The Lyra RSV + hMPV Assay is a multiplex Real-Time PCR (RT-PCR) assay for the qualitative detection and identification of respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) ribonucleic acid (RNA) extracted from nasal and nasopharyngeal swab specimens from patients with signs and symptoms of respiratory infection. This in vitro diagnostic test is intended to aid in the differential diagnosis of RSV and hMPV infections in humans in conjunction with clinical and epidemiological risk factors. This test is not intended to differentiate the two subtypes of RSV or the four genetic sub-lineages of hMPV.

Negative results do not preclude RSV infection and/or hMPV infection and should not be used as the sole basis for diagnosis, 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. The use of additional laboratory testing and clinical presentation must be considered in order to obtain the final diagnosis of respiratory viral infection.

The Lyra RSV + hMPV Assay can be performed using ether the Life Technologies QuantStudio Dx RT-PCR Instrument, the Applied Biosystems 7500 Fast Dx RT-PCR Instrument, or the Cepheid SmartCycler II System.

Device Description

The Lyra RSV + hMPV Assay detects viral nucleic acids that have been extracted from a patient sample using the NucliSENS® easyMAG® or NucliSENS® EMAG® automated extraction platform. A multiplex RT-PCR reaction is then performed in a single tube generating amplicons for each of the target viruses present in the sample. This reaction is performed utilizing either the Cepheid SmartCycler® II, the Applied Biosystems 7500 Fast DX, or the Life Technologies QuantStudio" Dx. Identification of RSV and hMPV and the PRC occurs by the use of target-specific primers and fluorescent-labeled probes that hybridize to conserved regions in the genomes of RSV and hMPV and the PRC.

AI/ML Overview

The acceptance criteria and the study proving the device meets these criteria for the Lyra RSV + hMPV Assay are detailed below. It's important to note that the provided documents primarily describe a change to an existing device (the addition of a new extraction platform, BioMerieux NucliSENS EMAG) and compare its performance to the previously cleared predicate device. Therefore, the "acceptance criteria" and "reported device performance" are framed around this equivalency.

1. Table of Acceptance Criteria and Reported Device Performance

Based on the information provided, the overall acceptance criterion is equivalent performance of the modified Lyra RSV + hMPV Assay (with the new extraction platform) to the predicate device (Quidel RSV+hMPV Assay using the original extraction platform). The performance is assessed through "non-clinical and clinical verification and validation activities."

Acceptance Criteria Category	Specific Acceptance Criteria (Inferred)	Reported Device Performance (Summary from provided text)
Overall Performance	The modified device must demonstrate equivalent performance to the predicate device for qualitative detection and identification of RSV and hMPV from specified specimen types.	"These studies demonstrated equivalent performance of the Lyra RSV+hMPV Assay to the predicate product K131813."
Limit of Detection	The limit of detection (LoD) for RSV and hMPV using the new extraction method (BioMerieux NucliSENS EMAG) should be equivalent to, or not significantly worse than, the predicate device.	"Non-clinical and clinical verification and validation activities conducted with the Lyra RSV+hMPV Assay demonstrate that the modified device met predetermined acceptance criteria, supporting equivalency of the modified device to the cleared device." (Specifically, a "Limit of Detection Equivalency Study" was performed.)
Clinical Equivalence	Clinical performance (e.g., sensitivity, specificity, positive predictive value, negative predictive value) of the modified device should be equivalent to the predicate device.	"Non-clinical and clinical verification and validation activities conducted with the Lyra RSV+hMPV Assay demonstrate that the modified device met predetermined acceptance criteria, supporting equivalency of the modified device to the cleared device." (Specifically, a "Clinical Equivalence Study" was performed.)
Verification of Changes	The changes introduced (new extraction platform) should not raise any new items of safety and effectiveness.	"Verification of the changes did not raise any new items of safety and effectiveness."

