Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description and intended use focus on standard real-time RT-PCR technology and reagents for detecting and characterizing influenza viruses. There is no mention of AI or ML in the text. The performance studies described are standard analytical and clinical evaluations for a diagnostic assay, not studies related to AI/ML model training or validation.

Therapeutic

No
The device is described as a diagnostic panel used for the qualitative detection and characterization of influenza virus RNA, and to provide epidemiological information for surveillance. It does not treat or alleviate disease, which would make it a therapeutic device.

Diagnostic

Yes
The "Intended Use / Indications for Use" section explicitly states that the kit is used for "qualitative detection of influenza virus type A or B viral RNA" in clinical specimens and for "determination of the subtype" and "genetic lineage" of influenza viruses. Furthermore, the "Device Description" states it is used for "in vitro qualitative detection and characterization of influenza virus RNA in respiratory specimens." These are all diagnostic functions.

SaMD (Software as a Medical Device)

No

The device description explicitly states that the kits consist of "oligonucleotide primers, fluorescently labeled hydrolysis probes, and controls," which are physical reagents, not software. The device is a diagnostic assay kit used with a hardware instrument (Applied Biosystems 7500 Fast Dx Real-Time PCR system).

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use: The intended use explicitly states that the kits are for "qualitative detection," "determination of the subtype," and "determination of the genetic lineage" of influenza viruses from "human patients" using "clinical specimens." This is a clear indication of a diagnostic purpose.
Device Description: The device description states that the panel is used for the "in vitro qualitative detection and characterization of influenza virus RNA in respiratory specimens from patients presenting with influenza-like illness (ILI)." "In vitro" means outside of the living body, which is a key characteristic of IVDs.
Clinical Performance Evaluation: The submission includes a "Clinical Performance Evaluation" using "retrospective clinical specimens" from human patients. This type of study is conducted to demonstrate the performance of a diagnostic device in a clinical setting.
Predicate Devices: The submission lists predicate devices with K numbers, which are FDA premarket notification numbers for medical devices, including IVDs. The names of the predicate devices also clearly indicate they are diagnostic panels.

The information provided strongly aligns with the definition and characteristics of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

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

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:

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 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.

Product codes (comma separated list FDA assigned to the subject device)

OZE, NSU, OOI, NXD, OEP, OQW

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.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

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.

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Not Found

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Analytical Performance Evaluation

Analytical Sensitivity - Limit of Detection (LOD) Equivalency Study: The study demonstrated LOD equivalency between cleared extraction methods and the Roche MagNA Pure 96 or QIAGEN EZ1 Advanced XL instruments. 5-fold serial dilutions of influenza A(H3N2) virus were tested. Each investigational instrument and method showed an equivalent endpoint concentration when compared to the cleared instrument and method.
Analytical Precision – Reproducibility Study: A reproducibility study was performed to assess the Roche MagNA Pure 96 and QIAGEN EZ1 Advanced XL instruments. A blinded panel of contrived samples (moderate positive, low positive, negative) was assembled. Three separate testing sites were selected for each extraction instrument platform. Each instrument and method showed good reproducibility with 100% agreement across different sites, analysts, and days.

Clinical Performance Evaluation

Clinical Performance Evaluation: The clinical performance of the Roche MagNA Pure 96 and QIAGEN EZ1 Advanced XL instruments was evaluated for equivalency to a currently cleared method. 30 specimens previously determined positive for influenza A(H3) virus and 30 negative specimens were evaluated. Each method demonstrated 100% agreement with the comparator.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Analytical Sensitivity - Limit of Detection (LOD) Equivalency Study:

Roche MagNA Pure 96 / DNA and Viral NA Small Volume Kit:
- InfA: 3/3 positive at 10^1.1 EID50/mL, 1/3 at 10^0.4 EID50/mL
- H3: 3/3 positive at 10^1.1 EID50/mL, 0/3 at 10^0.4 EID50/mL
QIAGEN EZ1 Advanced XL / DSP Virus Kit:
- InfA: 3/3 positive at 10^1.1 EID50/mL, 1/3 at 10^0.4 EID50/mL
- H3: 3/3 positive at 10^1.1 EID50/mL, 0/3 at 10^0.4 EID50/mL
QIAGEN EZ1 Advanced XL / RNA Tissue Mini Kit:
- InfA: 3/3 positive at 10^1.1 EID50/mL, 2/3 at 10^0.4 EID50/mL
- H3: 3/3 positive at 10^1.1 EID50/mL, 2/3 at 10^0.4 EID50/mL

