LIAISON PLEX Respiratory Flex Assay

K233410 · Luminex Corporation · QOF · Mar 1, 2024 · Microbiology

Device Facts

• Record ID: K233410
• Device Name: LIAISON PLEX Respiratory Flex Assay
• Applicant: Luminex Corporation
• Product Code: QOF · Microbiology
• Decision Date: Mar 1, 2024
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3981
• Device Class: Class 2

Intended Use

The LIAISON PLEX Respiratory Flex (RSP Flex) Assay is a multiplexed qualitative test for the simultaneous in vitro detection and identification of multiple bacterial and viral nucleic acids in nasopharyngeal swabs (NPS) obtained from individuals with clinical signs and symptoms of respiratory tract infection, including SARS-CoV-2. The test is performed on the automated LIAISON PLEX System utilizing reverse transcription (RT), polymerase chain reaction (PCR), and array hybridization to detect specific nucleic acid gene sequences of the following organism types and subtypes: Viruses: Adenovirus Human Coronavirus (HKU1, NL63, OC43, and 229E not differentiated) Human Enterovirus/Rhinovirus (not differentiated) Human Metapneumovirus, Influenza A Influenza A (subtype H1) Influenza A (subtype H3) Influenza B Parainfluenza 1 Parainfluenza 2 Parainfluenza 3 Parainfluenza 4 Respiratory Syncytial Virus Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) Bacteria: Bordetella holmesii Bordetella parapertussis Bordetella pertussis Chlamydia pneumoniae Mycoplasma pneumoniae Nucleic acids from the bacterial and viral organisms identified by this test are generally detectable in NPS specimens during the acute phase of infection. Detecting and identifying specific bacterial and viral nucleic acids from individuals exhibiting signs and symptoms of respiratory infection aids in the diagnosis of respiratory infection, if used in conjunction with other clinical, epidemiological, and laboratory findings. The results of this test should not be used as the sole basis for diagnosis, treatment, or patient management decisions. Negative results in the presence of a respiratory illness may be due to infection with pathogens that are not detected by this test or due to lower respiratory that is not detected by an NPS specimen. Conversely, positive results do not rule out infection or co-infection with organisms not detected by the LIAISON PLEX Respiratory Flex (RSP Flex) Assay. The agent(s) detected may not be the definite cause of disease. The use of additional laboratory testing (e.g., bacterial and viral culture, immunofluorescence, and radiography), may be necessary when evaluating a patient with possible respiratory tract infection.

Device Story

The LIAISON PLEX Respiratory Flex Assay is an automated, multiplexed, qualitative in vitro diagnostic test for respiratory pathogens. Input: nasopharyngeal swab (NPS) specimens in transport media. Operation: The LIAISON PLEX System performs automated sample preparation (chemical/mechanical lysis, magnetic bead isolation), multiplex RT-PCR/PCR amplification, and microarray hybridization. Gold nanoparticle probes bind to target amplicons; silver enhancement allows light scatter measurement for detection. Output: Qualitative 'Detected' or 'Not Detected' results for 19 viral/bacterial targets. Used in clinical laboratories by trained personnel. Results aid diagnosis in conjunction with other clinical/epidemiological findings; not for sole diagnostic use. Benefits: Rapid, simultaneous identification of multiple respiratory pathogens to inform patient management.

Clinical Evidence

Clinical performance evaluated via prospective multi-site study (N=1843) and archived specimens (N=256). Prospective study compared results to FDA-cleared molecular panels or PCR/BDS. PPA/NPA metrics reported for all 19 targets. Overall PPA ranged from 80.0% to 100% and NPA ranged from 95.7% to 100% across targets. Contrived specimen testing (N=300) supplemented low-prevalence targets. No carry-over or cross-contamination observed.

