The Human Influenza Virus Real-time RT-PCR Detection and Characterization Panel (rRT-PCR Flu Panel) is intended for use in Real-time RT-PCR assays on an AB1 7500 Fast Dx Real-time PCR instrument in conjunction with clinical and epidemiological information:

for qualitative detection of influenza virus type A or B in symptomatic patients from viral RNA in nasopharyngeal and/or nasal swab specimens,
for determination of the subtype of seasonal human influenza A virus, as seasonal A/H1 or A/H3, if present, from viral RNA in nasopharyngeal and/or nasal swab specimens,
for 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 for influenza viruses.

Device Description

The CDC Human Influenza Virus Real-time RT-PCR Detection and Characterization Panel (rRT-PCR Flu Panel) is a panel of oligonucleotide primers and dual-labeled hydrolysis (TagMan®) probes which may be used in real-time RT-PCR assays using the ABI 7500 Fast Dx Real-Time PCR instrument for the in vitro qualitative detection and characterization of human influenza viruses (RNA) in respiratory specimens from patients presenting with influenza-like illness (ILI). Detection of viral RNA not only aids in the diagnosis of illness caused by seasonal and novel influenza viruses in patients with ILI, but also provides epidemiologic information on influenza and aids in the presumptive laboratory identification of specific novel influenza A viruses.

AI/ML Overview

Acceptance Criteria and Device Performance for CDC Human Influenza Virus Real-time RT-PCR Detection and Characterization Panel

1. Table of Acceptance Criteria and Reported Device Performance

Performance Characteristic	Acceptance Criteria (Implicit)	Reported Device Performance
Clinical Sensitivity	>93% (for InfA, InfB, H1, H3)	InfA: 99.3% (96.1 - 99.9% CI) InfB: 97.6% (87.4 - 99.6% CI) H1: 93.1% (78.0 - 98.1% CI) H3: 100.0% (96.2 - 100.0% CI)
Clinical Specificity	>90% (for InfA, InfB, H1, H3)	InfA: 92.3% (88.5 - 94.9% CI) InfB: 98.1% (96.2 - 99.1% CI) H1: 99.5% (98.1 - 99.9% CI) H3: 90.5% (86.7 - 93.3% CI)
Percent Positive Agreement (H5a/H5b Clinical Specimens)	100%	100% (56.6% - 100% CI)
Percent Positive Agreement (H5a/H5b Cultured Specimens)	100%	100% (83.2% - 100% CI)
Percent Negative Agreement (H5a/H5b Prospective Specimens)	100%	100% (99.1% - 100% CI)
Analytical Specificity (Inclusivity)	100% concordance with expected detection for various influenza strains.	A/H1N1: 100% (10/10) A/H3N2: 100% (10/10) A/H5N1: 100% (24/24) Influenza B: 100% (10/10)
Analytical Specificity (Cross-Reactivity)	No detection (100% concordance for negative results) when tested with common non-influenza respiratory pathogens and commensal flora.	InfA: 100% (0/18 commensal flora, 0/9 non-influenza virus) InfB: 100% (0/18 commensal flora, 0/9 non-influenza virus) H1: 100% (0/18 commensal flora, 0/9 non-influenza virus) H3: 100% (0/18 commensal flora, 0/9 non-influenza virus) H5a: 100% (0/18 commensal flora, 0/9 non-influenza virus) H5b: 100% (0/18 commensal flora, 0/9 non-influenza virus)
Analytical Sensitivity (Limit of Detection - LoD)	>95% of all replicates tested positive at the LoD.	The LoD values for different influenza strains demonstrated detection at low concentrations (e.g., A/H1N1 at 10^1.2 EID50/mL, A/H5N1 at 10^1.0 EID50/mL, Influenza B at 10^0 EID50/mL). The document states >95% positivity for determined LoD.