Analytical Precision – Reproducibility:

QIAGEN EZ1 Advanced XL, EZ1 DSP Virus Kit: 100.0% agreement (95% CI: 88.7-100.0) for all panels (Moderate A(H3), Low A(H3), Negative) and all primer/probe sets (InfA, H3, RP).
QIAGEN EZ1 Advanced XL, EZ1 RNA Tissue Mini Kit: 100.0% agreement (95% CI: 88.7-100.0) for all panels (Moderate A(H3), Low A(H3), Negative) and all primer/probe sets (InfA, H3, RP).
Roche MagNA Pure 96, DNA and Viral NA Small Volume Kit: 100.0% agreement (95% CI: 88.7-100.0) for all panels (Moderate A(H3), Low A(H3), Negative) and all primer/probe sets (InfA, H3, RP).

Clinical Performance Evaluation:

Roche MagNA Pure 96, DNA and Viral NA Small Volume Kit: 100% agreement (95% CI: 88.7-100.0) for both positive (30/30) and negative (30/30) specimens.
QIAGEN EZ1 Advanced XL, EZ1 DSP Virus Kit: 100% agreement (95% CI: 88.7-100.0) for both positive (30/30) and negative (30/30) specimens.
QIAGEN EZ1 Advanced XL, EZ1 RNA Tissue Mini Kit: 100% agreement (95% CI: 88.7-100.0) for both positive (30/30) and negative (30/30) specimens.

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

K133869, K161556, K140857, K153148

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

Regulation Number and Section

§ 866.3980 Respiratory viral panel multiplex nucleic acid assay.

(a)
Identification. A respiratory viral panel multiplex nucleic acid assay is a qualitative in vitro diagnostic device intended to simultaneously detect and identify multiple viral nucleic acids extracted from human respiratory specimens or viral culture. The detection and identification of a specific viral nucleic acid from individuals exhibiting signs and symptoms of respiratory infection aids in the diagnosis of respiratory viral infection when used in conjunction with other clinical and laboratory findings. The device is intended for detection and identification of a combination of the following viruses:(1) Influenza A and Influenza B;
(2) Influenza A subtype H1 and Influenza A subtype H3;
(3) Respiratory Syncytial Virus subtype A and Respiratory Syncytial Virus subtype B;
(4) Parainfluenza 1, Parainfluenza 2, and Parainfluenza 3 virus;
(5) Human Metapneumovirus;
(6) Rhinovirus; and
(7) Adenovirus.
(b)
Classification. Class II (special controls). The special controls are:(1) FDA's guidance document entitled “Class II Special Controls Guidance Document: Respiratory Viral Panel Multiplex Nucleic Acid Assay;”
(2) For a device that detects and identifies Human Metapneumovirus, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Human Metapneumovirus (hMPV) Using Nucleic Acid Assays;” and
(3) For a device that detects and differentiates Influenza A subtype H1 and subtype H3, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Detection and Differentiation of Influenza A Virus Subtypes Using Multiplex Nucleic Acid Assays.” See § 866.1(e) for the availability of these guidance documents.

Summary

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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

1

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 (800) 638-2041 or (301) 796-7100 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 (800) 638-2041 or (301) 796-7100 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

5

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: 404-639-3046 Fax: 404-498-1106 Email: fkb8@cdc.gov

Date Prepared: July 10, 2017

DEVICE INFORMATION II.

| Proprietary 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) |
|------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Common Name: | Influenza A/B Typing Kit, Influenza A Subtyping Kit, Influenza B
Lineage Genotyping Kit, and Influenza A/H5 Subtyping Kit |
| Regulation Section: | 866.3980-Respiratory viral panel multiplex nucleic acid assay |
| Subsequent Regulation
Sections: | 866.3332-Reagents for detection of specific novel influenza A
viruses
862.2570-Instrumentation for clinical multiplex systems |
| Device Classification: | Class II |
| Product Code: | OZE |
| Subsequent Product Codes: | NSU, OOI, NXD, OEP, OQW |
| Panel: | Microbiology |

7

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.

8

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.

9

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:

10

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.

11

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.

