Performance Evaluation

Analytical sensitivity (Limit of Detection): Determined by analyzing 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). 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 across 3 unique lots of reagents. LoD for each specimen type is the concentration detected in ≥ 95% of replicates for all lots. (Tables 2, 3, 4 provide specific LoD values and Mean Ct Values for each strain/serovar in urine and vaginal swabs).
Inclusivity: Performed for 15 additional CT serovars, 43 NG strains, and 6 MG strains using one lot of reagents. Cultures were spiked into pools of negative clinical specimens. Three replicates per dilution level were tested for each subtype per specimen type. (Tables 5, 6, 7 report the lowest level at which all three replicates tested positive).
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. Organisms were spiked at concentrations of ≥1 x 10^6 units/mL* for bacteria or fungi and ≥1 x 10^5 units/mL for viruses into negative vaginal swab specimens and negative urine specimens. Testing was performed without, and mixed with, CT, NG, and MG cultures at ~3x LoD. 180 of the non-target organisms did not cause false positive or false negative results. One strain of Neisseria lactamica (CCUG 26479) at concentrations >1 x 10^4 CFU/mL interfered with NG detection at ~3x LoD. At 1 x 10^4 CFU/mL, this strain did not interfere, nor did 8 other N. lactamica strains at ≥1 x 10^6 CFU/mL.
Interference: Evaluated effects of over-the-counter or prescription products and endogenous substances. Products tested at the concentration listed in Table 9. Testing used pooled clinical specimens spiked with potential interferents at levels expected from normal patient usage, in negative and positive (~3x LoD) specimen pools. Five replicates each of negative and positive samples (for each of two culture subtypes per microorganism) were tested. No interference was observed in 15 substances at 1.5 mg/mL. Azo Urinary Pain Relief and carbomer-containing Replens™ Long-Lasting Vaginal Moisturizer at concentrations greater than 0.5 mg/mL, respectively, may interfere. For endogenous substances (Table 10), no interference was observed.
Competitive inhibition: Six different combinations of low concentration target (~2x LoD) were mixed with high concentrations of other targets in urine and vaginal swab matrices. Each combination was tested in 10 replicates using one lot of reagents. No interference was observed for microorganisms present at low concentrations.
Reproducibility Studies: Performed across different sites, lots, days, operators, instruments for cobas® liat CT/NG/MG panels from vaginal swabs and urine in cobas® PCR media. Three external sites with a minimum of 3 cobas® liat analyzers per site were used. 48 operators total, 43 CLIA-waived. Two operators per site tested 1 panel per specimen type per day for 15 days (3 panel members, each in triplicate). Total of 1618 tests (811 vaginal, 807 urine). (Tables 11, 12, 13 show site-to-site reproducibility results for CT, NG, and MG respectively, with % Agreement and 95% Confidence Interval for various concentrations including negative). (Tables 14, 15, 16 present total SD and total percent CV for Cycle Threshold Values for CT, NG, and MG respectively). PPA for CT in urine panel members was less than 95%.
Supplemental Precision Study: Performed at one site across different lots, days, operators, and instruments for CT detection in urine. Six untrained operators tested 1 panel per day for 5 non-consecutive days for each lot (3 panel members). Total of 810 evaluable tests. (Table 17 shows reproducibility results by operator and panel member concentration for CT in urine. Table 18 shows SD and CV of Cycle Threshold Values for each factor).

Clinical Performance Evaluation

Clinical study: Multi-site, prospective study comparing cobas® liat CT/NG/MG results to a Patient Infected Status (PIS) or Composite Comparator Algorithm (CCA) derived from FDA-cleared NAATs for CT, NG, MG. Male urine and vaginal swabs collected and tested at 13 geographically diverse clinical sites across the US. 48 operators (43 CLIA-waived, 5 experienced laboratorians).
Sample Size: 4852 subjects enrolled; 4780 evaluable subjects (2304 male, 2476 female).
Methodology: PIS/CCA for each analyte defined by concordance of 3 comparator NAATs (NAAT1, NAAT2, NAAT3 as tiebreaker). (Table 19 details PIS/CCA determination). Archived specimens used to supplement low NG prevalence.
Performance results: Sensitivity (SENS), specificity (SPEC), positive percent agreement (PPA), and negative percent agreement (NPA) calculated. Initial invalid rate 0.6%, final 0.1%.
CT Clinical Performance (Table 20):
- Male Urine:
  - Symptomatic: Sensitivity 98.2% (90.6%, 99.7%), Specificity 99.9% (99.3%, 100.0%)
  - Asymptomatic: Sensitivity 96.4% (87.7%, 99.0%), Specificity 99.9% (99.6%, 100.0%)
  - Total: Sensitivity 97.3% (92.4%, 99.1%), Specificity 99.9% (99.7%, 100.0%)
- Vaginal Swabs:
  - Symptomatic: PPA 98.4% (91.3%, 99.7%), NPA 99.7% (99.2%, 99.9%)
  - Asymptomatic: PPA 97.9% (89.1%, 99.6%), NPA 99.8% (99.4%,100.0%)
  - Total: PPA 98.2% (93.6%, 99.5%), NPA 99.8% (99.5%, 99.9%)
NG Clinical Performance (Table 21):
- Male Urine (Propsective):
  - Symptomatic: Sensitivity 100.0% (94.7%, 100.0%), Specificity 100.0% (99.5%, 100.0%)
  - Asymptomatic: Sensitivity 100.0% (74.1%, 100.0%), Specificity 99.8% (99.4%, 99.9%)
  - Total: Sensitivity 100.0% (95.4%, 100.0%), Specificity 99.9% (99.6%, 100.0%)
- Archived Male Urine:
  - Symptomatic: Sensitivity 100.0% (95.2%, 100.0%), Specificity 100.0% (92.6%, 100.0%)
  - Asymptomatic: Sensitivity 100.0% (56.6%, 100.0%), Specificity 100.0% (89.6%, 100.0%)
  - Total: Sensitivity 100.0% (95.5%, 100.0%), Specificity 100.0% (95.5%, 100.0%)
- Overall Male Urine:
  - Symptomatic: Sensitivity 100.0% (97.4%, 100.0%), Specificity 100.0% (99.5%, 100.0%)
  - Asymptomatic: Sensitivity 100.0% (80.6%, 100.0%), Specificity 99.8% (99.4%, 99.9%)
  - Total: Sensitivity 100.0% (97.7%, 100.0%), Specificity 99.9% (99.6%, 100.0%)
- Vaginal Swabs (Prospective):
  - Symptomatic: PPA 91.7% (74.2%, 97.7%), NPA 99.8% (99.3%, 99.9%)
  - Asymptomatic: PPA 100.0% (82.4%, 100.0%), NPA 99.9% (99.5%, 100.0%)
  - Total: PPA 95.2% (84.2%, 98.7%), NPA 99.8% (99.6%, 99.9%)
- Archived Vaginal Swabs:
  - Symptomatic: PPA 100.0% (83.9%, 100.0%), NPA 100.0% (85.1%, 100.0%)
  - Asymptomatic: PPA 100.0% (86.7%, 100.0%), NPA 100.0% (85.7%, 100.0%)
  - Total: PPA 100.0% (92.1%, 100.0%), NPA 100.0% (92.1%, 100.0%)
- Overall Vaginal Swabs:
  - Symptomatic: PPA 95.5% (84.9%, 98.7%), NPA 99.8% (99.3%, 100.0%)
  - Asymptomatic: PPA 100.0% (91.8%, 100.0%), NPA 99.9% (99.5%, 100.0%)
  - Total: PPA 97.7% (92.0%, 99.4%), NPA 99.8% (99.6%, 99.9%)
MG Clinical Performance (Table 22):
- Male Urine:
  - Symptomatic: Sensitivity 98.0% (93.0%, 99.4%), Specificity 98.7% (97.6%, 99.3%)
  - Asymptomatic: Sensitivity 96.3% (90.9%, 98.6%), Specificity 99.5% (99.0%, 99.8%)
  - Total: Sensitivity 97.1% (93.9%, 98.7%), Specificity 99.2% (98.8%, 99.5%)
- Vaginal Swabs:
  - Symptomatic: Sensitivity 95.2% (90.0%, 97.8%), Specificity 97.3% (96.1%, 98.1%)
  - Asymptomatic: Sensitivity 95.2% (90.0%, 97.8%), Specificity 98.2% (97.3%, 98.8%)
  - Total: Sensitivity 95.2% (91.9%, 97.3%), Specificity 97.8% (97.1%, 98.3%)
Expected values for urogenital specimens: Positivity rates of cobas® liat CT/NG/MG for CT, NG, and MG observed during the study are shown by specimen type and collection site in Table 23.
Summary of Positive Predictive Value, Negative Predictive Value for Hypothetical Prevalence: Hypothetical PPVs and NPVs derived from disease prevalences of 1% to 50% are shown. (Tables 24, 25, 26 provide PPV and NPV for CT, NG, and MG respectively for various hypothetical prevalences).

