K Number
K243346
Device Name
cobas liat SARS-CoV-2 v2 nucleic acid test
Date Cleared
2025-04-11

(165 days)

Product Code
Regulation Number
866.3982
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP Authorized
Intended Use
The cobas® liat SARS-CoV-2 v2 nucleic acid test is an automated real-time reverse transcription polymerase chain reaction (RT-PCR) test intended for the qualitative detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acids in anterior nasal (nasal) and nasopharyngeal swab specimens collected from individuals exhibiting signs and symptoms of respiratory tract infection (i.e., symptomatic). Additionally, this test is intended to be used with nasal and nasopharyngeal swab specimens collected from individuals without signs and symptoms of COVID-19 (i.e., asymptomatic). The cobas® liat SARS-CoV-2 v2 nucleic acid test is intended for use as an aid in the diagnosis of COVID-19 if used in conjunction with other clinical and epidemiological information and laboratory findings. SARS-CoV-2 RNA is generally detectable in nasal swab and nasopharyngeal swab specimens during the acute phase of infection. Positive results are indicative of the presence of SARS-CoV-2 RNA. Positive results do not rule out co-infection with other microorganisms. Negative results do not preclude SARS-CoV-2 infection. Negative results must be combined with clinical observations, patient history, and epidemiological information. The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. A negative result from an asymptomatic individual is presumptive. Additionally, a negative result obtained with a nasal or nasopharyngeal swab collected from an asymptomatic individual should be followed up by testing at least twice over three days with at least 48 hours between tests.
Device Description
The cobas® liat SARS-CoV-2 v2 nucleic acid 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 ORF1 a/b non-structural region and membrane protein gene that are unique to SARS-CoV-2. An Internal Control (IC) is included to control for adequate processing of the target virus through all steps of the assay process and to monitor the presence of inhibitors in the RT-PCR processes.
More Information

Not Found

No
The device description mentions automation and integration of sample purification, nucleic acid amplification, and detection using real-time PCR assays, with no mention of AI, machine learning, or deep learning.

No
The device is described as an automated real-time reverse transcription polymerase chain reaction (RT-PCR) test intended for the qualitative detection of SARS-CoV-2 nucleic acids to aid in the diagnosis of COVID-19. It does not provide therapy or treatment.

Yes

Explanation: The "Intended Use / Indications for Use" section explicitly states that the test is "intended for use as an aid in the diagnosis of COVID-19."

No

The device is a laboratory developed test that is performed on an automated physical analyzer (cobas® liat analyzer). It involves sample purification, nucleic acid amplification, and detection using real-time PCR assays, none of which are software-only functions.

Yes
The device is described as an automated real-time reverse transcription polymerase chain reaction (RT-PCR) test intended for the qualitative detection of SARS-CoV-2 nucleic acids in specimens, aids in the diagnosis of COVID-19, and performs analysis on biological samples (swabs) outside of the body. These are all characteristics of an In Vitro Diagnostic (IVD) device.

N/A

Intended Use / Indications for Use

The cobas® liat SARS-CoV-2 v2 nucleic acid test is an automated real-time reverse transcription polymerase chain reaction (RT-PCR) test intended for the qualitative detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acids in anterior nasal (nasal) and nasopharyngeal swab specimens collected from individuals exhibiting signs and symptoms of respiratory tract infection (i.e., symptomatic). Additionally, this test is intended to be used with nasal and nasopharyngeal swab specimens collected from individuals without signs and symptoms of COVID-19 (i.e., asymptomatic).

The cobas® liat SARS-CoV-2 v2 nucleic acid test is intended for use as an aid in the diagnosis of COVID-19 if used in conjunction with other clinical and epidemiological information and laboratory findings. SARS-CoV-2 RNA is generally detectable in nasal swab and nasopharyngeal swab specimens during the acute phase of infection.

Positive results are indicative of the presence of SARS-CoV-2 RNA. Positive results do not rule out co-infection with other microorganisms. Negative results do not preclude SARS-CoV-2 infection. Negative results must be combined with clinical observations, patient history, and epidemiological information. The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.

A negative result from an asymptomatic individual is presumptive. Additionally, a negative result obtained with a nasal or nasopharyngeal swab collected from an asymptomatic individual should be followed up by testing at least twice over three days with at least 48 hours between tests.

