(175 days)
Not Found
No.
The device uses RT-PCR technology for nucleic acid detection and differentiation. There is no mention of AI, ML, or DNN in the description or performance studies, nor are there any indications of image processing that might require AI. The device automates and integrates standard molecular diagnostic steps.
No
This device is a diagnostic test (RT-PCR) intended for the qualitative detection and differentiation of viral nucleic acids to aid in differential diagnosis. It does not provide treatment or therapy.
Yes
The "Intended Use / Indications for Use" section explicitly states that the test is "intended to aid in the differential diagnosis" of SARS-CoV-2, influenza A, influenza B, and RSV infections. Diagnosis is a core function of a diagnostic device.
No
The device is a laboratory diagnostic test performed on a specific hardware analyzer (cobas liat analyzer) that automates sample purification, nucleic acid amplification, and real-time PCR. It involves chemical reagents and physical processes, clearly indicating it is not a software-only medical device.
Yes
The device is described as a "multiplex real-time reverse transcription polymerase chain reaction (RT-PCR) test intended for the simultaneous qualitative detection and differentiation" of specific nucleic acids in "anterior nasal (nasal) and nasopharyngeal swab specimens" to "aid in the differential diagnosis" of infections. This clearly aligns with the definition of an in vitro diagnostic (IVD) device, which is an instrument, reagent or system intended for use in the in vitro examination of specimens derived from the human body for the purpose of providing information for diagnosis, monitoring, or screening.
N/A
Intended Use / Indications for Use
The cobas liat SARS-CoV-2, Influenza A/B & RSV nucleic acid test is an automated rapid multiplex real-time reverse transcription polymerase chain reaction (RT-PCR) test intended for the simultaneous qualitative detection and differentiation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus, influenza B virus and respiratory syncytial virus (RSV) nucleic acids in anterior nasal (nasal) and nasopharyngeal swab specimens from individuals exhibiting signs and symptoms of respiratory tract infection. Clinical signs and symptoms of respiratory viral infection due to SARS-CoV-2, influenza and RSV can be similar. This test is intended to aid in the differential diagnosis of SARS-CoV-2, influenza A, influenza B, and RSV infections in humans and is not intended to detect influenza C virus infections.
Nucleic acids from the viral organisms identified by this test are generally detectable in nasopharyngeal and nasal swab specimens during the acute phase of infection. The detection and identification of specific viral nucleic acids from individuals exhibiting signs and symptoms of respiratory tract infection are indicative of the presence of the identified virus, and aid in diagnosis if used in conjunction with other clinical and epidemiological information, and laboratory findings.
The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. Positive results do not rule out coinfection with other organisms. The organism(s) detected by the cobas liat SARS-CoV-2, Influenza A/B & RSV nucleic acid test may not be the definite cause of disease. Negative results do not preclude SARS-CoV-2, influenza A virus, influenza B virus, or RSV infections.
Product codes
QOF
Device Description
The cobas liat SARS-CoV-2, Influenza A/B & RSV 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, a well-conserved region of the matrix gene of influenza A (Flu A target), the nonstructural protein 1 (NS1) gene of influenza B (Flu B target) and the matrix gene of RSV (RSV target). 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
Not Found
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
Not Found
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, influenza A, influenza B, and RSV at which ≥95% of all replicates test positive. Two strains for each target were evaluated. Co-spiked panels were formulated using cultured or 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.
- Results (Concentration at LoD):
- SARS-CoV-2 (USA-WA1/2020): 0.0350 TCID50/mL
- SARS-CoV-2 (WHO International Standard 20/146, v3, 11/2021): 65.1 IU/mL
- Influenza A (Darwin/6/2021): 0.295 TCID50/mL
- Influenza A (Brisbane/02/2018): 0.00325 TCID50/mL
- Influenza B (B/Austria/1359417/2021): 0.979 TCID50/mL
- Influenza B (Phuket/3073/2013): 0.183 TCID50/mL
- RSV (9320 (Subtype B)): 0.269 TCID50/mL
- RSV (Long (Subtype A)): 0.0240 TCID50/mL
- Results (Concentration at LoD):
- Reactivity/inclusivity: Evaluated the ability of the test to detect SARS-CoV-2, influenza A, influenza B, and RSV isolates/variants. Tested at ~3x LoD in 3 replicates, doubling concentration until 3/3 replicates detected if hit rate
§ 866.3981 Device to detect and identify nucleic acid targets in respiratory specimens from microbial agents that cause the SARS-CoV-2 respiratory infection and other microbial agents when in a multi-target test.
(a)
Identification. A device to detect and identify nucleic acid targets in respiratory specimens from microbial agents that cause the SARS-CoV-2 respiratory infection and other microbial agents when in a multi-target test is an in vitro diagnostic device intended for the detection and identification of SARS-CoV-2 and other microbial agents when in a multi-target test in human clinical respiratory specimens from patients suspected of respiratory infection who are at risk for exposure or who may have been exposed to these agents. The device is intended to aid in the diagnosis of respiratory infection in conjunction with other clinical, epidemiologic, and laboratory data or other risk factors.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The intended use in the labeling required under § 809.10 of this chapter must include a description of the following: Analytes and targets the device detects and identifies, the specimen types tested, the results provided to the user, the clinical indications for which the test is to be used, the specific intended population(s), the intended use locations including testing location(s) where the device is to be used (if applicable), and other conditions of use as appropriate.
(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 descriptions of the performance characteristics of the device for each specimen type claimed in the intended use based on analytical studies including the following, as applicable: Limit of Detection, inclusivity, cross-reactivity, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, precision, reproducibility, and clinical studies;
(iii) Detailed descriptions of the test procedure(s), the interpretation of test results for clinical specimens, and acceptance criteria for any quality control testing;
(iv) A warning statement that viral culture should not be attempted in cases of positive results for SARS-CoV-2 and/or any similar microbial agents unless a facility with an appropriate level of laboratory biosafety (
e.g., BSL 3 and BSL 3+, etc.) is available to receive and culture specimens; and(v) A prominent statement that device performance has not been established for specimens collected from individuals not identified in the intended use population (
e.g., when applicable, that device performance has not been established in individuals without signs or symptoms of respiratory infection).(vi) Limiting statements that indicate 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) There is a risk of incorrect results due to the presence of nucleic acid sequence variants in the targeted pathogens;
(D) That positive and negative predictive values are highly dependent on prevalence;
(E) Accurate 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
(F) When applicable (
e.g., recommended by the Centers for Disease Control and Prevention, by current well-accepted clinical guidelines, or by published peer-reviewed literature), that the clinical performance may be affected by testing a specific clinical subpopulation or for a specific claimed specimen type.(4) Design verification and validation must include:
(i) Detailed documentation, including performance results, from a clinical study that includes prospective (sequential) samples for each claimed specimen type and, as appropriate, additional characterized clinical samples. The clinical study must be performed on a study population consistent with the intended use population and compare the device performance to results obtained using a comparator that FDA has determined is appropriate. Detailed documentation must include the clinical study protocol (including a predefined statistical analysis plan), study report, testing results, and results of all statistical analyses.
