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 B Lineage Genotyping Kit, CDC Human Influenza Virus Real-time RT-PCR, Influenza A/H5 Subtyping Kit

K172091 · Centers for Disease Control and Prevention · OZE · Aug 9, 2017 · Microbiology

Device Facts

• Record ID: K172091
• 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 B Lineage Genotyping 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: Aug 9, 2017
• 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 Applied Biosystems (ABI) 7500 Fast Dx Real-Time PCR instrument 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 [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. (Note: Similar statements apply to the Influenza A Subtyping Kit (VER 2), Influenza B Lineage Genotyping Kit, and Influenza A/H5 Subtyping Kit (VER 3) as described in the document).

Device Story

The CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel consists of four kits using rRT-PCR to detect and characterize influenza viral RNA. Input samples include upper and lower respiratory tract specimens. Nucleic acids are extracted using validated automated platforms (QIAGEN EZ1 Advanced XL or Roche MagNA Pure 96). Extracted RNA is amplified on the Applied Biosystems (ABI) 7500 Fast Dx Real-Time PCR instrument using specific primers and fluorescently labeled hydrolysis probes targeting conserved regions of viral genes (M, NS, NP, HA). The instrument monitors fluorescence intensity during PCR cycles to detect target amplification. Results are used by trained laboratory personnel in conjunction with clinical and epidemiological data to aid in diagnosis and surveillance. The device provides qualitative detection and subtyping/lineage information, assisting healthcare providers in patient management and public health monitoring.

Clinical Evidence

Retrospective clinical study using 60 specimens (30 positive for influenza A(H3), 30 negative) compared the new extraction methods (Roche MagNA Pure 96, QIAGEN EZ1 Advanced XL) against the cleared Roche MagNA Pure Compact method. Results showed 100% agreement (95% CI: 88.7-100.0) for all platforms tested.

Technological Characteristics

Real-time RT-PCR assay. Instrumentation: Applied Biosystems (ABI) 7500 Fast Dx. Nucleic acid extraction platforms: QIAGEN EZ1 Advanced XL (EZ1 DSP Virus Kit, EZ1 RNA Tissue Mini Kit) and Roche MagNA Pure 96 (DNA and Viral NA Small Volume Kit). Analyte: Viral RNA. Detection: Fluorescently labeled hydrolysis probes. Energy source: Electrical (PCR instrument).

Indications for Use

Indicated for qualitative detection, subtyping, or genotyping of influenza A and B viruses in human upper and lower respiratory tract specimens or viral culture from patients with signs/symptoms of respiratory infection. Not for sole basis of treatment decisions. Requires training by CDC 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 (K133869)
• Influenza A Subtyping Kit (VER 2) (K161556)
• Influenza B Lineage Genotyping Kit (K140857)
• Influenza A/H5 Subtyping Kit (VER 3) (K153148)

Submission Summary (Full Text)

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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an emblem that features a stylized image of three human profiles facing to the right, with a design that resembles a bird or eagle above them.

August 9, 2017

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

Centers for Disease Control and Prevention Yon Yu, Pharm. D. Associate Director for Regulatory Affairs Office of the Director National Center for Emerging and Zoonotic Infectious Diseases 1600 Clifton Road, MS E-51 Atlanta, GA 30329-4027

Re: K172091

Trade/Device Names: 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, and Influenza A/H5 Subtyping Kit (VER 3) Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory Viral Panel Multiplex Nucleic Acid Assay Regulatory Class: Class II Product Code: OZE, OEP, NXD, OQW, NSU, OOI Dated: July 10, 2017 Received: July 12, 2017

Dear Dr. Yu:

We have reviewed your Section 510(k) premarket notification of intent to market the devices referenced above and have determined the devices are 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 devices, subject to the general controls provisions of the Act. 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 devices are classified (see above) into either class II (Special Controls) or class III (PMA), they may be subject to additional controls. Existing major regulations affecting your devices can be found in the Code of Federal Regulations. Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your devices 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 devices comply with other requirements of the Act

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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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820): and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your devices on our labeling regulation (21 CFR Part 801). please contact the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely,

Uwe Scherf -S

Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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# Indications for Use

510(k) Number (if known) K172091

### Device Name

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, and Influenza A/H5 Subtyping Kit (VER 3)

Indications for Use (Describe)

## CDC Human Influenza Virus 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 Applied Biosystems (ABI) 7500 Fast Dx Real-Time PCR instrument 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 [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;
- o 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

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# CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel -Influenza A Subtyping Kit (VER 2):

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 Applied Biosystems (ABI) 7500 Fast Dx Real-Time PCR instrument 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.

# CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel -Influenza B Lineage Genotyping Kit:

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 Applied Biosystems (ABI) 7500 Fast Dx Real-Time PCR instrument in conjunction with clinical and epidemiological information:

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- 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 [NPS], nasal 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 found in approximately equal proportion.

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.