Product codes

QWR

Device Description

The cobas® liat SARS-CoV-2 v2 nucleic acid 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 ORF1 a/b non-structural region and membrane protein gene that are unique to SARS-CoV-2. An Internal Control (IC) is included to control for adequate processing of the target virus through all steps of the assay process and to monitor the presence of inhibitors in the RT-PCR processes.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

anterior nasal (nasal) and nasopharyngeal swab specimens

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Point-of-Care setting

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

Not Found

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

A reproducibility study assessed the total variability of the assay in detecting SARS-CoV-2 across operators, study sites, testing days, analyzers, and assay tube lots. The reproducibility was evaluated at three (3) study sites representative of intended use settings. Two (2) operators at each of the three sites tested a 3-member reproducibility panel in triplicate on five different days for three assay tube lots. The reproducibility panel comprises a low positive (1-2x LoD) and a moderate positive (3-5x LoD) for SARS-CoV-2 in addition to negative samples.

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

Non-Clinical Performance Evaluation

  • Analytical Sensitivity (Limit of Detection): LoD studies determined the lowest detectable concentration of SARS-CoV-2 at which ≥ 95% of all replicates test positive. Two strains were evaluated: SARS-CoV-2 USA-WA1/2020 at 0.0350 TCID50/mL (20/21 hit rate) and SARS-CoV-2 WHO International Standard 20/146, v3, 11/2021 at 65.1 IU/mL (21/21 hit rate).
  • Reactvity/Inclusivity: Evaluated with 10 SARS-CoV-2 isolates/variants tested at 3x LoD in 3 replicates. All strains were detected. In silico analysis (January 15, 2025) indicated 99.9% detection of available SARS-CoV-2 sequences (>7.94M sequences in GISAID and >15.04M sequences in NCBI).
  • Cross reactivity and microbial interference: A panel of microorganisms (viruses, bacteria, fungi) was tested. None of the organisms tested cross reacted or interfered with cobas® liat SARS-CoV-2 v2 performance at the concentrations tested. Testing concentrations for potentially interfering viruses were ≥1.0E+05 units/mL (except for 3 viruses, which were ≥1.0e+4 units/mL), and for other microorganisms ≥1.0E+06 units/mL.
  • Endogenous and exogenous interference: Potentially interfering substances encountered in respiratory specimens were evaluated. Five (5) replicates were tested with and five (5) replicates were tested without 3x LoD SARS-CoV-2 target. Substances tested did not interfere with detection or produce invalid results, with one exception for Cepacol which resulted in one invalid result, attributed to other factors.
  • Reproducibility study: Assessed total variability across operators, study sites, testing days, analyzers, and assay tube lots. Done at three (3) study sites, with two (2) operators at each site testing a 3-member panel (negative, 1x-2x LoD, 3x-5x LoD) in triplicate on five different days for three assay tube lots. Percent agreement with expected result was 100.0% for all panel members (Negative: 265/265 valid tests; 1x-2x LoD: 270/270 valid tests; 3x-5x LoD: 267/267 valid tests).

Clinical Performance Evaluation

  • Study Type: Non-interventional study using paired prospective fresh nasopharyngeal swab (NPS) and anterior nasal swab (ANS) specimens collected in Universal Viral Transport medium (UVT) or Universal Transport Medium (UTM).
  • Sample Size:
    • Symptomatic subjects: 1729 enrolled. 1705 NPS specimens evaluable for analysis, 1706 ANS specimens evaluable.
    • Asymptomatic subjects: 2713 enrolled. 2697 NPS specimens evaluable for analysis, 2700 ANS specimens evaluable.
  • Key Results: Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) were determined by comparing cobas® liat SARS-CoV-2 v2 results to an FDA-cleared Nucleic Acid Amplification Test (NAAT).
    • Symptomatic Subjects:
      • NPS: PPA 94.5% (207/219), NPA 97.6% (1451/1486).
      • ANS: PPA 96.7% (208/215), NPA 97.2% (1449/1491).
      • Initial invalid rate: 0.5% for NPS, 0.7% for ANS. Final invalid rate after retest: 0% for NPS, 0.1% for ANS.
    • Asymptomatic Subjects:
      • NPS: PPA 86.1% (62/72), NPA 97.9% (2569/2625).
      • ANS: PPA 89.5% (51/57), NPA 98.3% (2597/2643).
      • Initial invalid rate: 0.3% for both NPS and ANS. Final invalid rate after retest: 0.0% for both NPS and ANS.

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

Symptomatic Subjects:

  • NPS: Positive Percent Agreement (PPA) 94.5%, Negative Percent Agreement (NPA) 97.6%.
  • ANS: Positive Percent Agreement (PPA) 96.7%, Negative Percent Agreement (NPA) 97.2%.