Study Details:

2. Sample Size Used for the Test Set and Data Provenance:

Clinical Performance (Seasonal Influenza - InfA, InfB, H1, H3):
- Sample Size: 415 total prospective specimens.
- Data Provenance: Prospective collection from US state public health laboratories during the 2006-2007 respiratory virus season (February-April).
- Specimen Type: Nasal and nasopharyngeal swabs.
Clinical Performance (Influenza A/H5N1):
- Clinical Specimens: 24 retrospective A/H5 influenza samples.
- Data Provenance: Retrospective from suspect positive cases received at CDC, "diverse geographic locations."
- Cultured Specimens: Not explicitly stated sample size, but also used for H5 detection with 100% agreement.
- Prospective Clinical Specimens (for negative agreement): Implied to be part of the 415 prospective seasonal specimens, where no H5 was detected.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications:

No specific number or qualifications of experts are explicitly mentioned for establishing ground truth.
The reference method for prospective seasonal influenza samples was "rapid culture (shell vial) followed by direct fluorescent antibody screening and identification." This implies laboratory personnel with expertise in virology and cell culture.
Influenza A/H5 and discrepant prospective seasonal influenza samples were "further analyzed by bidirectional sequencing," suggesting molecular biology experts.

4. Adjudication Method for the Test Set:

No formal adjudication method (e.g., 2+1, 3+1) is explicitly described.
The ground truth for prospective seasonal influenza was based on rapid culture (shell vial) followed by direct fluorescent antibody screening and identification.
Discrepant prospective seasonal influenza samples and influenza A/H5 samples were further analyzed by bidirectional sequencing. This serves as an additional, higher-resolution method for resolving discrepancies or confirming difficult cases.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:

No, an MRMC comparative effectiveness study was not done. This device is a diagnostic assay (RT-PCR panel) for detecting and characterizing influenza viruses, not an imaging device or a device that requires human interpretation in the same way an AI-powered image analysis tool would. Therefore, the concept of "human readers improve with AI vs. without AI assistance" does not apply here.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop) Performance Was Done:

Yes, the performance presented for the rRT-PCR Flu Panel is standalone (algorithm only, without human-in-the-loop performance). This device is a molecular diagnostic kit, and its performance metrics (sensitivity, specificity, LoD, etc.) reflect the intrinsic analytical and clinical capabilities of the assay itself when executed according to protocol. Human involvement is in sample preparation, running the assay, and interpreting the raw output (e.g., Ct values), but the "diagnosis" of the presence and type of virus is determined by the output of the PCR reaction.

7. The Type of Ground Truth Used:

Expert Consensus and "Gold Standard" Laboratory Methods:
- For prospective seasonal influenza, the ground truth was established by gold standard virus culture testing (rapid culture (shell vial) followed by direct fluorescent antibody screening and identification).
- For influenza A/H5 and discrepant prospective seasonal influenza samples, the ground truth was further analyzed and confirmed by bidirectional sequencing. This suggests a form of expert-validated, highly accurate laboratory confirmation.

8. The Sample Size for the Training Set:

Not Applicable / Not Explicitly Stated for a "training set" as understood in machine learning. This device is a molecular diagnostic panel based on designed primers and probes, not a machine learning model that undergoes explicit training. The "development" and "optimization" would have involved testing various primer/probe combinations against known virus strains, but this isn't analogous to a "training set" for an AI algorithm.
However, for Analytical Specificity (Inclusivity), the document mentions initial testing with "ten (10) influenza virus strains of A/H/N1, A/H3N2, and influenza B" and "24 influenza A/H5N1 clinical samples tested retrospectively" to demonstrate the panel's ability to detect different strains. This could be considered akin to an internal validation set during development.

9. How the Ground Truth for the Training Set Was Established:

As above, the concept of a "training set" for this type of medical device (RT-PCR panel) is not directly applicable in the same way it would be for an AI algorithm.
The "ground truth" for the various influenza virus strains and non-influenza pathogens used in analytical studies would have been primarily established through known viral cultures, characterized bacterial/yeast cultures, and molecular sequencing (e.g., 16S ribosomal RNA bi-directional sequencing for bacteria, bi-directional sequencing for non-influenza respiratory viruses), all validated by standard laboratory practices.