Technological Characteristics

Multiplexed nucleic acid test using RT-PCR and microarray hybridization. Materials: disposable cartridge with magnetic beads, gold nanoparticle probes. Energy: electrical (LIAISON PLEX System). Connectivity: standalone instrument with touchscreen UI. Software: preinstalled system software. Sterilization: N/A (disposable cartridge).

Indications for Use

Indicated for individuals with clinical signs and symptoms of respiratory tract infection, including SARS-CoV-2, to detect and identify multiple bacterial and viral nucleic acids in nasopharyngeal swabs (NPS).

Regulatory Classification

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.

Special Controls

*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.

Predicate Devices

• BioFire Respiratory Panel 2.1 (RP2.1) (DEN200031)

Submission Summary (Full Text)

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March 1, 2024

Image /page/0/Picture/1 description: The image shows 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 blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

Luminex Corporation Tara Viviani Sr. Director Molecular Regulatory Affairs 4088 Commercial Avenue Northbrook, Illinois 60062

Re: K233410

Trade/Device Name: LIAISON PLEX Respiratory Flex Assay 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, OEM, OOU, OTG, OZE, OZX, OZY, OZZ, OCC, NSU Dated: October 6, 2023 Received: October 6, 2023

Dear Tara Viviani:

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.

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"

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(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 OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (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.

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

For comprehensive regulatory information about 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.

# Joseph Briggs -S

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

### Enclosure

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# Indications for Use

510(k) Number (if known) K233410

Device Name LIAISON PLEX Respiratory Flex Assay

### Indications for Use (Describe)

The LIAISON PLEX Respiratory Flex (RSP Flex) Assay is a multiplexed qualitative test for the simultaneous in vitro detection and identification of multiple bacterial and viral nucleic acids in nasopharyngeal swabs (NPS) obtained from individuals with clinical signs and symptoms of respiratory tract infection, including SARS-CoV-2. The test is performed on the automated LIAISON PLEX System utilizing reverse transcription (RT), polymerase chain reaction (PCR), and array hybridization to detect specific nucleic acid gene sequences of the following organism types and subtypes:

Viruses: Adenovirus Human Coronavirus (HKU1, NL63, OC43, and 229E not differentiated) Human Enterovirus/Rhinovirus (not differentiated) Human Metapneumovirus, Influenza A Influenza A (subtype H1) Influenza A (subtype H3) Influenza B Parainfluenza 1 Parainfluenza 2 Parainfluenza 3 Parainfluenza 4 Respiratory Syncytial Virus Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2)

Bacteria: Bordetella holmesii Bordetella parapertussis Bordetella pertussis Chlamydia pneumoniae Mycoplasma pneumoniae

Nucleic acids from the bacterial and viral organisms identified by this test are generally detectable in NPS specimens during the acute phase of infection. Detecting and identifying specific bacterial and viral nucleic acids from individuals exhibiting signs and symptoms of respiratory infection aids in the diagnosis of respiratory infection, if used in conjunction with other clinical, epidemiological, and laboratory findings. The results of this test should not be used as the sole basis for diagnosis, treatment, or patient management decisions.

Negative results in the presence of a respiratory illness may be due to infection with pathogens that are not detected by this test or due to lower respiratory that is not detected by an NPS specimen. Conversely, positive results do not rule out infection or co-infection with organisms not detected by the LIAISON PLEX Respiratory Flex (RSP Flex) Assay. The agent(s) detected may not be the definite cause of disease.

The use of additional laboratory testing (e.g., bacterial and viral culture, immunofluorescence, and radiography), may be necessary when evaluating a patient with possible respiratory tract infection.

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### 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.