Asymptomatic Subjects:

  • NPS: Positive Percent Agreement (PPA) 86.1%, Negative Percent Agreement (NPA) 97.9%.
  • ANS: Positive Percent Agreement (PPA) 89.5%, Negative Percent Agreement (NPA) 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® SARS-CoV-2 for use on the cobas® Liat® System (K223783)

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.

Not Found

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

N/A

U.S. Food & Drug Administration 510(k) Clearance Letter

Page 1

U.S. Food & Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993
www.fda.gov

Doc ID # 04017.07.05

April 11, 2025

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

Re: K243346
Trade/Device Name: cobas liat SARS-CoV-2 v2 nucleic acid test
Regulation Number: 21 CFR 866.3982
Regulation Name: Simple Point-Of-Care Device To Directly Detect Sars-Cov-2 Viral Targets From Clinical Specimens In Near-Patient Settings
Regulatory Class: Class II
Product Code: QWR
Dated: October 25, 2024
Received: October 28, 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.

Page 2

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 (QS) 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 (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-safety-reporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 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-devices/device-advice-comprehensive-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-devices/medical-device-safety/medical-device-reporting-mdr-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/medical-devices/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-devices/device-advice-comprehensive-regulatory-

Page 3

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,

Joseph Briggs -S

Joseph Briggs, Ph.D.
Deputy Division Director
Division of Microbiology Devices
OHT7: Office of In Vitro Diagnostics
Office of Product Evaluation and Quality
Center for Devices and Radiological Health

Enclosure

Page 4

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

Indications for Use

Form Approved: OMB No. 0910-0120
Expiration Date: 07/31/2026
See PRA Statement below.

510(k) Number (if known): K243346
Device Name: cobas liat SARS-CoV-2 v2 nucleic acid test

Indications for Use (Describe)

The cobas liat SARS-CoV-2 v2 nucleic acid test is an automated real-time reverse transcription polymerase chain reaction (RT-PCR) test intended for the qualitative detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acids in anterior nasal (nasal) and nasopharyngeal swab specimens collected from individuals exhibiting signs and symptoms of respiratory tract infection (i.e., symptomatic). Additionally, this test is intended to be used with nasal and nasopharyngeal swab specimens collected from individuals without signs and symptoms of COVID-19 (i.e., asymptomatic).

The cobas liat SARS-CoV-2 v2 nucleic acid test is intended for use as an aid in the diagnosis of COVID-19 if used in conjunction with other clinical and epidemiological information and laboratory findings. SARS-CoV-2 RNA is generally detectable in nasal swab and nasopharyngeal swab specimens during the acute phase of infection.

Positive results are indicative of the presence of SARS-CoV-2 RNA. Positive results do not rule out co-infection with other microorganisms. Negative results do not preclude SARS-CoV-2 infection. Negative results must be combined with clinical observations, patient history, and epidemiological information. The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.

A negative result from an asymptomatic individual is presumptive. Additionally, a negative result obtained with a nasal or nasopharyngeal swab collected from an asymptomatic individual should be followed up by testing at least twice over three days with at least 48 hours between tests.

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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

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"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

Page 5

cobas® liat SARS-CoV-2 v2 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 NameRoche Molecular Systems, Inc.
Address4300 Hacienda Drive, Pleasanton, CA 94588-2722
ContactDeborah Leu
Phone: 925-523-8362
Email: deborahleu@roche.com
Date PreparedApr 9, 2025
Proprietary Namecobas® liat SARS-CoV-2 v2 nucleic acid test
Common Namecobas® liat SARS-CoV-2 v2
Classification21 CFR 866.3982
Simple Point-Of-Care Device to Detect SARS-CoV-2 Nucleic Acid Targets From Clinical Specimens In Near-Patient Settings
Product CodesQWR
Predicate Devicescobas® SARS-CoV-2 for use on the cobas® Liat® System (K223783)
Establishment RegistrationRoche Molecular Systems, Inc. (2243471)

Page 6

1. DEVICE DESCRIPTION

The cobas® liat SARS-CoV-2 v2 nucleic acid 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 ORF1 a/b non-structural region and membrane protein gene that are unique to SARS-CoV-2. An Internal Control (IC) is included to control for adequate processing of the target virus through all steps of the assay process and to monitor the presence of inhibitors in the RT-PCR processes.

2. INDICATIONS FOR USE

The cobas® liat SARS-CoV-2 v2 nucleic acid test is an automated real-time reverse transcription polymerase chain reaction (RT-PCR) test intended for the qualitative detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acids in anterior nasal (nasal) and nasopharyngeal swab specimens collected from individuals exhibiting signs and symptoms of respiratory tract infection (i.e., symptomatic). Additionally, this test is intended to be used with nasal and nasopharyngeal swab specimens collected from individuals without signs and symptoms of COVID-19 (i.e., asymptomatic).