12

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
Diagnostic Panel Diagnostic Panel, Influenza A/B
Typing Kit [K133869]
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.	Same
Intended Use	Performance characteristics for influenza were
established during a season when seasonal influenza
viruses A(H1N1) and A(H3N2) were the
predominant influenza A viruses in circulation and
during a season when the A(H1N1)pdm09 influenza
virus was the predominant influenza A virus in
circulation. Performance characteristics may vary
with other emerging influenza A viruses.

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. | | | | | |
| Organism | | Influenza A viruses (animal and human), influenza B | CDC instructors or designees. | | Same | |
| Organism
Detected | Influenza A viruses (animal and human), influenza B viruses | Same | | | | |

Table 8-1: Device Comparison

13

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,
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
Characteristics | Real-time RT-PCR based assay | Same |
| Nucleic Acid
Extraction | • QIAamp® DSP Viral RNA Mini Kit, QIAGEN
• MagNA Pure Compact -Nucleic Acid Isolation Kit I,
Roche
• MagNA Pure Compact - RNA Isolation Kit, Roche
• MagNA Pure LC - Total Nucleic Acid Kit, Roche
• QIAcube – QIAamp® DSP Viral RNA Mini Kit,
QIAGEN
• NucliSENS® easyMAG®, bioMerieux | • QIAamp® DSP Viral RNA Mini Kit, QIAGEN
• MagNA Pure Compact -Nucleic Acid Isolation Kit I,
Roche
• MagNA Pure Compact – RNA Isolation Kit, Roche
• MagNA Pure LC - Total Nucleic Acid Kit, Roche
• QIAcube – QIAamp® DSP Viral RNA Mini Kit,
QIAGEN
• NucliSENS® easyMAG®, bioMerieux
• EZ1 Advanced XL – EZ1 DSP Virus Kit and EZ1 RNA
Tissue Mini Kit, QIAGEN
• MagNA Pure 96 - DNA and Viral NA Small Volume
Kit, Roche |
| Enzyme Master
Mix | Invitrogen SuperScript™ III Platinum® One-Step
Quantitative RT-PCR Kit (with or without ROX)
OR Quanta BioSciences qScript™ One-Step qRT-
PCR Kit, Low ROX | Same |
| Required
Instrumentation | Applied Biosystems 7500 Fast Dx Real-Time PCR
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
Diagnostic Panel Diagnostic Panel, Influenza A
Subtyping Kit (VER 2) [K161556]	CDC Human Influenza Virus Real-Time RT-
PCR Diagnostic Panel 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.

14

New Traditional 50(X)
CDC Human Millenza Virus Rel-Time RT-PCR Diagostic Parel-Influenza AB Typing Kit, Influenza B Lineage Genotyping Kit, Influerza
A H5 Subyping Kit

15

Item	Predicate Device	Proposed Device
Intended Use	CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel Diagnostic Panel, Influenza B Lineage Genotyping Kit [K140857]
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 genbotyping 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.	Same
Organism
Detected	Influenza B virus, lineages B/Victoria and B/Yamagata	Same
Specimen Types	Nasopharyngeal swabs, nasal swabs, throat swabs, nasal aspirates, nasal washes and dual nasopharyngeal/throat swabs from human patients with signs and symptoms of respiratory infection and/or from viral culture	Same
Technological
Characteristics	Real-time RT-PCR based assay	Same
Nucleic Acid
Extraction		• QIAamp® DSP Viral RNA Mini Kit, QIAGEN
• MagNA Pure Compact –Nucleic Acid Isolation Kit I, Roche
• MagNA Pure Compact – RNA Isolation Kit, Roche
• MagNA Pure LC - Total Nucleic Acid Kit, Roche
• QIAcube – QIAamp® DSP Viral RNA Mini Kit, QIAGEN
• NucliSENS® easyMAG®, bioMerieux		• QIAamp® DSP Viral RNA Mini Kit, QIAGEN
• MagNA Pure Compact –Nucleic Acid Isolation Kit I, Roche
• MagNA Pure Compact – RNA Isolation Kit, Roche
• MagNA Pure LC - Total Nucleic Acid Kit, Roche
• QIAcube – QIAamp® DSP Viral RNA Mini Kit, QIAGEN
• NucliSENS® easyMAG®, bioMerieux	• NucliSENS® easyMAG®, bioMerieux
		• EZ1 Advanced XL – EZ1 DSP Virus Kit and EZ1
RNA Tissue Mini Kit, QIAGEN
		• MagNA Pure 96 - DNA and Viral NA Small Volume
Kit, Roche

