cobas Influenza A/B & RSV Nucleic acid test for use on the cobas Liat System

K210234 · Roche Molecular Systems, Inc. · OCC · Feb 16, 2021 · Microbiology

Device Facts

• Record ID: K210234
• Device Name: cobas Influenza A/B & RSV Nucleic acid test for use on the cobas Liat System
• Applicant: Roche Molecular Systems, Inc.
• Product Code: OCC · Microbiology
• Decision Date: Feb 16, 2021
• Decision: SESE
• Submission Type: Special
• Regulation: 21 CFR 866.3980
• Device Class: Class 2

Intended Use

The cobas® Influenza A/B & RSV Nucleic acid test for use on the cobas® Liat® System (cobas® Influenza A/B & RSV) is an automated multiplex real-time RT-PCR assay for the rapid in vitro qualitative detection and discrimination of Influenza A virus, Influenza B virus and respiratory syncytial virus (RSV) RNA in nasopharyngeal swab specimens from patients with signs and symptoms of respiratory infection in conjunction with clinical and epidemiological risk factors. The test is intended for use as an aid in the differential diagnosis of Influenza A, Influenza B, and RSV in humans and is not intended to detect Influenza C. Negative results do not preclude Influenza virus or RSV infection and should not be used as the sole basis for treatment or other patient management decisions. Conversely, positive results do not rule out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease. Performance characteristics for Influenza A were established during the 2013-2014 and the 2014-2015 influenza seasons when Influenza A/H3 and A/H1N1 pandemic were the predominant Influenza A viruses in circulation. When other Influenza A viruses are emerging, performance characteristics may vary. 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 department for testing. Viral culture should not be attempted in these cases unless a BSL3+ facility is available to receive and culture specimens.

Device Story

Automated multiplex real-time RT-PCR assay for qualitative detection of Influenza A, Influenza B, and RSV RNA in nasopharyngeal swab specimens. System comprises cobas Liat Analyzer and single-use disposable assay tubes containing reagents for nucleic acid purification and RT-PCR. User inserts sample-loaded tube into analyzer; system performs automated sample prep, amplification, and detection. On-board computer analyzes real-time reaction data, interprets results, and displays them on integrated LCD touch screen. Results can be printed or exported to LIS/middleware. Used in clinical settings; operated by healthcare personnel. Provides rapid (approx. 20 min) differential diagnosis to aid clinical decision-making; negative results do not rule out infection; positive results do not rule out co-infection.

Clinical Evidence

Bench testing only. Performance of Assay Script v1.16 compared to v1.15 using negative controls, positive controls, negative specimens, and 3X LoD positive specimens across nine analyzers. Results demonstrated equivalent performance and mean Ct values between script versions.

Technological Characteristics

Automated real-time RT-PCR; silica-magnetic bead-based nucleic acid extraction. Targets: matrix gene (Inf A), non-structural protein gene (Inf B), matrix gene (RSV). Integrated system with PC, software, and touch-screen. Connectivity: USB, network, LIS. Assay Script v1.16.

Indications for Use

Indicated for patients with signs and symptoms of respiratory infection to aid in the differential diagnosis of Influenza A, Influenza B, and RSV. Not intended to detect Influenza C.

Regulatory Classification

Identification

A respiratory viral panel multiplex nucleic acid assay is a qualitative in vitro diagnostic device intended to simultaneously detect and identify multiple viral nucleic acids extracted from human respiratory specimens or viral culture. The detection and identification of a specific viral nucleic acid from individuals exhibiting signs and symptoms of respiratory infection aids in the diagnosis of respiratory viral infection when used in conjunction with other clinical and laboratory findings. The device is intended for detection and identification of a combination of the following viruses:(1) Influenza A and Influenza B; (2) Influenza A subtype H1 and Influenza A subtype H3; (3) Respiratory Syncytial Virus subtype A and Respiratory Syncytial Virus subtype B; (4) Parainfluenza 1, Parainfluenza 2, and Parainfluenza 3 virus; (5) Human Metapneumovirus; (6) Rhinovirus; and (7) Adenovirus.

