CDC Human Influenza Virus Real-time RT-PCR Diagnostic Panel, Influenza A/B Typing Kit, CDC Human Influenza Virus Real-time RT-PCR Diagnostic Panel, Influenza A Subtyping Kit, CDC Human Influenza Virus Real-time RT-PCR, Influenza A/H5 Subtyping Kit

K200370 · Centers for Disease Control and Prevention · OZE · Mar 10, 2020 · Microbiology

Device Facts

• Record ID: K200370
• Device Name: CDC Human Influenza Virus Real-time RT-PCR Diagnostic Panel, Influenza A/B Typing Kit, CDC Human Influenza Virus Real-time RT-PCR Diagnostic Panel, Influenza A Subtyping Kit, CDC Human Influenza Virus Real-time RT-PCR, Influenza A/H5 Subtyping Kit
• Applicant: Centers for Disease Control and Prevention
• Product Code: OZE · Microbiology
• Decision Date: Mar 10, 2020
• Decision: SESE
• Submission Type: Special
• 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], nasal 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. The Influenza A Subtyping 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 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 [NPS], nasal 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. 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: - 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 and viral culture in conjunction with clinical and epidemiological risk factors; - To provide epidemiological information for surveillance of circulating influenza viruses.

Device Story

The CDC Human Influenza Virus Real-time RT-PCR Diagnostic Panel is a molecular diagnostic assay used for the detection and subtyping of influenza viruses. The device utilizes real-time reverse transcription-polymerase chain reaction (RT-PCR) technology to identify viral RNA in clinical samples. The modification described in K200370 involves updating primer and probe sequences to maintain diagnostic sensitivity against evolving circulating influenza strains. The device is intended for use by laboratory professionals in clinical settings to provide rapid identification of influenza types and subtypes, aiding in clinical diagnosis and public health surveillance. The output is a qualitative result indicating the presence or absence of specific influenza viral targets.

Clinical Evidence

Retrospective study using 62 positive and 50 negative residual respiratory specimens. Modified InfA assay showed 100% positive agreement (95% CI: 93.0-100.0) and 100% negative agreement (95% CI: 93.4-100.0). Modified pdmInfA and pdmH1 assays showed 100% positive agreement and 100% negative agreement. Bench testing included LOD equivalency, inclusivity, and cross-reactivity studies.

Technological Characteristics

Real-time RT-PCR assay; utilizes primers and probes for nucleic acid amplification and detection. Designed for use with standard laboratory instrumentation for clinical multiplex test systems. Modification involves updated primer/probe sequences for influenza A virus detection.

Indications for Use

Indicated for the detection of influenza viruses, including influenza A/B typing, influenza A subtyping, and influenza A/H5 subtyping, in clinical specimens.

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 (K200370 - original clearance)

Submission Summary (Full Text)

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

Received: February 14, 2020

## March 10, 2020

Centers for Disease Control and Prevention Yon Yu Regulatory Affairs and Clinical Guidelines Team Lead 1600 Clifton Rd: MS H24-11 Atlanta, Georgia 30329

## Re: K200370

Trade/Device Name: CDC Human Influenza Virus Real-time RT-PCR Diagnostic Panel, Influenza A/B Typing Kit, CDC Human Influenza Virus Real-time RT-PCR Diagnostic Panel, Influenza A Subtyping Kit, CDC Human Influenza Virus Real-time RT-PCR, Influenza A/H5 Subtyping Kit Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory Viral Panel Multiplex Nucleic Acid Assay Regulatory Class: Class II Product Codes: OZE, OOI, NSU, OEP, OQW, NXD Dated: February 13, 2020

Dear Yon Yu:

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

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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 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 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-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

Steven Gitterman, M.D., Ph.D. Deputy Director 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) K200370

### Device Name

CDC Human Influenza Real-Time RT-PCR Diagnostic Panel: Influenza A/B Typing Kit (VER 2), Influenza A Subtyping Kit (VER 3), 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 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], nasal 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 3)

The Influenza A Subtyping 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 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 [NPS], nasal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) and

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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) )dm09 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/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:

- · 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 and viral culture in conjunction with clinical and epidemiological risk factors;
- · 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) pdm09 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 epidemiological 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

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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) |
|-------------------------------------------------|
|-------------------------------------------------|

Requisition Use (Part 31 CFR 801 Subpart B)
Own-Title Contract Use (31 CFR 801 Subpart C)
X Prescription Use (Part 21 CFR 801 Subpart D)