Table 8-3: Device Comparison

16

New Traditional 510(k)

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

| Enzyme Master
Mix | Invitrogen SuperScript™ III Platinum® One-Step
Quantitative RT-PCR Kit (with or without ROX) OR
Quanta BioSciences qScript™ One-Step qRT-PCR
Kit, Low ROX | Same |
|-----------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------|
| Required
Instrumentation | Applied Biosystems 7500 Fast Dx Real-Time PCR
Instrument with SDS software version 1.4 | Same |

	Predicate Device	Proposed Device
Item	CDC Human Influenza Virus Real-Time RT-PCR
Diagnostic Panel Diagnostic Panel, Influenza A/H5
Subtyping Kit (VER 3) [K153148]	CDC Human Influenza Virus Real-Time RT-
PCR Diagnostic Panel 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:
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	Same
Intended Use	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 | |
| 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. | | |
| Organism
Detected | Influenza A viruses (animal and human), Influenza A
subtype A(H5) (Asian lineage) | Same |
| Specimen Types | Human respiratory specimens and viral culture | Same |
| Technological
Characteristics | Real-time RT-PCR based assay | Same |
| Nucleic Acid
Extraction | • QIAamp® DSP Viral RNA Mini Kit, QIAGEN
• MagNA Pure Compact -Nucleic Acid Isolation Kit I,
Roche
• MagNA Pure Compact - RNA Isolation Kit, Roche
• MagNA Pure LC - Total Nucleic Acid Kit, Roche
• QIAcube - QIAamp® DSP Viral RNA Mini Kit, QIAGEN
• NucliSENS® easyMAG®, bioMerieux | • QIAamp® DSP Viral RNA Mini Kit, QIAGEN
• MagNA Pure Compact -Nucleic Acid Isolation Kit I,
Roche
• MagNA Pure Compact - RNA Isolation Kit, Roche
• MagNA Pure LC - Total Nucleic Acid Kit, Roche
• QIAcube – QIAamp® DSP Viral RNA Mini Kit,
QIAGEN
• NucliSENS® easyMAG®, bioMerieux
• EZ1 Advanced XL - EZ1 DSP Virus Kit and EZ1
RNA Tissue Mini Kit, QIAGEN
• MagNA Pure 96 - DNA and Viral NA Small Volume
Kit, Roche |
| Enzyme Master
Mix | Invitrogen SuperScript™ III Platinum® One-Step
Quantitative RT-PCR Kit (with or without ROX) OR
Quanta BioSciences qScript™ One-Step qRT-PCR
Kit, Low ROX | Same |
| Required
Instrumentation | Applied Biosystems 7500 Fast Dx Real-Time PCR
Instrument with SDS software version 1.4 | Same |

Table 8-4: Device Comparison

appropriate infection control precautions for novel

17

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

VIII. ANALYTICAL PERFORMANCE EVALUATION

Analytical Sensitivity - Limit of Detection (LOD) Equivalency Study

The LOD performance equivalency between a cleared extraction method and either the Roche MagNA Pure 96 or the QIAGEN EZ1 Advanced XL instruments was demonstrated by testing 5-fold serial dilutions of a characterized influenza A(H3N2) virus, A/Hong Kong/4801/2014, of known infectious dose 50% titer. Virus dilutions were prepared using a suspension of beta-propiolactone (BPL) treated A549 cells in viral transport medium (VTM) as diluent. Triplicate samples of each dilution were extracted separately with the cleared Roche MagNA Pure Compact RNA Isolation Kit as well as the investigational instrument and method. The Roche MagNA Pure 96 was evaluated with the Roche DNA and Viral NA Small Volume Kit. The QIAGEN EZ1 Advanced XL was evaluated with the QIAGEN DSP Virus Kit and the QIAGEN RNA Tissue Mini Kit. Extracted RNA was tested with the InfA and H3 assays from the CDC Human Influenza Real-Time RT-PCR Diagnostic Panel using Invitrogen SuperScript™ III Platinum® One-Step RT-PCR System (Invitrogen SuperScript™) and utilizing the Applied Biosystems 7500 Fast Dx (ABI 7500 Fast Dx) real-time PCR system. The acceptance criteria for LOD equivalence between the cleared and investigational methods was defined as a demonstration of 100% positivity (3 out of 3 replicates) at either the same endpoint concentration or within one 5-fold dilution. The results of the study are summarized in Tables 8-5 to 8-7. Each investigational instrument and method showed an equivalent endpoint concentration when compared to the cleared instrument and method.