Special Controls

*Classification.* Class II (special controls). The special controls are:(1) FDA's guidance document entitled “Class II Special Controls Guidance Document: Respiratory Viral Panel Multiplex Nucleic Acid Assay;” (2) For a device that detects and identifies Human Metapneumovirus, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Human Metapneumovirus (hMPV) Using Nucleic Acid Assays;” and (3) For a device that detects and differentiates Influenza A subtype H1 and subtype H3, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Detection and Differentiation of Influenza A Virus Subtypes Using Multiplex Nucleic Acid Assays.” See § 866.1(e) for the availability of these guidance documents.

Predicate Devices

• cobas® Influenza A/B & RSV Nucleic Acid Test for use on the cobas® Liat® System (K200065)

Submission Summary (Full Text)

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February 16, 2021

Roche Molecular Systems, Inc. Kaitlyn Hameister Senior Regulatory Affairs Specialist I 4300 Hacienda Drive Pleasanton, California 94588-2722

# Re: K210234

Trade/Device Name: cobas Influenza A/B & RSV Nucleic acid test for use on the cobas Liat System Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory Viral Panel Multiplex Nucleic Acid Assay Regulatory Class: Class II Product Code: OCC, OOI, OZE Dated: January 26, 2021 Received: January 28, 2021

## Dear Kaitlyn Hameister:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. 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 located 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.

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

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801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-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 4. Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

Maria Ines Garcia, Ph.D. Branch Chief Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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# Indications for Use

510(k) Number (if known) K210234

### Device Name

cobas® Influenza A/B & RSV nucleic acid test for use on the cobas® Liat® System

## Indications for Use (Describe)

The cobas® Influenza A/B & RSV Nucleic acid test for use on the cobas® Influenza A/B & RSV) is an automated multiplex real-time RT-PCR assay for the rapid in vitro qualitative detection and discrimination of Influenza A virus, Influenza B virus and respiratory syncytial virus (RSV) RNA in nasopharyngeal swab specimens from patients with signs and symptoms of respiratory infection with clinical and epidemiological risk factors. The test is intended for use as an aid in the differential diagnosis of Influenza B, and RSV in humans and is not intended to detect Influenza C.

Negative results do not preclude Influenza virus or RSV infection and should not be used as the sole basis for treatment or other patient management decisions. Conversely, positive results do not rule-out bacterial infection with other viruses. The agent detected may not be the definite cause of disease.

Performance characteristics for Influenza A were established during the 2013-2014 and the 2014-2015 Influenza seasons when Influenza A/H3 and A/H/N1 pandemic were the predominant Influenza A viruses in circulation. When other Influenza A viruses are emerging, performance characteristics may vary.

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 department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.

| Type of Use (Select one or both, as applicable) | |
|-------------------------------------------------|---------------------------------------------|
| X Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) |

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# cobas® Influenza A/B & RSV Nucleic Acid Test for use on the cobas® Liat® System 510(k) Summary

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

| Submitter Name | Roche Molecular Systems, Inc. |
|----------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Address | 4300 Hacienda Drive<br>Pleasanton, CA 94588-2722 |
| Contact | Kaitlyn Hameister<br>Phone: [phone]<br>FAX: [phone]<br>Email: [e-mail] |
| Date Prepared | January 18, 2021 |
| Proprietary Name | cobas® Influenza A/B & RSV Nucleic acid test for use on the<br>cobas® Liat® System |
| Common Name | Influenza A, B, RSV Panel |
| Classification Name | Respiratory viral panel multiplex nucleic acid assay<br>Real Time Nucleic Acid Amplification System |
| Product Codes | OCC, 21 CFR 866.3980<br>OOI, 21 CFR 862.2570 |
| Predicate Devices | cobas® Influenza A/B & RSV Nucleic Acid Test for use on the<br>cobas® Liat® System (K200065) |
| Establishment Registration | Roche Molecular Systems, Inc. Branchburg, NJ<br>Establishment Number: 2243471<br>Roche Molecular Systems, Inc. Pleasanton, CA<br>Establishment Number: 3004141078 |

#### DEVICE DESCRIPTION 1.

The cobas® Influenza A/B & RSV Nucleic Acid Test for use on the cobas® Liat® System (cobas® Influenza A/B & RSV) is an automated in vitro diagnostic test for the qualitative detection of Influenza A, Influenza B, and RSV RNA in nasopharyngeal swab (NPS) specimens. The sample-to-result time is ~20 minutes.