__ Over-The-Counter Use (21 CFR 801 Subpart C)

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## 8. 510(k) Summary

#### GENERAL INFORMATION I.

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

Contact Person: CAPT Yon Yu, Pharm.D. Regulatory Affairs and Clinical Guidelines Team Lead Emergency Preparedness and Response Branch Division of Preparedness and Emerging Infections National Center for Emerging and Zoonotic Infectious Diseases Centers for Disease Control and Prevention (Registration Number: 1050190) 1600 Clifton Road, MS H24-11 Atlanta, GA 30329-4027 [phone] (office) [phone] (fax) [e-mail] (Email)

## Date Prepared: February 13, 2020

#### DEVICE INFORMATION II.

| Proprietary Name: | CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel,<br>Influenza A/B Typing Kit (Ver2), Influenza A Subtyping Kit (Ver3),<br>Influenza A/H5 Subtyping Kit (Ver4) |
|------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Common Name: | Influenza A/B Typing Kit, Influenza A Subtyping Kit, Influenza A/H5 Subtyping Kit |
| Regulation Section: | 866.3980-Respiratory viral panel multiplex nucleic acid assay |
| Subsequent Regulation<br>Sections: | 866.3332-Reagents for detection of specific novel influenza A<br>viruses<br>862.2570-Instrumentation for clinical multiplex systems |
| Device Classification: | Class II |
| Product Code: | OZE |
| Subsequent Product Codes: | NSU, NXD, OEP, OQW, OOI |
| Panel: | Microbiology |

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#### III. PREDICATE DEVICE

CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel (K190302)

### DEVICE DESCRIPTION IV.

The CDC Human Influenza Real-Time RT-PCR Diagnostic Panel is used in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR system. The panel is configured in four separate kits. 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 and characterization of influenza virus RNA in respiratory specimens from patients presenting with influenza-like illness (ILI). 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)pdm(9 viruses and genetic lineages of influenza B 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 is also included in the panel.

### V. INTENDED USE

# CDC Human Influenza Real-Time RT-PCR Diagnostic Panel: Influenza A/B Typing Kit

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 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)odm09 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

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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.

# CDC Human Influenza Real-Time RT-PCR Diagnostic Panel: Influenza A Subtyping Kit

The Influenza A Subtyping 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 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 [NPS], nasal 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 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.

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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## CDC Human Influenza Real-Time RT-PCR Diagnostic Panel: Influenza A/H5 Subtyping Kit

The Influenza A/H5 Subtyping 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 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 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 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.

Testing with the influenza H5a and H5b primer and probe sets should not be performed unless the patient meets 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 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.

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.

### VI. TECHNOLOGICAL CHARACTERISTICS

The technological characteristics of the modified CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel remain the same as the predicate device. Modifications were made primarily to address recent evolutionary changes in circulating influenza A viruses that may impact the reactivity of the current Influenza A/B Typing Kit, Influenza A Subtyping Kit, and Influenza A/H5 Subtyping

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Kit. No modifications were made to the assay designs of the Influenza B Lineage Genotyping Kit.

### SUBSTANTIAL EQUIVALENCE COMPARISON VII.

The CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel (K190302), will serve as the predicate for the proposed change. See tables 8-1 to 8-3 below for a detailed comparison of the modified device to the predicate.