18

| Titer (EID50/mL)¹ | Roche MagNA Pure
Compact- RNA
Isolation Kit | | Roche MagNA Pure
96 - DNA and Viral
NA Small Volume Kit | |
|-------------------|---------------------------------------------------|-----|---------------------------------------------------------------|-----|
| | InfA | H3 | InfA | H3 |
| 103.2 | 3/3 | 3/3 | 3/3 | 3/3 |
| | (+) | (+) | (+) | (+) |
| 102.3 | 3/3 | 3/3 | 3/3 | 3/3 |
| | (+) | (+) | (+) | (+) |
| 101.8 | 3/3 | 3/3 | 3/3 | 3/3 |
| | (+) | (+) | (+) | (+) |
| 101.1 | 3/3 | 3/3 | 3/3 | 3/3 |
| | (+) | (+) | (+) | (+) |
| 100.4 | 1/3 | 0/3 | 2/3 | 2/3 |
| | (+) | (+) | (+) | (+) |

Table 8-5. LOD Equivalency Determination - Roche MagNA Pure 96/ DNA and Viral NA Small Volume Kit

1EID50 = Egg Infectious Dose 50%

Table 8-6. LOD Equivalency Determination – QIAGEN EZ1 Advanced XL/ DSP Virus Kit

| Titer (EID 50 /mL) | Roche MagNA Pure
Compact- RNA
Isolation Kit | | QIAGEN EZ1
Advanced XL – DSP
Virus Kit | |
|------------------------------------------------------------|---------------------------------------------------|------------|----------------------------------------------|------------|
| | InfA | H3 | InfA | H3 |
| 10 3.2 | 3/3
(+) | 3/3
(+) | 3/3
(+) | 3/3
(+) |
| 10 2.3 | 3/3
(+) | 3/3
(+) | 3/3
(+) | 3/3
(+) |
| 10 1.8 | 3/3
(+) | 3/3
(+) | 3/3
(+) | 3/3
(+) |
| 10 1.1 | 3/3
(+) | 3/3
(+) | 3/3
(+) | 3/3
(+) |
| 10 0.4 | 1/3
(+) | 0/3
(+) | 1/3
(+) | 0/3
(+) |

19

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

Titer (EID50/mL)	Roche MagNA Pure Compact- RNA Isolation Kit		QIAGEN EZ1 Advanced XL – RNA Tissue Mini Kit
	InfA	H3	InfA	H3
$10^{3.2}$	3/3
(+)	3/3
(+)	3/3
(+)	3/3
(+)
$10^{2.3}$	3/3
(+)	3/3
(+)	3/3
(+)	3/3
(+)
$10^{1.8}$	3/3
(+)	3/3
(+)	3/3
(+)	3/3
(+)
$10^{1.1}$	3/3
(+)	3/3
(+)	3/3
(+)	3/3
(+)
$10^{0.4}$	1/3
(+)	0/3
(+)	2/3
(+)	2/3
(+)

Table 8-7. LOD Equivalency Determination - QIAGEN EZ1 Advanced XL / RNA Tissue Mini Kit

Analytical Precision – Reproducibility

A study was performed to assess the reproducibility of the Roche MagNA Pure 96 and QIAGEN EZ1 Advanced XL instruments. The Roche MagNA Pure 96 was evaluated with the Roche DNA and Viral NA Small Volume Kit. The QIAGEN EZ1 Advanced XL was evaluated with the QIAGEN DSP Virus Kit and the QIAGEN RNA Tissue Mini Kit. A blinded panel of contrived samples containing a background of BPL treated A549 cells in VTM was assembled by adding a BPL treated influenza A(H3N2) virus, A/Hong Kong/4801/2014. The samples included a moderate positive sample, a low positive sample near the established assay LOD for the CDC Influenza A Subtyping Kit, and a negative sample consisting of background A549 cells and VTM. Three separate testing sites were selected for each extraction instrument platform. The sample panel was tested 5 times by two different analysts at each site over 5 different days. Analysts performed extractions with the investigational instrument and method and tested nucleic acids with the InfA, H3, and RP assays from the from the CDC Influenza A Subtyping Kit using Invitrogen SuperScript™ and utilizing the ABI 7500 Fast Dx real-time PCR system. The results for the reproducibility studies of each instrument and method are summarized in Tables 8-8 to 8-10. Each instrument and method showed good reproducibility with 100% agreement across different sites, analysts, and days.