(ii) Risk analysis and documentation demonstrating how risk control measures are implemented to address device system hazards, such as Failure Modes Effects Analysis and/or Hazard Analysis. This documentation must include a detailed description of a protocol (including all procedures and methods) for the continuous monitoring, identification, and handling of genetic mutations and/or novel respiratory pathogen isolates or strains (
e.g., regular review of published literature and periodic in silico analysis of target sequences to detect possible mismatches). All results of this protocol, including any findings, must be documented and must include any additional data analysis that is requested by FDA in response to any performance concerns identified under this section or identified by FDA during routine evaluation. Additionally, if requested by FDA, these evaluations must be submitted to FDA for FDA review within 48 hours of the request. Results that are reasonably interpreted to support the conclusion that novel respiratory pathogen strains or isolates impact the stated expected performance of the device must be sent to FDA immediately.(iii) A detailed description of the identity, phylogenetic relationship, and other recognized characterization of the respiratory pathogen(s) that the device is designed to detect. In addition, detailed documentation describing how to interpret the device results and other measures that might be needed for a laboratory diagnosis of respiratory infection.
(iv) A detailed device description, including device components, ancillary reagents required but not provided, and a detailed explanation of the methodology, including molecular target(s) for each analyte, design of target detection reagents, rationale for target selection, limiting factors of the device (
e.g., saturation level of hybridization and maximum amplification and detection cycle number, etc.), internal and external controls, and computational path from collected raw data to reported result (e.g., how collected raw signals are converted into a reported signal and result), as applicable.(v) A detailed description of device software, including software applications and hardware-based devices that incorporate software. The detailed description must include documentation of verification, validation, and hazard analysis and risk assessment activities, including an assessment of the impact of threats and vulnerabilities on device functionality and end users/patients as part of cybersecurity review.
(vi) For devices intended for the detection and identification of microbial agents for which an FDA recommended reference panel is available, design verification and validation must include the performance results of an analytical study testing the FDA recommended reference panel of characterized samples. Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses.
(vii) For devices with an intended use that includes detection of Influenza A and Influenza B viruses and/or detection and differentiation between the Influenza A virus subtypes in human clinical specimens, the design verification and validation must include a detailed description of the identity, phylogenetic relationship, or other recognized characterization of the Influenza A and B viruses that the device is designed to detect, a description of how the device results might be used in a diagnostic algorithm and other measures that might be needed for a laboratory identification of Influenza A or B virus and of specific Influenza A virus subtypes, and a description of the clinical and epidemiological parameters that are relevant to a patient case diagnosis of Influenza A or B and of specific Influenza A virus subtypes. An evaluation of the device compared to a currently appropriate and FDA accepted comparator method. Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses.
(5) When applicable, performance results of the analytical study testing the FDA recommended reference panel described in paragraph (b)(4)(vi) of this section must be included in the device's labeling under § 809.10(b) of this chapter.
(6) For devices with an intended use that includes detection of Influenza A and Influenza B viruses and/or detection and differentiation between the Influenza A virus subtypes in human clinical specimens in addition to detection of SARS-CoV-2 and similar microbial agents, the required labeling under § 809.10(b) of this chapter must include the following:
(i) Where applicable, a limiting statement that performance characteristics for Influenza A were established when Influenza A/H3 and A/H1-2009 (or other pertinent Influenza A subtypes) were the predominant Influenza A viruses in circulation.
(ii) Where applicable, a warning statement that reads if infection with a novel Influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent influenza viruses and sent to State or local health departments for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
(iii) Where the device results interpretation involves combining the outputs of several targets to get the final results, such as a device that both detects Influenza A and differentiates all known Influenza A subtypes that are currently circulating, the device's labeling must include a clear interpretation instruction for all valid and invalid output combinations, and recommendations for any required followup actions or retesting in the case of an unusual or unexpected device result.
(iv) A limiting statement that if a specimen yields a positive result for Influenza A, but produces negative test results for all specific influenza A subtypes intended to be differentiated (
i.e., H1-2009 and H3), this result requires notification of appropriate local, State, or Federal public health authorities to determine necessary measures for verification and to further determine whether the specimen represents a novel strain of Influenza A.(7) If one of the actions listed at section 564(b)(1)(A) through (D) of the Federal Food, Drug, and Cosmetic Act occurs with respect to an influenza viral strain, or if the Secretary of Health and Human Services determines, under section 319(a) of the Public Health Service Act, that a disease or disorder presents a public health emergency, or that a public health emergency otherwise exists, with respect to an influenza viral strain:
(i) Within 30 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation, the manufacturer must have testing performed on the device with those influenza viral samples in accordance with a standardized protocol considered and determined by FDA to be acceptable and appropriate.
(ii) Within 60 days from the date that FDA notifies manufacturers that characterized influenza viral samples are available for test evaluation and continuing until 3 years from that date, the results of the influenza emergency analytical reactivity testing, including the detailed information for the virus tested as described in the certificate of authentication, must be included as part of the device's labeling in a tabular format, either by:
(A) Placing the results directly in the device's labeling required under § 809.10(b) of this chapter that accompanies the device in a separate section of the labeling where analytical reactivity testing data can be found, but separate from the annual analytical reactivity testing results; or
(B) In a section of the device's label or in other labeling that accompanies the device, prominently providing a hyperlink to the manufacturer's public website where the analytical reactivity testing data can be found. The manufacturer's website, as well as the primary part of the manufacturer's website that discusses the device, must provide a prominently placed hyperlink to the website containing this information and must allow unrestricted viewing access.
U.S. Food & Drug Administration FDA 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 25, 2025
Roche Molecular Systems, Inc.