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

CT:
- Male Urine: Sensitivity 97.3% (92.4%, 99.1%), Specificity 99.9% (99.7%, 100.0%)
- Vaginal Swabs: PPA 98.2% (93.6%, 99.5%), NPA 99.8% (99.5%, 99.9%)
NG:
- Overall Male Urine: Sensitivity 100.0% (97.7%, 100.0%), Specificity 99.9% (99.6%, 100.0%)
- Overall Vaginal Swabs: PPA 97.7% (92.0%, 99.4%), NPA 99.8% (99.6%, 99.9%)
MG:
- Male Urine: Sensitivity 97.1% (93.9%, 98.7%), Specificity 99.2% (98.8%, 99.5%)
- Vaginal Swabs: Sensitivity 95.2% (91.9%, 97.3%), Specificity 97.8% (97.1%, 98.3%)

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

cobas® 6800/8800 CT/NG, cobas® 6800/8800 TV/MG

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

K173887, K190433

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

Regulation Number and Section

§ 866.3393 Device to detect nucleic acids from non-viral microorganism(s) causing sexually transmitted infections and associated resistance marker(s).

(a)
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.(b)
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.

Summary

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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 (DICE@fda.hhs.gov) or phone (1-800-638-2041 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,
Pleasanton, CA 94588-2722
Contact	Deborah Leu
Phone: 925-523-8362
Email: deborahleu@roche.com
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
Sexually Transmitted Infections
DNA probe, Nucleic Acid Amplification, Chlamydia
Neisseria spp. direct serological test reagents
Product Codes	QEP
MKZ
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.

6

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

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

7

8

9

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
Serovar D LoD
(EB/mL) | CT
Serovar D Mean
Ct Value | CT
Serovar I LoD
(EB/mL) | CT
Serovar I Mean Ct
Value |
|-------------------------------------|--------------------------------|----------------------------------|--------------------------------|----------------------------------|
| Urine in cobas® PCR Media | 0.085 | 36.2 | 0.784 | 36.0 |
| Vaginal Swab in cobas® PCR
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
Strain 2948 LoD
(CFU/mL) | NG
Strain 2948 Mean
Ct Value | NG
Strain 891 LoD
(CFU/mL) | NG
Strain 891 Mean
Ct Value |
|-------------------------------------|-----------------------------------|------------------------------------|----------------------------------|-----------------------------------|
| Urine in cobas® PCR Media | 0.250 | 34.7 | 0.200 | 34.5 |
| Vaginal Swab in cobas® PCR
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
M30 LoD (cp/mL) | MG
M30 Mean Ct
Value | MG
G37 LoD (cp/mL) | MG
G37 Mean Ct
Value |
|---------------------------|-----------------------|----------------------------|-----------------------|----------------------------|
| Urine in cobas® PCR Media | 0.250 | 35.2 | 0.500 | 33.7 |

10

| Specimen Types | MG
M30 LoD (cp/mL) | MG
M30 Mean Ct
Value | MG
G37 LoD (cp/mL) | MG
G37 Mean Ct
Value |
|-------------------------------------|-----------------------|----------------------------|-----------------------|----------------------------|
| Vaginal Swab in cobas® PCR
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
(PITT)	0.02	0.02
NRL PITT 94-8561 - PITTSBURGH
(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
RDN001-00193	0.02	0.03
Roche Diagnostics, Australia 04D125:
Darwin Northern Territory, Australia	0.09	0.1
Roche Diagnostics, Australia 04D127:
Darwin Northern Territory, Australia	0.09	0.1
Strain ID	Urine Specimens (CFU/mL)	Vaginal Swab Specimens (CFU/mL)
Roche Diagnostics, Australia 04D129:
Darwin Northern Territory, Australia	0.09	0.1
Roche Diagnostics, Australia 04D130:
Darwin Northern Territory, Australia	0.4	0.1
Roche Diagnostics, Australia 04D132:
Darwin Northern Territory, Australia	0.09	0.09
Roche Diagnostics, Australia 05D003:
Darwin Northern Territory, Australia	0.02	0.03
Roche Diagnostics, Australia 05D004:
Darwin Northern Territory, Australia	0.006	0.004
Roche Diagnostics, Australia 4551 -
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
anaerobius |
|-----------------------------------------------------------|--------------------------------------------------------------------------|-------------------------------------------------------|---------------------------------------------------------|
| Acholeplasma oculi a,c | Enterobacter aerogenes
(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
strains) | Morganella morganii | Proteus mirabilis |
| Actinomyces pyogenes
(Trueperella pyogenes) | Enterococcus faecium (2
strains) | Mycobacterium smegmatis | Proteus vulgaris |
| Aerococcus viridans | Erwinia herbicola
(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
(Fannyhessea vaginae) | Flavobacterium
meningosepticum
(Elizabethkingia
meningoseptica) | Mycoplasma orale | Pseudomonas putida |
| Bacillus subtilis | Fusobacterium nucleatum | Mycoplasma penetrans | Rahnella aquatilis |
| Bacteroides fragilis | Gardnerella vaginalis | Mycoplasma pirum | Rhizobium radiobacter
(Agrobacterium
tumefaciens) |
| Bacteroides ureolyticus
(Campylobacter
ureolyticus) | Gemella haemolysans | Mycoplasma pneumoniae | Rhodospirillum rubrum |
| Bifidobacterium
adolescentis | Giardia Intestinalis | Mycoplasma primatum | Saccharomyces cerevisiae |
| Bifidobacterium breve | Haemophilus ducreyi | Mycoplasma salivarium | Salmonella minnesota |
| Blautia producta | Haemophilus influenzae | Mycoplasma
spermatophilum | Salmonella typhimurium |
| Brevibacterium linens | Herpes simplex virus I | Neisseria cinerea (4
strains) | Serratia marcescens |
| Campylobacter jejuni | Herpes simplex virus II | Neisseria denitrificans
(Bergeriella denitrifican) | Staphylococcus aureus |
| Candida albicans (2 strains) | HIV-1 | Neisseria elongata (3
strains) | Staphylococcus epidermidis |
| Candida glabrata
(Nakaseomyces glabratus) | Human papilloma virus 16
(CaSki cells) | Neisseria flava | Staphylococcus
saprophyticus |
| Candida parapsilosis | Kingella denitrificans | Neisseria flavescens (2
strains) | Streptococcus agalactiae |
| Candida tropicalis | Kingella kingae | Neisseria lactamica (9
strains)b | Streptococcus bovis |
| Chlamydia pneumoniae | Klebsiella oxytoca | Neisseria macacae | Streptococcus mitis |
| Chlamydia psittaci | Klebsiella pneumoniae | Neisseria meningitidis
Serogroup A | Streptococcus mutans |
| Chromobacterium
violaceum | Lactobacillus acidophilus | Neisseria meningitidis
Serogroup B | Streptococcus pneumoniae |
| Citrobacter braakii | Lactobacillus brevis
(Levilactobacillus brevis) | Neisseria meningitidis
Serogroup C
(4 strains) | Streptococcus pyogenes |
| Citrobacter freundii | Lactobacillus crispatus | Neisseria meningitidis
Serogroup D | Streptococcus salivarius |
| Clostridium difficile
(Clostridioides difficile) | Lactobacillus jensenii | Neisseria meningitidis
Serogroup W135 | Streptococcus sanguinis |
| Clostridium perfringens | Lactobacillus lactis | Neisseria meningitidis
Serogroup Y | Streptomyces griseinus |
| Corynebacterium
genitalium | Lactobacillus vaginalis
(Limosilactobacillus
vaginalis) | Neisseria mucosa (3
strains) | Trichomonas tenax |
| Corynebacterium xerosis | Legionella pneumophila (2
strains) | Neisseria perflava | Ureaplasma parvum |
| Cryptococcus neoformans | Leptotrichia buccalis | Neisseria polysaccharea | Ureaplasma urealyticum a,c |
| Cytomegalovirus | Leuconostoc
mesenteroides | Neisseria sicca (3 strains) | Veillonella parvula |
| Deinococcus radiodurans | Leuconostoc
paramesenteroides
(Weissella
paramesenteroides) | Neisseria subflava (14
strains) | Vibrio parahaemolyticus |
| Derxia gummosa | Listeria monocytogenes | Paracoccus denitrificans | Yersinia enterocolitica |
| Dientamoeba fragilis | Micrococcus luteus | Pentatrichomonas hominis | |

