The Lyra Influenza A+B Assay is a multiplex Real Time RT-PCR assay for the in vitro qualitative detection and differentiation of influenza A and influenza B viral RNA in nasal and nasopharyngeal swabs from patients with signs and symptoms of respiratory infection. This test is intended for use as an aid in the differential diagnosis of influenza A and influenza B viral infections in humans in conjunction with clinical and endemiological risk factors. The assay does not detect the presence of influenza C virus.

Negative results do not preclude influenza virus infection and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.

Performance characteristics for influenza A were established during the 2013 influenza seasons when influenza A/H3 and 2009 H1N1 influenza 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.

The assay can be performed using either the Life Technologies QuantStudio Dx, the Applied Biosystems 7500 Fast Dx or the Cepheid SmartCycler II.

Device Description

The Lyra Influenza A+B Assay detects viral RNA that have been extracted from a patient sample using the NucliSENS easyMAG or EMAG automated extraction platform. A multiplex RT-PCR is carried out under optimized conditions in a single tube generating amplicons for each of the target viruses present in the sample. This reaction is performed utilizing either the Life Technologies QuantStudio™ Dx, the Applied Biosystems® 7500 Fast Dx, or the Cepheid® SmartCycler® II. Identification of influenza A occurs by the use of target specific primers and a fluorescent-labeled probe that hybridizes to a conserved influenza A sequence within the matrix protein gene. Identification of influenza B occurs by the use of target specific primers and fluorescent-labeled probes that will hybridize to a conserved influenza B sequence within the neuraminidase gene.

AI/ML Overview

The provided text describes a 510(k) premarket notification for the Lyra Influenza A+B Assay. The notification primarily focuses on a modification to the device, specifically the inclusion of a new nucleic acid extraction platform (BioMerieux NucliSENS EMAG) while maintaining the original intended use and other core functionalities.

Here's an analysis of the acceptance criteria and study information based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document explicitly states that "All verification and validation activities were performed in accordance with relevant standards, established plans, protocols, and Design Control procedures. Testing verified all acceptance criteria were met." However, the specific quantitative acceptance criteria (e.g., sensitivity, specificity thresholds) are not detailed in the provided text. Similarly, the specific quantitative reported device performance metrics (e.g., exact sensitivity and specificity values) from the studies are not presented in the provided summary.

The summary only states: "Non-clinical and clinical verification activities conducted with the Lyra Influenza A+B Assay demonstrate that the modified device met predetermined acceptance criteria, supporting equivalency of the modified device to the cleared device."

2. Sample Sizes Used for the Test Set and Data Provenance

The text mentions a "Clinical Equivalency Study" but does not provide details on the sample size used for its test set or the data provenance (e.g., country of origin, retrospective/prospective nature).

3. Number of Experts and Qualifications for Ground Truth

The document does not provide information on the number of experts used to establish ground truth for the test set or their qualifications.

4. Adjudication Method for the Test Set

The document does not provide information on the adjudication method used for the test set.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

The text does not indicate that a multi-reader multi-case (MRMC) comparative effectiveness study was done. The focus is on the performance of the assay itself, not human reader improvement with/without AI assistance.

6. Standalone Performance Study

The studies mentioned ("Limit of Detection Equivalency Study" and "Clinical Equivalency Study") describe the performance of the device (algorithm/assay only), implying a standalone performance evaluation. However, the text does not explicitly use the term "standalone" or specify that it was "algorithm only without human-in-the-loop performance." Given that it's an RT-PCR assay, its performance by definition is standalone.

7. Type of Ground Truth Used

The text does not explicitly state the type of ground truth used for the clinical equivalency study. For diagnostic assays like this, ground truth is typically established through a combination of:

Confirmatory laboratory methods (e.g., viral culture, another highly sensitive and specific PCR method, or sequencing as a gold standard).
Clinical diagnosis by a physician.

However, this information is not provided.

8. Sample Size for the Training Set

The text does not provide information on a training set sample size. This is a modification to an existing assay, and the studies mentioned are verification/validation studies for the modification, not development studies for a new algorithm that would typically involve a separate training set.

9. How Ground Truth for the Training Set was Established

Since no training set information is provided, there is no information on how its ground truth was established.

Summary of Missing Information:

A significant amount of detail regarding the studies, particularly the quantitative acceptance criteria, reported performance, sample sizes, and ground truth methodologies, is not present in the provided FDA 510(k) summary letter. The letter serves as an approval notification and summary of the device's substantial equivalence, focusing on the change (new extraction platform) rather than a comprehensive, detailed clinical study report.

Summary

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Date: March 3, 2023

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 consists of 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.

Quidel Corporation Selena Liu Senior Regulatory Specialist 10165 McKellar Court San Diego, California 92121

Re: K230236

Trade/Device Name: Lyra Influenza A+B Assay Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory Viral Panel Multiplex Nucleic Acid Assay Regulatory Class: Class II Product Code: OZE, OOI Dated: January 27, 2023 Received: January 30, 2023

Dear Selena Liu:

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 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 (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerelv.

Himani Bisht -S

Himani Bisht. Ph.D. Assistant Director Viral Respiratory and HPV Branch 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) K230236

Device Name Lyra Influenza A+B Assay

Indications for Use (Describe)

The Lyra Influenza A+B Assay is a multiplex Real Time RT-PCR assay for the in vitro qualitative detection and differentiation of influenza B viral RNA in nasal and nasopharyngeal swabs from patients with signs and symptoms of respiratory infection. This test is intended for use as an aid in the differential diagnosis of influenza A and influenza B viral infections in humans in conjunction with clinical and endemiological risk factors. The assay does not detect the presence of influenza C virus.