The cobas® liat SARS-CoV-2 v2 nucleic acid test is intended for use as an aid in the diagnosis of COVID-19 if used in conjunction with other clinical and epidemiological information and laboratory findings. SARS-CoV-2 RNA is generally detectable in nasal swab and nasopharyngeal swab specimens during the acute phase of infection.

Positive results are indicative of the presence of SARS-CoV-2 RNA. Positive results do not rule out co-infection with other microorganisms. Negative results do not preclude SARS-CoV-2 infection. Negative results must be combined with clinical observations, patient history, and epidemiological information. The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.

A negative result from an asymptomatic individual is presumptive. Additionally, a negative result obtained with a nasal or nasopharyngeal swab collected from an asymptomatic individual should be followed up by testing at least twice over three days with at least 48 hours between tests.

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3. TECHNOLOGICAL CHARACTERISTICS

The primary technological characteristics and intended use of the RMS cobas® liat SARS-CoV-2 v2 test are substantially equivalent to other legally marketed nucleic acid amplification tests intended for the qualitative detection of SARS-CoV-2.

As indicated in Table 1, the RMS cobas® liat SARS-CoV-2 v2 nucleic acid test is substantially equivalent to the identified predicate device, the cleared cobas® SARS-CoV-2 for use on the cobas® Liat® System (K223783).

Table 1: Comparison of the cobas® liat SARS-CoV-2 v2 nucleic acid test and the Predicate Device

Submitted Device: cobas® liat SARS-CoV-2 v2 nucleic acid testPredicate Device: cobas® SARS-CoV-2 for use on the cobas® Liat® System (K223783)
Regulation Name21 CFR 866.3982Same
Product CodeQWRSame
Intended UseThe cobas® liat SARS-CoV-2 v2 nucleic acid test is an automated real-time reverse transcription polymerase chain reaction (RT-PCR) test intended for the qualitative detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acids in anterior nasal (nasal) and nasopharyngeal swab specimens collected from individuals exhibiting signs and symptoms of respiratory tract infection (i.e., symptomatic). Additionally, this test is intended to be used with nasal and nasopharyngeal swab specimens collected from individuals without signs and symptoms of COVID-19 (i.e., asymptomatic).

The cobas® liat SARS-CoV-2 v2 nucleic acid test is intended for use as an aid in the diagnosis of COVID-19 if used in conjunction with other clinical and epidemiological information and laboratory findings. SARS-CoV-2 RNA is generally detectable in nasal swab and nasopharyngeal swab specimens during the acute phase of infection. | The cobas® SARS-CoV-2 Nucleic acid test for use on the cobas® Liat® System (cobas® SARS-CoV-2) is an automated, real-time reverse transcriptase polymerase chain reaction (RT-PCR) test intended for the rapid in vitro qualitative detection of nucleic acid from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in anterior nasal (nasal) and nasopharyngeal swab specimens collected from individuals with signs and symptoms of respiratory tract infection (i.e., symptomatic). Additionally, this test is intended to be used with nasal and nasopharyngeal swab specimens collected from individuals without signs and symptoms suspected of COVID-19 (i.e., asymptomatic).

The cobas® SARS-CoV-2 performed on the cobas® Liat® System is intended for use as an aid in the diagnosis of COVID-19 if used in conjunction with other clinical, epidemiologic, and laboratory findings. SARS-CoV-2 RNA is generally detectable in nasal and nasopharyngeal swab specimens during the acute phase of infection.

Positive results are indicative of the presence of SARS-CoV-2 RNA. Positive results do not rule out co-infection with other microorganisms.

A negative result from an asymptomatic individual is presumptive. Additionally, a |

Page 8

Submitted Device: cobas® liat SARS-CoV-2 v2 nucleic acid testPredicate Device: cobas® SARS-CoV-2 for use on the cobas® Liat® System (K223783)
Positive results are indicative of the presence of SARS-CoV-2 RNA. Positive results do not rule out co-infection with other microorganisms. Negative results do not preclude SARS-CoV-2 infection. Negative results must be combined with clinical observations, patient history, and epidemiological information. The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.

A negative result from an asymptomatic individual is presumptive. Additionally, a negative result obtained with a nasal or nasopharyngeal swab collected from an asymptomatic individual should be followed up by testing at least twice over three days with at least 48 hours between tests. | negative result obtained with a nasal swab collected from an asymptomatic patient should be followed up by testing at least twice over three days with at least 48 hours between tests. Negative results do not preclude SARS-CoV-2 infection.

