CDC Human Influenza Virus Real-time RT-PCR Diagnostic Panel: Influenza A/B Typing Kit (VER 2); Influenza A Subtyping Kit (VER 4); Influenza B Lineage Genotyping Kit (VER 1.1 and 2); and Influenza A/H5 Subtyping Kit (VER 4)

K243931 · Centers for Disease Control and Prevention · OZE · Mar 14, 2025 · Microbiology

Device Facts

• Record ID: K243931
• Device Name: CDC Human Influenza Virus Real-time RT-PCR Diagnostic Panel: Influenza A/B Typing Kit (VER 2); Influenza A Subtyping Kit (VER 4); Influenza B Lineage Genotyping Kit (VER 1.1 and 2); and Influenza A/H5 Subtyping Kit (VER 4)
• Applicant: Centers for Disease Control and Prevention
• Product Code: OZE · Microbiology
• Decision Date: Mar 14, 2025
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3980
• Device Class: Class 2

Intended Use

The Influenza A/B Typing Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information: · For qualitative detection of influenza virus type A or B viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW and dual nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture. · To provide epidemiological information for surveillance of circulating influenza viruses. Performance characteristics for influenza were established during a seasonal influenza viruses A(H1N1) and A(H3N2) were the predominant influenza A viruses in circulation and during a season when the A(H1N) Jodm09 influenza virus was the predominant influenza A virus in circulation. Performance characteristics may vary with other emerging influenza A viruses. 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 with other viruses. The agent detected may not be the definite cause of disease. 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 unless a BSL 3E facility is available to receive and culture specimens. All users, and any person reporting results from use of this device should be trained to perform and interpret the results from this procedure by a competent instructor prior to use. CDC Influenza Division will limit the distribution of this device to only those users who have successfully completed a training course provided by CDC instructors or designees.

Device Story

The CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel is a molecular diagnostic tool used to detect and characterize influenza A and B viruses. This submission specifically modifies the Influenza A/H5 Subtyping Kit to include conjunctival swabs as an acceptable specimen type. The device utilizes real-time RT-PCR (rRT-PCR) to amplify and detect viral RNA from clinical specimens. It uses oligonucleotide primers and fluorescently labeled hydrolysis probes targeting highly conserved regions of the HA gene for A(H5) identification. The assay is performed on FDA-cleared real-time PCR instruments. Results are interpreted by trained laboratory personnel in conjunction with clinical and epidemiological data to support surveillance and presumptive identification of novel influenza A(H5) infections. The device is intended for use in public health laboratories and clinical settings where appropriate biosafety measures are in place. It aids in identifying patients requiring further confirmatory testing for novel influenza A viruses.

Clinical Evidence

Clinical performance was evaluated using specimens from 44 confirmed and 2 probable human cases of A/H5N1 collected during 2024. Performance assessment included 35 confirmed and 2 probable cases. Results showed that 25/33 (75.8%) of patients tested positive for A/H5 on conjunctival swabs, while 14/33 (42.4%) tested positive on upper respiratory tract (URT) swabs. The data indicates that conjunctival swabs are a viable specimen type for A/H5 detection, particularly in patients presenting with conjunctivitis.

Technological Characteristics

The device uses real-time RT-PCR (rRT-PCR) technology. It consists of oligonucleotide primers and fluorescently labeled hydrolysis probes targeting conserved viral gene regions (M, NS, NP, HA). It is designed for use on FDA-cleared real-time PCR instruments. The assay is a qualitative molecular test. No specific materials of construction or connectivity standards are detailed beyond the requirement for compatible PCR instrumentation.

Indications for Use

Indicated for qualitative detection, subtyping, or genotyping of influenza A and B viruses from human respiratory specimens (NPS, TS, NA, NW, NPS/TS, BAL, BW, TA, sputum, lung tissue) and conjunctival swabs (for H5 subtyping). Intended for patients with signs/symptoms of respiratory infection or conjunctivitis. Provides epidemiological surveillance data. Not for sole basis of treatment decisions. Requires training by CDC-authorized instructors.