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 Virus Real-Time RT-PCR Diagnostic Panel -Influenza A/H5 Subtyping Kit (VER 3):

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 (tRT-PCR) assays on an Applied Biosystems (ABI) 7500 Fast Dx Real-Time PCR instrument 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(H1)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

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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.

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

> Prescription Use (Part 21 CFR 801 Subpart D)

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

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New Traditional 510(k) CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Parliyang Kit, Influenza A Subtyping Kit, Influenza B Lineage Genotyping Kit, Influenza A/H5 Subtyping Kit

### 8. 510(k) Summary

#### GENERAL INFORMATION I.

Submitter: Centers for Disease Control and Prevention 1600 Clifton Road, NE Atlanta, GA 30333

Contact Person: CDR Yon Yu, Pharm. D. Associate Director for Regulatory Affairs Office of the Director National Center for Emerging and Zoonotic Infectious Diseases Centers for Disease Control and Prevention 1600 Clifton RD, MS E-51; Atlanta, GA 30329-4027 Phone: [phone] Fax: [phone] Email: [e-mail]

# Date Prepared: July 10, 2017

#### DEVICE INFORMATION II.

| Proprietary Name: | CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel,<br>Influenza A/B Typing Kit, Influenza A Subtyping Kit (VER 2),<br>Influenza B Lineage Genotyping Kit, and Influenza A/H5 Subtyping<br>Kit (VER 3) |
|------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Common Name: | 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 |
| 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, OOI, NXD, OEP, OQW |
| Panel: | Microbiology |

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New Traditional 510(k) CDC Human Influenza Vins Real-Time RT-PCR Diagnostic Parel-Influenza A Subyping Kit, Influenza B Lineage Genotying Kit, Influenza A/H5 Subtyping Kit

### III. PREDICATE DEVICE

CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel, Influenza A/B Typing Kit (K133869), Influenza A Subtyping Kit (VER 2) (K161556), Influenza B Lineage Genotyping Kit (K140857), and Influenza A/H5 Subtyping Kit (VER 3) (K153148)

### IV. DEVICE DESCRIPTION

The CDC Human Influenza Real-Time RT-PCR Diagnostic Panel is used in real-time RT-PCR (rRT-PCR) assays on the Applied Biosystems® (ABI) 7500 Fast Dx 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 of influenza A(H3) and A(H1)pdm09 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.

### INTENDED USE V.

# CDC Human Influenza Virus 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 Applied Biosystems (ABI) 7500 Fast Dx Real-Time PCR instrument 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 [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.

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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.

# CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel - Influenza A Subtyping Kit (VER 2):

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 Applied Biosystems (ABI) 7500 Fast Dx Real-Time PCR instrument 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.

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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.

# CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel - Influenza B Lineage Genotyping Kit:

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 Applied Biosystems (ABI) 7500 Fast Dx Real-Time PCR instrument 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 [NPS], nasal 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 found in approximately equal proportion.

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.

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 Virus Real-Time RT-PCR Diagnostic Panel - Influenza A/H5 Subtyping Kit (VER 3):

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 Applied Biosystems (ABI) 7500 Fast Dx Real-Time PCR instrument in conjunction with clinical and epidemiological information:

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New Traditional 510(k) CDC Human Influenza Vins Real-Time RT-PCR Diagnostic Parel-Influenza A Subyping Kit, Influenza B Linerge Gencyping Kit, Influenza A/H5 Subtyping Kit

- . 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.

#### TECHNOLOGICAL CHARACTERISTICS VI.

The technological characteristics of the modified CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel- Influenza A/B Typing Kit, Influenza A Subtyping Kit, Influenza B Lineage Genotyping Kit, and Influenza A/H5 Subtyping Kit remain the same as their respective predicate device. Additional options for viral RNA isolation are added to the CDC device to allow use of more recently available commercial nucleic acid isolation platforms and their accompanying chemistries.

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New Traditional 510(k) CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Parliyang Kit, Influenza A Subtyping Kit, Influenza B Lineage Genotyping Kit, Influenza A/H5 Subtyping Kit

### SUBSTANTIAL EQUIVALENCE COMPARISON VII.

The CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel, Influenza A/B Typing Kit (K133869), Influenza A Subtyping Kit (VER 2) (K161556), Influenza B Lineage Genotyping Kit (K140857), and Influenza A/H5 Subtyping Kit (VER 3) (K153148) will serve as the predicates for the proposed change to each of the bundled devices. See tables 8-1 through 8-4 below for a detailed comparison of each device to the corresponding predicate.