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

The exact sample sizes for the "Limit of Detection Equivalency Study" and "Clinical Equivalence Study" are not explicitly stated in the provided 510(k) summary.

Test Set Sample Size: Not specified.
Data Provenance: Not specified (e.g., country of origin, retrospective or prospective). The nature of "clinical equivalence study" typically implies prospective or retrospectively collected clinical samples, but details are lacking.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Those Experts

This information is not provided in the given text. For a PCR-based assay like this, ground truth is typically established using a highly sensitive and specific reference method (e.g., another validated PCR assay or sequencing), rather than expert clinical consensus in the traditional sense of image interpretation.

4. Adjudication Method for the Test Set

This information is not provided in the given text. Given that this is a molecular diagnostic assay, adjudication methods like N+1 for expert review (common in imaging studies) are generally not applicable. Instead, the "ground truth" would be determined by the reference method itself.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. This type of study is primarily relevant for medical imaging interpretation where different human readers interpret cases, often with and without AI assistance. This device is a molecular diagnostic assay (RT-PCR) and does not involve human interpretation of complex images in the same way.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, implicitly. The device itself is an in vitro diagnostic test, specifically a Real-Time PCR assay. Its performance (qualitative detection of RNA) is inherently "standalone" as it produces a result without direct human interpretive input during the assay itself. The studies ("Limit of Detection Equivalency Study" and "Clinical Equivalence Study") would evaluate the accuracy of the assay's output against a reference method, which is a standalone performance assessment.

7. The Type of Ground Truth Used

The type of ground truth used is not explicitly stated but can be inferred to be a highly reliable reference method, likely another validated molecular diagnostic test (e.g., gold standard PCR assay or culture/sequencing) for detecting RSV and hMPV. For Limit of Detection studies, ground truth would be established by precisely quantifying viral RNA in samples.

8. The Sample Size for the Training Set

This information is not applicable in the context of this device. The Lyra RSV + hMPV Assay is a Real-Time PCR assay, which is a biochemical reaction-based test, not an AI/Machine Learning algorithm that requires a "training set" in the traditional sense. The "training" for such an assay involves optimization of reagents, primers, probes, and reaction conditions.

9. How the Ground Truth for the Training Set Was Established

This information is not applicable as there is no "training set" in the context of an AI/ML algorithm for this device. The development of the assay involves establishing analytical ground truth through various laboratory experiments to ensure the primers and probes are specific and sensitive to the target viruses, and that the internal control functions correctly.

Summary

{0}------------------------------------------------

Date: March 10, 2023

Image /page/0/Picture/1 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo is in blue and includes the letters "FDA" in a square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION".

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

Re: K230349

Trade/Device Name: Lyra RSV + hMPV Assay Regulation Number: 21 CFR 21 CFR 866.3980 Regulation Name: Respiratory Viral Panel Multiplex Nucleic Acid Assay Regulatory Class: Class II Product Code: OEM, OCC Dated: February 8, 2023 Received: February 9, 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

{1}------------------------------------------------

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

Sincerely,

Joseph Briggs -S

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

Enclosure

{2}------------------------------------------------

Indications for Use

510(k) Number (if known) K230349

Device Name Lyra RSV + hMPV Assay

Indications for Use (Describe)

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

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

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{3}------------------------------------------------

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

Feb 08, 2023

Proprietary and Established Names Lyra RSV + hMPV Assay

Common Name Lyra RSV + hMPV Assay

Classification

Product Code	Classification	Regulatory Section	Description
OEM, OCC	II	21 CFR 866.3980	Respiratory Viral panel multiplex nucleicacid assay

Panel

Microbiology

Predicate Device K131813

Device Description

Intended Use

The Lyra RSV + hMPV Assay is a multiplex Real-Time PCR (RT-PCR) assay for the qualitative detection and identification of respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) ribonucleic acid (RNA) extracted from nasal and nasopharyngeal swab specimens from patients with signs and symptoms of respiratory infection. This in vitro diagnostic test is intended to aid in the differential diagnosis of RSV and hMPV infections in conjunction with clinical and epidemiological risk factors. This test is not intended to differentiate the two subtypes of RSV or the four

{4}------------------------------------------------

genetic sub-lineages of hMPV.