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

• CDC Human Influenza Virus Real-time RT-PCR Diagnostic Panel: Influenza A/B Typing Kit, Influenza A Subtyping Kit (VER 2), Influenza B Lineage Genotyping Kit (VER 1.1 and 2), and Influenza A/H5 Subtyping Kit (VER 3) (K190302)

Submission Summary (Full Text)

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Image /page/0/Picture/0 description: The image contains the logos of the U.S. Department of Health & Human Services and the U.S. Food & Drug Administration (FDA). The Department of Health & Human Services logo is on the left, and the FDA logo is on the right. The FDA logo is a blue square with the letters "FDA" in white, followed by the words "U.S. Food & Drug Administration" in blue.

March 14, 2025

Centers for Disease Control and Prevention Melissa Ivev Regulatory Affairs Specialist 1600 Clifton Rd Atlanta, Georgia 30329

Re: K243931

Trade/Device Name: CDC Human Influenza Virus Real-time RT-PCR Diagnostic Panel: Influenza A/B Typing Kit (VER 2); Influenza A Subtyping Kit (VER 4); Influenza B Lineage Genotyping Kit (VER 1.1 and 2); and Influenza A/H5 Subtyping Kit (VER 4) Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory Viral Panel Multiplex Nucleic Acid Assay Regulatory Class: Class II Product Code: OZE Dated: December 16, 2024 Received: December 20, 2024

Dear Melissa Ivey:

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.

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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" (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 (OS) 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 QS 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 (OS) 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.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

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 medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatory

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assistance/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,

# Anna M. Mielech -S

Anna Mielech, PhD. Deputy Branch Chief (Acting) 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

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# Indications for Use

510(k) Number (if known) K243931

### Device Name

CDC Human Influenza Real-Time RT-PCR Diagnostic Panel:Influenza A/B Typing Kit (VER 2), Influenza A Subtyping Kit (VER 4), Influenza B Lineage Genotyping Kit (VER 1.1 and 2), and Influenza A/H5 Subtyping Kit (VER 4)

### Indications for Use (Describe)

CDC Human Influenza Real-Time RT-PCR Diagnostic Panel: Influenza A/B Typing Kit (VER 2)

The Influenza A/B Typing Kit contains reagents and controls of the CDC Human Influenza Virus RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and evidemiological information:

· For qualitative detection of influenza virus type A or B viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW and dual nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture.

· To provide epidemiological information for surveillance of circulating influenza viruses.

Performance characteristics for influenza were established during a seasonal influenza viruses A(H1N1) and A(H3N2) were the predominant influenza A viruses in circulation and during a season when the A(H1N) Jodm09 influenza virus was the predominant influenza A virus in circulation. Performance characteristics may vary with other emerging influenza A viruses.

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 with other viruses. The agent detected may not be the definite cause of disease.

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 unless a BSL 3E facility is available to receive and culture specimens.

All users, and any person reporting results from use of this device should be trained to perform and interpret the results from this procedure by a competent instructor prior to use. CDC Influenza Division will limit the distribution of this device to only those users who have successfully completed a training course provided by CDC instructors or designees.

CDC Human Influenza Real-Time RT-PCR Diagnostic Panel: Influenza A Subtyping Kit (VER 4)

The Influenza A Subtyping Kit contains reagents and controls of the CDC Human Influenza Virus RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:

· For determination of the subtype of seasonal human influenza A viruses as seasonal A(H3) and/or A(H1)pdm09 from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) and lower

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respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture:

· To provide epidemiological information for surveillance of circulating influenza viruses.

Performance characteristics for influenza were established during a seasonal influenza viruses A(HIN1) and A(H3N2) were the predominant influenza A viruses in circulation and during a season when the A(H1N) Jodm09 influenza virus was the predominant influenza A virus in circulation. Performance characteristics may vary with other emerging influenza A viruses.

Negative results do not preclude influenza virus infection and should not be used as the sole basis for 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.

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 unless a BSL 3E facility is available to receive and culture specimens.

All users, and any person reporting results from use of this device should be trained to perform and interpret the results from this procedure by a competent instructor prior to use. CDC Influenza Division will limit the distribution of this device to only those users who have successfully completed a training course provided by CDC instructors or designees.

CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel: Influenza B Lineage Genotyping Kit (VER 1.1 and 2)

The Influenza B Lineage Genotyping Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic realtime PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:

• For the determination of the genetic lineage of human influenza B viruses as B/Victoria or B/Yamagata lineage from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) from human patients with signs and symptoms of respiratory infection and/or from viral culture;

· To provide epidemiologic information for surveillance of circulating influenza viruses.

Performance characteristics for influenza B lineage genotyping were established during a season when influenza B/Victoria and B/Yamagata lineages were in circulation.

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 with other viruses. The agent detected may not be the definite cause of disease.

All users, and any person reporting results from use of this device should be trained to perform and interpret the results from this procedure by a competent instructor prior to use. CDC Influenza Division will limit the distribution of this device to only those users who have successfully completed a training course provided by CDC instructors or designees.

CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel: Influenza A/H5 Subtyping Kit (VER 4)

The Influenza A/H5 Subtyping Kit contains reagents and controls of the CDC Human Influenza Virus RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:

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· For the presumptive identification of virus in patients who may be infected with influenza A subtype A(H5) (Asian lineage) from viral RNA in human respiratory specimens, conjunctival swabs, and viral culture in conjunction with clinical and epidemiological risk factors;

· To provide epidemiologic information for surveillance of circulating influenza viruses.

Performance characteristics for influenza were established during a seasonal influenza viruses A(H1N1) and A(H3N2) were the predominant influenza A viruses in circulation and during a season when the A(H1N) Jodm09 influenza virus was the predominant influenza A virus in circulation. Performance characteristics may vary with other emerging influenza A viruses.

Testing with the influenza H5a and H5b primer and probe sets should not be performed unless the most current U.S.Department of Health and Human Services (DHHS) clinical and epidemiologic criteria for testing suspect A(H5) specimens. The definitive identification of influenza A(H5) (Asian lineage) either directly from patient specimens or from virus cultures requires additional laboratory testing, along with clinical and epidemiological assessment in consultation with national influenza surveillance experts.

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 with other viruses. The agent detected may not be the definite cause of disease.

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 unless a BSL 3E facility is available to receive and culture specimens.

All users, and any person reporting results from use of this device should be trained to perform and interpret the results from this procedure by a competent instructor prior to use. CDC Influenza Division will limit the distribution of this device to only those users who have successfully completed a training course provided by CDC instructors or designees.

Type of Use (Select one or both, as applicable)

| <label><input checked="" type="checkbox"/> Prescription Use (Part 21 CFR 801 Subpart D)</label> |
|-------------------------------------------------------------------------------------------------|
| <label><input type="checkbox"/> Over-The-Counter Use (21 CFR 801 Subpart C)</label> |

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### 510(k) Summary

#### I. GENERAL INFORMATION

Submitter

Centers for Disease Control and Prevention 1600 Clifton Road, NE Atlanta, GA 30329

Contact Person

Marie Kirby Lead, Genomics and Diagnostics Team Virology, Surveillance and Diagnostic Branch, Influenza Division National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention [e-mail] [phone]

Date Prepared: December 16, 2024

#### II. DEVICE INFORMATION

| Proprietary Name: | CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel: Influenza A/B Typing Kit<br>(VER 2), Influenza A Subtyping Kit (VER 4), Influenza B Lineage Genotyping Kit (VER 1.1 and<br>2), and Influenza A/H5 Subtyping Kit (VER 4) |
|---------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Common Name: | CDC Flu rRT-PCR Dx Panel: Influenza A/B Typing Kit, Influenza A Subtyping Kit, Influenza B<br>Lineage Genotyping Kit, and Influenza A/H5 Subtyping Kit |
| Regulation Section: | 866.3980-Respiratory viral panel multiplex nucleic acid assay |

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Device Classification: Class II

Product Code: OZE

Panel: Microbiology

#### PREDICATE DEVICES III.

K 190302 - CDC Human Influenza Virus Real-time RT-PCR Diagnostic Panel: Influenza A Subtyping Kit (VER 2), Influenza B Lineage Genotyping Kit (VER 1.1 and 2), and Influenza A/H5 Subtyping Kit (VER 3)