Sumedha Sinha
Clinical Development Lead
4300 Hacienda Drive
Pleasanton, California 94588
Re: K243406
Trade/Device Name: cobas liat SARS-CoV-2, Influenza A/B & RSV nucleic acid test
Regulation Number: 21 CFR 866.3981
Regulation Name: Device To Detect And Identify Nucleic Acid Targets In Respiratory Specimens From Microbial Agents That Cause The SARS-Cov-2 Respiratory Infection And Other Microbial Agents When In A Multi-Target Test
Regulatory Class: Class II
Product Code: QOF
Dated: October 31, 2024
Received: November 1, 2024
Dear Sumedha Sinha:
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
K243406 - Sumedha Sinha 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
K243406 - Sumedha Sinha 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
Form Approved: OMB No. 0910-0120
Expiration Date: 07/31/2026
See PRA Statement below.
Indications for Use
510(k) Number (if known): K243406
Device Name: cobas liat SARS-CoV-2, Influenza A/B & RSV nucleic acid test
Indications for Use (Describe)
The cobas liat SARS-CoV-2, Influenza A/B & RSV nucleic acid test is an automated rapid multiplex real-time reverse transcription polymerase chain reaction (RT-PCR) test intended for the simultaneous qualitative detection and differentiation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus, influenza B virus and respiratory syncytial virus (RSV) nucleic acids in anterior nasal (nasal) and nasopharyngeal swab specimens from individuals exhibiting signs and symptoms of respiratory tract infection. Clinical signs and symptoms of respiratory viral infection due to SARS-CoV-2, influenza and RSV can be similar. This test is intended to aid in the differential diagnosis of SARS-CoV-2, influenza A, influenza B, and RSV infections in humans and is not intended to detect influenza C virus infections.
Nucleic acids from the viral organisms identified by this test are generally detectable in nasopharyngeal and nasal swab specimens during the acute phase of infection. The detection and identification of specific viral nucleic acids from individuals exhibiting signs and symptoms of respiratory tract infection are indicative of the presence of the identified virus, and aid in diagnosis if used in conjunction with other clinical and epidemiological information, and laboratory findings.
The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. Positive results do not rule out coinfection with other organisms. The organism(s) detected by the cobas liat SARS-CoV-2, Influenza A/B & RSV nucleic acid test may not be the definite cause of disease. Negative results do not preclude SARS-CoV-2, influenza A virus, influenza B virus, or RSV infections.
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:
Department of Health and Human Services
Food and Drug Administration
Office of Chief Information Officer
Paperwork Reduction Act (PRA) Staff
PRAStaff@fda.hhs.gov
"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."
FORM FDA 3881 (8/23) Page 1 of 1 PSC Publishing Services (301) 443-6740 EF
Page 5
cobas® liat SARS-CoV-2,Influenza A/B & RSV 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 | Sumedha Sinha Phone: 925-366-0146 Email: sumedha.sinha@roche.com |
| Date Prepared | 2 April 2025 |
| Proprietary Name | cobas® liat SARS-CoV-2, Influenza A/B & RSV nucleic acid test |
| Common Name | cobas® liat SARS-CoV-2, Influenza A/B & RSV |
| Classification | 21 CFR 866.3981 Device To Detect And Identify Nucleic Acid Targets In Respiratory Specimens From Microbial Agents That Cause The SARS-Cov-2 Respiratory Infection And Other Microbial Agents When In A Multi-Target Test |
| Product Codes | QOF |
| Predicate Devices | HOLOGIC Panther Fusion® SARS-CoV-2/Flu A/B/RSV Assay (K241240) |
| Establishment Registration | Roche Molecular Systems, Inc. (2243471) |
Page 6
1. DEVICE DESCRIPTION
The cobas® liat SARS-CoV-2, Influenza A/B & RSV 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, a well-conserved region of the matrix gene of influenza A (Flu A target), the nonstructural protein 1 (NS1) gene of influenza B (Flu B target) and the matrix gene of RSV (RSV target). 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, Influenza A/B & RSV nucleic acid test is an automated rapid multiplex real-time reverse transcription polymerase chain reaction (RT-PCR) test intended for the simultaneous qualitative detection and differentiation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus, influenza B virus and respiratory syncytial virus (RSV) nucleic acids in anterior nasal (nasal) and nasopharyngeal swab specimens from individuals exhibiting signs and symptoms of respiratory tract infection. Clinical signs and symptoms of respiratory viral infection due to SARS- CoV-2, influenza and RSV can be similar. This test is intended to aid in the differential diagnosis of SARS-CoV-2, influenza A, influenza B, and RSV infections in humans and is not intended to detect influenza C virus infections.
Nucleic acids from the viral organisms identified by this test are generally detectable in nasopharyngeal and nasal swab specimens during the acute phase of infection. The detection and identification of specific viral nucleic acids from individuals exhibiting signs and symptoms of respiratory tract infection are indicative of the presence of the identified virus, and aid in diagnosis if used in conjunction with other clinical and epidemiological information, and laboratory findings.
The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.
Positive results do not rule out coinfection with other organisms. The organism(s) detected by the cobas® liat SARS-CoV-2, Influenza A/B & RSV nucleic acid test may not be the definite
Page 7
cause of disease. Negative results do not preclude SARS-CoV-2, influenza A virus, influenza B virus, or RSV infections.
3. TECHNOLOGICAL CHARACTERISTICS
The primary technological characteristics and intended use of the Roche cobas® liat SARS-CoV- 2, Influenza A/B & RSV nucleic acid test are substantially equivalent to other legally marketed nucleic acid amplification tests intended for the qualitative detection of SARS-CoV-2, influenza A/B & RSV.
As indicated in Table 1, the Roche cobas® liat SARS-CoV-2, Influenza A/B & RSV nucleic acid test is substantially equivalent to the identified predicate device, the cleared HOLOGIC Panther Fusion® SARS-CoV-2/Flu A/B/RSV Assay (K241240).