20

Panel	Primer		Site 1		Site 2			Site 3
Sample	/ Probe										Agreement
Total	95%CI
	Set	Agreement	Ave. Ct	%CV	Agreement	Ave. Ct	%CV	Agreement	Ave. Ct	%CV
A(H3)	InfA	10/10	25.46	2.36	10/10	26.45	2.80	10/10	28.46	4.12	30/30	100.0 (88.7-100.0)
Moderate	H3	10/10	27.15	2.92	10/10	28.22	3.25	10/10	28.61	4.40	30/30	100.0 (88.7-100.0)
	RP	10/10	22.45	1.44	10/10	23.47	2.42	10/10	24.50	5.68	30/30	100.0 (88.7-100.0)
A(H3)	InfA	10/10	28.96	3.41	10/10	30.35	1.87	10/10	32.21	2.55	30/30	100.0 (88.7-100.0)
Low	нз	10/10	30.56	2.60	10/10	31.70	1.96	10/10	32.63	3.18	30/30	100.0 (88.7-100.0)
	RP	10/10	22.26	1.08	10/10	23.53	1.12	10/10	24.58	4.63	30/30	100.0 (88.7-100.0)
	InfA	10/10	0.00	n/a	10/10	0.00	n/a	10/10	0.00	n/a	30/30	100.0 (88.7-100.0)
Negative	H3	10/10	0.00	n/a	10/10	0.00	n/a	10/10	0.00	n/a	30/30	100.0 (88.7-100.0)
	RP	10/10	24.80	1.49	10/10	25.35	3.91	10/10	26.93	4.83	30/30	100.0 (88.7-100.0)
n/a = not applicable
					Table 8-9. Reproducibility Summary -QIAGEN EZ1 Advanced XL, EZ1 RNA Tissue Mini Kit
	Primer		Site 1			Site 2			Site 3
Panel	/ Probe										Agreement	95%CI
Sample	Set	Agreement	Ave. Ct	%CV	Agreement	Ave. Ct	%CV	Agreement	Ave. Ct	%CV	Total
	InfA	10/10	25.97	3.48	10/10	26.40	4.06	10/10	28.59	2.01	30/30	100.0 (88.7-100.0)
A(H3)
Moderate	H3	10/10	27.40	4.13	10/10	27.56	2.35	10/10	28.66	0.79	30/30	100.0 (88.7-100.0)
	RP	10/10	22.08	3.31	10/10	23.52	1.56	10/10	24.77	2.14	30/30	100.0 (88.7-100.0)
A(H3)	InfA	10/10	30.07	2.04	10/10	30.30	3.26	10/10	32.37	2.44	30/30	100.0 (88.7-100.0)
Low	H3	10/10	31.02	3.14	10/10	30.94	2.06	10/10	32.59	1.15	30/30	100.0 (88.7-100.0)
	RP	10/10	21.88	2.37	10/10	23.29	2.32	10/10	24.30	2.93	30/30	100.0 (88.7-100.0)
	InfA	10/10	0.00	n/a	10/10	0.00	n/a	10/10	0.00	n/a	30/30	100.0 (88.7-100.0)
Negative	H3	10/10	0.00	n/a	10/10	0.00	n/a	10/10	0.00	n/a	30/30	100.0 (88.7-100.0)
	RP	10/10	24.36	2.57	10/10	25.32	1.55	10/10	27.38	1.85	30/30	100.0 (88.7-100.0)
Table 8-10. Reproducibility Summary -Roche MagNA Pure 96, DNA and Viral NA Small Volume Kit
	Primer		Site 1		Site 2		Site 3
Panel	/ Probe										Agreement	95%CI
Sample	Set	Agreement	Ave. Ct	%CV	Agreement	Ave. Ct	%CV	Agreement	Ave. Ct	%CV	Total
	InfA	10/10	31.29	3.97	10/10	30.05	3.37	10/10	27.61	3.93	30/30	100.0 (88.7-100.0)
A(H3)	H3	10/10	32.00	3.36	10/10	31.92	3.32	10/10	28.44	4.05	30/30	100.0 (88.7-100.0)
Moderate	RP	10/10	27.16	4.07	10/10	24.25	1.66	10/10	23.35	3.48	30/30	100.0 (88.7-100.0)