Preparation Date: 21-February-2024

### A. 510(k) Number:

K233410

### B. Purpose for Submission:

Traditional 510(k), New Device

### C. Measurand:

Adenovirus, Bordetella holmesii, Bordetella parapertussis, Bordetella pertussis, Chlamydia pneumoniae, Human Coronavirus (HKU1, NL63, OC43, and 229E not differentiated), Human Enterovirus (Rhinovirus (not differentiated), Human Metapneumovirus, Influenza A (subtype H1), Influenza A (subtype H3), Influenza B, Mycoplasma pneumoniae, Parainfluenza 1, Parainfluenza 2, Parainfluenza 3, Parainfluenza 4, Respiratory Syncytial Virus (RSV), and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) nucleic acid target sequences

### D. Type of Test:

Qualitative Multiplexed Nucleic Acid Test that Utilizes Reverse Transcription, Real Time Polymerase Chain Reaction (PCR), and Array Hybridization.

### E. Applicant:

Tara Viviani, Luminex Corporation 4088 Commercial Avenue Northbrook, IL 60062 [phone]

### F. Proprietary and Established Names:

LIAISON PLEX® Respiratory Flex Assay

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### G. Regulatory Information:

| Primary<br>Product<br>Code | Classification | Regulation Section | Panel |
|----------------------------|----------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------|
| QOF | II | 21 CFR 866.3981 - Device To Detect And<br>Identify Nucleic Acid Targets In Respiratory<br>Specimens From Microbial Agents That Cause<br>The SARS-CoV-2 Respiratory Infection And<br>Other Microbial Agents When In A Multi-<br>Target Test | MI - Microbiology |

### H. Intended Use:

### Intended use(s):

The LIAISON PLEX Respiratory Flex (RSP Flex) Assay is a multiplexed qualitative test for the simultaneous in vitro detection and identification of multiple bacterial and viral nucleic acids in nasopharyngeal swabs (NPS) obtained from individuals with clinical signs and symptoms of respiratory tract infection, including SARS-CoV-2. The test is performed on the automated LIAISON PLEX System utilizing reverse transcription (RT), polymerase chain reaction (PCR), and array hybridization to detect specific nucleic acid gene sequences of the following organism types and subtypes:

### Viruses:

Adenovirus Human Coronavirus (HKU1, NL63, OC43, and 229E not differentiated) Human Enterovirus/Rhinovirus (not differentiated) Human Metapneumovirus, Influenza A Influenza A (subtype H1) Influenza A (subtype H3) Influenza B Parainfluenza 1 Parainfluenza 2 Parainfluenza 3 Parainfluenza 4 Respiratory Syncytial Virus Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2)

### Bacteria:

- Bordetella holmesii Bordetella parapertussis Bordetella pertussis Chlamydia pneumoniae Mycoplasma pneumoniae

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Nucleic acids from the bacterial and viral organisms identified by this test are generally detectable in NPS specimens during the acute phase of infection. Detecting and identifying specific bacterial and viral nucleic acids from individuals exhibiting signs and symptoms of respiratory infection aids in the diagnosis of respiratory infection, if used in conjunction with other clinical, epidemiological, and laboratory findings. The results of this test should not be used as the sole basis for diagnosis, treatment, or patient management decisions.

Negative results in the presence of a respiratory illness may be due to infection with pathogens that are not detected by this test or due to lower respiratory tract infection that is not detected by an NPS specimen. Conversely, positive results do not rule out infection or coinfection with organisms not detected by the LIAISON PLEX Respiratory Flex (RSP Flex) Assay. The agent(s) detected may not be the definite cause of disease.

The use of additional laboratory testing (e.g., bacterial and viral culture, immunofluorescence, and radiography), may be necessary when evaluating a patient with possible respiratory tract infection.

### Indication(s) for use:

Same as intended use.

Special conditions for use statement(s):

For prescription use only.

For in vitro diagnostic use only

### Special instrument requirements:

For use with LIAISON PLEX Systems only

### l. Device Description:

The LIAISON PLEX® Respiratory Flex Assay is a multiplexed nucleic acid test system composed of the LIAISON PLEX Instrument, the LIAISON PLEX® System Software (preinstalled on the LIAISON PLEX Instrument), the LIAISON PLEX® Respiratory Flex Assay cartridge, and the LIAISON PLEX® Respiratory Flex Assay File. The LIAISON PLEX® Respiratory Flex Assay cartridge contains the reagents to perform nucleic acid extraction and purification, reverse transcription, PCR, and array hybridization. Specifically, the LIAISON PLEX® Respiratory Flex Assay detects bacteria and viruses from nasopharyngeal swab (NPS) specimens collected from individuals with signs and symptoms of respiratory infection.