Microorganisms tested for analytical specificity/cross reactivity Table 8:

14

ªOrganism was tested at a concentration of 7.0e+4 units/mL.

15

*One strain of organism was tested at a concentration of 1.0e+4 units/mL. CTested at highest concentration possible per stock concentration.

4.4. Interference

The effects of over-the-counter or prescription products that may be present in urine or vaginal swab clinical specimens were evaluated at the concentration listed in Table 9. Testing was executed using pooled clinical specimens spiked with potential interferents at levels expected from normal patient usage. Interferents were tested in CT/NG/MG negative specimen pools as well as in positive specimen pools spiked with CT/NG/MG at ~3x LoD for each specimen type using one lot of reagents. Five replicates each of CT/NG/MG negative sample and CT/NG/MG positive sample (for each of two culture subtypes per microorganism) were tested with each exogenous substance in each specimen type, except for Azo Urinary Pain Relief, which was tested in urine only.

Of the products tested, no interference was observed in 15 substances when tested at concentrations of 1.5 mg/mL. Azo Urinary Pain Relief and carbomer-containing Replens™ Long-Lasting Vaginal Moisturizer resulted in false negative results in at least one replicate when tested at higher concentrations. Azo Urinary Pain Relief and Replens™ Long-Lasting Vaginal Moisturizer at concentrations greater than 0.5 mg/mL, respectively, may interfere with the assay performance. Levels of substances tolerated by the assay for all specimen types are shown in Table 9.

Product Name	Urine (mg/mL)	Vaginal Swabs (mg/mL)
Azo Urinary Pain Relief (urine only)	0.5*	-
Clindamycin Phosphate Vaginal Cream	1.5	1.5
Equate tioconazole 1 Day	1.5	1.5
Equate Vagicaine Anti-Inch Cream	1.5	1.5
Estradiol Vaginal Cream	1.5	1.5
7 Day vaginal cream	1.5	1.5
K-Y® UltraGel	1.5	1.5
Metronidazole Vaginal Gel	1.5	1.5
Monistat Miconazole Nitrate Vaginal Cream (2%)	1.5	1.5
Monistat® Instant Itch Relief Cream	1.5	1.5
Norforms Deodorant Suppositories	1.5	1.5
Premarin Vaginal Cream	1.5	1.5

Table 9: List of products tested for interference

16

Product Name	Urine (mg/mL)	Vaginal Swabs (mg/mL)
Replens™ Long-Lasting Vaginal Moisturizer	1.0*	1.5
Summer's Eve Ultra Freshening Spray	1.5	1.5
VCF - Vaginal Contraceptive Gel	1.5	1.5
Yeast Gard Gel Treatment	1.5	1.5
RepHresh™ Vaginal Gel	1.5	1.5

*Note: Concentrations above this level may cause interference in clinical samples.

Endogenous substances that may be present in urine or vaginal swab clinical specimens were evaluated at the concentration listed in Table 10. Testing was executed using pooled clinical specimens spiked with potential endogenous interferents at levels expected in a typical clinical sample. Endogenous substances were tested in CT/NG/MG negative specimen pools as well as in positive specimen pools spiked with CT/NG/MG at ~3x LoD for each relevant specimen type using one lot of reagents. Five replicates each of CT/NG/MG negative sample and CT/NG/MG positive sample (for each of two culture subtypes per microorganism) were tested with each endogenous substance in each relevant sample type.

For all endogenous substances tested, no interference was observed. Levels of endogenous substances tolerated by the assay for each specimen types are shown in Table 10

		Table 10: Summary of endogenous substance concentrations that do not show interference
--	--	----------------------------------------------------------------------------------------	--	--

Endogenous Substance	Urine	Vaginal Swab
Human cells (PBMCs) cells/mL	1.0E+06	1.0E+06
Mucus	1 swab dipped into mucus	1 swab dipped into mucus
Whole blood (v/v)	10%	10%
Semen (v/v) (vaginal swab only)	-	1.5%
Albumin (w/v) (urine only)	5%	-
Bilirubin (w/v) (urine only)	1% (w/v)	-
Glucose (w/v) (urine only)	1% (w/v)	-
Acidic pH (urine only)	pH 4	-
Alkaline pH (urine only)	pH 9	-

17

4.5. Competitive inhibition

To assess competitive inhibition between CT. NG. and MG, at total of six different combinations of low concentration of target (~2x LoD) were mixed with high concentrations of the other targets in both urine and vaginal swab clinical specimen matrices. Each combination was tested in replicates of 10 using one lot of reagents.

Testing results indicated that when one or two target microorganisms were present at high concentrations, no interference was observed for microorganisms that were present at low concentrations (~2x LoD), when tested in both urine and vaginal swab clinical specimen matrices.

5. REPRODUCIBILITY STUDIES

A reproducibility study was performed across different sites, lots, days, operators, instruments for cobas® liat CT/NG/MG panels prepared from vaginal swabs and urine in cobas® PCR media. Testing was performed at three external sites with a minimum of 3 cobas® liat analyzers per site. Operators at the CLIA-waived sites that met the definition of intended use operators were considered for this study. Selected operators were provided with the assay's IFU, Quick Reference Instructions, and the cobas® liat system User Guide. Operators were asked to read the materials before beginning any study testing. No assay or instrument training was provided to the operators.