Table 1: Comparison of the cobas® liat SARS-CoV-2, Influenza A/B & RSV test and the Predicate Device
| Submitted Device: cobas® liat SARS-CoV-2, Influenza A/B & RSV nucleic acid test | Predicate Device: Panther Fusion SARS-CoV-2/Flu A/B/RSV Assay (K241240) | |
|---|---|---|
| Regulation Name | 21 CFR 866.3981 | 21 CFR 866.3981 |
| Product Code | QOF | QOF |
| Intended Use | The cobas® liat SARS-CoV-2, Influenza A/B & RSV nucleic acid test is an automated rapid multiplex real-time reverse transcription polymerase chain reaction (RT-PCR) test intended for the simultaneous qualitative detection and differentiation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus, influenza B virus and respiratory syncytial virus (RSV) nucleic acids in anterior nasal (nasal) and nasopharyngeal swab specimens from individuals exhibiting signs and symptoms of respiratory tract infection. Clinical signs and symptoms of respiratory viral infection due to SARS- CoV-2, influenza and RSV can be similar. This test is intended to aid in the differential diagnosis of SARS-CoV-2, influenza A, influenza B, and RSV infections in humans and is not intended to detect influenza C virus infections. Nucleic acids from the viral organisms identified by this test are generally detectable in nasopharyngeal and nasal swab specimens during the acute phase of infection. The detection and identification of specific viral nucleic acids from individuals exhibiting signs | The Panther Fusion SARS-CoV-2/Flu A/B/RSV assay is a fully automated multiplexed real-time polymerase chain reaction (RT-PCR) in vitro diagnostic test intended for the qualitative detection and differentiation of severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2), influenza A virus (Flu A), influenza B virus (Flu B), and respiratory syncytial virus (RSV). Nucleic acids are isolated and purified from nasopharyngeal (NP) swab specimens and anterior nasal (AN) swab specimens obtained from individuals exhibiting signs and symptoms of a respiratory tract infection. Clinical signs and symptoms of respiratory viral infection due to SARS-CoV-2, influenza, and RSV can be similar. This assay is intended to aid in the differential diagnosis of SARS-CoV-2, Flu A, Flu B, and RSV infections in humans and is not intended to detect influenza C virus infections. Nucleic acids from the viral organisms identified by this test are generally detectable in NP and AN swab specimens during the acute phase of infection. The detection and identification of specific viral nucleic acids from individuals exhibiting signs and symptoms of respiratory tract |
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| Submitted Device: cobas® liat SARS-CoV-2, Influenza A/B & RSV nucleic acid test | Predicate Device: Panther Fusion SARS-CoV-2/Flu A/B/RSV Assay (K241240) | |
|---|---|---|
| and symptoms of respiratory tract infection are indicative of the presence of the identified virus, and aid in diagnosis if used in conjunction with other clinical and epidemiological information, and laboratory findings. The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. Positive results do not rule out coinfection with other organisms. The organism(s) detected by the cobas® liat SARS-CoV-2, Influenza A/B & RSV nucleic acid test may not be the definite cause of disease. Negative results do not preclude SARS-CoV-2, influenza A virus, influenza B virus, or RSV infections. | infection are indicative of the presence of the identified virus and aids in diagnosis if used in conjunction with other clinical and epidemiological information, and laboratory findings. The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. Positive results do not rule out coinfection with other organisms. The organism(s) detected by the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay may not be the definite cause of disease. Negative results do not preclude SARS-CoV-2, influenza A virus, influenza B virus, or RSV infections. This assay is designed for use on the Panther Fusion system. The Hologic RespDirect Collection Kit is cleared for NP swab specimens only for testing with the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay. | |
| Sample Type | Nasopharyngeal and anterior nasal swabs | Nasopharyngeal and anterior nasal swabs |
| Analyte | SARS-CoV-2, Flu A, Flu B, RSV RNA | SARS-CoV-2, Flu A, Flu B, RSV RNA |
| 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) – Remel™ M4RT, M4, M5 and M6 • 0.9% Saline | • RespDirect Swab, intended for collection of NPS specimens with UTM™/ VTM or eSTM • Enhanced Direct Load Tube (eDLT), containing enhanced specimen transport media (eSTM) |
| Time to result | About 15 minutes | ~ 2.5 hours |
| Amplification Technology | Real-time PCR | Real-time PCR |
| Detection Chemistry | Assay using different reporter dyes for target and control | Assay using different reporter dyes for target and control |
| Controls Used | Sample processing control (IC), Positive and negative control | Sample processing control (IC), Positive and negative control |
| Instrumentation | cobas® liat System | Panther Fusion System |
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4. SPECIAL CONTROLS/STANDARDS/GUIDANCE REFERENCED
Class II Special Controls as per 21 CFR 866.3981.
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, influenza A, influenza B, and RSV at which equal to or greater than 95% of all replicates test positive.
Two strains for each target (SARS-CoV-2, influenza A, influenza B, and RSV) were evaluated. To determine the LoD for each target, co-spiked panels were formulated using cultured or 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, influenza A, influenza B, and RSV strains
| Virus | Strain | Concentration at LoD | Hit rate (Mean Ct) |
|---|---|---|---|
| SARS-CoV-2* | USA-WA1/2020 | 0.0350 TCID50/mL | 20/21 (35.5) |
| SARS-CoV-2* | WHO International Standard 20/146, v3, 11/2021 | 65.1 IU/mL | 21/21 (34.9) |
| Influenza A | Darwin/6/2021 | 0.295 TCID50/mL | 21/21 (35.0) |
| Influenza A | Brisbane/02/2018 | 0.00325 TCID50/mL | 21/21 (36.4) |
| Influenza B | B/Austria/1359417/2021 | 0.979 TCID50/mL | 20/21 (34.6) |
| Influenza B | Phuket/3073/2013 | 0.183 TCID50/mL | 21/21 (34.1) |
| RSV | 9320 (Subtype B) | 0.269 TCID50/mL | 21/21 (34.9) |
| RSV | Long (Subtype A) | 0.0240 TCID50/mL | 21/21 (33.8) |
*Inactivated virus
A separate study was performed to demonstrate that the LoD of each strain individually was equivalent to the co-spiked LoD.
5.2. Reactivity/inclusivity
The inclusivity study evaluates the ability of the test to detect SARS-CoV-2, influenza A influenza B, and RSV isolates/variants. The reactivity/inclusivity was evaluated with 10 SARS-CoV-2, 28
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influenza A (15 H1N1, 10 H3N2, 1 H5N1, 1 H5N2 and 1 H7N9), ten (10) influenza B (5 Victoria and 5 Yamagata), and five (5) RSV isolates/variants. All strains were individually tested at ~3x LoD in 3 replicates to evaluate inclusivity. If 7.94M sequences) and NCBI (>15.04M sequences) databases.