The LIAISON PLEX System consists of a touchscreen user interface that includes the software for running and analyzing assay results, one to six processing/imaging LIAISON PLEX modules, and a handheld barcode reader. Each LIAISON PLEX module processes one sample at a time under the control of the LIAISON PLEX System software.

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LIAISON PLEX® automates the sample processing through analysis within a single cartridge. Processing steps include 1.) Sample Preparation: Nucleic acid extraction from organisms by chemical and mechanical means and isolation of nucleic acid on magnetic beads 2.) Target Amplification: Multiplex PCR and RT-PCR based amplification of extracted nucleic acid to generate target specific amplicons 3.) Hybridization: Amplicons hybridize with their target specific DNA probe arranged in a microarray format and that are attached to mediator and gold nanoparticles 4.) Analysis: Gold nanoparticles specifically bound to target amplicons are silver enhanced and the light scatter from microarray spot is measured and analyzed to confirm presence (Detected) or absence (not Detected) of a target.

The LIAISON PLEX Respiratory Flex Assay has the option of creating and processing results for custom panels using Flex® Software. Flex Software allows users to randomly select and group targets in tiers for result processing. Up to 7 targets may be selected for the initial test tier. After the first tier, each additional tier requires a specific number of credits. Flex™ credits allow the end-user to create custom panels and pay for a smaller subset of results tailored to the individual patient's clinical presentation. Alternatively, a laboratory may choose the fixed price option where all target results are processed at the same time.

### Substantial Equivalence Information: J.

Predicate device name(s):

BioFire Respiratory Panel 2.1 (RP2.1)

Predicate 510(k) number(s):

DEN200031

Comparison with predicate:

The following table compares Luminex's LIAISON PLEX® Respiratory Flex Assay to the BioFire Respiratory Panel 2.1 (RP2.1) (DEN200031).

| Comparison to Predicate | | | |
|-------------------------|--|--|--|
|-------------------------|--|--|--|

