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/HS Subtyping Kit

K190302 · Centers for Disease Control and Prevention · OZE · Mar 27, 2019 · Microbiology

Device Facts

• Record ID: K190302
• 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/HS Subtyping Kit
• Applicant: Centers for Disease Control and Prevention
• Product Code: OZE · Microbiology
• Decision Date: Mar 27, 2019
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3980
• Device Class: Class 2

Intended Use

The Influenza A/B Typing Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information: For qualitative detection of influenza virus type A or B viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], 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.

Device Story

Diagnostic panel consists of four kits (Influenza A/B Typing, A Subtyping, B Lineage Genotyping, A/H5 Subtyping) using rRT-PCR; inputs are respiratory specimens (swabs, aspirates, washes, BAL, sputum, tissue) or viral culture; reagents include primers, probes, and controls targeting conserved regions of M, NS, NP, and HA genes; detects influenza A, B, and specific subtypes/lineages (H1pdm09, H3, H5, Victoria, Yamagata); used in clinical/public health labs by trained personnel; output is qualitative detection/characterization of viral RNA; results support epidemiological surveillance and clinical management; device now compatible with additional FDA-cleared real-time PCR instruments (QuantStudio Dx, Rotor-Gene Q MDx) alongside original ABI 7500 Fast Dx.

Clinical Evidence

Retrospective study using 50 positive (10 each: A/H1pdm09, A/H3, A/H5, B/Victoria, B/Yamagata) and 50 negative clinical specimens. Contrived samples used for A/H5. Testing performed on Applied Biosystems QSDx and QIAGEN QMDx compared to 7500 Fast Dx. Results showed 100% PPA (50/50) and 100% NPA (50/50) for both instruments (95% CI: 92.9% to 100%). Reproducibility studies across three sites, two analysts, and five days showed >=93.3% agreement.

Technological Characteristics

Real-time RT-PCR assay; uses oligonucleotide primers and fluorescently labeled hydrolysis probes; targets conserved viral genes (M, NS, NP, HA); compatible with multiple nucleic acid extraction kits (e.g., QIAamp DSP, MagNA Pure, NucliSENS easyMAG); requires FDA-cleared real-time PCR instrumentation; enzyme master mixes include Invitrogen SuperScript III or Quanta qScript.

Indications for Use

Indicated for qualitative detection, subtyping, or lineage genotyping of influenza A and B viral RNA in human respiratory specimens (NPS, NS, TS, NA, NW, NPS/TS, BAL, BW, TA, sputum, lung tissue) from patients with signs/symptoms of respiratory infection or viral culture. Used for clinical diagnosis and epidemiological surveillance. Prescription use only.

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 (K172091)
• CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel: Influenza A Subtyping Kit (VER 2) (K172091)
• CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel: Influenza B Lineage Genotyping Kit (VER 1.1 and VER 2) (K172091)
• CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel: Influenza A/H5 Subtyping Kit (VER 3) (K181736)

Submission Summary (Full Text)

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March 27, 2019

Centers for Disease Control and Prevention CAPT Yon Yu, Pharm. D. Senior Advisor for Regulatory Affairs Division of Preparedness and Emerging Infections National Center for Emerging and Zoonotic Infectious Diseases 1600 Clifton Rd: MS VI 8-4 Atlanta, Georgia 30329-4027

Re: K190302

Trade/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 (VER 1.1 and VER 2), 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, NSU, OEP, NXD, OQW, OOI Dated: February 11, 2019 Received: February 12, 2019

Dear Dr. 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.

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Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely.

# Steven R. Gitterman -S

for

Uwe Scherf, 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) K190302

### 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 (VER 1.1 and VER 2), 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 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 seasonal influenza viruses A(H1N) 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 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 in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:

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

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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 seasonal influenza viruses A(H1N) 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 Virus Real-Time RT-PCR Diagnostic Panel - Influenza B Lineage Genotyping Kit (VER 1.1 and VER 2):

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

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

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

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

Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions. Conversely, positive results do not rule out bacterial infection with other viruses. The agent detected may not be the definite cause of disease.

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

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

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 ) assays on an in vitro diagnostic real-time

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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 seasonal influenza viruses A(H1N) 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 epidemiologic criteria for testing suspect A(H5) specimens. The definitive identification of influenza A(H5) (Asian lineage) either directly from patient specimens or from virus cultures requires additional laboratory testing, along with clinical and epidemiological assessment in consultation with national influenza surveillance experts.

Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions. Conversely, positive results do not rule out bacterial infection with other viruses. The agent detected may not be the definite cause of disease.

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

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

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

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. Senior Advisor for Regulatory Affairs Division of Preparedness and Emerging Infections National Center for Emerging and Zoonotic Infectious Diseases Centers for Disease Control and Prevention 1600 Clifton RD, MS V18-4; Atlanta, GA 30329-4027 Phone: [phone] Fax: [phone] Email: [e-mail]

### Date Prepared: February 11, 2019

#### 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 (VER 1.1 and VER 2), and<br>Influenza A/H5 Subtyping 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, NXD, OEP, OQW, OOI |
| Panel: | Microbiology |

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#### III. PREDICATE DEVICE

CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel (K181736 and K172091)

#### IV. DEVICE DESCRIPTION

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

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 [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

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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.

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

For the determination of the genetic lineage of human influenza B viruses as B/Victoria or . B/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 in circulation.

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

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

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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 remain the same. Additional options for real-time PCR instrumentation used with the CDC device to perform real-time RT-PCR assays are added to allow use of more recently available commercial instrument platforms.

#### VII. SUBSTANTIAL EQUIVALENCE COMPARISON

The CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel (K181736 and K172091), consisting of the Influenza A/B Typing Kit, Influenza A Subtyping Kit, Influenza B Lineage Genotyping Kit, and Influenza A/H5 Subtyping Kit will serve as the predicate for the proposed change. See tables 8-1 through 8-4 below for a detailed comparison to the predicate.

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| Item | Predicate Device<br>CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel Diagnostic Panel:<br>Influenza A/B Typing Kit [K172091] | Proposed Device<br>CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel Diagnostic Panel:<br>Influenza A/B Typing Kit |
|----------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 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:<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. To provide epidemiologic information for surveillance of circulating influenza viruses. | 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 <i>in vitro</i> diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit 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. 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.<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 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.<br>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. | 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 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.<br>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. |
| Organism Detected | Influenza A viruses (animal and human), influenza B viruses | Same |
| Specimen Types | Nasopharyngeal swabs, nasal swabs, throat swabs, nasal aspirates, nasal washes and dual nasopharyngeal/throat swabs, bronchoalveolar lavages, bronchial aspirates, bronchial washes, tracheal aspirates, sputum, and lung tissue from human patients with signs and symptoms of 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, 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®, bioMerieux<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 | • 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 |
| Enzyme Master<br>Mix | Invitrogen SuperScript™ III Platinum® One-Step 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 | • 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® version 1.0.4.1 and Epsilon version 1.0.1 software |

## Table 8-1: Device Comparison

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# New Traditional 510(k)
CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel

| 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 [K172091] | CDC Human Influenza Virus Real-Time RT-<br>PCR Diagnostic Panel Diagnostic Panel:<br>Influenza A Subtyping Kit |
| Intended Use | 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;To provide epidemiologic information for<br>surveillance of circulating influenza viruses. | 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>this kit in conjunction with clinical and<br>epidemiological information:<br>For determination of the subtype of seasonal<br>human influenza A viruses as seasonal<br>A(H3), and/or A(H1)pdm09 from viral RNA<br>in upper respiratory tract clinical specimens<br>(including nasopharyngeal swabs [NPS],<br>nasal swabs [NS], throat swabs [TS], nasal<br>aspirates [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. |
| | 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<br>predominant influenza A virus in circulation.<br>Performance characteristics may vary with other<br>emerging influenza A viruses. | 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. |
| | 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 agent<br>detected may not be the definite cause of disease. | 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. |
| | If infection with a novel influenza A virus is suspected<br>based on current clinical and epidemiological<br>screening criteria recommended by public health<br>authorities, specimens should be collected with<br>appropriate infection control precautions for novel<br>virulent influenza viruses and sent to state or local<br>health department for testing. Viral culture should not<br>be attempted unless a BSL 3E facility is available to<br>receive and culture 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 | 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<br>Detected | Influenza A viruses (animal and human), Swine-<br>origin influenza A viruses, Influenza A subtypes:<br>seasonal A(H3), A(H1)pdm09 | Same |
| 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…