Summary

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Centers for Disease Control and Prevention Human Influenza Virus Real-time RT-PCR Detection and Characterization Panel 510(k) 080570

5. 510(k) Summary

SEP 3 0 2008

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

Assigned 510(k) number:

K080570

Submitted by:

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

Contact Person:

Hye-Joo Kim, Pharm.D. Chief, Regulatory Affairs Strategic Science and Program Unit Coordinating Center for Infectious Diseases Centers for Disease Control and Prevention 1600 Clifton Road, NE, MS C-12 Atlanta, GA 30333 (404) 639-4643 (office) (404) 639-1275 (fax) (404) 729-7015 (cell) hek6@cdc.gov

Date prepared:

September 26, 2008

Device Name:

CDC Human Influenza Virus Real-time RT-PCR Detection and Characterization Panel

Common or Usual Name:

rRT-PCR Flu Panel

Predicate devices:

Influenza A/H5 (Asian lineage) Virus Real-time RT-PCR Primer and Probe Set and the Prodesse Multiplex RT-PCR ProFlu+TM Assay

Device Description:

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Centers for Disease Control and Prevention Human Influenza Virus Real-time RT-PCR Detection and Characterization Panel 510(k) 080570

epidemiologic information on influenza and aids in the presumptive laboratory identification of specific novel influenza A viruses.

Assay Principle:

The TRT-PCR Flu Panel assay is based on real-time RT-PCR technology which is used in many molecular diagnostic assays to date. The rRT-PCR Flu Panel influenza A and B primer and probe sets are designed for universal detection of type A and type B influenza viruses. Influenza A subtyping primer and probe sets are designed to specifically detect contemporary A/H1, A/H3, and A/H5 (Asian lineage) influenza viruses in humans.

The rRT-PCR Flu Panel also includes internal positive control materials. The human RNase P (RP) primer and probe set detects human RP and is used with human clinical specimens to indicate that adequate isolation of nucleic acid resulted from the extraction of the clinical specimen. A positive result in the RP assay indicates adequate specimen was present, ensures that common reagents and equipment are functioning properly, and demonstrates the absence of inhibitory substances. A Human Specimen Control (HSC) is a noninfectious cultured human cell material that demonstrates successful recovery of RNA as well as extraction reagent integrity. The Seasonal Influenza Virus Control (SIVC) consists of three different influenza viruses representing influenza A/H1, A/H3, and influenza B viruses and cultured human cells. The SIVC demonstrates that the master mix and primer and probe sets for influenza A (InfA), influenza B (InfB), influenza A/H1 (H1), influenza A/H3 (H3), and RP are functioning properly. The Influenza Virus A/H5N1 Positive Control (H5VC) consists of a genetically modified reassortant human influenza virus (Influenza A/Vietnam/1203/04 x PR/8/34) (BSL2 category) and cultured human cells. The H5VC demonstrates that the master mix and primer and probe sets for InfA, influenza A/H5 (H5a, H5b), and RP are functioning properly. All controls (HSC, SIVC, and H5VC) are inactivated using betapropiolactone and are noninfectious.

Intended Use:

The Human Influenza Virus Real-time RT-PCR Detection and Characterization Panel (rRT-PCR Flu Panel) is intended for use in Real-time RT-PCR assays on an 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 in symptomatic patients from viral � RNA in nasopharyngeal and/or nasal swab specimens,
. for determination of the subtype of seasonal human influenza A virus, as seasonal A/H1 or A/H3, if present, from viral RNA in nasopharyngeal and/or nasal swab specimens,
for 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 for influenza viruses.

