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.

Device Description

The Influenza A/H5 Subtyping Kit contains components of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel that is used in real-time RT-PCR (rRT-PCR) assays on the ABI 7500 Fast Dx Real-Time PCR Instrument. The Influenza A/H5 Subtyping Kit consists of oligonucleotide primers and dual-labeled hydrolysis (TaqMan®) probes to be used in rRT-PCR for the in vitro qualitative detection and characterization of human influenza viruses from viral RNA in respiratory specimens from patients presenting with influenza-like illness (ILI).

The Influenza A/H5 Subtyping Kit is based on technology which is used in many molecular diagnostic assays. rRT-PCR assays are one-tube assays that first reverse-transcribe specific regions of RNA into cDNA copies. The cDNA then serves as a template for a polymerase chain reaction that utilizes a thermocyclic heating and cooling of the reaction to logarithmically amplify a specific region of DNA. The probe anneals to a specific internal target sequence located between the target loci of the forward and reverse primers. During the extension phase of the PCR cycle, the 5' nuclease activity of Tag polymerase degrades any probe molecules hybridized to amplified target sequence, causing the reporter dye to separate from the quencher dye, and generating a fluorescent signal. With each cycle, additional reporter dye molecules are cleaved from their respective probes, increasing the fluorescence intensity. Fluorescence intensity is monitored at each PCR cycle. Amplification of targets is reflected by logarithmic increase in fluorescence over time in comparison to the background signal.

AI/ML Overview

This document is a 510(k) premarket notification from the FDA, asserting substantial equivalence for the "CDC Human Influenza Virus Real-time RT-PCR Diagnostic Panel, Influenza A/H5 Subtyping Kit." The document does not contain acceptance criteria or a study proving device performance against such criteria. Instead, it compares the proposed device to a predicate device (K132508) and concludes that the changes are primarily for labeling and do not alter the device's design, technological attributes, or intended use.

Therefore, I cannot provide the requested information from this document. The document explicitly states:

"The changes proposed to the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel subject to this special 510(k) are for labeling purposes only and will not alter the technological attributes of the device." (Page 6)
"The changes proposed to the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel do not alter the device's design or technological attributes. In addition, the indications for use and intended use of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel will remain the same." (Page 9)

This type of 510(k) submission (a Special 510(k)) is used for modifications to a manufacturer's own legally marketed device where the modification does not affect the device's fundamental scientific technology or its intended use. As such, it relies on the previous clearance of the predicate device (K132508) for performance data rather than presenting new performance studies against acceptance criteria.

Summary

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

August 1, 2014

Centers for Disease Control and Prevention Yon Yu, Pharm.D. Associate Director for Regulatory Affairs 1600 Clifton Road NE, MS C-18 Atlanta, GA 30333

Re: K141859

Trade/Device Name: CDC Human Influenza Virus Real-time RT-PCR Diagnostic Panel, Influenza A/H5 Subtyping Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory viral panel multiplex nucleic acid assay Regulatory Class: II Product Code: OZE, NSU, NXD Dated: July 09, 2014 Received: July 10, 2014

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. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal 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 (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), 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" (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 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 yours,

Tamara V. Feldblyum -S for

Sally A. Hojvat 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) K141859

Device Name

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

Indications for Use (Describe)

The Influenza A/H5 Subtyping Kit contains reagents and controls of the CDC Human Influenza Virus RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an Applied Biosystems (ABI) 7500 Fast Dx Real Time PCR Instrument in conjunction with clinical and epidemiological information:

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

Performance characteristics for influenza were established during a season when seasonal influenza viruses A/H1 and A/H3 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 most current U.S. Department of Health and Human Services (DHHS) clinical and epidemiological criteria for testing suspect A/H5 specimens. The definitive identification of influenza A/H5 (Asian lineage) either directly from patient specimens or from virus cultures requires additional laboratory testing, along with clinical and epidemiological assessment in consultation with national influenza surveillance experts.