Two operators at each site each tested 1 panel per specimen type per day (1 complete panel consists of 3 panel members each tested in triplicate) for a total of 15 days. All replicates for each panel member were always tested on the same analyzer. Each panel, per specimen type, consisted of a negative panel member (negative for all 3 analytes), a low positive panel member, and a moderate positive panel member with each positive panel member being co-formulated with all 3 analytes. For each panel member, approximately 270 results were produced.

The Reproducibility Study was executed with a total of 1618 tests consisting of 811 tests for the vaginal specimen type and 807 tests for the urine specimen type. Table 11, Table 12 and Table 13 show the site-to-site Reproducibility Study results for cobas® liat CT/NG/MG by sample type and panel member concentration, respectively, for CT, NG, and MG.

18

| Specimen
Type | Panel
Member
Concentratio
n | Site 1* | Site 2* | Site 3* | Overall* |
|------------------|--------------------------------------|-------------------------------------|-------------------------------------|-------------------------------------|---------------------------------------|
| Vaginal | 1-2x LoD | 100%
(90/90)
(95.9% - 100.0%) | 100%
(89/89)
(95.9% - 100.0%) | 100%
(90/90)
(95.9% - 100.0%) | 100%
(269/269)
(98.6% - 100.0%) |
| Vaginal | 3-5x LoD | 100%
(90/90)
(95.9% - 100.0%) | 100%
(90/90)
(95.9% - 100.0%) | 100%
(90/90)
(95.9% - 100.0%) | 100%
(270/270)
(98.6% - 100.0%) |
| Vaginal | Negative | 100%
(90/90)
(95.9% - 100.0%) | 100%
(83/83)
(95.6 - 100.0%) | 100%
(90/90)
(95.9% - 100.0%) | 100%
(263/263)
(98.6% - 100.0%) |
| Urine | 1-2x LoD | 87.8%
(79/90)
(79.4% - 93.0%) | 93.3%
(83/89)
(86.1% - 96.9%) | 91.1%
(82/90)
(83.4% - 95.4%) | 90.7%
(244/269)
(86.6% - 93.6%) |
| Urine | 3-5x LoD | 95.6%
(86/90)
(89.1% - 98.3%) | 98.9%
(88/89)
(93.9% - 99.8%) | 94.4%
(85/90)
(87.6% - 97.6%) | 96.3%
(259/269)
(93.3% - 98.0%) |
| Urine | Negative | 100%
(90/90)
(95.9% - 100.0%) | 100%
(80/80)
(95.6% - 100.0%) | 100%
(90/90)
(95.9% - 100.0%) | 100%
260/260
(98.5% - 100.0%) |

Table 11: Summary CT of site-to-site reproducibility results with cobas® liat CT/NG/MG

Note: LoD: limit of detection

*Percent Agreement with expected results (n/N) (95% Confidence Interval)

19

| Specimen
Type | Panel
Member
Conc. | Site 1* | Site 2* | Site 3* | Overall* |
|------------------|--------------------------|-------------------------------------|-------------------------------------|-------------------------------------|---------------------------------------|
| Vaginal | 1-2x LoD | 100%
(90/90)
(95.9% - 100.0%) | 100%
(89/89)
(95.9% - 100.0%) | 100%
(90/90)
(95.9% - 100.0%) | 100%
(269/269)
(98.6% - 100.0%) |
| Vaginal | 3-5x LoD | 100%
(90/90)
(95.9% - 100.0%) | 100%
(90/90)
(95.9% - 100.0%) | 100%
(90/90)
(95.9% - 100.0%) | 100%
(270/270)
(98.6% - 100.0%) |
| Vaginal | Negative | 100%
(90/90)
(95.9% - 100.0%) | 100%
(83/83)
(95.6 - 100.0%) | 100%
(90/90)
(95.9% - 100.0%) | 100%
(263/263)
(98.6% - 100.0%) |
| Urine | 1-2x LoD | 100%
(90/90)
(95.9% - 100.0%) | 98.9%
(88/89)
(93.9% - 99.8%) | 100%
(90/90)
(95.9% - 100.0%) | 99.6%
(268/269)
(97.9% - 99.9%) |
| Urine | 3-5x LoD | 100%
(90/90)
(95.9% - 100.0%) | 100%
(89/89)
(95.9% - 100.0%) | 100%
(90/90)
(95.9% - 100.0%) | 100%
(269/269)
(98.6% - 100.0%) |
| Urine | Negative | 100%
(90/90)
(95.9% - 100.0%) | 100%
(80/80)
(95.6% - 100.0%) | 100%
(90/90)
(95.9% - 100.0%) | 100%
260/260
(98.5% - 100.0%) |

Table 12: Summary NG of site-to-site reproducibility results with cobas® liat CT/NG/MG

Note: LoD: limit of detection.

*Percent Agreement with expected results (n/N) (95% Confidence Interval)

	Table 13: Summary MG of site-to-site reproducibility results with cobas® liat CT/NG/MG
Specimen
Type	Panel
Member
Conc.	Site 1*	Site 2*	Site 3*	Overall*
Vaginal	1-2x LoD	100%
(90/90)
(95.9% - 100.0%)	98.9%
(88/89)
(93.9% - 99.8%)	100%
(90/90)
(95.9% - 100.0%)	99.6%
(268/269)
(97.9% - 99.9%)
Vaginal	3-5x LoD	100%
(90/90)
(95.9% - 100.0%)	100%
(90/90)
(95.9% - 100.0%)	100%
(90/90)
(95.9% - 100.0%)	100%
(270/270)
(98.6% - 100.0%)
Vaginal	Negative	100%
(90/90)
(95.9% - 100.0%)	100%
(83/83)
(95.6 - 100.0%)	100%
(90/90)
(95.9% - 100.0%)	100%
(263/263)
(98.6% - 100.0%)
Urine	1-2x LoD	100%
(90/90)
(95.9% - 100.0%)	100%
(89/89)
(95.9% - 100.0%)	98.9%
(89/90)
(94.0% - 100.0%)	99.6%
(268/269)
(97.9% - 99.9%)

20

| Specimen
Type | Panel
Member
Conc. | Site 1* | Site 2* | Site 3* | Overall* |
|------------------|--------------------------|--------------------------------------|-------------------------------------|-------------------------------------|---------------------------------------|
| Urine | 3-5x LoD | 100%
(90/90)
(95.9% - 100.0%) | 100%
(89/89)
(95.9% - 100.0%) | 100%
(90/90)
(95.9% - 100.0%) | 100%
(269/269)
(98.6% - 100.0%) |
| Urine | Negative | 98.9%
(89/90)
(94.0% - 100.0%) | 100%
(80/80)
(95.6% - 100.0%) | 100%
(90/90)
(95.9% - 100.0%) | 100%
260/260
(98.5% - 100.0%) |

Note: LoD : limit of detection.

*Percent Agreement with expected results (n/N) (95% Confidence Interval)

Table 14, Table 15 and Table 16 present the total SD, and total percent CV (%) for Cycle Threshold Values from the Reproducibility Study for each specimen panel type run in cobas® liat CT/NG/MG, respectively, for CT, NG, and MG.