#### DEVICE DESCRIPTION IV.

The CDC Human Influenza Real-Time RT-PCR Diagnostic Panel consists of four real-time RT-PCR (rRT-PCR) assays used on IVD-labeled real-time PCR instruments that has been FDA-cleared for use with this device. The panel is configured in four separate kits: Influenza A/B Typing kit, Influenza A/H5 Subtyping kit, and Influenza B Genotyping kit. Each kit consists of oligonucleotide primers, fluorescently labeled hydrolysis probes, and controls which are used in rRT-PCR assays for the in vitro qualitative detection of influenza virus RNA in respiratory and conjunctival specimens from patients presenting with influenza-like illness (IL). Oligonucleotide primers and probes for detection of influenza A, influenza B, and 2009 influenza A (swine origin) were selected from highly conserved regions of the matrix (M), non-structural (NS), and nucleoprotein (NP) genes, respectively. Oligonucleotide primers and probes for characterization and differentiation of influenza A(H3) and A(H1)pdm09 viruses, genetic lineages of influenza A(H5) viruses were selected from highly conserved regions of their HA genes. Oligonucleotide primers and probes to detect the human RNase P gene (RP) in control samples and clinical specimens are also included in the panel.

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### V. INTENDED USE

# Influenza A/B Typing Kit (VER 2)

The Influenza A/B Typing Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR) assays on an in vitro diagnostic real-ime PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:

· For qualitative detection of influenza virus type A or B viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], nasal swabs [TS], throat swabs [TS], nasal washes [NW] and dual nasopharyneal/throat swabs [NPSTS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture.

· To provide epidemiological information for surveillance of circulating influenza viruses.

Performance characteristics for influenza were established during a season when seasonal influenza viruses A(HIN) and A(H3N2) were the predominant influenza A viruses in circulation and during a season when the A(H1N) pdm09 influenza virus was the predominant influenza A virus in circulation. Performance characteristics may vary with other emerging influenza A viruses. 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 with other viruses. The agent detected may not be the definite cause of disease.

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 for novel virulent influenza viruses and sent to state or local health department for testing. Viral culture should not be attempted unless a BSL 3E facility is available to receive and culture specimens.

> All users, analysts, and any person reporting results from use of this device should be trained to perform and interpret the results from this procedure by a competent instructor prior to use. CDC Influenza Division will limit the distribution of this device to only those users who have successfully completed a training course provided by CDC instructors or designees.

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# Influenza A Subtvping Kit (VER 4)

The Influenza A Subtying Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDAcleared for use with this kit in conjunction with clinical and epidemiological information:

• For determination of the subtype of seasonal human influenza A viruses as seasonal A(H3) and/or A(H1) pdm09 from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture;

· To provide epidemiological information for surveillance of circulating influenza viruses.

Performance characteristics for influenza were established during a season influenza viruses A(HIN) and A(H3N2) were the predominant influenza A viruses in circulation and during a season when the A(H1N) pdm09 influenza virus was the predominant influenza A virus in circulation. Performance characteristics may vary with other emerging influenza A viruses. 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 with other viruses. The agent detected may not be the definite cause of disease.

If infection with a novel influenza A virus is suspected based on current clinical and epideria recommended by public health authorities, specimens should be collected with appropriate infection for novel virulent influenza viruses and sent to state or local health department for testing. Viral culture should not be attempted unless a BSL 3E facility is available to receive and culture specimens.

> All users, analysts, and any person reporting results from use of this device should be trained to perform and interpret the results from this procedure by a competent instructor prior to use. CDC Influenza Division will limit the distribution of this device to only those users who have successfully completed a training course provided by CDC instructors or designees.

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# Influenza B Genotyping Kit (VER 1.1 and 2)

The Influenza B Lineage Genotyping Kit contains reagents and controls of the CDC Human Influenza Virus RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:

• For the determination of the genetic lineage of human influenza B viruses as B/Victoria or B/Y amagata lineage from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) from human patients with signs and symptoms of respuntory infection and/or from viral culture;

· To provide epidemiologic information for surveillance of circulating influenza viruses.