Table 8-8. Reproducibility Summary -QIAGEN EZ1 Advanced XL, EZ1 DSP Virus Kit

n/a = not applicable

A(H3)

Negative

Low

InfA

H3

RP

InfA

нз

RP

10/10

2.97

2.54

3.85

n/a

3.66

10/10

34.91

35.45

26.97

0.00

29.40

2.86

2.75

0.98

n/a

1.36

10/10

31.40

32.37

23.11

0.00

25.58

3.07

3.30

2.70

n/a

2.91

30/30

100.0 (88.7-100.0)

33.49

35.35

24.22

0.00

26.64

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IX. CLINICAL PERFORMANCE EVALUATION

The clinical performance of the Roche MagNA Pure 96 and QIAGEN EZ1 Advanced XL instruments was evaluated to demonstrate equivalency to a method currently cleared with the CDC Human Influenza Real-Time Diagnostic Panel. The Roche MagNA Pure 96 was evaluated using the Roche DNA and Viral NA Small Volume Kit. The QIAGEN EZ1 Advanced XL was evaluated using the OIAGEN DSP Virus Kit and the OIAGEN RNA Tissue Mini Kit. The comparator was the Roche MagNA Pure Compact instrument using the RNA Isolation Kit. The study was performed internally using retrospective clinical specimens collected during the 2011-2012 and 2013-2014 influenza seasons. A total of thirty specimens that were previously determined to be positive for influenza A(H3) virus and thirty negative specimens were evaluated with the InfA, H3, and RP assays from the CDC Human Influenza Real-Time Diagnostic Panel. Testing was performed using Invitrogen SuperScript™ and utilizing the ABI 7500 Fast Dx real-time PCR system. The results are summarized in the Tables 8-11 to 8-13. Each method demonstrated 100% agreement with the comparator.

		Table 8-11. Retrospective Clinical Results- Roche MagNA Pure 96, DNA and Viral NA Small Volume Kit

| | | Roche MagNA Pure
Compact- RNA Isolation Kit | | | |
|---------------------------------------------------------------|----------|------------------------------------------------|-------|----------------------|------------|
| Roche MagNA Pure 96

DNA and Viral NA
Small Volume Kit | Positive | Negative | Total | Percent
Agreement | 95% CI |
| Positive | 30 | 0 | 30 | 100 | 88.7-100.0 |
| Negative | 0 | 30 | 30 | 100 | 88.7-100.0 |
| Total | 30 | 30 | 60 | | |

	Table 8-12. Retrospective Clinical Results- QIAGEN EZ1 Advanced XL, EZ1 DSP Virus Kit


Roche MagNA Pure
Compact- RNA Isolation Kit
QIAGEN EZ1
Advanced XL – EZ1
DSP Virus Kit	Positive	Negative	Total	Percent
Agreement	95% CI
Positive	30	0	30	100	88.7-100.0
Negative	0	30	30	100	88.7-100.0
Total	30	30	60

Table 8-13. Retrospective Clinical Results- OIAGEN EZ1 Advanced XL, EZ1 RNA Tissue Mini Kit

| | Roche MagNA Pure
Compact- RNA Isolation Kit | | | | |
|--------------------------------------------------------|------------------------------------------------|----------|-------|----------------------|------------|
| QIAGEN EZ1
Advanced XL – EZ1
RNA Tissue Mini Kit | Positive | Negative | Total | Percent
Agreement | 95% CI |
| Positive | 30 | 0 | 30 | 100 | 88.7-100.0 |
| Negative | 0 | 30 | 30 | 100 | 88.7-100.0 |
| Total | 30 | 30 | 60 | | |

22

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

X. CONCLUSION

Performance studies were conducted to evaluate the modification of the CDC Human Influenza Virus rRT-PCR Diagnostic Panel to add nucleic acid isolation options. Evaluation of the LOD equivalency, reproducibility, and clinical performance demonstrated that the modified device is substantially equivalent to the predicate. The change raises no new issues of safety and effectiveness and the indications for use remain the same.