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The assay 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 RT-PCR assays. The assay targets a well-conserved region of the matrix gene of Influenza A (Inf A target), the non-structure protein gene of Influenza B (Inf B target), and the matrix gene of RSV (RSV target). An Internal Process Control (IPC) is also included. The IPC is present 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 reactions.

The cobas® Liat® System consists of an instrument and preloaded software for running tests and viewing the results. The system requires the use of a single-use disposable cobas® Influenza A/B & RSV assay tube that holds the nucleic acid purification and RT-PCR reagents, and hosts the sample preparation and RT-PCR processes.

The detection module monitors the reaction in real-time, while an on-board computer analyzes the collected data and outputs an interpreted result. The latter is displayed in the assay report on the integrated LCD touch screen of the cobas® Liat® Analyzer and in an electronic file. The report can be printed directly through a USB or network-connected printer. The results can also be exported to an external server, middleware or data management system, or to a Laboratory Information System (LIS).

#### Test Workflow 1.1.

Nasopharyngeal swab can be collected following the user institution's standard procedures. For nasopharyngeal swab samples suspended in collection media, a user transfers the sample into cobas® Influenza A/B & RSV assay tube.

A user then scans the assay tube barcode to identify the test and scans the sample barcode to code the sample ID using the cobas® Liat® System. The assay tube is then inserted into the cobas® Liat® Analyzer (Figure 1). The analyzer performs all test steps and outputs interpreted results in approximately 20 minutes. A report of the interpreted results can be viewed in the View Results window, and printed directly through a USB connected printer.

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# Figure 1: Illustration of cobas® Liat® Analyzer Assay Testing Process

Image /page/5/Picture/1 description: The image shows three different steps of a medical test being performed. In the first image, a gloved hand is holding a blue test tube with a swab inside, next to a machine with a screen. The second image shows a gloved hand inserting the blue test tube into the machine. The third image shows a gloved hand placing a clear test tube into the machine.

#### 2. INTENDED USE

The cobas® Influenza A/B & RSV Nucleic acid test for use on the cobas® Liat® System (cobas® Influenza A/B & RSV) is an automated multiplex real-time RT-PCR assay for the rapid in vitro qualitative detection and discrimination of Influenza A virus, Influenza B virus and respiratory syncytial virus (RSV) RNA in nasopharyngeal swab specimens from patients with signs and symptoms of respiratory infection in conjunction with clinical and epidemiological risk factors. The test is intended for use as an aid in the differential diagnosis of Influenza A, Influenza B, and RSV in humans and is not intended to detect Influenza C.

Negative results do not preclude Influenza virus or RSV infection and should not be used as the sole basis for treatment or other patient management decisions. Conversely, positive results do not rule out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease.

Performance characteristics for Influenza A were established during the 2013-2014 and the 2014-2015 influenza seasons when Influenza A/H3 and A/H1N1 pandemic were the predominant Influenza A viruses in circulation. When other Influenza A viruses are emerging, performance characteristics may vary.

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 department for testing. Viral culture should not be attempted in these cases unless a BSL3+ facility is available to receive and culture specimens.

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#### TECHNOLOGICAL CHARACTERISTICS 3.

The technological characteristics and intended use of cobas® Influenza A/B & RSV for use on the cobas® Liat® System, when used with cobas® Influenza A/B & RSV Assay Script v1.16 has not changed from the predicate device. Table 1 provides a comparison of the modified device to the predicate device, as cleared through K200065.

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## Comparison of the cobas® Influenza A/B & RSV Assay with cobas® Influenza A/B & RSV Assay Script v1.16 to the Predicate Table 1: Device