The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.

This test is intended for prescription use only and can be used in Point-of-Care setting |
| Sample Type | Nasopharyngeal and anterior nasal swabs | Same |
| Target Analyte | SARS-CoV-2 ORF1 a/b non-structural region and SARS-CoV-2 membrane protein gene | SARS-CoV-2 ORF1 a/b non-structural region and SARS-CoV-2 nucleocapsid protein gene |
| Ancillary Collection Kits | Copan FLOQSwabs™ with UTM™,
BD UVT with flocked swab
Sterile flocked swabs with a synthetic tip with other viral transport media (VTM) –M4RT, M4, M5 and M6
0.9% Saline | Copan FLOQSwabs™ with UTM™,
UVT and other swabs with other viral transport media (VTM) – e.g., M4RT, M4, M5 and M6
0.9% and 0.85% Saline |
| Amplification Technology | Real-time PCR | Same |
| Detection Chemistry | Assay using different reporter dyes for target and control | Same |
| Controls Used | Sample processing control (IC) Positive and negative control | Internal Control (a process control for sample purification, nucleic acid amplification, and for monitoring presence of inhibitors)
External Positive and Negative Controls |
| Instrumentation | cobas® liat System | Same |

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4. SPECIAL CONTROLS/STANDARDS/GUIDANCE REFERENCED

Class II Special Controls as per 21 CFR 866.3982.

5. NON-CLINICAL PERFORMANCE EVALUATION

5.1. Analytical Sensitivity (Limit of Detection)

Limit of detection (LoD) studies determine the lowest detectable concentration of SARS-CoV-2 at which equal to or greater than 95% of all replicates test positive. Two strains of SARS-CoV-2 were evaluated. To determine the LoD, panels were formulated using inactivated viral material diluted in pooled negative nasopharyngeal swab matrix. Twenty-one replicates per lot of assay tubes per dilution were tested for five or six 2-fold dilutions using three lots of assay tubes. The strains evaluated, as well as their corresponding LoD values are shown in Table 2.

Table 2: LoD determination for SARS-CoV-2 strains

VirusStrainConcentration at LoDHit rate (Mean Ct)
SARS-CoV-2USA-WA1/20200.0350 TCID50/mL20/21 (35.5)
SARS-CoV-2WHO International Standard 20/146, v3, 11/202165.1 IU/mL21/21 (34.9)

5.2. Reactivity/inclusivity

The inclusivity study evaluates the ability of the test to detect SARS-CoV-2 isolates/variants. The reactivity/inclusivity was evaluated with 10 SARS-CoV-2 isolates/variants. All strains were individually tested at 3x LoD in 3 replicates to evaluate inclusivity.

The SARS-CoV-2 isolates/variants were tested as inactivated viruses in the study and the lowest concentrations detected are listed in Table 3.

In silico analysis on January 15, 2025 indicates 99.9% detection of all available SARS-CoV-2 sequences in the GISAID (>7.94M sequences) and NCBI (>15.04M sequences) databases.

Table 3: Results of Testing SARS-CoV-2 Isolate/Variants

Lineage/SubtypeIsolate/Variant*Test Concentration (TCID50/mL)Relative to LoD
AlphaHong Kong/VM20001061/20200.1053x

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Lineage/SubtypeIsolate/Variant*Test Concentration (TCID50/mL)Relative to LoD
Beta, B.1.595_2020 (was B.1.2)NY-Wadsworth-33126-01/20200.1053x
Delta, B.1.617.2USA/MD-HP05285/20210.1053x
Epsilon, B.1.427USA/CA/VRLC009/20210.1053x
Gamma, P.1Japan/TY7-503/20210.1053x
Iota, B.1.526_2021USA/NY-Wadsworth-21025952-01/20210.1053x
Kappa, B.1.617.1USA/CA-Stanford-15_S02/20210.1053x
Omicron, B.1.1.529, CH.1.1USA/MD-HP41275/20220.1053x
Omicron, B.1.1.529, XBB.1.5USA/MD-HP40900/20220.1053x
Zeta, P2_2021USA/NY-Wadsworth-21006055-01/20210.1053x

*These strains are in addition to the SARS-CoV-2 USA-WA1/2020 and WHO Standard 20/146, v3, 11/2021 used in the analytical sensitivity study.

