Cobas Influenza A/B Nucleic Acid Test for Use on the Cobas Liat System

K191729 · Roche Molecular Systems, Inc. · OCC · Jul 24, 2019 · Microbiology

Device Facts

• Record ID: K191729
• Device Name: Cobas Influenza A/B Nucleic Acid Test for Use on the Cobas Liat System
• Applicant: Roche Molecular Systems, Inc.
• Product Code: OCC · Microbiology
• Decision Date: Jul 24, 2019
• Decision: SESE
• Submission Type: Special
• Regulation: 21 CFR 866.3980
• Device Class: Class 2

Intended Use

The cobas® Influenza A/B Nucleic acid test for use on the cobas® Liat® System (cobas® Influenza A/B) is an automated multiplex real-time RT-PCR assay for the rapid in vitro qualitative detection and discrimination of Influenza A virus and Influenza B virus 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 and Influenza B in humans and is not intended to detect Influenza C. Negative results do not preclude Influenza virus 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 when Influenza A/H1 and A/H3 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

The cobas® Influenza A/B assay is a rapid, automated in vitro diagnostic test for qualitative detection and differentiation of Influenza A and B viral RNA. The system uses a single-use disposable assay tube containing pre-packed reagents. The user adds a nasopharyngeal swab sample to the tube and inserts it into the cobas® Liat® Analyzer. The analyzer uses multiple actuators to compress the tube, moving the sample through segments to perform automated sample preparation, nucleic acid extraction (silica-magnetic bead-based), target enrichment, inhibitor removal, and real-time RT-PCR. An embedded microprocessor controls these processes. The detection module monitors the reaction in real-time; an on-board computer analyzes data and outputs interpreted results on an integrated LCD touch screen. Results can be printed or exported to LIS/middleware. The device is used in clinical settings to provide rapid (20-minute) diagnostic results, aiding healthcare providers in patient management and treatment decisions.

Clinical Evidence

No new clinical data was required. Performance was evaluated using data from previous submissions (K111386, CW150003), internal studies, release testing, and field data. Evaluation demonstrated that the modified FABA v1.35 script maintains equivalent performance to the predicate, with no changes to analytical or clinical performance characteristics.

Technological Characteristics

Multiplex real-time RT-PCR assay; utilizes cobas Liat System platform; software-based analysis; fundamental scientific technology unchanged from predicate.

Indications for Use

Indicated for qualitative detection and differentiation of influenza A and B viral RNA in nasopharyngeal swab specimens from symptomatic individuals. Intended for use by healthcare professionals in point-of-care settings to aid in diagnosis.

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

• Liat™ Influenza A/B Assay (K111387)

Submission Summary (Full Text)

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

Roche Molecular Systems, Inc. Kaitlyn Hameister Regulatory Affairs Specialist II 4300 Hacienda Drive Pleasanton, CA 94588-2722

July 24, 2019

Re: K191729

Trade/Device Name: Cobas Influenza A/B 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 Dated: June 26, 2019 Received: June 27, 2019

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

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requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 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 (OS) 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 mediation-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,

Tamara Feldblyum, Ph.D. 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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# cobas® Influenza A/B 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 | May 1, 2018 | |
| Proprietary Name | cobas® Influenza A/B Nucleic acid test for use on the cobas® Liat® System | |
| Common Name | Influenza A, B, 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 | Liat™ Influenza A/B Assay (K111387 cleared 08/04/2011) | |
| 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 assay is a rapid, automated in vitro diagnostic test for qualitative detection and differentiation of Influenza type A and type B viral RNA. The assay is performed on the cobas® Liat® System. The system automates and integrates sample purification, nucleic acid amplification, and detection of the target sequence in biological samples using real-time RT-PCR assays. The cobas® Liat® Analyzer consists of an instrument and preloaded software for running tests and viewing the results. The cobas® Liat® System consists of the analyzer and a single-use disposable cobas® Influenza A/B assay tube that holds the sample purification and RT-PCR reagents and hosts the sample preparation and RT-PCR processes. Other than adding

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the sample to the cobas® Influenza A/B assay tube, no reagent preparation or additional steps are required. Because each cobas® Influenza A/B assay tube is self-contained, cross-contamination between samples is minimized. Turnaround time for a test is 20 minutes.