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

If infection with a novel influenza A virus is suspected based on current clinical and epidemiological screening criteria 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 3+ 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)

2 Prescription Use (Part 21 CFR 801 Subpart D)

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

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PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

FOR FDA USE ONLY

Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

Tamara V. Feldblyum -S 2014.07.31 16:25:13 -04I00

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"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

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8. 510(k) Summary

CDC hereby submits this Special 510(k) in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

Submitter

Centers for Disease Control and Prevention 1600 Clifton Road NE Atlanta, GA 30333 Establishment Registration: 1050190

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 Road, NE, MS C-18 Atlanta, GA 30333 (404) 639-3046 (office) (404) 639-1275 (fax) fkb8@cdc.gov

Proprietary Name

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

Common or Usual Name

Influenza A/H5 Subtyping Kit

Regulatory Information

Classification Regulation Section: 866.3980 - Respiratory viral panel multiplex nucleic acid assay Subsequent Regulation Sections: 862.2570 - Instrumentation for clinical multiplex test systems 866.3332 - Reagents for detection of specific novel influenza A viruses Classification: Class II

Classification Product Code: OZE Subsequent Product Codes: NSU, NXD Panel: Microbiology

Predicate Device

CDC Human Influenza Virus Real-time RT-PCR Diagnostic Panel (K132508)

Device Description

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detection and characterization of human influenza viruses from viral RNA in respiratory specimens from patients presenting with influenza-like illness (ILI).

Intended Use

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/H1 and A/H3 were the predominant influenza A viruses in circulation and during a season when the A/H1pdm09 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 epidemiological criteria for testing suspect A/H5 specimens. The definitive identification of influenza A/H5 (Asian lineage) either directly from patient specimens or from virus cultures requires additional laboratory testing, along with clinical and epidemiological assessment in consultation with national influenza surveillance experts.

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

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health department for testing. Viral culture should not be attempted unless a BSL 3+ 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

The changes proposed to the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel subject to this special 510(k) are for labeling purposes only and will not alter the technological attributes of the device.

Substantial Equivalence Comparison

The CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel (K132508) will serve as the predicate for the intended change. Please see Table 1 for a detailed comparison.