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New Traditional 510(k)
CDC Human Influenza Vins Real-Time RT-PCR Diagostic Parel-Influenza A Subtyping Kit, Influenza B Lineage Genotyping Kit, Influerza A/H5 Subtyping Kit

| Item | Predicate Device | Proposed Device | | | | |
|----------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------|-------------------------------|--|------|--|
| CDC Human Influenza Virus Real-Time RT-PCR<br>Diagnostic Panel Diagnostic Panel, Influenza A/B<br>Typing Kit [K133869]<br> | The Influenza A/B Typing Kit contains reagents and<br>controls of the CDC Human Influenza Virus Real-<br>Time RT-PCR Diagnostic Panel and is intended for<br>use in real-time RT-PCR (rRT-PCR) assays on an<br>Applied Biosystems (ABI) 7500 Fast Dx Real-Time<br>PCR instrument in conjunction with clinical and<br>epidemiological information:<br>For qualitative detection of influenza virus<br>type A or B viral RNA in upper respiratory<br>tract clinical specimens (including<br>nasopharyngeal swabs [NPS], nasal swabs<br>[NS], throat swabs [TS], nasal aspirates<br>[NA], nasal washes [NW] and dual<br>nasopharyngeal/throat swabs [NPS/TS]) and<br>lower respiratory tract specimens (including<br>bronchoalveolar lavage [BAL], bronchial<br>wash [BW], tracheal aspirate [TA], sputum,<br>and lung tissue) from human patients with<br>signs and symptoms of respiratory infection<br>and/or from viral culture; To provide epidemiologic information for<br>surveillance of circulating influenza viruses. | Same | | | | |
| Intended Use | Performance characteristics for influenza were<br>established during a season when seasonal influenza<br>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 influenza<br>virus was the predominant influenza A virus in<br>circulation. Performance characteristics may vary<br>with other emerging influenza A viruses.<br><br>Negative results do not preclude influenza virus<br>infection and should not be used as the sole basis for<br>treatment or other patient management decisions.<br>Conversely, positive results do not rule out bacterial<br>infection or co-infection with other viruses. The<br>agent detected may not be the definite cause of<br>disease.<br><br>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.<br>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 | | Influenza A viruses (animal and human), influenza B | CDC instructors or designees. | | Same | |
| <b>Organism</b><br><b>Detected</b> | Influenza A viruses (animal and human), influenza B viruses | Same | | | | |

# Table 8-1: Device Comparison

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New Traditional 510(k)

New Traditional 510(k)
CDC Human Influenza Vins Real-Time RT-PCR Diagostic Parel-Influenza A Subtyping Kit, Influenza B Lineage Genotyping Kit, Influerza A/H5 Subtyping Kit

| Specimen Types | Nasopharyngeal swabs, nasal swabs, throat swabs,<br>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 I,<br>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,<br>QIAGEN<br>• NucliSENS® easyMAG®, bioMerieux | • 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<br>• MagNA Pure LC - Total Nucleic Acid Kit, Roche<br>• QIAcube – QIAamp® DSP Viral RNA Mini Kit,<br>QIAGEN<br>• NucliSENS® easyMAG®, bioMerieux<br>• EZ1 Advanced XL – EZ1 DSP Virus Kit and EZ1 RNA<br>Tissue Mini Kit, QIAGEN<br>• MagNA Pure 96 - DNA and Viral NA Small Volume<br>Kit, Roche |
| Enzyme Master<br>Mix | Invitrogen SuperScript™ III Platinum® One-Step<br>Quantitative RT-PCR Kit (with or without ROX)<br>OR Quanta BioSciences qScript™ One-Step qRT-<br>PCR Kit, Low ROX | Same |
| Required<br>Instrumentation | Applied Biosystems 7500 Fast Dx Real-Time PCR<br>Instrument with SDS software version 1.4 | Same |

# Table 8-2: Device Comparison

| | Predicate Device | Proposed Device |
|-----------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------|
| Item | CDC Human Influenza Virus Real-Time RT-PCR<br>Diagnostic Panel Diagnostic Panel, Influenza A<br>Subtyping Kit (VER 2) [K161556] | CDC Human Influenza Virus Real-Time RT-<br>PCR Diagnostic Panel Diagnostic Panel,<br>Influenza A Subtyping Kit (VER 2) |
| | The Influenza A Subtyping Kit contains reagents and<br>controls of the CDC Human Influenza Virus Real-<br>Time RT-PCR Diagnostic Panel and is intended for<br>use in real-time RT-PCR (rRT-PCR) assays on an<br>Applied Biosystems (ABI) 7500 Fast Dx Real-Time<br>PCR instrument in conjunction with clinical and<br>epidemiological information:<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<br>[NS], throat swabs [TS], nasal aspirates [NA],<br>nasal washes [NW] and dual<br>nasopharyngeal/throat swabs [NPS/TS]) and<br>lower respiratory tract specimens (including<br>bronchoalveolar lavage [BAL], bronchial wash<br>[BW], tracheal aspirate [TA], sputum, and lung<br>tissue) from human patients with signs and<br>symptoms of respiratory infection and/or from<br>viral culture;<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 influenza<br>viruses A(H1N1) and A(H3N2) were the predominant<br>influenza A viruses in circulation and during a season<br>when the A(H1N1)pdm09 influenza virus was the | Same |
| Intended Use | | |
| | | |
| | 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…