| Item | Predicate Device | Proposed Device |
|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------|
| | CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel, Influenza A/B Typing Kit [K190302] | CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel, Influenza A/B Typing Kit (Ver2) |
| | 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 the CDC device in conjunction with clinical and epidemiological information:<br>• For qualitative detection of influenza virus type A or B viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], nasal 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.<br>• To provide epidemiologic information for surveillance of circulating influenza viruses. | Same |
| Intended Use | | |
| | 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.<br><br>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.<br><br>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 | |
| Viral culture should not be attempted unless a BSL<br>3E facility is available to receive and culture<br>specimens. | | |
| All users, analysts, and any person reporting results from use of this device should be<br>trained to perform and interpret the results from this procedure by a competent<br>instructor prior to use. CDC Influenza Division will limit the distribution of this device<br>to only those users who have successfully completed a training course provided by<br>CDC instructors or designees. | | |
| Organism<br>Detected | Influenza A viruses (animal and human), influenza<br>B viruses | Same |
| Specimen Types | Nasopharyngeal swabs, nasal swabs, throat<br>swabs, nasal aspirates, nasal washes and dual<br>nasopharyngeal/throat swabs, bronchoalveolar<br>lavages, bronchial aspirates, bronchial washes,<br>tracheal aspirates, sputum, and lung tissue from<br>human patients with signs and symptoms of<br>respiratory infection and/or from viral culture | Same |
| Technological<br>Characteristics | Real-time RT-PCR based assay | Same |
| Nucleic Acid<br>Extraction | • QIAamp® DSP Viral RNA Mini Kit, QIAGEN<br>• MagNA Pure Compact -Nucleic Acid Isolation Kit<br>I, Roche<br>• MagNA Pure Compact - RNA Isolation Kit, Roche<br>• MagNA Pure LC - Total Nucleic Acid Kit, Roche<br>• QIAcube - QIAamp® DSP Viral RNA Mini Kit, QIAGEN<br>• NucliSENS® easyMAG®, bioMérieux<br>• EMAG®, bioMérieux<br>• EZ1 Advanced XL – EZ1 DSP Virus Kit and EZ1<br>RNA Tissue Mini Kit, QIAGEN<br>• MagNA Pure 96 - DNA and Viral NA Small<br>Volume Kit, Roche | Same |
| Enzyme Master<br>Mix | Invitrogen SuperScript™ III Platinum® One-Step<br>Quantitative RT-PCR Kit (with or without ROX) OR<br>Quanta BioSciences qScript™ One-Step qRT-PCR<br>• Kit, Low ROX | Same |
| Required<br>Instrumentation | • Applied Biosystems™ 7500 Fast Dx Real-<br>Time PCR Instrument with SDS software<br>version 1.4<br>• Applied Biosystems™ QuantStudio™ Dx<br>with version 1.0.3 software<br>• QIAGEN Rotor-Gene® Q MDx with<br>AssayManager® 1.0.4 and Epsilon version 1.0.1<br>software | Same |

Table 8-1: Device Comparison

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# Table 8-2: Device Comparison