Table 3: Results of Testing SARS-CoV-2 Isolate/Variants
| Lineage/Subtype | Isolate/Variant* | Test Concentration (TCID50/mL) | Relative to LoD |
|---|---|---|---|
| Alpha | Hong Kong/VM20001061/2020 | 0.105 | 3x |
| Beta, B.1.595_2020 (was B.1.2) | NY-Wadsworth-33126-01/2020 | 0.105 | 3x |
| Delta, B.1.617.2 | USA/MD-HP05285/2021 | 0.105 | 3x |
| Epsilon, B.1.427 | USA/CA/VRLC009/2021 | 0.105 | 3x |
| Gamma, P.1 | Japan/TY7-503/2021 | 0.105 | 3x |
| Iota, B.1.526_2021 | USA/NY-Wadsworth-21025952-01/2021 | 0.105 | 3x |
| Kappa, B.1.617.1 | USA/CA-Stanford-15_S02/2021 | 0.105 | 3x |
| Omicron, B.1.1.529, CH.1.1 | USA/MD-HP41275/2022 | 0.105 | 3x |
| Omicron, B.1.1.529, XBB.1.5 | USA/MD-HP40900/2022 | 0.105 | 3x |
| Zeta, P2_2021 | USA/NY-Wadsworth-21006055-01/2021 | 0.105 | 3x |
*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.
Influenza A
The influenza A isolates/variants tested in the study and the lowest concentrations detected are listed in Table 4.
Table 4: Results of Testing Influenza A Isolate/Variants
| Lineage/Subtype | Isolate/Variant* | Test Concentration (TCID50/mL)ä | Relative to LoD |
|---|---|---|---|
| H1N1 | A/Brisbane/59/07 | 0.885 | 3x |
| H1N1 | A/Christ Church/16/2020 | 1.77EID50/mL | 6x |
| H1N1 | A/Denver/01/57 | 0.885 | 3x |
| H1N1 | A/England/221740513/2022** | 75 copies/mL‡ | 1x |
| H1N1 | A/England/224020815/2022** | 91.5 copies/mL‡ | 1x |
| H1N1 | A/Fort Monmouth/01/47 | 0.885 | 3x |
| H1N1 | A/Malaya/302/54 | 0.885 | 3x |
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| Lineage/Subtype | Isolate/Variant* | Test Concentration (TCID50/mL)ä | Relative to LoD |
|---|---|---|---|
| H1N1 | A/New Caledonia/20/99 | 0.885 | 3x |
| H1N1 | A/Swine/Iowa/15/30 | 1.77 CEID50/mL | 6x |
| H1N1 | A/Sydney/5/2021β | 1.77 | 6x |
| H1N1 | A/Victoria/2570/2019 | 3.54EID50/mL | 12x |
| H1N1 | A/WS/33 | 0.885 | 3x |
| H1N1 | A/Brisbane/14/2023 | 75 copies/mL‡ | 1x |
| H1N1 | A/Townsville/1A/2023 | 75 copies/mL‡ | 1x |
| H1N1 | A/ Townsville/2A/2023 | 75 copies/mL‡ | 1x |
| H3N2 | A/Aichi/2/68 | 0.885 CEID50/mL | 3x |
| H3N2 | A/Brisbane/10/07 | 0.885 | 3x |
| H3N2 | A/Cambodia/E0826360/2020 | 0.885 | 3x |
| H3N2 | A/Darwin/9/2021 | 1.77 | 6x |
| H3N2 | A/Hong Kong/8/68 | 0.885 | 3x |
| H3N2 | A/H3/Perth/16/09 | 0.885 | 3x |
| H3N2 | A/Tasmania/503/2020 | 0.885 EID50/mL | 3x |
| H3N2 | A/Victoria/3/75 | 0.885 CEID50/mL | 3x |
| H3N2 | A/Wisconsin/67/2005 | 0.885 | 3x |
| H3N2 | A/Singapore/INFIMH-16-0019/2016 | 0.885 | 3x |
| H5N1† | A/mallard/Wisconsin/2576/2009 | 0.885 CEID50/mL | 3x |
| H5N2† | A/ruddy turnstone/New Jersey/828212/2001 | 0.885 CEID50/mL | 3x |
| H7N9† | A/northern shoveler/Mississippi/11OS145/2011 | 3.54 CEID50/mL | 12x |
*These strains are in addition to the influenza A Darwin/6/2021 and Brisbane/02/2018 strains used in the analytical sensitivity study.
**A/England/221740513/2022 GISAID ID is EPI_ISL_14387941 and for A/England/224020815/2022 GISAID ID is EPI_ISL_15803829.
‡ The concentrations tested are near the 1x LOD value (69 copies/mL) determined by digital PCR for the influenza A/Darwin/6/2021 strain. ä Concentrations are shown in TCID50/mL unless otherwise indicated.
β Inactivated virus
Influenza B
The influenza B isolates/variants tested in the study and the lowest concentrations detected are listed in Table 5.
Table 5: Results of Testing Influenza B Isolate/Variants
| Lineage/Subtype | Isolate/Variant* | Test Concentration (TCID50/mL) ä | Relative to LoD |
|---|---|---|---|
| Victoria | B/Brisbane/60/2008 | 2.937 | 3x |
| Victoria | B/Colorado/06/2017 | 2.937 | 3x |
| Victoria | B/Malaysia/2506/04 | 2.937 | 3x |
| Victoria | B/Michigan/09/2011 | 2.937 EID50/mL | 3x |
| Victoria | B/Washington/02/2019 | 2.937 | 3x |
| Yamagata | B/Florida/04/06 | 2.937 | 3x |
| Yamagata | B/Massachusetts/2/2012 | 2.937 | 3x |
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| Yamagata | B/Texas/6/2011 | 2.937 | 3x |
|---|---|---|---|
| Yamagata | B/Texas/81/2016 | 2.937 EID50/mL | 3x |
| Yamagata | B/Wisconsin/1/2010 | 2.937 | 3x |
*These strains are in addition to the influenza B Austria/1359417/2021 and Phuket/3073/2013 strains used in the analytical sensitivity study.
ä Concentrations are shown in TCID50/mL unless otherwise indicated.
RSV
The RSV isolates/variants tested in the study and the lowest concentrations detected are listed in Table 6.
Table 6: Results of Testing RSV Isolate/Variants
| Lineage/Subtype | Isolate/Variant* | Test Concentration (TCID50/mL) | Relative to LoD |
|---|---|---|---|
| RSV-A | RSV-A 2006 isolate | 0.807 | 3x |
| RSV-A | RSV-A2 | 0.807 | 3x |
| RSV-B | RSV-B Ch93(18)-18 | 0.807 | 3x |
| RSV-B | RSV-B Wash/18537/62 | 0.807 | 3x |
| RSV-B | RSV-B WV/14617/85 | 0.807 | 3x |
*These strains are in addition to the RSV 9320 (Subtype B) and Long (Subtype A) strains 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 7). High titer stocks of the potentially cross-reacting microorganisms were tested for cross-reactivity, and also in the presence of SARS-CoV-2, influenza A, influenza B, and RSV 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 (concentrations were unknown). None of the organisms tested cross reacted or interfered with cobas® liat SARS-CoV-2, Influenza A/B & RSV nucleic acid test performance at the concentrations tested.