Table 14: CT - Overall mean estimate, standard deviations, and coefficients of variation (%) for cycle threshold values by sample type and expected concentration for cobas® liat CT/NG/MG by sample type and positive panel member concentration

| Sample
Type | Panel
Member
Concentration | n/Na | Mean
Ct | Between
Site
SD | Between
Site
CV% | Between
Lot
SD | Between
Lot
CV% | Between
Day
SD | Between
Day
CV% | Between
Operator
/ Run SD | Between
Operator/
Run CV% | Within
Run
SD | Within
RunCV
% | Total
SD | Total
CV% |
|----------------|----------------------------------|-------------|------------|-----------------------|------------------------|----------------------|-----------------------|----------------------|-----------------------|---------------------------------|---------------------------------|---------------------|----------------------|-------------|--------------|
| Vagin
al | 1×-2×
LoD | 269/
269 | 33.4 | 0.00 | 0.00 | 0.53 | 1.60 | 0.22 | 0.67 | 0.00 | 0.00 | 0.84 | 2.52 | 1.0
2 | 3.06 |
| Vagin
al | 3×-5×
LoD | 270/
270 | 32.1 | 0.21 | 0.64 | 0.58 | 1.82 | 0.30 | 0.93 | 0.00 | 0.00 | 1.00 | 3.13 | 1.2
2 | 3.79 |
| Urine | 1×-2×
LoD | 244/
269 | 34.8 | 0.15 | 0.44 | 0.84 | 2.41 | 0.31 | 0.88 | 0.00 | 0.00 | 0.91 | 2.61 | 1.2
8 | 3.69 |
| Urine | 3×-5×
LoD | 259/
269 | 34.0 | 0.15 | 0.45 | 0.70 | 2.07 | 0.23 | 0.68 | 0.00 | 0.00 | 0.98 | 2.89 | 1.2
4 | 3.65 |

Ct: cycle threshold; CV%: percent coefficient of variation; LOD: Limit of Detection; SD: standard deviation. ªn is the number of tests in agreement with expected results. N is the total number of valid tests for the panel member.

21

Table 15: NG - Overall mean estimate, standard deviations, and coefficients of variation (%) for cycle threshold values by sample type and expected concentration for cobas® liat CT/NG/MG by sample type and positive panel member concentration

| Sample
Type | Panel
Member
Concen-
tration | n/Na | Bet-
ween
Site
SD | Be-
tween
Site
CV% | Be-
tween
Lot
SD | Be-
tween
Lot
CV% | Be-
tween
Day
SD | Be-
tween
Day
CV% | Between
Operator
/ Run SD | Between
Operator
/ Run
CV% | Within
Run
SD | Within
Run
CV% | Total
SD | Total
CV% | Total
CV% |
|----------------|---------------------------------------|-------------|----------------------------|-----------------------------|---------------------------|----------------------------|---------------------------|----------------------------|---------------------------------|-------------------------------------|---------------------|----------------------|-------------|--------------|--------------|
| Vagin
al | 1×-2×
LoD | 269/
269 | 32.2 | 0.11 | 0.34 | 0.59 | 1.83 | 0.29 | 0.89 | 0.14 | 0.42 | 0.59 | 1.83 | 0.90 | 2.79 |
| Vagin
al | 3×-5×
LoD | 270/
270 | 30.9 | 0.10 | 0.33 | 0.15 | 0.50 | 0.18 | 0.57 | 0.00 | 0.00 | 0.41 | 1.33 | 0.48 | 1.56 |
| Urine | 1×-2×
LoD | 268/
269 | 32.9 | 0.16 | 0.47 | 0.70 | 2.12 | 0.26 | 0.78 | 0.46 | 1.41 | 0.74 | 2.25 | 1.16 | 3.51 |
| Urine | 3×-5×
LoD | 269/
269 | 31.4 | 0.07 | 0.23 | 0.25 | 0.80 | 0.16 | 0.51 | 0.00 | 0.00 | 0.56 | 1.79 | 0.64 | 2.04 |

Ct: cycle threshold; CV%: percent coefficient of variation; LOD: Limit of Detection; SD: standard deviation. ªn is the number of tests in agreement with expected results. N is the total number of valid tests for the panel member.

Table 16: MG - Overall mean estimate, standard deviations, and coefficients of variation (%) for cycle threshold values by sample type and expected concentration for cobas® liat CT/NG/MG by sample type and positive panel member concentration

| Sample
Type | Panel
Member
Concentration | n/Na | Between
Site
SD | Between
Site
CV% | Between
Lot
SD | Between Lot
CV% | Between
Day
SD | Between
Day
CV% | Between
Operator/
Run
SD | Between
Operator / Run
CV% | Within
Run
SD | Within
RunCV
% | Total
SD | Total
CV
% | Total
CV
% |
|----------------|----------------------------------|-------------|-----------------------|------------------------|----------------------|--------------------|----------------------|-----------------------|-----------------------------------|----------------------------------|---------------------|----------------------|-------------|------------------|------------------|
| Vaginal | 1×-2×
LoD | 268/
269 | 33.3 | 0.18 | 0.54 | 0.52 | 1.58 | 0.08 | 0.23 | 0.00 | 0.00 | 0.89 | 2.68 | 1.05 | 3.16 |
| Vaginal | 3×-5×
LoD | 270/
270 | 32.0 | 0.21 | 0.65 | 0.66 | 2.07 | 0.11 | 0.34 | 0.14 | 0.44 | 0.88 | 2.76 | 1.14 | 3.55 |
| Urine | 1×-2×
LoD | 268/269 | 34.2 | 0.23 | 0.67 | 0.59 | 1.73 | 0.24 | 0.70 | 0.00 | 0.00 | 1.08 | 3.16 | 1.28 | 3.73 |
| Urine | 3×-5×
LoD | 269/
269 | 33.1 | 0.27 | 0.82 | 0.75 | 2.25 | 0.23 | 0.70 | 0.10 | 0.29 | 1.03 | 3.11 | 1.32 | 4.00 |

Ct: cycle threshold; CV%: percent coefficient of variation; LOD: Limit of Detection; SD: standard deviation.

ªn is the number of tests in agreement with expected results. N is the total number of valid tests for the panel member.

22

In the Reproducibility Study, the PPA for CT in urine panel members was less than the expected 95%. Therefore, a supplemental Precision Study was performed at one site across different lots, days, operators and instruments for cobas® liat CT/NG/MG for the detection of CT in urine from urine panels prepared at negative, 1x-2x and 3x-5xLOD concentration levels. There were six total untrained operators and the level of instructional material were the same for this supplemental Precision Study. Each operator tested 1 panel per day for 5 non-consecutive days for each lot (1 complete panel consisted of 3 panel members). This supplemental Precision Study was executed with a total of 810 evaluable tests on urine panel members.

Table 17 shows the supplemental between operator Precision Study for cobas® liat CT/NG/MG by panel member concentration for CT in urine.

| Panel Member
Concentration | Operator | Results (%) |
|-------------------------------|-- | 1-2x LoD | 1 | | 2 | | 3 | | 4 | | 5 | | 6 | 3-5x LoD | 1 | | 2 | | 3 | | 4 | | 5 | | 6 | Negative | 1 | | 2 | | 3 | | 4 | | 5 | | 6 n/N a | Agreement with Expected
--------|-------|----------------------------------------|
| 44/45 | 97.8% |
| 44/44 | 100.0% |
| 45/45 | 100.0% |
| 44/44 | 100.0 % |
| 45/45 | 100.0% |
| 45/45 | 100.0% |
| 45/45 | 100.0% |
| 45/45 | 100.0% |
| 45/45 | 100.0% |
| 45/45 | 100.0% |
| 45/45 | 100.0% |
| 44/44 | 100.0% |
| 43/44 | 97.7% |
| 45/45 | 100.0% |
| 45/45 | 100.0% |
| 45/45 | 100.0% |
| 45/45 | 100.0% |
| 44/44 | 100.0% |

Table 17: Summary of CT Precision/Repeatability study results

a n is the number of tests with expected results. N is the total number of valid tests.