Performance characteristics for influenza A were established when influenza A/H3 and A/H1 were the predominant influenza A viruses in circulation. When other influenza A viruses are emerging, performance characteristics may vary.

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

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Centers for Disease Control and Prevention Human Influenza Virus Real-time RT-PCR Detection and Characterization Panel 510(k) 080570

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.

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

Device comparison:

The rRT-PCR Flu Panel is substantially equivalent to the Prodesse Multiplex RT-PCR ProFlu+™ Assay because it utilizes real-time PCR technology to detect influenza A and influenza B in human respiratory specimens. The rRT-PCR Flu Panel further detects and differentiates influenza A/H1 and A/H3 subtypes. The rRT-PCR Flu Panel is substantially equivalent to the influenza A/H5 (Asian lineage) Virus Real-time RT-PCR Primer and Probe Set because it utilizes real-time PCR technology to detect influenza A/H5 (Asian lineage). Influenza A/H5 (Asian lineage) Virus Real-time RT-PCR Primers and Probe Set and the Prodesse Multiplex RT-PCR ProFlu+™ Assay have been granted marketing clearance by the Food and Drug Administration (FDA) following 510(k) submissions. Based on clinical and analytical data, the rRT-PCR Flu Panel device has been determined to be as safe and effective and peforms as well as legally marketed devices described below. The device has demonstrated clinical utility and supports the label claims.

	rRT-PCR Flu Panel	Influenza A/H5 (Asianlineage) Virus Real-timeRT-PCR Primers andProbe Set (K060159)	Prodesse MultiplexRT-PCR ProFlu+TMAssay (K073029)
Intended Use	Qualitative in-vitro detection ofinfluenza A/H1, A/H3, A/H5(Asian lineage), and influenza Bviruses	Qualitative in vitrodetection of influenzaA/H5N1 (Asian lineage)virus	Detection/differentiationbetween influenza Avirus, influenza B virusand respiratory syncytialvirus (RSV)
Specimen Types	Nasopharygeal or nasal swabrespiratory specimens, or virusculture	Human respiratoryspecimens or virus cultures	Nasopharyngeal swabspecimens
Technology	Real-time RT-PCR	Real-time RT-PCR	Real-time RT-PCR
OrganismDetected	Influenza A/H1, A/H3, A/H5(Asian lineage), and influenza Bviruses	Influenza A virus, subtypeH5N1 (Asian lineage)	Influenza type A andtype B viruses, RSV
ExtractionMethod	• QIAamp® Viral RNA MiniKit, Qiagen Inc.• Qiagen RNeasy® Mini Kit,Qiagen, Inc.• MagNA Pure LC RNAIsolation Kit II, Roche AppliedScience• MagNA Pure Total NucleicAcid Isolation Kit, RocheApplied Science	• QIAamp® Viral RNAMini Kit, Qiagen, Inc.• RNeasy® Mini Kit,Qiagen, Inc.• MagNA Pure LC TotalNucleic Acid IsolationKit, Roche AppliedScience	• MagNA Pure TotalNucleic Acid IsolationKit, Roche AppliedScience

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Centers for Disease Control and Prevention Iuman Influenza Virus Real-time RT-PCR Detection and Characterization Panel 510(k) 080570

Enzyme MasterMix	Invitrogen SuperScriptTM IIIPlatinum® One-StepQuantitative RT-PCR Kits (withor without ROX)	Qiagen QuantiTectTM ProbeRT-PCR Kit, Qiagen, Inc.	Supplied in theProFlu+TM Detection Kit
Clinical Sensitivity	> 93%	N/A*	98%
Clinical Specificity	> 90%	N/A*	83%
RequiredInstrumentation	Applied Biosystems 7500 FastDx Real-Time PCR Instrumentwith SDS software version 1.4	• Roche LightCycler®• Cepheid SmartCycler®• Applied Biosystems 7000Sequence DetectionSystem• Applied BiosystemsPrism® 7700 SequenceDetection System	Cepheid SmartCycler®II instrument

Sensitivity and specificity could not be estimated duc to scarcity of Asian lineage) virus infections.