| | Predicate<br>Device | Proposed<br>Device |
|---------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------|
| Item | CDC Human Influenza Virus Real-Time RT-<br>PCR Diagnostic Panel, Influenza A<br>Subtyping Kit (Ver2) [K190302] | CDC Human Influenza Virus Real-<br>Time RT- PCR Diagnostic Panel,<br>Influenza A Subtyping Kit (Ver3) |
| Intended Use | The Influenza A Subtyping Kit contains reagents<br>and controls of the CDC Human Influenza Virus<br>Real- Time RT-PCR Diagnostic Panel and is<br>intended for use in real-time RT-PCR (rRT-PCR)<br>assays on an in vitro diagnostic real-time PCR<br>instrument that has been FDA-cleared for use with<br>the CDC device in conjunction with clinical and<br>epidemiological information:<br><br>• For determination of the subtype of seasonal<br>human influenza A viruses as seasonal A(H3),<br>and/or A(H1)pdm09 from viral RNA in upper<br>respiratory tract clinical specimens (including<br>nasopharyngeal swabs [NPS], nasal swabs [NS],<br>throat swabs [TS], nasal aspirates [NA], nasal | Same |
| | | |
| | washes [NW] and dual nasopharyngeal/throat<br>swabs [NPS/TS]) and lower respiratory tract<br>specimens (including bronchoalveolar lavage<br>[BAL], bronchial wash [BW], tracheal aspirate<br>[TA], sputum, and lung tissue) from human<br>patients with signs and symptoms of respiratory<br>infection and/or from viral culture; | |
| | • To provide epidemiologic information for<br>surveillance of circulating influenza viruses. | |
| | Performance characteristics for influenza were<br>established during a season when seasonal<br>influenza viruses A(H1N1) and A(H3N2) were the<br>predominant influenza A viruses in circulation and<br>during a season when the A(H1N1)pdm09<br>influenza virus was the predominant influenza A<br>virus in circulation. Performance characteristics<br>may vary with other emerging influenza A viruses. | |
| | Negative results do not preclude influenza virus<br>infection and should not be used as the sole basis<br>for treatment or other patient management<br>decisions. Conversely, positive results do not rule<br>out bacterial infection or co-infection with other<br>viruses. The agent detected may not be the<br>definite cause of disease. | |
| | If infection with a novel influenza A virus is<br>suspected based on current clinical and<br>epidemiological screening criteria recommended by<br>public health authorities, specimens should be<br>collected with appropriate infection control<br>precautions for novel virulent influenza viruses and<br>sent to state or local health department for testing.<br>Viral culture should not be attempted unless a BSL<br>3E facility is available to receive and culture<br>specimens. | |
| | All users, analysts, and any person reporting results from use of this device should be<br>trained to perform and interpret the results from this procedure by a competent<br>instructor prior to use. CDC Influenza Division will limit the distribution of this device<br>to only those users who have successfully completed a training course provided by<br>CDC instructors or designees | |
| Organism<br>Detected | Influenza A viruses (animal and human), Swine-<br>origin influenza A viruses, Influenza A<br>subtypes: seasonal A(H3), A(H1)pdm09 | Same |
| Specimen Types | Nasopharyngeal swabs, nasal swabs, throat<br>swabs, nasal aspirates, nasal washes and dual<br>nasopharyngeal/throat swabs, bronchoalveolar<br>lavages, bronchial aspirates, bronchial washes,<br>tracheal aspirates, sputum, and lung tissue from<br>human patients with signs and symptoms of<br>respiratory infection and/or from viral<br>culture | Same |
| Technological<br>Characteristic | Real-time RT-PCR based assay | Same |
| Nucleic Acid<br>Extraction | • QIAamp® DSP Viral RNA Mini Kit, QIAGEN<br>• MagNA Pure Compact –Nucleic Acid Isolation Kit I, Roche<br>• MagNA Pure Compact – RNA Isolation Kit, Roche<br>• MagNA Pure LC – Total Nucleic Acid Kit, Roche<br>• QIAcube – QIAamp® DSP Viral RNA Mini Kit, QIAGEN<br>• NucliSENS® easyMAG®, bioMérieux<br>• EMAG®, bioMérieux<br>• EZ1 Advanced XL – EZ1 DSP Virus Kit and EZ1 RNA Tissue Mini Kit, QIAGEN<br>• MagNA Pure 96 – DNA and Viral NA Small Volume Kit, Roche | Same |
| Enzyme Master Mix | Invitrogen SuperScript™ III Platinum® One-Step<br>Quantitative RT-PCR Kit (with or without ROX)<br>OR Quanta BioSciences qScript™ One-Step qRT-PCR Kit, Low ROX | Same |
| Required<br>Instrumentation | • Applied Biosystems™ 7500 Fast Dx Real-Time PCR Instrument with 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 and Epsilon version | Same |

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# Table 8-3: Device Comparison

| Item | Predicate Device | Proposed Device |
|---------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------|
| | CDC Human Influenza Virus Real-Time RT-PCR<br>Diagnostic Panel, Influenza A/H5 Subtyping<br>Kit (Ver3) [K190302] | CDC Human Influenza Virus Real-Time<br>RT-<br>PCR Diagnostic Panel, Influenza<br>A/H5 Subtyping Kit (Ver4) |
| Intended Use | The Influenza A/H5 Subtyping Kit contains reagents<br>and controls of the CDC Human Influenza Virus<br>Real-Time RT-PCR Diagnostic Panel and is<br>intended for use in real-time RT-PCR (rRT-PCR)<br>assays on an in vitro diagnostic real-time PCR<br>instrument that has been FDA-cleared for use with<br>the CDC device in conjunction with clinical and<br>epidemiological information:<br><br>• For the presumptive identification of virus in<br>patients who may be infected with influenza A<br>subtype A(H5) (Asian lineage) from viral RNA in<br>human respiratory specimens and viral culture in<br>conjunction with clinical and epidemiological risk<br>factors;<br><br>• To provide epidemiologic information for<br>surveillance of circulating influenza viruses.<br><br>Performance characteristics for influenza were<br>established during a season when seasonal<br>influenza viruses A(H1N1) and A(H3N2) were the<br>predominant influenza A viruses in circulation and<br>during a season when the A(H1N1)pdm09<br>influenza virus was the predominant influenza A<br>virus in circulation. Performance characteristics<br>may vary with other emerging influenza A viruses.<br><br>Testing with the influenza H5a and H5b primer and<br>probe sets should not be performed unless the<br>patient meets the most current U.S. Department of<br>Health and Human Services (DHHS) clinical and<br>epidemiologic criteria for testing suspect A(H5) | Same |
| | 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…