23

Table 18 shows the supplemental precision Study for cobas® liat CT/NG/MG standard deviation (SD) and coefficient of variation (CV) of Cycle Threshold Values for each factor as well as the total SD and total CV (%) for each positive panel member.

Table 18: CT - Overall mean estimate, standard deviations, and coefficients of variation (%) for cvcle threshold values and expected concentration for cobas® liat CT/NG/MG by positive panel member concentration in urine

| Panel
Member
Concentration | n/Na | Mean
Ct | Between
Instrument
SD | Between
Instrument
CV% | Between
Lot | Be-
tween
Lot
CV% | Be-
twee
n
Day
SD | Be-
tween
Day
CV% | Between
Operator/
Run SD | Between
Operator/
Run
CV% | Within
Run
SD | Within
Run
CV% | Total
SD | Total
CV% |
|----------------------------------|-------------|------------|-----------------------------|------------------------------|----------------|----------------------------|-------------------------------|----------------------------|--------------------------------|------------------------------------|---------------------|----------------------|-------------|--------------|
| 1x-2x LoD | 267/2
68 | 35.3 | 0.00 | 0.00 | 0.03 | 0.08 | 0.00 | 0.00 | 0.00 | 0.00 | 0.85 | 2.41 | 0.85 | 2.41 |
| 3x-5x LoD | 269/2
69 | 33.7 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.46 | 1.35 | 1.07 | 3.19 | 1.17 | 3.47 |

Note: Ct = cycle threshold, CT=Chlamydia trachomatis, CV(%) = percent coefficient of variation, LOD = Limit of Detection, MG=Mycoplasma genitalium, NG=Neisseria gonorrhoeae, SD = standard deviation. ân is the number of tests in agreement with expected results. N is the total number of valid tests for the panel member.

CLINICAL PERFORMANCE EVALUATION 6.

6.1. Clinical study

The clinical utility and performance of cobas® liat CT/NG/MG was established in a multi-site, prospective study by comparing the results to a Patient Infected Status (PIS) or a Composite Comparator Algorithm (CCA) derived from a combination of FDA-cleared NAATs for the 3 analytes. A CCA result was generated for vaginal swabs tested for CT or NG. A PIS result was generated for the remaining specimen types and analyte (i.e., MG in vaginal swabs and CT/NG/MG in male urine). Male urine and vaginal swabs were collected and tested at 13 geographically diverse intended use clinical sites across the US. There were 48 operators that took part in cobas® liat CT/NG/MG testing, of which, 43 represented CLIA-waived operators. Five of the 48 operators represented experienced laboratorians in a moderate complexity laboratory.

A total of 4852 subjects (2512 females and 2340 males) were enrolled in the study and provided specimens for collection. Note, two subjects, declared male at birth, provided vaginal swab

24

specimens. Of these subjects, 72 were non-evaluable due to protocol deviations and incidents (18), invalid cobas and/or final comparator result (45), or sample collection incidents (9). Of the evaluable subjects, 2304 male subjects provided 2302 male urine specimens (2 subjects provided vaginal swab specimens) and 2476 females provided 1240 clinician-collected vaginal swabs and 1236 self-collected vaginal swabs for evaluation in the clinical study.

Prospectively enrolled female subjects provided 4 vaginal swab specimens, three for comparator tests and one for the cobas liat CT/NG/MG nucleic acid test. Vaginal swab specimen for the cobas® liat CT/NG/MG nucleic acid test was either collected by clinician or self-collected.

Prospectively enrolled male subjects provided a urine specimen that was aliquoted into the respective manufacturers' collection devices and cobas® PCR Media.

Specimens were tested for CT, NG, and MG using cobas® liat CT/NG/MG and the comparator NAATs. All tests were run according to the respective IFU.

The clinical performance of cobas® liat CT/NG/MG was evaluated by comparing the results from collected specimen types to a pre-specified PIS/CCA result. The PIS/CCA result for each analyte was derived from a combination of 3 comparator NAATs (NAAT1, NAAT2, and NAAT3). If NAAT1 and NAAT2 are concordant, then the final PIS/CCA result for the respective analyte is the concordant result obtained from NAAT1 and NAAT2. If NAAT1 and NAAT2 are discordant, then NAAT3 is performed to be the tiebreaker between the first 2 discordant results. Table 19 below shows the PIS and CCA algorithm for each analyte.

| NAAT 1 | NAAT 2 | NAAT 3 (if needed) | Patient Infected
Statusª | Composite
Comparator
Algorithm |
|---------|---------|--------------------|-----------------------------|--------------------------------------|
| + | + | N/A | Infected | Positive |
| + | - | + | Infected | Positive |
| - | + | + | Infected | Positive |
| - | - | N/A | Not Infected | Negative |
| + | - | - | Not Infected | Negative |
| - | + | - | Not Infected | Negative |
| - | Invalid | + | Indeterminate | Indeterminate |
| - | Invalid | - | Not Infected | Negative |
| Invalid | - | + | Indeterminate | Indeterminate |
| Invalid | - | - | Not Infected | Negative |

Table 19: Determination of the PIS/CCA result for CT, NG, and MG, respectively

25

| NAAT 1 | NAAT 2 | NAAT 3 (if needed) | Patient Infected
Statusa | Composite
Comparator
Algorithm |
|---------|---------|--------------------|-----------------------------|--------------------------------------|
| + | Invalid | - | Indeterminate | Indeterminate |
| Invalid | + | - | Indeterminate | Indeterminate |
| + | Invalid | + | Infected | Positive |
| Invalid | + | + | Infected | Positive |
| Invalid | Invalid | N/A | Indeterminate | Indeterminate |

N/A = not applicable; NAAT = nucleic acid amplification test.

a The results from NAAT1 and NAAT2 determined if NAAT3 needed to be performed. The "Not Infected" patient infected status was derived from the total combination of results obtained from the reference NAATs.

The sample types of male urine and vaginal swab were used to create the PIS and CCA results, respectively, for men and women. The cobas® liat CT/NG/MG results of each analyte from each

sample type (male urine and vaginal swab) were compared to the PIS/CCA result to determine the clinical performance of the assay. Sensitivity (SENS), specificity (SPEC), positive percent agreement (PPA), and negative percent agreement (NPA) of cobas® liat CT/NG/MG were calculated separately for CT, NG, and MG.

Supplementation with archived specimens was included in this study due to the expected low NG prevalence for male urine and vaginal swabs. The archived specimens were prospectively collected samples from a prior clinical trial study (K173887).

6.2. Performance results

Sensitivity/PPA and specificity/NPA of cobas® liat CT/NG/MG as defined by the PIS/CCA results are presented by sample type, and symptom status in Table 20 for CT, Table 21 for NG collected specimens, and Table 22 for MG.

Upon initial testing, the cobas® liat CT/NG/MG invalid rate was 0.6% and after retesting the final invalid rate was 0.1%.