Performance characteristics:

1. Analytical Specificity - Inclusivity & Reactivity

The rRT-PCR Flu Panel analytical specificity was demonstrated by inclusivity and reactivity testing. The inclusivity testing utilized ten (10) influenza virus strains of A/H/N1, A/H3N2, and influenza B at low virus concentrations at or near the limit of detection (102 TCIDsofmL) to demonstrate the flexibility of the primer and probe sets to detect multiple strains of influenza virus. There were 24 influenza A/H5N1 clinical samples tested retrospectively from diverse geographic locations from suspect positive cases received at CDC. The rRT-PCR Flu Panel analytical specificity indicated 100% concordance with expected results for all primer and probe sets included in the device. This testing demonstrated that the primer and probe sets are highly specific for detecting and differentiating influenza viruses A/H1, A/H13, A/H5 and influenza B as defined previously.

Influenza Strains Tested	Strains Detected	Expected Detection	Concordance
A/H1N1 Influenza	10 / 10	10 / 10	100 %
A/H3N2 Influenza	10 / 10	10 / 10	100 %
A/H5N1 Influenza	24 / 24	24 / 24	100 %
Influenza B	10 / 10	10 / 10	100 %

Analytical Reactivity with Human Seasonal Influenza Viruses A/H1, A/H3, and Influenza B and A/H5N1 (Asian lineage) Influenza Virus

2. Analytical Specificity - Reactivity with Common Non-Influenza Respiratory Viral and Bacterial Pathogens

Analytical spccificity (cross-reactivity) was evaluated by testing each primer/probe set within the device panel with nucleic acids extracted from 27 organisms (9 viruscs, 17 bacteria, and 1

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Centers for Disease Control and Prevention Centers for Disease Control and Prevention

Human Influenza Virus Real-time RT-PCR Detection and Characterization Panel 510(k) 080570

yeast) representing common respiratory pathogens or flora commonly present in specimens yeast) representing common respion. All organisms tested in this study were propagated, Conceled from the nasophia Juni regioners on to testing. The identity of the commensal thered, and enatueterial was confirmed by 16S ribosomal RNA bi-directional sequencing. It spiratory bacterial was comments were determined at the CDC by standard practices. Commensal respiratory of the non-influenza respiratory viruses was confirmed by bi-directional I he luentiny of the non-mirations were tested at concentrations greater than or equal to10 Sequencing. "Dacteria and yeast wobocterium tuberculosis where DNA was extracted from environ with the exceptioned by spectrophotometry (0.25 ng/μl). Non-influenza respiratory ptire ourtere and qualimations greater than 106 TCIDso/ml with the exception of human parainfluenza type 2 (1031 TCID56/ml due to difficulty generating a high titer virus numali parammacinza type = (190 = extracted from viral cultures of Coronaviruses CoV 229E stock in cantare). Total rentrations were determined by spectrophotometry (31.6 ng/ul and 50.4 ng/ul, respectively).

Each sample (bacteria and virus) was extracted in parallel using both the Qiagen QIAamp® Luch Bangle Mini Kit and the Qiagen RNeasy® Mini Kit. Each RNA sample was tested following the testing procedure previously described for the rRT-PCR Flu Panel and the Applied Biosystems 7500 Fast Real-Time PCR System. The dual extraction method was risplied Bloofstenme ross method equivalency and ensure no cross reactivity with the performed to announcesets since negative results were expected for all samples.

Markers Tested	CommensalFlora Detected	Non-InfluenzaRespiratory VirusDetected	ExpectedDetection	Concordance
Inf A	0 / 18	0 / 9	No	100 %
Inf B	0 / 18	0 / 9	No	100 %
H1	0 / 18	0 / 9	No	100 %
H3	0 / 18	0 / 9	No	100 %
H5a	0 / 18	0 / 9	No	100 %
H5b	0 / 18	0 / 9	No	100 %

Analytical Specificity with Common Non-influenza Human Respiratory Pathogens.