| Item Name | Submitted Device:<br>cobas® Influenza A/B & RSV w/ cobas® Influenza A/B & RSV Assay Script (FRTA) v1.16 | Predicate Device: K200065<br>cobas® Influenza A/B & RSV w/ cobas® Influenza A/B & RSV Assay Script (FRTA) v1.15 |
|-----------------------------------------------------|------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | Same | The cobas® Influenza A/B & RSV Nucleic acid test for use on the<br>cobas® Liat® System (cobas® Influenza A/B & RSV) is an automated multiplex real-<br>time RT-PCR assay for the rapid in vitro qualitative detection and discrimination of<br>Influenza A virus, Influenza B virus and respiratory syncytial virus (RSV) RNA in<br>nasopharyngeal swab specimens from patients with signs and symptoms of<br>respiratory infection in conjunction with clinical and epidemiological risk factors. The<br>test is intended for use as an aid in the differential diagnosis of Influenza A, Influenza<br>B, and RSV in humans and is not intended to detect Influenza C.<br>Negative results do not preclude Influenza virus or RSV infection and should not be<br>used as the sole basis for treatment or other patient management decisions.<br>Conversely, positive results do not rule out bacterial infection or co-infection with<br>other viruses. The agent detected may not be the definite cause of disease.<br>Performance characteristics for Influenza A were established during the 2013-2014<br>and the 2014-2015 influenza seasons when Influenza A/H3 and A/H1N1 pandemic<br>were the predominant Influenza A viruses in circulation. When other Influenza A<br>viruses are emerging, performance characteristics may vary.<br>If infection with a novel Influenza A virus is suspected based on current clinical and<br>epidemiological screening criteria recommended by public health authorities,<br>specimens should be collected with appropriate infection control precautions for<br>novel virulent Influenza viruses and sent to state or local health department for<br>testing. Viral culture should not be attempted in these cases unless a BSL3+ facility is<br>available to receive and culture specimens. |
| Regulation | Same | 21 CFR 866.3980 |
| Product Code | Same | OCC, OOI |
| Assay Target | Same | Influenza A, Influenza B, RSV |
| Sample Type | Same | Nasopharyngeal Swab |
| Internal Control | Same | Yes for sample preparation and RT-PCR performance using encapsulated RNA |
| Item Name | Submitted Device:<br>cobas® Influenza A/B & RSV w/ cobas® Influenza A/B & RSV Assay<br>Script (FRTA) v1.16 | Predicate Device: K200065<br>cobas® Influenza A/B & RSV w/ cobas® Influenza A/B & RSV Assay Script<br>(FRTA) v1.15 |
| Influenza A Viral<br>Target | Same | Well conserved region of the matrix gene |
| Influenza B Viral<br>Target | Same | Well conserved region of the non-structural protein (NSP) gene |
| RSV Viral Target | Same | Well conserved region of the matrix (M) gene |
| Assay Instrument | Same | cobas® Liat® Analyzer |
| CORE Software | Same | cobas® Liat® Analyzer Core Software 3.3 (K200065) |
| Assay Script<br>(FRTA) | 1.16 | 1.15 |
| Self-contained<br>System | Same | Yes, Integrated PC, software, and touch-screen display |
| All Assay<br>Reagents<br>Contained in<br>Disposable | Same | Yes, no manual reagent addition required |
| Sample Volume<br>Detection | Same | Yes, automatically checks that input sample volume exceeds lower limit |
| Automated Assay | Same | Yes, sample preparation, amplification and result interpretation |
| Error Diagnostic<br>System | Same | Yes, monitors and records system parameters for error recover or abort if<br>unrecoverable |
| Extraction<br>Method | Same | Silica-magnetic bead-based nucleic acid extraction |
| Assay Method | Same | RT-PCR for detecting the presence/absence of viral RNA in clinical specimens |
| Detection<br>Technique | Same | Multiplex assay using different reporter dyes for each target |
| Result<br>Interpretation | Same | Automated |
| Item Name | Submitted Device:<br>cobas® Influenza A/B & RSV w/ cobas® Influenza A/B & RSV Assay<br>Script (FRTA) v1.16 | Predicate Device: K200065<br>cobas® Influenza A/B & RSV w/ cobas® Influenza A/B & RSV Assay Script<br>(FRTA) v1.15 |
| PCR Curve<br>Pattern<br>Recognition | Same | Yes, ensures abnormal PCR curves are called "Invalid" or "Indeterminate" |
| Assay Result | Same | Qualitative |
| User | CLIA Waived (CW150018) | CLIA Waived (CW150018) |
| Test Availability | Same | Random access, on-demand test |
| Time-to-result | Same | ~20 minutes |
| Limit of Detection | Same | $10^{-3} - 10^{-1}$ TCID50/mL |
| Reactivity | Same | Reactive against 28 Flu A, 15 Flu B, and 7 RSV strains tested |
| Cross Reactivity | Same | 35 microorganisms and human genomic DNA tested. No cross reactivity found.…