Table 20: CT - clinical performance of cobas® liat CT/NG/MG compared with PIS/CCA by specimen type and symptom status

| Specimen
Type | Symptom
Status | N | Sensitivity
Estimate
(95% CI) | Sensitivity
n/N | Specificity
Estimate
(95% CI) | Specificity
n/N |
|--------------------------|-------------------|-----|-------------------------------------|--------------------|-------------------------------------|--------------------|
| Male Urine | Symptomatic | 808 | 98.2%
(90.6%, 99.7%) | 55/56 | 99.9%
(99.3%, 100.0%) | 751/752 |

26

| | Asymptomatic | 1488 | 96.4%
(87.7%, 99.0%) | 53/55 | 99.9%
(99.6%, 100.0%) | 1432/1433 | |
|---------------|------------------|-------------------|-------------------------|-------------------------------------------------------|--------------------------------------|-------------------------------------------------------|--------------------------------------|
| | Total | 2296 | 97.3%
(92.4%, 99.1%) | 108/111 | 99.9%
(99.7%, 100.0%) | 2183/2185 | |
| | Specimen
Type | Symptom
Status | N | Positive Percent
Agreement
Estimate
(95% CI) | Positive Percent
Agreement
n/N | Negative Percent
Agreement
Estimate
(95% CI) | Negative Percent
Agreement
n/N |
| Vaginal Swabs | Symptomatic | 1116 | 98.4%
(91.3%, 99.7%) | 60/61 | 99.7%
(99.2%, 99.9%) | 1052/1055 | |
| | Asymptomatic | 1357 | 97.9%
(89.1%, 99.6%) | 47/48 | 99.8%
(99.4%,100.0%) | 1307/1309 | |
| | Total | 2473 | 98.2%
(93.6%, 99.5%) | 107/109 | 99.8%
(99.5%, 99.9%) | 2359/2364 | |

CI: confidence interval

Table 21: NG - Clinical performance of cobas® liat CT/NG/MG compared with PIS/CCA by specimen type and symptom status

| Specimen
Type | Symptom
Status | N | Sensitivity
Estimate
(95% CI) | Sensitivity
n/N | Specificity
Estimate
(95% CI) | Specificity
n/N |
|------------------------|-------------------|------|-------------------------------------------------------|--------------------------------------|-------------------------------------------------------|-----------------------------------------|
| Male Urine | Symptomatic | 813 | 100.0%
(94.7%, 100.0%) | 68/68 | 100.0%
(99.5%, 100.0%) | 745/745 |
| | Asymptomatic | 148 | 100.0%
(74.1%, 100.0%) | 11/11 | 99.8%
(99.4%, 99.9%) | 1474/1477 |
| | Total | 2301 | 100.0%
(95.4%, 100.0%) | 79/79 | 99.9%
(99.6%, 100.0%) | 2219/2222 |
| Archived
Male Urine | Symptomatic | 125 | 100.0%
(95.2%, 100.0%) | 77/77 | 100.0%
(92.6%, 100.0%) | 48/48 |
| | Asymptomatic | 38 | 100.0%
(56.6%, 100.0%) | 5/5 | 100.0%
(89.6%, 100.0%) | 33/33 |
| | Total | 163 | 100.0%
(95.5%, 100.0%) | 82/82 | 100.0%
(95.5%, 100.0%) | 81/81 |
| Overall Male
Urine | Symptomatic | 938 | 100.0%
(97.4%, 100.0%) | 145/145 | 100.0%
(99.5%, 100.0%) | 793/793 |
| | Asymptomatic | 1526 | 100.0%
(80.6%, 100.0%) | 16/16 | 99.8%
(99.4%, 99.9%) | 1507/1510 |
| | Total | 2464 | 100.0%
(97.7%, 100.0%) | 161/161 | 99.9%
(99.6%, 100.0%) | 2300/2303 |
| Specimen
Type | Symptom
Status | N | Positive Percent
Agreement
Estimate
(95% CI) | Positive Percent
Agreement
n/N | Negative Percent
Agreement
Estimate
(95% CI) | Negative
Percent
Agreement
n/N |
| Vaginal
Swabs | Symptomatic | 1115 | 91.7%
(74.2%, 97.7%) | 22/24 | 99.8%
(99.3%, 99.9%) | 1089/1091 |
| | Asymptomatic | 1357 | 100.0%
(82.4%, 100.0%) | 18/18 | 99.9%
(99.5%, 100.0%) | 1337/1339 |
| | Total | 2472 | 95.2%
(84.2%, 98.7%) | 40/42 | 99.8%
(99.6%, 99.9%) | 2426/2430 |
| | Symptomatic | 42 | 100.0%
(83.9%, 100.0%) | 20/20 | 100.0%
(85.1%, 100.0%) | 22/22 |

27

| Archived
Vaginal
Swabs | Asymptomatic | 48 | 100.0%
(86.7%, 100.0%) | 25/25 | 100.0%
(85.7%, 100.0%) | 23/23 |
|------------------------------|--------------|------|---------------------------|-------|---------------------------|------------|
| | Total | 90 | 100.0%
(92.1%, 100.0) | 45/45 | 100.0%
(92.1%, 100.0%) | 45/45 |
| Overall
Vaginal
Swabs | Symptomatic | 1157 | 95.5%
(84.9%, 98.7%) | 42/44 | 99.8%
(99.3%, 100.0%) | 1111/1113 |
| | Asymptomatic | 1405 | 100.0%
(91.8%, 100.0%) | 43/43 | 99.9%
(99.5%, 100.0%) | 1360/1362) |
| | Total | 2562 | 97.7%
(92.0%, 99.4%) | 85/87 | 99.8%
(99.6%, 99.9%) | 2471/2475 |

CI: confidence interval

Table 22: MG - Clinical performance of cobas® liat CT/NG/MG compared with patient infected status by specimen type and symptom status

			Sensitivity	Sensitivity	Specificity	Specificity
Specimen
Type	Symptom
Status	N	Estimate
(95% CI)	n/N	Estimate
(95% CI)	n/N
Male Urine	Symptomatic	811	98.0%
(93.0%,
99.4%)	98/100	98.7%
(97.6%, 99.3%)	702/711
	Asymptomati
C	1487	96.3%
(90.9%,
98.6%)	104/108	99.5%
(99.0%, 99.8%)	1372/1379
	Total	2298	97.1%
(93.9%,
98.7%)	202/208	99.2%
(98.8%, 99.5%)	2074/2090

			Sensitivity	Sensitivity	Specificity	Specificity
Specimen
Type	Symptom
Status	N	Estimate
(95% CI)	n/N	Estimate
(95% CI)	n/N
Vaginal
Swabs	Symptomatic	1116	95.2%
(90.0%,
97.8%)	120/126	97.3%
(96.1%, 98.1%)	963/990
	Asymptomati
C	1356	95.2%
(90.0%,
97.8%)	120/126	98.2%
(97.3%, 98.8%)	1208/1230
	Total	2472	95.2%
(91.9%,
97.3%)	240/252	97.8%
(97.1%, 98.3%)	2171/2220

CI: confidence interval

6.3. Expected values for urogenital specimens

The positivity rate of the cobas® liat CT/NG/MG nucleic acid assay test for CT, NG, and MG observed during the study is shown for each specimen type, by collection site in Table 23 below.