3. Analytical Sensitivity - Limit of Detection

Analytical sensitivity was demonstrated by determining the limit of detection (LoD) of each primer and probe set in the rRT-PCR Flu Panel. Ten-fold serial dilutions of two different influenza virus strains of each subtype were tested to identify an end-point for detection of each primer and probe set included in the rRT-PCR Flu Panel. RNA was extracted from each of the characterized viruses with the Qiagen QIAamp® Viral RNA Purification kit. The LoD for each primer and probe set (InfA, InfB, HI, H3, H5a, and H5b) was calculated to dctermine the lowest detectable concentration range of influenza virus (EID50/mL) at which >95% of all replicates tested positive. The lowest concentration of influenza virus detected

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Centers for Disease Control and Prevention Centers for Disease Control and Prevention

Human Influenza Virus Real-time RT-PCR Detection and Characterization Panel 510(k) 080570

was determined to be the end-point concentration where the type and subtype primer and was determined to oe the end point two end-points differed in concentration, the higher (or limiting) point was used.

Influenza Virus Tested	Influenza Strain Designation	Limit of Detection (EID50/mL)
A/H1N1	A/New Caledonia/20/1999	101.2
A/H1N1	A/Hawaii/15/2001	101.5
A/H3N2	A/New York/55/2004	102.2
A/H3N2	A/Wisconsin/67/2005	101.2
A/H5N1	A/Vietnam/1203/2004×A/Puerto Rico/8/34 reassortant(A/Vietnam/1203/2004 PR8- VNH5N1- PR8/CDC-RG)	101.0
A/H5N1	A/Anhui/01/2005×A/Puerto Rico/8/34 reassortant(A/Anhui/01/2005- PR8-IBCDC-RG5)	101.0
B	B/Florida/07/2004 (B/Victoria/2/87 genetic group)	100
B	B/Ohio/01/2005 (B/Yamagata/16/88 genetic group)	100.5

Limit of Detection Summary

4. Clinical Performance

Chinean I characteristics of the rRT-PCR Flu Panel were established during a prospective r virormal.1005. state public health laboratories during the 2006-2007 respiratory virus season (February-April). Samples used for this study were nasal and nasopharyngeal swabs collected for routine influenza testing at each site.

The reference method was rapid culture (shell vial) followed by direct fluorescent antibody screening and identification. Specimens tested at the public health testing sites followed routine diagnostic influenza rapid culture protocols and the rRT-PCR Flu Panel protocol to demonstrate performance and agreement.

A total of 415 total specimens were collected and tested at the 4 public health laboratory testing sites during the 2006-2007 influenza season for this prospective clinical study. Four hundred thirty-nine specimen results (415 prospective seasonal and 24 retrospective A/H5 influenza samples) from nasal, nasopharyngeal swabs, or cultured specimens in the case of influenza A/H5 samples were confirmed by gold standard virus culture testing. Influenza A/H5 and discrepant prospective seasonal influenza samples were further analyzed by bidirectional sequencing.

Clinical Sensitivity and Specificity Performance Summary - Prospective Specimen Testing

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Centers for Disease Control and Prevention Centers for Disease Control and Prevention

Human Influenza Virus Real-time RT-PCR Detection and Characterization Panel 510(k) 080570

Analyte Tested	Sensitivity % (95% CI)	Specificity % (95% CI)
InfA	99.3 (96.1 - 99.9)	92.3 (88.5 - 94.9)
InfB	97.6 (87.4 - 99.6)	98.1 (96.2 - 99.1)
H1	93.1 (78.0 - 98.1)	99.5 (98.1 - 99.9)
H3	100.0 (96.2 - 100.0)	90.5 (86.7 - 93.3)

A formal clinical evaluation of human and/or avian influenza A/H5N1 virus was not A formal enniour overances of mical Evaluation Study due to the absence of susport cases accomplished during the The CD e Sore, performance specificity and detection capability of the within the Onlies blates. In the rRT-PCR Flu Panel could not be evaluated at the ITS and 1190 primer and provins during the clinical study. Retrospective data from 0.0. succe public nealing lace thens from human cases received by the twenty - four (21) baspeco were used to demonstrate clinical performance of the H5a and H5b components of the panel.