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

The Lyra RSV + hMPV Assay can be performed using either the Life Technologies QuantStudio Dx RT-PCR Instrument, the Applied Biosystems 7500 Fast Dx RT-PCR Instrument, or the Cepheid SmartCycler II System.

Comparison with Predicate

The Lyra RSV+hMPV Assay was modified to include a validated nucleic acid extraction platform, BioMerieux NucliSENS EMAG. The predicate device was cleared under K131813 for use with the BioMerieus NucliSENS easyMAG extraction platform. The purpose of the change is to allow customers to continue to use Lyra RSV+hMPV Assay after easyMAG is discontinued.

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

{5}------------------------------------------------

Image /page/5/Picture/0 description: The image shows the logo for Quidel. The logo consists of a square with a smaller square cut out of the bottom right corner. The larger square is filled with a gradient of colors, ranging from red to yellow to green to blue. Below the square is the word "QUIDEL" in a sans-serif font.

Features	Predicate Device / Unmodified DeviceQuidel RSV+hMPV Assay (K131813)	Modified DeviceLyra RSV + hMPVAssay
Intended Use	The Quidel Molecular RSV + hMPV Assay is amultiplex Real-Time PCR (RT-PCR) assay for thequalitative detection and identification of respiratorysyncytial virus (RSV) and human metapneumovirus(hMPV) ribonucleic acid (RNA) extracted from nasaland nasopharyngeal swab specimens from patients withsigns and symptoms of respiratory infection. This invitro diagnostic test is intended to aid in the differentialdiagnosis of RSV and hMPV infections in humans inconjunction with clinical and epidemiological riskfactors. This test is not intended to differentiate the twosubtypes of RSV or the four genetic sub-lineages ofhMPV.Negative results do not preclude RSV infection and/orhMPV infection and should not be used as the solebasis for diagnosis, treatment or other patientmanagement decisions.Conversely, positive results do not rule-out bacterialinfection or co-infection with other viruses. The agentdetected may not be the definite cause of disease. Theuse of additional laboratory testing and clinicalpresentation must be considered in order to obtain thefinal diagnosis of respiratory viral infection.The Quidel Molecular RSV + hMPV Assay can beperformed using either the Life TechnologiesQuantStudio Dx RT-PCR Instrument, the AppliedBiosystems 7500 Fast Dx RT-PCR Instrument, or theCepheid SmartCycler II System.	Same*
Test Principle	Multiplex RT-PCR	Same
Detection Method	Multiplex assay using different reporter dyes foreach target	Same
Assay Result	Qualitative	Same
Analyte	RSV and hMPV	Same
Specimen Type	Nasal swab and nasopharyngeal swab	Same
Extraction Method	BioMerieux NucliSENS easyMAG	BioMerieux NucliSENSeasyMAG and EMAG
Quality Control	Process Control (PRC)	Same
*The predicate device name was changed from Quidel Molecular RSV + hMPV Assay to Lyra RSV +hMPV Assay in CR210354.

{6}------------------------------------------------

Image /page/6/Picture/0 description: The image contains the logo for QuidelOrtho Corporation. The logo features a square with rounded corners that is filled with a gradient of colors, including red, orange, yellow, green, blue, and purple. The word "QUIDEL" is written in a sans-serif font below the square.

Summary of Performance Data

Non-clinical and clinical verification and validation activities conducted with the Lyra RSV+hMPV Assay demonstrate that the modified device met predetermined acceptance criteria, supporting equivalency of the modified device to the cleared device. All verification 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 Equivalence Study

Conclusion

These studies demonstrated equivalent performance of the Lyra RSV+hMPV Assay to the predicate product K131813.

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.