Negative results do not preclude influenza virus infection and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.

The assay can be performed using either the Life Technologies QuantStudio Dx, the Applied Biosystems 7500 Fast Dx or the Cepheid SmartCycler II.

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

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510(K) SUMMARY

Submitter

Quidel Corporation 10165 McKellar Court San Diego, CA 92121 Telephone: (800) 874-1517

Submission Contact

Selena Liu Senior Regulatory Specialist (619) 818-6642 Selena.liu@quidel.com

Date Prepared

Jan 27, 2023

Proprietary and Established Names

Lyra Influenza A+B Assay

Common Name

Lyra Influenza A+B Assay

Classification

Product Code	Classification	Panel	RegulatorySection	Description
OZE	II	Microbiology	21 CFR 866.3980	Influenza A AndInfluenza BMultiplex NucleicAcid Assay
OOI	II	ClinicalChemistry	21 CFR 862.2570	Real Time NucleicAcid AmplificationSystem

Predicate Device

K131728

Device Description

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Intended Use

The Lyra Influenza A+B Assay is a multiplex Real Time RT-PCR assay for the in vitro qualitative detection and differentiation of influenza A and influenza B viral RNA in nasal and nasopharyngeal swabs from patients with signs and symptoms of respiratory infection. This test is intended for use as an aid in the differential diagnosis of influenza A and influenza B viral infections in conjunction with clinical and epidemiological risk factors. The assay does not detect the presence of influenza C virus.

Negative results do not preclude influenza virus infection and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.

Performance characteristics for influenza A were established during the 2011 and 2013 influenza seasons when influenza A/H3 and 2009 H1N1 influenza were the predominant influenza A viruses in circulation. When other influenza A viruses are emerging, performance characteristics may vary.

The assay can be performed using either the Life Technologies QuantStudio™ Dx, the Applied Biosystems® 7500 Fast Dx, or the Cepheid® SmartCycler® II.

Comparison with Predicate

The Lyra Influenza A+B Assay was modified to include a validated nucleic acid extraction platform, BioMerieux NucliSENS EMAG. The predicate device was cleared under K131728 for use with the BioMerieux NucliSENS easyMAG extraction platform. The purpose of the change is to allow customers to continue to use Lyra Influenza A+B Assay after easyMAG is discontinued.

A comparison of the similarities and differences between the devices is provided in the following table.

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Features	Predicate Device / Unmodified DeviceLyra Influenza A+B Assay (K131728)	Modified DeviceLyra InfluenzaA+B Assay
Intended Use	The Lyra Influenza A+B Assay is a multiplex RealTime RT-PCR assay for the in vitro qualitativedetection and differentiation of influenza A andinfluenza B viral RNA in nasal and nasopharyngealswabs from patients with signs and symptoms ofrespiratory infection. This test is intended for use asan aid in the differential diagnosis of influenza Aand influenza B viral infections in humans inconjunction with clinical and epidemiological riskfactors. The assay does not detect the presence ofinfluenza C virus.Negative results do not preclude influenza virusinfection and should not be used as the sole basis fordiagnosis, treatment or other patient managementdecisions.Performance characteristics for influenza A wereestablished during the 2011 and 2013 influenzaseasons when influenza A/H3 and 2009 H1N1influenza were the predominant influenza A virusesin circulation. When other influenza A viruses areemerging, performance characteristics may vary.If infection with a novel influenza A virus issuspected based on current clinical andepidemiological screening criteria recommended bypublic health authorities, specimens should becollected with appropriate infection controlprecautions for novel virulent Influenza viruses andsent to state or local health department for testing.Viral culture should not be attempted in these casesunless a BSL 3+ facility is available to receive andculture specimens.The assay can be performed using either the LifeTechnologies QuantStudio™ Dx, the AppliedBiosystems® 7500 Fast Dx, or the Cepheid®SmartCycler® II.	Same
Test Principle	Multiplex RT-PCR	Same
Detection Method	Multiplex assay using different reporter dyes foreach target	Same
Assay Result	Qualitative	Same
Analyte	Influenza A virus, influenza B virus	Same
Specimen Type	Nasal swab and nasopharyngeal swab	Same
Extraction Method	BioMerieux NucliSENS easyMAG	BioMerieux NucliSENSeasyMAG and EMAG
Quality Control	Process Control (PRC)	Same

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Summary of Performance Data

Non-clinical and clinical verification activities conducted with the Lyra Influenza A+B Assay demonstrate that the modified device met predetermined acceptance criteria, supporting equivalency of the modified device to the cleared device. All verification and validation activities were performed in accordance with relevant standards, established plans, protocols, and Design Control procedures. Testing verified all acceptance criteria were met. Verification of the changes did not raise any new items of safety and effectiveness. Evidence is demonstrated through the following studies:

Limit of Detection Equivalency Study ●
Clinical Equivalency Study ●

Conclusion

These studies demonstrated equivalent performance of the Lyra Influenza A+B Assay to the predicate product K131728.

Regulation Number and Section

§ 866.3980 Respiratory viral panel multiplex nucleic acid assay.

(a)
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.
(b)
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.