5.3. Cross reactivity and microbial interference

Cross-reactivity and microbial interference were evaluated by testing a panel of microorganisms (Table 4). High titer stocks of the potentially cross-reacting microorganisms were tested for cross-reactivity, and also in the presence of SARS-CoV-2 at 3x LoD concentrations for microbial interference. Three (3) replicates in target negative background and three (3) replicates in target positive background were tested for each non-target microorganism. The testing concentrations for potentially interfering viruses are ≥1.0E+05 units/mL except for three viruses (SARS Coronavirus, Urbani, Human Rhinovirus Type 1A, and Human Parainfluenza Virus Type 4A) which were tested at a concentration less than 1.0e+5, but higher than 1.0e+4 units/mL due to their low stock concentration. Other microorganisms (non virus) were tested at ≥1.0E+06 units/mL. Clinical specimens containing Human Coronavirus HKU1 and Pneumocystis jirovecii were also tested (concentration was unknown). None of the organisms tested cross reacted or interfered with cobas® liat SARS-CoV-2 v2 performance at the concentrations tested.

Table 4: Microorganisms Tested for Cross-reactivity and Microbial Interference

Adenovirus Type 1 βInfluenza A (Darwin/6/2021)Legionella pneumophila
Adenovirus Type 7Influenza B (Austria/1359417/2021)Moraxella catarrhalis
CytomegalovirusInfluenza B (Phuket/3073/2013)Mycobacterium tuberculosis
Epstein-Barr virus βMERS-Coronavirus βMycoplasma genitalium β
Human Coronavirus OC43MeaslesMycoplasma pneumoniae

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Human Coronavirus 229EMumpsNeisseria elongata
Human Coronavirus HKU ƗRSV (Long/Subtype A)Neisseria flava
Human Coronavirus NL63 βRSV (9320/Subtype B)Neisseria meningitidis
Human Enterovirus 68SARS Coronavirus, Urbani* βPneumocystis jirovecii Ɨ
Human Metapneumovirus 27Bordetella parapertussisPseudomonas aeruginosa
Human Parainfluenza Virus Type 1 βBordetella pertussisStaphylococcus aureus
Human Parainfluenza Virus Type 2Chlamydophila pneumoniaeStaphylococcus epidermidis
Human Parainfluenza Virus Type 3Corynebacterium flavescensStreptococcus pneumoniae
Human Parainfluenza Virus Type 4A* βEscherichia coliStreptococcus pyogenes
Human Rhinovirus Type 1A* βFusobacterium necrophorum subsp. necrophorumStreptococcus salivarius
Human Rhinovirus BHaemophilus influenzaeAspergillus flavus var. flavus
Influenza A (Brisbane/02/2018)Lactobacillus crispatusCandida albicans
  • Tested at highest concentration available
    β Inactivated virus
    Ɨ Clinical specimens at unknown concentrations were tested.

5.4. Endogenous and exogenous interference

Potentially interfering substances that may be commonly encountered in respiratory specimens were evaluated. Each substance was tested, by introducing potential interferents. Five (5) replicates were tested with and five (5) replicates were tested without 3x LoD SARS-CoV-2 target. The substances listed in Table 5 at the concentrations tested did not interfere with the detection of SARS-CoV-2 nor did they produce invalid results in negative samples.

Table 5: Endogenous and Exogenous Interference

Potential InterferentConcentration Tested
Peripheral blood mononuclear cell (PBMC)1.00E+06 cell/mL
Mucin: bovine submaxillary gland, type I-S5 mg/mL
Human Whole Blood5% v/v
Nasal spray - Afrin / Anefrin15% v/v
Nasal corticosteroids - Flonase5% (v/v)
Nasal gel - Zicam5% (v/v)
Throat lozenges, oral anesthetic and analgesic – Cepacol*5 mg/mL
Antibiotic, nasal ointment - Bactroban mupirocin ointment5 mg/mL
Antiviral drug – Relenza5 mg/mL

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Potential InterferentConcentration Tested
Antiviral drug - Tamiflu7.5 mg/mL
Antimicrobial, systemic- Tobramycin4 µg/mL
Intranasal Vaccine – FluMist6.25% (v/v)
  • One invalid result was obtained in the presence of SARS-CoV-2. Repeat testing was performed and SARS-CoV-2 was detected. The one invalid result was most likely caused by other factors such as general tube processing error, lot variation, etc. that are not related to the interference test condition.

5.5. Reproducibility study

A reproducibility study assessed the total variability of the assay in detecting SARS-CoV-2 across operators, study sites, testing days, analyzers, and assay tube lots. The reproducibility was evaluated at three (3) study sites representative of intended use settings. Two (2) operators at each of the three sites tested a 3-member reproducibility panel in triplicate on five different days for three assay tube lots. The reproducibility panel comprises a low positive (1-2x LoD) and a moderate positive (3-5x LoD) for SARS-CoV-2 in addition to negative samples. The expected result for the true negative panel member is "Not Detected," while the expected result for the low positive and moderate positive panel members is "Detected." Percent agreement with expected result is shown in Table 6.