Performance Summary - Influenza A/H5N1 Testing with Prospective and Retrospective Specimens

	Analyte Tested	Percent Positive Agreement (%)
Influenza A/115 PositiveClinical Specimens	H5a / H5b	100 % Percent Positive Agreement(56.6% -100%) 95% CI
Influenza A/H5 PositiveCultured Specimens	H5a / H5b	100 % Percent Positive Agreement(83.2% -100%) 95% CI
Prospective Clinical Specimens	H5a / H5b	100 % Percent Negative Agreement(99.1%-100%) 95% CI

The clinical sensitivity for all markers tested was greater than 93 % and the clinical specificity for all markers was greater than 90 %. The accuracy, often referred to as percent agreement, was greater than 92 % for all markers tested.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/7/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three stripes forming its body and wings. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Dr. Hye-Joo Kim Chief, Regulatory Affairs Strategic Science and Program Unit Centers for Disease Control and Prevention 1600 Clifton Road, NE MS C-12 Atlanta, GA 30333

SEP 3 0 2008

Re: K080570

Trade/Device Name: Human Influenza Virus Real-time RT-PCR Detection and Characterization Panel

Regulation Number: 21 CFR 866.3332 Regulation Name: Reagent for detection of specific novel influenza A viruses Regulatory Class: Class II Product Code: NXD, OEP, OCC, NSU Dated: February 27, 2008 Received: February 29, 2008

Dear Dr. Kim:

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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at 240-276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Sally attaym

Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Centers for Disease Control and Prevention Human Influenza Virus Real-Time RT-PCR Detection and Characterization Panel 510(k) Notification

4. Indications for Use

510(k) Number (if known): K080570

Device Name: CDC Human Influenza Virus Real-Time RT-PCR Detection and Characterization Panel

Common Name: rRT-PCR Flu Panel

for qualitative detection of influenza virus type A or B in symptomatic patients from viral RNA in . nasopharyngeal and/or nasal swab specimens,
for determination of the subtype of seasonal human influenza A virus, as seasonal A/H1 or A/H3, . if present, from viral RNA in nasopharyngeal and/or nasal swab specimens,
for 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 for influenza 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.

Prescription Use (Per 21 CFR 801.109)

Over-The-Counter Use (Optional Format 1-2-96)

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Division Sign-Off

Atro Dlaar

510(k) K080570

Page 4-1

Regulation Number and Section

§ 866.3332 Reagents for detection of specific novel influenza A viruses.

(a)
Identification. Reagents for detection of specific novel influenza A viruses are devices that are intended for use in a nucleic acid amplification test to directly detect specific virus RNA in human respiratory specimens or viral cultures. Detection of specific virus RNA aids in the diagnosis of influenza caused by specific novel influenza A viruses in patients with clinical risk of infection with these viruses, and also aids in the presumptive laboratory identification of specific novel influenza A viruses to provide epidemiological information on influenza. These reagents include primers, probes, and specific influenza A virus controls.(b)
Classification. Class II (special controls). The special controls are:(1) FDA's guidance document entitled “Class II Special Controls Guidance Document: Reagents for Detection of Specific Novel Influenza A Viruses.” See § 866.1(e) for information on obtaining this document.
(2) The distribution of these devices is limited to laboratories with experienced personnel who have training in standardized molecular testing procedures and expertise in viral diagnosis, and appropriate biosafety equipment and containment.