Performance characteristics for influenza B lineage genotyping were established during a season when influenza B/Victoria and B/Yamagata lineages were in circulation.

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 with other viruses. The agent detected may not be the definite cause of disease.

> All users, analysts, and any person reporting results from use of this device should be trained to perform and interpret the results from this procedure by a competent instructor prior to use. CDC Influenza Division will limit the distribution of this device to only those users who have successfully completed a training course provided by CDC instructors or designees.

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### Influenza A/H5 Subtyping Kit (VER 4)

The Influenza A/H5 Subtyping Kit contains reagents and controls of the Centers for Disease Control and Prevention (CDC) Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:

· For the presumptive identification of virus in patients who mfluenza A subtype A(HS) (Asian lineage) from viral RNA in human respiratory specimens, conjunctival swabs and viral culture in conjunction with clinical and epidemiological risk factors;

· To provide epidemiologic information for surveillance of circulating influenza viruses.

Performance characteristics for influenza were established during a season influenza viruses A(HIN) and A(H3N2) were the predominant influenza A viruses in circulation and during a season when the A(H1N) jpdm09 influenza virus was the predominant influenza A virus in circulation. Performance characteristics may vary with other emerging influenza A viruses.

Testing with the influenza H5a and H56 primer and probe sets should not be patient meets the most current U.S. Department of Health and Human Services (DHHS) clinical and epidemiologic criteria for testing suspect A(HS) specimens. The definitive identification of influenza A(H5) (Asian linectly from patient specimens or from virus cultures requires additional laboratory testing, along with clinical assessment in consultation with national influenza survellance experts.

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 with other viruses. The agent detected may not be the definite cause of disease.

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 infections for novel virulent influenza viruses and sent to state or local health department for testing. Viral culture should not be attempted unless a BSL 3E facilable to receive and culture specimens.

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All users, analysts, and any person reporting results from use of this device should be trained to perform and interpret the results from this procedure by a competent instructor prior to use. CDC Influenza Division will limit the distribution of this device to only those users who have successfully completed a training course provided by CDC instructors or designees.

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### VI. TECHNOLOGICAL CHARACTERISTICS

The technological characteristics of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel remains the same as the predicate device.

### VII. SUBSTANTIAL EQUIVALENCE COMPARISON

| | CDC Human Influenza Virus Real-Time RT-PCR<br>Diagnostic Panel: Influenza A/B Typing Kit<br>(K190302) | CDC Human Influenza Virus Real-Time RT-PCR<br>Diagnostic Panel: Influenza A/B Typing Kit (VER 2)<br>(K243931) |
|--------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------|
| General Device<br>Characteristic<br>Similarities | | |
| Intended Use | The Influenza A/B Typing Kit contains reagents and<br>controls of the CDC Human Influenza Virus Real-Time<br>RT-PCR Diagnostic Panel and is intended for use in real-<br>time RT-PCR (rRT-PCR) assays on an in vitro diagnostic<br>real-time PCR instrument that has been FDA-cleared for<br>use with this kit in conjunction with clinical and<br>epidemiological information:<br>For qualitative detection of influenza virus type A or B<br>viral RNA in upper respiratory tract clinical specimens<br>(including nasopharyngeal swabs [NPS], nasal swabs<br>[NS], throat swabs [TS], nasal aspirates [NA], nasal<br>washes [NW] and dual nasopharyngeal/throat swabs<br>[NPS/TS]) and lower respiratory tract specimens<br>(including bronchoalveolar lavage [BAL], bronchial wash<br>[BW], tracheal aspirate [TA], sputum, and lung tissue)<br>from human patients with signs and symptoms of<br>respiratory infection and/or from viral culture.To provide epidemiological information for surveillance | Same |

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of circulating influenza viruses. Performance characteristics for influenza were established during a season when seasonal influenza viruses A(H1N1) and A(H3N2) were the predominant influenza A viruses in circulation and during a season when the A(H1N1)pdm09 influenza virus was the predominant influenza A virus in circulation. Performance characteristics may vary with other emerging influenza A viruses. 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. [f 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 unless a BSL 3E facility is available to receive and culture specimens. [black box: All users, analysts, and any person reporting results from use of this device should be trained to perform and interpret the results from this procedure by a competent instructor prior to use. CDC Influenza Division will limit the distribution of this device to only those users who have successfully completed a training course provided by CDC instructors or designees.]