Table 6: Reproducibility Results for cobas® liat SARS-CoV-2 v2 nucleic acid test

Target AnalyteExpected Panel Member ConcentrationValid Tests (N)Results in Agreement with Target Analyte (n)Percent Agreement n/N x 10095% Score CI
Negative0265265100.0(98.6, 100.0)
SARS-CoV-21x-2x LoD270270100.0(98.6, 100.0)
SARS-CoV-23x-5x LoD267267100.0(98.6, 100.0)

Note: Results were in agreement when a positive panel member had a valid result of "Detected" for the analyte or when the negative panel member had a valid result of "Not Detected" for the analyte.

The means, standard deviations, and coefficients of variation (%) for cycle threshold (Ct) values by target analyte and expected concentration (Positive Panel Members) are shown in Table 7.

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Table 7: Overall Mean Estimate, Standard Deviations, and Coefficients of Variation (%) for Cycle Threshold Values by Target Analyte and Expected Concentration (Positive Panel Members) for the cobas® liat SARS-CoV-2 v2 nucleic acid test

Expected Concentrationn/N^aMean CtSite SDSite CV%Lot SDLot CV%Day SDDay CV%Run SD^bRun CV%Within-Run (Residual) SDWithin-Run (Residual) CV%Total SDTotal CV%
1x-2x LoD270/27033.80.000.00.381.10.170.50.361.11.033.01.163.4
3x-5x LoD267/26732.40.130.40.541.70.270.80.000.01.003.11.183.6

Note: Ct = cycle threshold; LoD = Limit of Detection; SD = standard deviation; CV% = percent coefficient of variation.
^a n is the number of positive tests, which contribute Ct values to the analysis. N is the total number of valid tests for the panel member.
^b In the reproducibility study, each panel member was tested in triplicate, defining one run.

6. CLINICAL PERFORMANCE EVALUATION

The clinical performance of cobas® liat SARS-CoV-2 v2 for the detection of SARS-CoV-2 was evaluated using paired prospective fresh nasopharyngeal swab (NPS) and anterior nasal swab (ANS) specimens collected in Universal Viral Transport medium (UVT) or Universal Transport Medium (UTM) from individuals with and without signs and symptoms of respiratory viral infection. For prospectively enrolled subjects an NPS specimen was collected from each subject along with either a self-collected or a healthcare-provider collected ANS specimen. Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) were determined by comparing the results of cobas® liat SARS-CoV-2 v2 to the results of an FDA-cleared Nucleic Acid Amplification Test (NAAT).

Prospective clinical (Category I) specimens were collected and tested in a non-interventional study between September 2023 and March 2024 at 14 point of care testing sites in the United States (US). Of the 1729 prospective symptomatic subjects enrolled, 1705 NPS specimens were evaluable for analyses, 19 were non-evaluable due to missing or invalid cobas® liat test results, and 5 were non-evaluable due to specimen handling issues. Of the 1729 prospective symptomatic subjects enrolled, 1706 ANS specimens were evaluable, 22 were non-evaluable due to missing or invalid cobas® liat test results, and 1 was non-evaluable due to specimen handling issues. Of the 2713 prospective asymptomatic subjects enrolled, 2697 NPS specimens were evaluable for analyses, 13 were non-evaluable due to missing or invalid cobas® liat test results, and 3 were

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non-evaluable due to specimen handling issues. Of the 2713 prospective asymptomatic subjects enrolled, 2700 ANS specimens were evaluable, 10 were non-evaluable due to missing or invalid cobas® liat test results, and 3 were non-evaluable due to specimen handling issues. Available demographic data regarding the individuals from whom specimens were obtained are presented in Table 8.

Table 8: Demographics of Prospectively Enrolled Individuals

CharacteristicsSymptomatic (N=1729)Asymptomatic (N=2713)
Sex at Birth--
Male681 (39.4%)1086 (40.0%)
Female1048 (60.6%)1627 (60.0%)
Age Group (Years)--
=60254 (14.7%)466 (17.2%)
Ethnicity--
Hispanic / Latino244 (14.1%)416 (15.3%)
Not Hispanic / Latino1478 (85.5%)2288 (84.3%)
Not Reported4 (0.2%)6 (0.2%)
Unknown3 (0.2%)3 (0.1%)
Race--
American Indian / Alaska Native8 (0.5%)10 (0.4%)
Asian24 (1.4%)91 (3.4%)
Black / African American212 (12.3%)737 (27.2%)
Native Hawaiian / Other Pacific Islander3 (0.2%)3 (0.1%)
White1413 (81.7%)1774 (65.4%)
Other Race52 (3.0%)89 (3.3%)
Not Reported17 (1.0%)9 (0.3%)