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Table 7: Microorganisms tested for cross-reactivity and microbial interference
| Adenovirus Type 1β | Human Rhinovirus B | Mycobacterium tuberculosis |
| Adenovirus Type 7 | MERS-Coronavirusβ | Mycoplasma genitaliumβ |
| Cytomegalovirus | Measles | Mycoplasma pneumoniae |
| Epstein-Barr virusβ | Mumps | Neisseria elongata |
| Human Coronavirus OC43 | SARS Coronavirus, Urbani*β | Neisseria flava |
| Human Coronavirus 229E | Bordetella parapertussis | Neisseria meningitidis |
| Human Coronavirus HKU Ɨ | Bordetella pertussis | Pneumocystis jirovecii Ɨ |
| Human Coronavirus NL63β | Chlamydophila pneumoniae | Pseudomonas aeruginosa |
| Human Enterovirus 68 | Corynebacterium flavescens | Staphylococcus aureus |
| Human Metapneumovirus 27 | Escherichia coli | Staphylococcus epidermidis |
| Human Parainfluenza Virus Type 1β | Fusobacterium necrophorum subsp. necrophorum | Streptococcus pneumoniae |
| Human Parainfluenza Virus Type 2 | Haemophilus influenzae | Streptococcus pyogenes |
| Human Parainfluenza Virus Type 3 | Lactobacillus crispatus | Streptococcus salivarius |
| Human Parainfluenza Virus Type 4A*β | Legionella pneumophila | Aspergillus flavus var. flavus |
| Human Rhinovirus Type 1A*β | Moraxella catarrhalis | Candida albicans |
- Tested at highest concentration available
β Inactivated virus
Ɨ Clinical specimens at unknown concentrations were tested.
5.4. Competitive inhibition
To assess competitive inhibition between SARS-CoV-2, influenza A, influenza B, and RSV, each target prepared at high concentrations with the other three targets at low concentrations (approximately three times the respective LoD) was tested to evaluate any potential impact by the high concentration target on the detection of the other targets (Table 8). Five (5) replicates were tested for each concentration combination.
Testing results indicated that when one viral target was present at high concentrations tested, no interference was observed for the other three viral targets that were present at low concentrations (~3x LoD).
Table 8: Competitive inhibition strains and concentrations tested with the cobas® liat SARS-CoV-2, Influenza A/B & RSV nucleic acid test
| Assay Target | Strain | 3x LoD Concentration (TCID50/mL) | High Concentration Used in Combination with other Low Concentration Targets (TCID50/mL) |
|---|---|---|---|
| SARS-CoV-2* | SARS WA 1/2020 | 0.105 | 1.14E+05 |
| Influenza A | A/Darwin/6/2021 | 0.885 | 1.48E+06 |
| Influenza B | B/Austria/1359417/2021 | 2.937 | 9.79E+06 |
| RSV | RSV 9320 | 0.807 | 1.35E+06 |
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- Inactivated virus
5.5. 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, influenza A, influenza B, and RSV targets. The substances listed in Table 9 at the concentrations tested did not interfere in the detection of SARS-CoV-2, influenza A, influenza B or RSV nor did they produce invalid results in negative samples.
Table 9: Endogenous and Exogenous Interference
| Potential Interferent | Concentration Tested |
|---|---|
| Peripheral blood mononuclear cell (PBMC) | 1.00E+06 cell/mL |
| Mucin: bovine submaxillary gland, type I-S | 5 mg/mL |
| Human Whole Blood | 5% v/v |
| Nasal spray - Afrin / Anefrin | 15% v/v |
| Nasal corticosteroids - Flonase | 5% (v/v) |
| Nasal gel - Zicam | 5% (v/v) |
| Throat lozenges, oral anesthetic and analgesic – Cepacol** | 5 mg/mL |
| Antibiotic, nasal ointment - Bactroban mupirocin ointment | 5 mg/mL |
| Antiviral drug – Relenza | 5 mg/mL |
| Antiviral drug - Tamiflu | 7.5 mg/mL |
| Antimicrobial, systemic- Tobramycin | 4 µg/mL |
| Intranasal Vaccine – FluMist* | 6.25% (v/v) |
*FluMist® contains influenza A and B virus and will test positive if present in the sample.
** One invalid result was obtained in the presence of target analytes. Repeat testing was performed and all targets were 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.
5.6. Reproducibility study
A reproducibility study assessed the total variability of the assay in detecting SARS-CoV-2, influenza A, influenza B, and RSV 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 (3) sites tested a 3-member reproducibility panel in triplicate on five (5) different days for three (3) assay tube lots. The reproducibility panel comprises a low positive (1-2x LoD) and a moderate positive (3-5x LoD) co-formulated for SARS-CoV-2, influenza A, influenza B, and RSV, 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
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agreement with expected result is shown in Table 10.
Table 10: Reproducibility Results for the cobas® liat SARS-CoV-2, Influenza A/B & RSV nucleic acid test
| Target Analyte | Expected Panel Member Concentration | Valid Tests (N) | Results in Agreement with Target Analyte (n) | Percent Agreement n/N x 100 | 95% Score CI |
|---|---|---|---|---|---|
| Negative | 0 | 265 | 265 | 100.0 | (98.6, 100.0) |
| SARS-CoV-2 | 1x-2x LoD | 270 | 270 | 100.0 | (98.6, 100.0) |
| SARS-CoV-2 | 3x-5x LoD | 267 | 267 | 100.0 | (98.6, 100.0) |
| Influenza A | 1x-2x LoD | 269 | 268 | 99.6 | (97.9, 99.9) |
| Influenza A | 3x-5x LoD | 267 | 267 | 100.0 | (98.6, 100.0) |
| Influenza B | 1x-2x LoD | 269 | 268 | 99.6 | (97.9, 99.9) |
| Influenza B | 3x-5x LoD | 267 | 267 | 100.0 | (98.6, 100.0) |
| RSV | 1x-2x LoD | 270 | 270 | 100.0 | (98.6, 100.0) |
| RSV | 3x-5x LoD | 267 | 267 | 100.0 | (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 11.