The cobas® Influenza A/B assay includes reagents for the detection and differentiation of Influenza A and B viral RNA in nasopharyngeal swab (NPS) specimens in universal transport media (UTM) from patients suspected of having Influenza. The assay targets a well-conserved region of the matrix gene of Influenza A viral RNA (Inf A target) and non-structural protein (NS) gene of Influenza B (Inf B target). An Internal Process Control (IPC) is also included. The IPC is present to control for adequate processing of the target viruses through all steps of the assay process and to monitor the presence of inhibitors in the RT-PCR reactions.

The cobas® Influenza A/B assay tube uses a flexible tube as a sample processing vessel. It contains all requisite PCR reagents pre-packed in assay tube segments separated by breakable seals. When a cobas® Influenza A/B assay tube containing a raw biological sample is inserted into the cobas Liat® Analyzer. multiple sample processing actuators in the cobas® Liat Analyzer compress the cobas® Influenza A/B assay tube to selectively release the reagents, moving the sample from one segment to the next, and controlling reaction conditions. An embedded microprocessor controls and coordinates these actions to perform all required assay processes, including sample preparation, nucleic acid extraction, target concentration enrichment, inhibitor removal, nucleic acid elution, and real-time PCR. All assay steps are performed within the closed and self-contained cobas® Influenza A/B assay tube, minimizing cross-contamination between samples.

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).

#### 1.1. Test Workflow

Nasopharyngeal swab can be collected following the user institution's standard procedures. For nasopharyngeal swab samples suspended in UTM, a user transfers 100 µL of the UTM sample into cobas® Influenza A/B assay tube.

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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 "Liate Analyzer. The analyzer performs all test steps and outputs interpreted results in 20 minutes. A report of the interpreted results can be viewed in the View Results window, and printed directly through a USB connected printer.

Image /page/4/Figure/3 description: The image is a title for a figure. The title reads "Figure 1: Illustration of cobas® Liat® Analyzer Assay Testing Process". The title is written in a bold, sans-serif font. The figure is likely an illustration of the testing process for the cobas® Liat® Analyzer Assay.

Image /page/4/Picture/4 description: The image shows three different views of a medical device being used. The device is a small, white machine with a screen and buttons. In the first view, a gloved hand is holding a blue tube with a barcode and inserting it into the machine. In the second view, a gloved hand is inserting a blue tube into the machine. In the third view, a gloved hand is placing a clear tube into the machine.

## INTENDED USE 2.

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

Negative results do not preclude Influenza virus 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 when Influenza A/H1 and A/H3 were the predominant Influenza A viruses in circulation. When other Influenza A viruses are emerging, performance characteristics may vary.

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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 intenza AB for use on the cobas® Liate System, when used with cobas Influenza A/B assay script (FABA) v1.35, are substantially equivalent to the legally marketed device, which was originally cleared for use with FABA script v1.31. Table 1 provides a comparison of the modified device to the predicate device, as originally cleared through K111387.

| Item Name | Submitted Device:<br>cobas® Influenza A/B assay w/ FABA v1.35 | Predicate Device:<br>cobas® Influenza A/B assay w/ FABA v1.31 |
|--------------|---------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | Same | The cobas® Influenza A/B Nucleic acid test for use on the cobas® Liat® System<br>(cobas® Influenza A/B) is an automated multiplex real-time RT-PCR assay for the<br>rapid in vitro qualitative detection and discrimination of Influenza A virus and<br>Influenza B virus RNA in nasopharyngeal swab specimens from patients with signs<br>and symptoms of respiratory infection in conjunction with clinical and epidemiological<br>risk factors. The test is intended for use as an aid in the differential diagnosis of<br>Influenza A and Influenza B in humans and is not intended to detect Influenza C.<br>Negative results do not preclude Influenza virus infection and should not be used as<br>the sole basis for treatment or other patient management decisions. Conversely,<br>positive results do not rule out bacterial infection or co-infection with other viruses.<br>The agent detected may not be the definite cause of disease.<br>Performance characteristics for Influenza A were established when Influenza A/H1<br>and A/H3 were the predominant Influenza A viruses in circulation. When other<br>Influenza A 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 |
| Regulation | Same | 21 CFR 866.3980 |