| Comparison to<br>Predicate Device | Predicate Device:<br>BioFire Respiratory Panel 2.1 (RP2.1)<br>(DEN200031) | Candidate Device:<br>LIAISON PLEX® Respiratory Flex<br>Assay |
|----------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Product Code | QOF | QOF |
| Regulation Number | 21 CFR 866.3981 | 21 CFR 866.3981 |
| Comparison to<br>Predicate Device | Predicate Device:<br>BioFire Respiratory Panel 2.1 (RP2.1)<br>(DEN200031) | Candidate Device:<br>LIAISON PLEX® Respiratory Flex<br>Assay |
| Organisms Detected | Adenovirus, Coronavirus 229E,<br>Coronavirus HKU1, Coronavirus NL63,<br>Coronavirus OC43, Severe Acute<br>Respiratory Syndrome Coronavirus<br>(SARS-CoV-2), Human<br>Metapneumovirus, Human<br>Rhinovirus/Enterovirus, Influenza A,<br>including subtypes H1, H1-2009, and<br>H3, Influenza B, Parainfluenza Virus 1,<br>Parainfluenza Virus 2, Parainfluenza<br>Virus 3, Parainfluenza Virus 4,<br>Respiratory Syncytial Virus, Bordetella<br>parapertussis (IS1001), Bordetella<br>pertussis (ptxP), Chlamydia<br>pneumoniae, and Mycoplasma<br>pneumoniae | Adenovirus, Bordetella holmesii,<br>Bordetella parapertussis, Bordetella<br>pertussis, Chlamydia pneumoniae,<br>Coronavirus 229E, Coronavirus<br>HKU1, Coronavirus NL63,<br>Coronavirus OC43,<br>Enterovirus/Rhinovirus, Human<br>Metapneumovirus, Influenza A,<br>Influenza A (subtype H1), Influenza A<br>(subtype H3), Influenza B,<br>Mycoplasma pneumoniae,<br>Parainfluenza 1, Parainfluenza 2,<br>Parainfluenza 3, Parainfluenza 4,<br>Respiratory Syncytial Virus, and<br>SARS-CoV-2 |
| Measurand | Nucleic acid from Organisms detected | Nucleic acid from Organisms detected |
| Intended Use | The BioFire Respiratory Panel 2.1 (RP2.1)<br>is a PCR-based multiplexed nucleic acid<br>test intended for use with the BioFire<br>FilmArray 2.0 or BioFire FilmArray Torch<br>systems for the simultaneous qualitative<br>detection and identification of multiple<br>respiratory viral and bacterial nucleic<br>acids in nasopharyngeal swabs (NPS)<br>obtained from individuals suspected of<br>respiratory tract infections, including<br>COVID-19.<br>The following organism types and<br>subtypes are identified using the BioFire<br>RP2.1: | The LIAISON PLEX Respiratory Flex<br>(RSP Flex) Assay is a multiplexed<br>qualitative test for the simultaneous in<br>vitro detection and identification of<br>multiple bacterial and viral nucleic<br>acids in nasopharyngeal swabs (NPS)<br>obtained from individuals with clinical<br>signs and symptoms of respiratory<br>tract infection, including SARS-CoV-2.<br>The test is performed on the<br>automated LIAISON PLEX System<br>utilizing reverse transcription (RT),<br>polymerase chain reaction (PCR), and<br>array hybridization to detect specific<br>nucleic acid gene sequences of the<br>following organism types and<br>subtypes: |
| | Adenovirus,<br>Coronavirus 229E,<br>Coronavirus HKU1,<br>Coronavirus NL63,<br>Coronavirus OC43,<br>Severe Acute Respiratory Syndrome<br>Coronavirus (SARS-CoV-2),<br>Human Metapneumovirus,<br>Human Rhinovirus/Enterovirus,<br>Influenza A, including subtypes H1, H1-<br>2009, and H3,<br>Influenza B,<br>Parainfluenza Virus 1,<br>Parainfluenza Virus 2,<br>Parainfluenza Virus 3,<br>Parainfluenza Virus 4,<br>Respiratory Syncytial Virus,<br>Bordetella parapertussis (IS1001), | Viruses:<br>Adenovirus<br>Human Coronavirus (HKU1, NL63,<br>OC43, and 229E not differentiated)<br>Human Enterovirus/Rhinovirus (not<br>differentiated)<br>Human Metapneumovirus,<br>Influenza A<br>Influenza A (subtype H1)<br>Influenza A (subtype H3)<br>Influenza B<br>Parainfluenza 1<br>Parainfluenza 2<br>Parainfluenza 3<br>Parainfluenza 4<br>Respiratory Syncytial Virus<br>Severe Acute Respiratory Syndrome<br>Coronavirus (SARS-CoV-2) |
| Comparison to<br>Predicate Device | Predicate Device:<br>BioFire Respiratory Panel 2.1 (RP2.1)<br>(DEN200031) | Candidate Device:<br>LIAISON PLEX® Respiratory Flex<br>Assay |