Table 11: 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, Influenza A/B & RSV nucleic acid test
| Target Analyte | Expected Concentration | n/Na | Mean Ct | Site SD | Site CV% | Lot SD | Lot CV% | Day SD | Day CV% | Run SDb | Run CV% | Within-Run (Residual) SD | Within-Run (Residual) CV% | Total SD | Total CV% |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SARS-CoV-2 | 1x-2x LoD | 270/270 | 33.8 | 0.00 | 0.0 | 0.38 | 1.1 | 0.17 | 0.5 | 0.36 | 1.1 | 1.03 | 3.0 | 1.16 | 3.4 |
| SARS-CoV-2 | 3x-5x LoD | 267/267 | 32.4 | 0.13 | 0.4 | 0.54 | 1.7 | 0.27 | 0.8 | 0.00 | 0.0 | 1.00 | 3.1 | 1.18 | 3.6 |
| Influenza A | 1x-2x LoD | 268/269 | 34.8 | 0.11 | 0.3 | 0.08 | 0.2 | 0.13 | 0.4 | 0.00 | 0.0 | 0.62 | 1.8 | 0.65 | 1.9 |
| Influenza A | 3x-5x LoD | 267/267 | 33.8 | 0.00 | 0.0 | 0.05 | 0.2 | 0.00 | 0.0 | 0.11 | 0.3 | 0.39 | 1.2 | 0.41 | 1.2 |
| Influenza B | 1x-2x LoD | 268/269 | 33.8 | 0.04 | 0.1 | 0.29 | 0.9 | 0.00 | 0.0 | 0.13 | 0.4 | 0.66 | 2.0 | 0.73 | 2.2 |
| Influenza B | 3x-5x LoD | 267/267 | 32.8 | 0.05 | 0.2 | 0.47 | 1.4 | 0.12 | 0.4 | 0.00 | 0.0 | 0.52 | 1.6 | 0.71 | 2.2 |
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| RSV | 1x-2x LoD | 270/270 | 34.3 | 0.00 | 0.0 | 0.19 | 0.5 | 0.07 | 0.2 | 0.00 | 0.0 | 0.82 | 2.4 | 0.84 | 2.5 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| RSV | 3x-5x LoD | 267/267 | 33.0 | 0.06 | 0.2 | 0.17 | 0.5 | 0.00 | 0.0 | 0.14 | 0.4 | 0.69 | 2.1 | 0.73 | 2.2 |
Note: Ct = cycle threshold; LoD = Limit of Detection; SARS-CoV-2 = Severe acute respiratory syndrome coronavirus-2; RSV = Respiratory syncytial virus; 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 by target analyte.
b In the reproducibility study, each panel member was tested in triplicate, defining one run.
6. CLINICAL PERFORMANCE EVALUATION
6.1. Prospective Study
The clinical performance of cobas® liat SARS-CoV-2, Influenza A/B & RSV for the detection of SARS-CoV-2, influenza A, influenza B, and RSV 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 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, Influenza A/B & RSV 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, 1704 NPS specimens were evaluable in the SARS-CoV-2, influenza A, and influenza B analyses, 20 were non-evaluable due to missing or invalid cobas® liat test results, and 5 were non-evaluable due to specimen handling issues. 1705 NPS specimens were evaluable in the RSV 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, 1705 ANS specimens were evaluable in the SARS-CoV-2 and influenza B analyses, 23 were non-evaluable due to missing or invalid cobas® liat test results, and 1 was non-evaluable due to specimen handling issues. Two (2) additional ANS specimens obtained inconclusive comparator results for influenza A, leaving 1703 ANS specimens in the influenza A analysis. 1706 ANS specimens were evaluable in the RSV analyses, 22 were non-evaluable due to missing or invalid cobas® liat
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test results, and 1 was non-evaluable due to specimen handling issues. Available demographic data regarding the individuals from whom specimens were obtained are presented in Table 12.
Table 12: Demographics of Prospectively Enrolled Individuals
| Characteristics | Overall N(%) (N=1729) |
|---|---|
| Sex at Birth | - |
| Male | 681 ( 39.4%) |
| Female | 1048 ( 60.6%) |
| Age Group (Years) | - |
| =60 | 254 ( 14.7%) |
| Ethnicity | - |
| Hispanic / Latino | 244 ( 14.1%) |
| Not Hispanic / Latino | 1478 ( 85.5%) |
| Not Reported | 4 ( 0.2%) |
| Unknown | 3 ( 0.2%) |
| Race | - |
| American Indian / Alaska Native | 8 ( 0.5%) |
| Asian | 24 ( 1.4%) |
| Black / African American | 212 (12.3%) |
| Native Hawaiian / Other Pacific Islander | 3 ( 0.2%) |
| White | 1413 ( 81.7%) |
| Other Race | 52 ( 3.0%) |
| Not Reported | 17 ( 1.0%) |
For the NPS specimens, cobas® liat SARS-CoV-2, Influenza A/B & RSV demonstrated a PPA and NPA of 94.5% and 97.6% for SARS-CoV-2, respectively; 100.0% and 99.3% for influenza A, respectively; 100.0% and 99.3% for influenza B, respectively; and 100.0% and 99.0% for RSV, respectively (Table 13). For the ANS specimens, cobas® liat SARS-CoV-2, Influenza A/B & RSV demonstrated a PPA and NPA of 96.7% and 97.2% for SARS-CoV-2, respectively; 100.0% and 99.3% for influenza A, respectively; 100.0% and 99.5% for influenza B, respectively; and 97.5% and 98.8% for RSV, respectively (Table 13). The initial invalid rate of cobas® liat SARS-CoV-2, Influenza A/B & RSV on NPS and ANS specimens was 0.5% and 0.7% respectively. Upon repeat testing, the final assay invalid rate on NPS and ANS was 0% and 0.1% respectively.
Page 18
Table 13: Clinical Performance of cobas® liat SARS-CoV-2, Influenza A/B & RSV Relative to the Comparator by Specimen Type and Target
| Target | Specimen Type | a/(a+c) | PPA (%) | PPA 95% CI | d/(b+d) | NPA (%) | NPA 95% CI |
|---|---|---|---|---|---|---|---|
| SARS-CoV-2* | NPS | 207/219 | 94.5 | 90.7-96.8 | 1450/1485 | 97.6 | 96.7-98.3 |
| SARS-CoV-2** | ANS | 208/215 | 96.7 | 93.4-98.4 | 1448/1490 | 97.2 | 96.2-97.9 |
| Influenza A# | NPS | 54/54 | 100.0 | 93.4-100.0 | 1639/1650 | 99.3 | 98.8-99.6 |
| Influenza A## | ANS | 53/53 | 100.0 | 93.2-100.0 | 1639/1650 | 99.3 | 98.8-99.6 |
| Influenza B& | NPS | 22/22 | 100.0 | 85.1-100.0 | 1670/1682 | 99.3 | 98.8-99.6 |
| Influenza B&& | ANS | 24/24 | 100.0 | 86.2-100.0 | 1672/1681 | 99.5 | 99.0-99.7 |
| RSV$ | NPS | 70/70 | 100.0 | 94.8-100.0 | 1618/1635 | 99.0 | 98.3-99.3 |
| RSV$$ | ANS | 79/81 | 97.5 | 91.4-99.3 | 1606/1625 | 98.8 | 98.2-99.3 |
Abbreviations: PPA = Positive Percent Agreement; CI = Score Confidence Interval; NPA = Negative Percent Agreement; NPS = Nasopharyngeal swab; ANS = Anterior Nasal Swab; RSV=Respiratory syncytial virus; SARS-CoV-2 = Severe acute respiratory syndrome coronavirus 2.