In symptomatic subjects, for the NPS specimens cobas® liat SARS-CoV-2 v2 demonstrated a PPA and NPA of 94.5% and 97.6%, respectively; (Table 9). For the ANS specimens cobas® liat SARS-CoV-2 v2 demonstrated a PPA and NPA of 96.7% and 97.2%, respectively (Table 9). The

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initial invalid rate of cobas® liat SARS-CoV-2 v2 on NPS and ANS symptomatic specimens was 0.5% and 0.7% respectively. Upon repeat testing, the final assay invalid rate on NPS and ANS symptomatic specimens was 0% and 0.1% respectively.

Table 9: Clinical Performance of cobas® liat SARS-CoV-2 v2 in Symptomatic Subjects Relative to the Comparator by Specimen Type

Specimen Typea/ (a+c)PPA (%)PPA 95% CId/ (b+d)NPA (%)NPA 95% CI
NPS*207/21994.590.7-96.81451/148697.696.7-98.3
ANS**208/21596.793.4-98.41449/149197.296.2-97.9

Abbreviations: PPA = Positive Percent Agreement; CI = Confidence Interval; NPA = Negative Percent Agreement; NPS = Nasopharyngeal swab; ANS = Anterior nasal Swab; SARS-CoV-2 = Severe acute respiratory syndrome coronavirus 2.

Note: N = Total number of specimens; a = number of specimens where both cobas® liat and the comparator are positive; b = number of specimens where cobas® liat is positive and the comparator is negative; c = number of specimens where cobas® liat is negative and the comparator is positive; d = number of specimens where both cobas® liat and the comparator are negative.

  • NPS discrepant NAAT results: Of 12 specimens negative on cobas® liat and positive on the comparator, 8 were positive and 4 were negative. Of 35 specimens positive on cobas® liat and negative on the comparator, 12 were positive and 23 were negative.

** ANS discrepant NAAT results: Of 7 specimens negative on cobas® liat and positive on the comparator, 6 were positive and 1 was negative. Of 42 specimens positive on cobas® liat and negative on the comparator, 8 were positive and 34 were negative.

In asymptomatic subjects, for the NPS specimens cobas® liat SARS-CoV-2 v2 demonstrated a PPA and NPA of 86.1% and 97.9%, respectively; (Table 9). For the ANS specimens cobas® liat SARS-CoV-2 v2 demonstrated a PPA and NPA of 89.5% and 98.3%, respectively, (Table 10). The initial invalid rate of cobas® liat SARS-CoV-2 v2 was 0.3% for both NPS and ANS asymptomatic specimens. Upon repeat testing, the final assay invalid rate was 0.0% for both NPS and ANS asymptomatic specimens.

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Table 10: Clinical Performance of cobas® liat SARS-CoV-2 v2 in Asymptomatic Subjects Relative to the Comparator by Specimen Type

Specimen typea/ (a+c)PPA (%)PPA 95% CId/ (b+d)NPA (%)NPA 95% CI
NPS*62/7286.176.3-92.32569/262597.997.2-98.4
ANS**51/5789.578.9-95.12597/264398.397.7-98.7

Abbreviations: PPA = Positive Percent Agreement; CI = Confidence Interval; NPA = Negative Percent Agreement; NPS = Nasopharyngeal swab; ANS = Anterior nasal Swab.

Note:N = Total number of specimens; a = number of specimens where both cobas® liat and the comparator are positive; b = number of specimens where cobas® liat is positive and the comparator is negative; c = number of specimens where cobas® liat is negative and the comparator is positive; d = number of specimens where both cobas® liat and the comparator are negative.

  • NPS discrepant NAAT results: Of 10 specimens negative on cobas® liat and positive on the comparator, 6 were positive and 4 were negative. Of 56 specimens positive on cobas® liat and negative on the comparator, 17 were positive and 39 were negative.

** ANS discrepant NAAT results: Of 6 specimens negative on cobas® liat and positive on the comparator, 3 were positive and 3 were negative. Of 46 specimens positive on cobas® liat and negative on the comparator, 6 were positive and 40 were negative.

7. CONCLUSIONS

A comparison of the intended use, technological characteristics, and the results of non-clinical analytical and clinical performance studies demonstrate that cobas® liat SARS-CoV-2 v2 nucleic acid test is substantially equivalent to the predicate device.