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| Specimen Types | Upper respiratory tract clinical specimens (including<br>nasopharyngeal swabs [NPS], nasal swabs [NS], throat<br>swabs [TS], nasal aspirates [NA], nasal washes [NW] and<br>dual nasopharyngeal/throat swabs [NPS/TS]) and lower<br>respiratory tract specimens (including bronchoalveolar<br>lavage [BAL], bronchial wash [BW], tracheal aspirate<br>[TA], sputum, and lung tissue), and/or viral culture | Same |
|-----------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------|
| Organisms<br>Detected | Influenza A and Influenza B | Same |
| Analytes | RNA- InfA, InfB, RP | Same |
| Technological<br>Principles | Real-time RT-PCR | Same |
| Instrumentation | Applied Biosystems 7500 Fast Dx Real-time PCR system<br>with SDS software version 1.4<br>Applied Biosystems QuantStudio Dx with version 1.0.3<br>software<br>QIAGEN Rotor-Gene Q MDx with AssayManager<br>1.0.4.1 and Epsilon version 1.0.1 software | Same |
| Enzyme Master<br>Mix | Invitrogen SuperScript III Platinum One-Step<br>Quantitative RT-PCR Kit (with or without ROX)<br>Quanta BioSciences qScript One-Step qRT PCR Kit, Low<br>ROX | Same |
| Nucleic Acid<br>Extraction | QIAamp DSP Viral RNA Mini Kit, QIAGEN<br>MagNA Pure Compact - Nucleic Acid Isolation Kit I,<br>Roche<br>MagNA Pure Compact – RNA Isolation Kit, Roche | Same |

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| | MagNA Pure LC – Total Nucleic Acid Kit, Roche<br>MagNA Pure 96 - DNA and Viral NA Small Volume Kit,<br>Roche | |
|--------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------|
| | QIAcube - QIAamp DSP Viral RNA Mini Kit, QIAGEN | |
| | NucliSENS easyMAG, bioMérieux<br>EMAG, bioMérieux* | |
| | EZ1 Advanced XL - EZ1 DSP Virus Kit and EZ1 RNA<br>Tissue Mini Kit, QIAGEN | |
| | CDC Human Influenza Virus Real-Time RT-PCR<br>Diagnostic Panel: Influenza A Subtyping Kit (VER 2)<br>(K190302) | CDC Human Influenza Virus Real-Time RT-PCR<br>Diagnostic Panel: Influenza A Subtyping Kit (VER 4)<br>(K243931) |
| General Device<br>Characteristic<br>Similarities | | |
| | The Influenza A Subtyping Kit contains reagents and controls of<br>the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic<br>Panel and is intended for use in real-time RT-PCR (rRT-PCR)<br>assays on an in vitro diagnostic real-time PCR instrument that has<br>been FDA-cleared for use with this kit in conjunction with<br>clinical and epidemiological information: | |
| Intended Use | · For determination of the subtype of seasonal human influenza<br>A viruses as seasonal A(H3), and/or A(H1)pdm09 from viral<br>RNA in upper respiratory tract clinical specimens (including<br>nasopharyngeal swabs [NPS], nasal swabs [NS], throat swabs<br>[TS], nasal aspirates [NA], nasal washes [NW] and dual<br>nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory<br>tract specimens (including bronchoalveolar lavage [BAL] | Same |