Note: N = Total number of specimens; a = number of specimens where both cobas® liat and the comparator are positive; b = number of specimens where cobas® liat is positive and the comparator is negative; c = number of specimens where cobas® liat is negative and the comparator is positive; d = number of specimens where both cobas® liat and the comparator are negative.
- SARS-CoV-2 NPS discrepant NAAT results: Of 12 specimens negative on cobas® liat and positive on the comparator, 8 were positive and 4 were negative. Of 35 specimens positive on cobas® liat and negative on the comparator, 12 were positive and 23 were negative.
Influenza A NPS discrepant NAAT results: Of 11 specimens positive on cobas® liat and negative on the comparator, 2 were positive and 9 were negative.
& Influenza B NPS discrepant NAAT results: Of 12 specimens positive on cobas® liat and negative on the comparator, all 12 were negative.
$ RSV NPS discrepant NAAT results: Of 17 specimens positive on cobas® liat and negative on the comparator, 2 were positive and15 were negative.
** SARS-CoV-2 ANS discrepant NAAT results: Of 7 specimens negative on cobas® liat and positive on the comparator, 6 were positive and 1 was negative. Of 42 specimens positive on cobas® liat and negative on the comparator, 8 were positive and 34 were negative.
Influenza A ANS discrepant NAAT results: Of 11 specimens positive on cobas® liat and negative on the comparator, 1 was positive and 10 were negative.
&& Influenza B ANS discrepant NAAT results: Of 9 specimens positive on cobas® liat and negative on the comparator, all 9 were negative.
$$ RSV ANS discrepant NAAT results: Of 2 specimens negative on cobas® liat and positive on the comparator, 1 was positive and 1 was negative. Of 19 specimens positive on cobas® liat and negative on the comparator, all 19 specimens were negative.
6.2. Retrospective Study
Influenza B was of lower prevalence and was not encountered in sufficiently large numbers during the prospective clinical study to adequately demonstrate assay performance. To supplement the results of the prospective clinical study, retrospective frozen clinical NPS and ANS specimens collected in Universal Viral Transport medium (UVT) or Universal Transport Medium (UTM) from individuals with signs and symptoms of respiratory viral infection were tested. Frozen archived (Category III) influenza B positive and negative NPS (n=223) and ANS (n=206) specimens obtained between 2019 and 2023 were distributed to 6 sites and tested in the course of the daily workflow. One NPS sample pre-characterized as positive for influenza B was non-evaluable due to missing/invalid results on the
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comparator method. The comparator method was an acceptable FDA-cleared molecular assay. Available demographic data regarding the individuals from the retrospective study are shown in Table 14.
Table 14: Demographics of Subjects from Retrospective Population
| Characteristics | Overall N(%) (N=429) |
|---|---|
| Sex at Birth | - |
| Male | 151 ( 35.20%) |
| Female | 226 ( 52.68%) |
| Not Reported | 52 ( 12.12%) |
| Age Group (Years) | - |
| =60 | 23 ( 5.36%) |
| Not Reported | 79 ( 18.41%) |
| Ethnicity | - |
| Hispanic / Latino | 98 ( 22.84%) |
| Not Hispanic / Latino | 112 ( 26.11%) |
| Not Reported | 213 ( 49.65%) |
| Other | 5 ( 1.17%) |
| Unknown | 1 ( 0.23%) |
| Race | - |
| American Indian / Alaska Native | 2 ( 0.47%) |
| Asian | 3 ( 0.70%) |
| Black / African American | 12 ( 2.80%) |
| White | 196 ( 45.69%) |
| Other Race | 3 ( 0.70%) |
| Unknown | 5 ( 1.17%) |
| Not Reported | 208 ( 48.48%) |
For the retrospective NPS specimens, cobas® liat SARS-CoV-2, Influenza A/B & RSV demonstrated a PPA and NPA of 100.0% and 97.9% for influenza B, respectively (Table 15). For the retrospective ANS specimens, cobas® liat SARS-CoV-2, Influenza A/B & RSV demonstrated a PPA and NPA of 100.0% and 98.3% for influenza B, respectively (Table 15). No invalid results were observed for the cobas® liat SARS-CoV-2, Influenza A/B & RSV with retrospective NPS or ANS specimens for an invalid rate of 0.0%.
Table 15: Agreement of cobas® liat SARS-CoV-2, Influenza A/B & RSV nucleic acid test and Comparator Test for influenza B in Retrospective Samples
| Target | Specimen Type | a/(a+c) | PPA (%) | PPA 95% CI | d/(b+d) | NPA (%) | NPA 95% CI |
|---|---|---|---|---|---|---|---|
| Influenza B* | NPS | 34/34 | 100.0 | 89.8-100.0 | 184/188 | 97.9 | 94.7-99.2 |
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| Influenza B* | ANS | 34/34 | 100.0 | 89.8-100.0 | 169/172 | 98.3 | 95.0-99.4 |
|---|
Abbreviations: PPA = Positive Percent Agreement; CI = Confidence Interval; NPA = Negative Percent Agreement; NPS = Nasopharyngeal swab; ANS = Anterior Nasal Swab; RSV=Respiratory syncytial virus; 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.
- Influenza B NPS discrepant NAAT results: Of 4 specimens positive on cobas® liat and negative on the comparator, all 4 were negative.
** Influenza B ANS discrepant NAAT results: Of 3 specimens positive on cobas® liat and negative on the comparator, 1 was positive and 2 were negative.
7. CONCLUSIONS
A comparison of the intended use, technological characteristics, and the results of analytical (non-clinical) and clinical performance studies demonstrates that cobas® liat SARS-CoV-2, Influenza A/B & RSV nucleic acid test is substantially equivalent to the predicate device.