| | Bordetella pertussis (ptxP),<br>Chlamydia pneumoniae, and<br>Mycoplasma pneumoniae<br>Nucleic acids from the respiratory viral<br>and bacterial organisms identified by this<br>test are generally detectable in NPS<br>specimens during the acute phase of<br>infection. The detection and identification<br>of specific viral and bacterial nucleic acids<br>from individuals exhibiting signs and/or<br>symptoms of respiratory infection is<br>indicative of the presence of the identified<br>microorganism and aids in the diagnosis<br>of respiratory infection if used in<br>conjunction with other clinical and<br>epidemiological information. The results of<br>this test should not be used as the sole<br>basis for diagnosis, treatment, or other<br>patient management decisions.<br>Negative results in the setting of a<br>respiratory illness may be due to<br>infection with pathogens that are not<br>detected by this test, or lower respiratory<br>tract infection that may not be detected<br>by an NPS specimen. Positive results do<br>not rule out coinfection with other<br>organisms. The agent(s) detected by the<br>BioFire RP2.1 may not be the definite<br>cause of disease. Additional laboratory<br>testing (e.g. bacterial and viral culture,<br>immunofluorescence, and radiography)<br>may be necessary when evaluating a<br>patient with possible respiratory tract<br>infection. | Bacteria:<br>Bordetella holmesii<br>Bordetella parapertussis<br>Bordetella pertussis<br>Chlamydia pneumoniae<br>Mycoplasma pneumoniae<br>Nucleic acids from the bacterial and<br>viral organisms identified by this test<br>are generally detectable in NPS<br>specimens during the acute phase of<br>infection. Detecting and identifying<br>specific bacterial and viral nucleic<br>acids from individuals exhibiting signs<br>and symptoms of respiratory infection<br>aids in the diagnosis of respiratory<br>infection, if used in conjunction with<br>other clinical, epidemiological, and<br>laboratory findings. The results of this<br>test should not be used as the sole<br>basis for diagnosis, treatment, or<br>patient management decisions.<br>Negative results in the presence of a<br>respiratory illness may be due to<br>infection with pathogens that are not<br>detected by this test or due to lower<br>respiratory tract infection that is not<br>detected by an NPS specimen.<br>Conversely, positive results do not rule<br>out infection or co-infection with<br>organisms not detected by the<br>LIAISON PLEX Respiratory Flex (RSP<br>Flex) Assay. The agent(s) detected<br>may not be the definite cause of<br>disease.<br>The use of additional laboratory testing<br>(e.g., bacterial and viral culture,<br>immunofluorescence, and radiography),<br>may be necessary when evaluating a<br>patient with possible respiratory tract<br>infection. |
| Automated System<br>(Sample to Answer) | Automated | Same |
| Instrumentation | BioFire® FilmArray® 2.0 or BioFire®<br>FilmArray® Torch Systems | LIAISON PLEX® |
| Sample Types | Nasopharyngeal Swab (NPS) Specimens | Same |
| Technological Principles | Highly multiplexed nested nucleic acid<br>amplification with melt analysis. | Highly multiplexed nucleic acid PCR<br>and RT-PCR test with microarray<br>detection |
| Internal Controls | Two controls are included in each reagent<br>pouch to control for sample processing | Multiple internal controls contained in<br>the cartridge monitor sample<br>processing and RT and PCR |
| Comparison to<br>Predicate Device | Predicate Device:<br>BioFire Respiratory Panel 2.1 (RP2.1)<br>(DEN200031) | Candidate Device:<br>LIAISON PLEX® Respiratory Flex<br>Assay |
| | and both stages of PCR and melt analysis. | functions. |
| Bordetella Species<br>Detected | Bordetella parapertussis<br>Bordetella pertussis | Bordetella parapertussis Bordetella pertussis Bordetella holmesii |
| Human Coronavirus<br>Result Reporting | Each target human coronavirus species<br>(i.e., HKU1, OC43, 229E, NL63) is<br>reported independently. | The human coronavirus target species<br>(i.e., HKU1, OC43, 229E, NL63) are<br>not differentiated. |
| Influenza A Subtyping | Influenza A subtypes H1, H1-2009, and H3<br>detected/reported. | Influenza A subtypes H1 and H3<br>detected/reported. |
| Time to Result | ~45 minutes | ~2 hours |

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