28

Collection Site	CT		NG		MG
	Male Urine	VS	Male Urine	VS	Male Urine	VS
1	8.7%
(30/343)	9.2%
(14/152)	11.0%
(38/346)	3.3%
(5/152)	14.2%
(49/344)	15.1%
(23/152)
2	2.6%
(9/346)	6.2%
(15/241)	1.7%
(6/346)	3.7%
(9/241)	8.1%
(28/346)	14.9%
(36/241)
3	11.9%
(18/151)	8.2%
(30/366)	6.6%
(10/151)	0.55%
(2/364)	12.6%
(19/151)	9.9%
(36/365)
4	11.2%
(12/107)	0.63%
(1/160)	9.3%
(10/107)	1.25%
(2/160)	18.7%
(20/107)	16.3%
(26/160)
5	0.0%
(0/4)	NC	0.0%
(0/4)	NC	25.0%
(1/4)	NC
6	0.9%
(1/117)	1.2%
(1/85)	0.0%
(0/118)	1.2%
(1/85)	1.7%
(2/118)	3.5%
(3/85)
7	5.3%
(3/57)	5.7%
(2/35)	1.8%
(1/57)	2.9%
(1/35)	14.0%
(8/57)	17.1%
(6/35)
8	0.0%
(0/80)	0.0%
(0/19)	2.5%
(2/80)	0.0%
(0/19)	7.5%
(6/80)	10.5%
(2/19)
9	1.3%
(6/468)	1.9%
(10/527)	0.4%
(2/469)	2.3%
(12/528)	8.8%
(41/467)	12.7%
(67/527)
10	0.5%
(1/198)	1.4%
(5/347)	1.0%
(2/198)	0.86%
(3/347)	4.0%
(8/199)	3.2%
(11/347)
11	17.1%
(18/105)	5.6%
(17/305)	4.8%
(5/105)	2.0%
(6/305)	9.4%
(10/106)	15.4%
(47/305)
12	3.5%
(10/289)	8.8%
(12/136)	1.7%
(5/289)	1.5%
(2/136)	8.0%
(23/288)	9.6%
(13/136)
13	6.5%
(2/31)	5.0%
(5/100)	3.2%
(1/31)	1.0%
(1/100)	9.7%
(3/31)	19.0%
(19/100)

Table 23: Positivity of CT/NG/MG as Determined by the cobas liat CT/NG/MG nucleic acid test by Specimen Type and Clinical Site

Note: two subjects were born male, but were evaluated using self-collected vaginal swabs.

VS: vaginal swabs (clinician-collected vaginal swabs and self-collected)

NC: non calculable as no female subjects were enrolled at this site

29

Summary of Positive Predictive Value, Negative Predictive Value for 6.3.1. Hypothetical Prevalence

The hypothetical PPVs and NPVs of cobas® liat CT/NG/MG derived from disease prevalences of 1% to 50% are shown in , Table 24, Table 25 and Table 26, respectively, for CT, NG, and MG.

| Specimen type for CNMA
testing | Hypothetical Prevalence
(%) | PPV (%) | NPV (%) |
|-----------------------------------|--------------------------------|---------|---------|
| Male Urine | 1 | 91.5 | 100.0 |
| Male Urine | 3 | 97.0 | 99.9 |
| Male Urine | 5 | 98.2 | 99.9 |
| Male Urine | 10 | 99.2 | 99.7 |
| Male Urine | 15 | 99.5 | 99.5 |
| Male Urine | 20 | 99.6 | 99.3 |
| Male Urine | 30 | 99.8 | 98.9 |
| Male Urine | 50 | 99.9 | 97.4 |
| Vaginal Swabs | 1 | 82.4 | 100.0 |
| Vaginal Swabs | 3 | 93.5 | 99.9 |
| Vaginal Swabs | 5 | 96.1 | 99.9 |
| Vaginal Swabs | 10 | 98.1 | 99.8 |
| Vaginal Swabs | 15 | 98.8 | 99.7 |
| Vaginal Swabs | 20 | 99.1 | 99.5 |
| Vaginal Swabs | 30 | 99.5 | 99.2 |
| Vaginal Swabs | 50 | 99.8 | 98.2 |

Table 24: CT - Positive predictive value and negative predictive value for hypothetical
CT prevalence

Note: NPV: negative predictive value; PPV: positive value; PPA: positive percent agreement; NPA: negative percent agreement;

The PPV and NPV were calculated using the sensitivity/PPA and specificity/NPA of cobas® liat CT/NG/MG from the prospectively collected population.

30

| Specimen type for CNMA
testing | Hypothetical Prevalence
(%) | PPV (%) | NPV (%) |
|-----------------------------------|--------------------------------|---------|---------|
| Male Urine | 1 | 88.2 | 100.0 |
| Male Urine | 3 | 95.8 | 100.0 |
| Male Urine | 5 | 97.5 | 100.0 |
| Male Urine | 10 | 98.8 | 100.0 |
| Male Urine | 15 | 99.2 | 100.0 |
| Male Urine | 20 | 99.5 | 100.0 |
| Male Urine | 30 | 99.7 | 100.0 |
| Male Urine | 50 | 99.9 | 100.0 |
| Vaginal Swabs | 1 | 85.4 | 100.0 |
| Vaginal Swabs | 3 | 94.7 | 99.9 |
| Vaginal Swabs | 5 | 96.8 | 99.7 |
| Vaginal Swabs | 10 | 98.5 | 99.5 |
| Vaginal Swabs | 15 | 99.0 | 99.2 |
| Vaginal Swabs | 20 | 99.3 | 98.8 |
| Vaginal Swabs | 30 | 99.6 | 98.0 |
| Vaginal Swabs | 50 | 99.8 | 95.4 |

Table 25: NG - Positive predictive value and negative predictive value for hypothetical NG prevalence

Note: NPV: negative predictive value; PPV: positive value; PPA: positive percent agreement; NPA: negative

percent agreement;

The PPV and NPV were calculated using the sensitivity/PPA and specificity/NPA of cobas® liat CT/NG/MG from the prospectively collected population.

31

| Specimen type for CNMA
testing | Hypothetical Prevalence
(%) | PPV (%) | NPV (%) |
|-----------------------------------|--------------------------------|---------|---------|
| Male Urine | 1 | 56.2 | 100.0 |
| Male Urine | 3 | 79.7 | 99.9 |
| Male Urine | 5 | 87.0 | 99.8 |
| Male Urine | 10 | 93.4 | 99.7 |
| Male Urine | 15 | 95.7 | 99.5 |
| Male Urine | 20 | 96.9 | 99.3 |
| Male Urine | 30 | 98.2 | 98.8 |
| Male Urine | 50 | 99.2 | 97.2 |
| Vaginal Swabs | 1 | 30.4 | 100.0 |
| Vaginal Swabs | 3 | 57.2 | 99.8 |
| Vaginal Swabs | 5 | 69.4 | 99.7 |
| Vaginal Swabs | 10 | 82.7 | 99.5 |
| Vaginal Swabs | 15 | 88.4 | 99.1 |
| Vaginal Swabs | 20 | 91.5 | 98.8 |
| Vaginal Swabs | 30 | 94.9 | 98.0 |
| Vaginal Swabs | 50 | 97.7 | 95.4 |

Table 26: MG - Positive predictive value and negative predictive value for hypothetical MG prevalence

Note: NPV: negative predictive value; PPV: positive predictive value;

The PPV and NPV were calculated using the sensitivity of cobas® liat CT/NG/MG from the prospectively collected population.

CONCLUSIONS 7.

A comparison of the intended use, technological characteristics, and the results of non-clinical analytical and clinical performance studies demonstrate that cobas® liat CT/NG/MG nucleic acid test is substantially equivalent to the predicate devices.