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Table 1. Device Comparison
	CDC Human Influenza Virus Real-time PCR Diagnostic Panel (K132508)	Influenza A/H5 Subtyping Kit
	The CDC Human Influenza Virus Real-Time PCR Diagnostic Panel is intended for usein Real-time RT- PCR assays on an Applied Biosystems (ABI) 7500 Fast Dx Real-TimePCR Instrument in conjunction with clinical and epidemiological information:For qualitative detection of influenza virus type A or B from viral RNA in upperrespiratory tract clinical specimens (including nasopharyngeal swabs, nasal swabs,throat swabs, nasal aspirates, nasal washes and dual nasopharyngeal/throat swabs),and lower respiratory tract specimens (including bronchoalveolar lavages,bronchial washes, tracheal aspirates, sputum, and lung tissue) from human patientswith signs and symptoms of respiratory infection and/or from viral culture;	The Influenza A/H5 Subtyping Kit contains reagents and controls of theCDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and isintended for use in Real-time RT-PCR assays on an Applied Biosystems(ABI) 7500 Fast Dx Real-Time PCR Instrument in conjunction withclinical and epidemiological information:For the presumptive identification of virus in patients who may beinfected with influenza A subtype A/H5(Asian Lineage) from viralRNA in human respiratory specimens and viral culture in
Intended Use	For determination of the subtype of seasonal human influenza A virus as seasonalA/H1, A/H3, and/or A/H1pdm09 from viral RNA in upper respiratory tractclinical specimens (including nasopharyngeal swabs, nasal swabs, throat swabs,nasal aspirates, nasal washes and dual nasopharyngeal/throat swabs), and lowerrespiratory tract specimens (including bronchoalveolar lavages, bronchial washes,tracheal aspirates, sputum, and lung tissue) from human patients with signs andsymptoms of respiratory infection and/or from viral culture; For the determination of the genetic lineage of human influenza B viruses asB/Victoria or B/Yamagata lineage from viral RNA in upper respiratory tractclinical specimens (including NPS, NS, TS, NA, NW, and NPS/TS) from humanpatients with signs and symptoms of respiratory infection and/or from viral culture; For the presumptive identification of virus in patients who may be infected withinfluenza A subtype A/H5(Asian Lineage) from viral RNA in human respiratoryspecimens and viral culture in conjunction with clinical and epidemiological riskfactors; To provide epidemiologic information for surveillance of the circulatinginfluenza viruses. Performance characteristics for influenza were established during a season whenseasonal influenza viruses A/H1 and A/H3 were the predominant influenza Aviruses in circulation and during a season when the A/H1pdm09 influenza viruswas the predominant influenza A virus in circulation. Performance characteristicsmay vary with other emerging influenza A viruses.Testing with the influenza H5a and H5b primer and probe sets should not beperformed unless the patient meets the most current U.S. Department of Health and	conjunction with clinical and epidemiological risk factors;To provide epidemiologic information for surveillance of thecirculating influenza viruses. Performance characteristics for influenza were established during aseason when seasonal influenza viruses A/H1 and A/H3 were thepredominant influenza A viruses in circulation and during a seasonwhen the A/H1pdm09 influenza virus was the predominant influenzaA virus in circulation. Performance characteristics may vary withother emerging influenza A viruses.Testing with the influenza H5a and H5b primer and probe sets shouldnot be performed unless the patient meets the most current U.S.Department of Health and Human Services (DHHS) clinical andepidemiological criteria for testing suspect A/H5 specimens. Thedefinitive identification of influenza A/H5 (Asian lineage) either directlyfrom patient specimens or from virus cultures requires additionallaboratory testing, along with clinical and epidemiological assessment inconsultation with national influenza surveillance experts.Negative results do not preclude influenza virus infection and should notbe used as the sole basis for treatment or other patient managementdecisions. Conversely, positive results do not rule out bacterial infectionor co-infection with other viruses. The agent detected may not be thedefinite cause of disease.If infection with a novel influenza A virus is suspected based on currentclinical and epidemiological screening criteria recommended by public
	Human Services (DHHS) clinical and epidemiological criteria for testing suspectA/H5 specimens. The definitive identification of influenza A/H5 (Asian lineage)either directly from patient specimens or from virus cultures requires additionallaboratory testing, along with clinical and epidemiological assessment inconsultation with national influenza surveillance experts.	health authorities, specimens should be collected with appropriateinfection control precautions for novel virulent influenza viruses and sentto state or local health department for testing. Viral culture should not beattempted unless a BSL 3+ facility is available to receive and culturespecimens.
	CDC Human Influenza Virus Real-time PCR Diagnostic Panel (K132508)	Influenza A/H5 Subtyping Kit
Intended Use(Cont'd)	Negative results do not preclude influenza virus infection and should not be used as thesole basis for treatment or other patient management decisions. Conversely, positiveresults do not rule out bacterial infection or co-infection with other viruses. The agentdetected may not be the definite cause of disease.If infection with a novel influenza A virus is suspected based on current clinical andepidemiological screening criteria recommended by public health authorities, specimensshould be collected with appropriate infection control precautions for novel virulentinfluenza viruses and sent to state or local health department for testing. Viral cultureshould not be attempted unless a BSL 3+ facility is available to receive and culturespecimens.
Specimen Types	Nasopharyngeal swabs, nasal swabs, throat swabs, nasal aspirates, nasal washes anddual nasopharyngeal/throat swabs, bronchoalveolar lavages, bronchial aspirates,bronchial washes, tracheal aspirates, sputum, and lung tissue. Only upper respiratoryspecimens for influenza B genetic lineage determination	Nasopharyngeal swabs, nasal swabs, throat swabs, nasal aspirates, nasalwashes and dual nasopharyngeal/throat swabs, bronchoalveolar lavages,bronchial aspirates, bronchial washes, tracheal aspirates, sputum, and lungtissue.
Technology	Real-time RT-PCR	Same
RequiredInstrumentation	Applied Biosystems 7500 Fast Dx Real- Time PCRInstrument with SDS software version 1.4	Same
OrganismDetected	Universal influenza A viruses (animal and human), Swine-origin influenza A viruses,Influenza B viruses, Influenza A subtypes: seasonal A/H1, A/H3, A/H1pdm09, andA/H5, Influenza B/Yamagata and B/Victoria lineages	Universal influenza A viruses (animal and human), Influenza A/H5 (Asianlineage) subtypes
Nucleic AcidExtraction	Yes	Same

Table 1: Device Comparison

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Risk Analysis

The Influenza A/H5 Subtyping Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel. A risk analysis of the labeling modification to create a separate Package Insert for the Influenza A/H5 Subtyping Kit was performed to verify that the change in the package insert did not present increased or new risks to the user. No new significant risks were identified as a result of the proposed modification.

Substantial Equivalence Conclusion

The changes proposed to the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel do not alter the device's design or technological attributes. In addition, the indications for use and intended use of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel will remain the same. The modification to the package insert included with the Influenza A/H5 Subtyping Kit made available to users retains all required label information, and is determined to be substantially equivalent to the predicate.

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.