| Table 1: Comparison of the cobas® Influenza A/B Assay Script (FABA) v1.35 with the Predicate Device | |
|-----------------------------------------------------------------------------------------------------|--|
|-----------------------------------------------------------------------------------------------------|--|

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| Item Name | Submitted Device:<br>cobas® Influenza A/B assay w/ FABA v1.35 | Predicate Device:<br>cobas® Influenza A/B assay w/ FABA v1.31 |
|-----------------------------------------------------|---------------------------------------------------------------|--------------------------------------------------------------------------------------------|
| Product Code | Same | OCC, OOI |
| Assay Target | Same | Influenza A, Influenza B |
| Sample Type | Same | Nasopharyngeal Swab |
| 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 |
| Assay Instrument | Same | cobas® Liat® Analyzer (Rebranded from Liat™ Analyzer) |
| Software | cobas® Liat® Analyzer Core Software v3.2<br>FABA v1.35 | cobas® Liat® Analyzer Core Software v1.5.4<br>FABA v1.31 |
| 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 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 |
| Item Name | Submitted Device:<br>cobas® Influenza A/B assay w/ FABA v1.35 | Predicate Device:<br>cobas® Influenza A/B assay w/ FABA v1.31 |
| Result<br>Interpretation | Same | Automated |
| PCR Curve<br>Pattern<br>Recognition | Same | Yes, ensures abnormal PCR curves are called "Invalid" or "Indeterminate" |
| Assay Result | Same | Qualitative |
| User | CLIA Waived (CW150003) | Hospital nurse and CLIA moderate complexity laboratory technologist |
| Test Availability | Same | Random access, on-demand test |
| Time-to-result | Same | ~20 minutes |

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# DESCRIPTION OF CHANGE: FABA SOFTWARE 4.

cobas® Influenza A/B assay script (FABA) v1.35 incorporates the following changes:

- Updates to the Result Interpretation Concept logic and new checks and cut-offs implemented to address results erroneously reported as Invalid and prevent False Positives
- Bug fixes .

## DESIGN AND DEVELOPMENT ACTIVITY SUMMARY 5.

Roche Molecular Diagnostics (RMD), Pleasanton, CA created and formally released the assay script component of the cobas® Liat® System software. The cobas® Liat® Analyzer core software was created and released by Roche Molecular Diagnostics in Rotkreuz, Switzerland. For information on the development of the cobas® Liat® Analyzer, details of development activities associated with FABA v1.35 have been included in this submission.

RMD in Pleasanton coordinated the development and verification of cobas® Influenza A/B assay script v1.35 at the Product Requirements, Technical Requirements and Technical Requirement Specifications (Unit Specifications) level. These activities included risk management, requirements management, configuration management, verification testing, and regression analysis.

# ASSAY PERFORMANCE 6.

Performance of the cobas® Influenza A/B assay with FABA v1.35 was evaluated using data from submissions (K111386, CW150003), internal studies, release testing, and the field. The result of this evaluation determined that the overall cobas® Influenza A/B assay performance and claims were not impacted by changes implemented in FABA v1.35, when compared to the current commercially available FABA script version.

#### 7. CONCLUSION

Equivalent performance of the modified device and the current commercial device has been demonstrated, and analytical or clinical performance has not changed. The modified device is substantially equivalent to the predicate device, as originally cleared through K111386 and CLIA waived through CW150003.