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| bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture; |
|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| • To provide epidemiologic information for surveillance of circulating influenza viruses. |
| Performance characteristics for influenza were established during a season when seasonal influenza viruses A(H1N1) and A(H3N2) were the predominant influenza A viruses in circulation and during a season when the A(H1N1)pdm09 influenza virus was the predominant influenza A virus in circulation. Performance characteristics may vary with other emerging influenza A viruses. |
| 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. |
| 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 unless a BSL 3E facility is available to receive and culture specimens. |
| [black box: All users, analysts, and any person reporting results from use of this device should be trained to perform and interpret the results from this procedure by a competent instructor prior to use. CDC Influenza Division will limit the distribution of this device to only those users who have successfully completed a training course provided by CDC |

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| | instructors or designees.] | |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Specimen Types | Upper respiratory tract clinical specimens (including<br>nasopharyngeal swabs [NPS], nasal swabs [NS], throat swabs<br>[TS], nasal aspirates [NA], nasal washes [NW] and dual<br>nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory<br>tract specimens (including bronchoalveolar lavage [BAL],<br>bronchial wash [BW], tracheal aspirate [TA], sputum, and lung<br>tissue) from human patients with signs and symptoms of<br>respiratory infection and/or from viral culture | Same |
| Organisms<br>Detected | Influenza A viruses (animal and human), swine-origin influenza<br>A viruses, influenza A subtypes: seasonal A(H3) and<br>A(H1)pdm09 | Same |
| Analytes | RNA- InfA, H3, pdmInfA, pdmH1 and RP | Same |
| Technological<br>Principles | Real-time RT-PCR | Same |
| Instrumentation | Applied Biosystems 7500 Fast Dx Real-time PCR system with<br>SDS software version 1.4<br>Applied Biosystems QuantStudio Dx with version 1.0.3 software<br>QIAGEN Rotor-Gene Q MDx with AssayManager 1.0.4.1 and<br>Epsilon version 1.0.1 software | Same |
| Enzyme Master<br>Mix | Invitrogen SuperScript III Platinum One-Step Quantitative RT-<br>PCR Kit (with or without ROX)<br>Quanta BioSciences qScript One-Step qRT PCR Kit, Low ROX | Same |
| Nucleic Acid<br>Extraction | QuIAamp DSP Viral RNA Mini Kit, QIAGEN<br>MagNA Pure Compact – Nucleic Acid Isolation Kit I,<br>Roche | QIAamp DSP Viral RNA Mini Kit, QIAGEN<br>MagNA Pure LC – Total Nucleic Acid Kit, Roche |
| MagNA Pure Compact - RNA Isolation Kit, Roche | MagNA Pure 96 - DNA and Viral NA Small Volume Kit, Roche | |
| MagNA Pure LC – Total Nucleic Acid Kit, Roche | QIAcube – QIAamp DSP Viral RNA Mini Kit, QIAGEN | |
| MagNA Pure 96 - DNA and Viral NA Small Volume Kit, Roche | NucliSENS easyMAG, bioMérieux | |
| QIAcube - QIAamp DSP Viral RNA Mini Kit, QIAGEN | EMAG, bioMérieux*<br>EZ1 Advanced XL – EZ1 DSP Virus Kit and EZ1 RNA | |
| NucliSENS easyMAG, bioMérieux | Tissue Mini Kit, QIAGEN | |
| EMAG, bioMérieux* | | |
| EZ1 Advanced XL - EZ1 DSP Virus Kit and EZ1 RNA<br>Tissue Mini Kit, QIAGEN | | |
| CDC Human Influenza Virus Real-Time RT-PCR<br>Diagnostic Panel: Influenza B Genotyping Kit (VER 1.1 and 2)<br>(K190302) | CDC Human Influenza Virus Real-Time RT-PCR<br>Diagnostic Panel: Influenza B Genotyping Kit (VER 1.1 and 2)<br>(K243931) | |
| General Device<br>Characteristic<br>Similarities | | |
| | nasopharyngeal/throat swabs [NPS/TS]) from human patients<br>with signs and symptoms of respiratory infection and/or from<br>viral culture; | |
| | • To provide epidemiologic information for surveillance of<br>circulating influenza viruses. | |
| | Performance characteristics for influenza B lineage genotyping<br>were established during a season when influenza B/Victoria and<br>B/Yamagata lineages were in circulation. | |
|…