Predicate Devices

Reference Devices

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description and performance studies focus on the analytical and clinical performance of a real-time RT-PCR panel, which is a molecular diagnostic technique. There is no mention of AI or ML in the intended use, device description, or performance evaluation sections.

Therapeutic

No

This device is a diagnostic tool used to detect and characterize influenza viruses, providing information to aid in diagnosis and surveillance. It does not provide any form of therapy or treatment.

Diagnostic

Yes

The device is intended for the qualitative detection and differentiation of influenza virus RNA from human patients with signs and symptoms of respiratory infection. This directly aids in the diagnosis of illness.

SaMD (Software as a Medical Device)

No

The device is a panel of oligonucleotide primers and probes, which are physical reagents used in a laboratory assay, not software.

IVD (In Vitro Diagnostic)

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

Here's why:

Intended Use: The intended use explicitly states the device is for the "qualitative detection of influenza virus type A viral RNA" and "differentiation of 2009 H1N1 influenza virus RNA" from human respiratory specimens. This is a diagnostic purpose performed in vitro (outside the body).
Device Description: The description states the panel is used in "real-time RT-PCR (rRT-PCR) assays for the in vitro qualitative detection and characterization of human influenza viruses (RNA) in respiratory specimens from patients presenting with influenza-like illness (ILI)." The phrase "in vitro" is explicitly used.
Clinical Performance Studies: The document details clinical performance studies comparing the device's results to reference methods (virus culture and sequencing) using human patient specimens. This is characteristic of an IVD device evaluation.
Predicate Devices: The mention of predicate devices (K100148 and K080570) which are also IVDs further supports this classification.

The device is designed to analyze biological samples (respiratory specimens) in vitro to provide diagnostic information about a patient's health status (presence and type of influenza virus).

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The CDC Influenza 2009 A(H1N1)pdm Real-Time RT-PCR Panel (CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel) is intended for use in real-time RT-PCR assays on an Applied Biosystems (ABI) 7500 Fast Dx Real-Time PCR Instrument in conjunction with clinical and epidemiological information:

For the qualitative detection of influenza virus type A viral RNA from . nasopharyngeal swabs (NPS), nasal swabs (NS), nasal aspirates (NA), nasal washes (NW), dual nasopharyngeal / throat swabs (NPS/TS), broncheoalveolar lavage (BAL), tracheal aspirate (TA), and bronchial wash (BW), collected from the respiratory tract of human patients with signs and symptoms of respiratory infection and/or from viral culture.
For differentiation of 2009 H1N1 influenza virus RNA from nasopharyngeal . swabs (NPS), nasal swabs (NS), nasal aspirates (NA), nasal washes (NW) .dual nasopharyngeal / throat swabs (NPS/TS), broncheoalveolar lavage (BAL), tracheal aspirate (TA), and bronchial wash (BW) collected from the respiratory tract of human patients with signs and symptoms of respiratory infection and/or from viral culture.
To provide epidemiologic information for surveillance of the 2009 H1N1 influenza virus.

Performance characteristics for influenza A were established during the 2009-2010 influenza season when 2009 H1N1 influenza virus was the predominant influenza A virus in circulation. Performance characteristics may vary against other emerging influenza A viruses.

A negative test result for the bronchoalveolar lavage (BAL), tracheal aspirate (TA), and bronchial wash (BW) is presumptive and it is recommended these results be confirmed by viral culture.

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

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 in these cases unless a BSL 3+ facility is available to receive and culture specimens.

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

NXD, OQW

Device Description

The CDC Influenza 2009 A(H1N1)pdm Real-time RT-PCR Panel (CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel) is a panel of oligonucleotide primers and dual-labeled hydrolysis (TaqMan®) probes which may be used in real-time RT-PCR (rRT-PCR) assays 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.

The influenza A primer and probe sets are designed for universal detection of type A influenza viruses, Influenza A subtyping primer and probe sets are designed to specifically detect 2009 A (H1N1) influenza virus.

The CDC rRT-PCR 2009 A(H1N1)ødm Flu Panel is an updated version of the assay distributed by CDC. during the 2009 A(H1N1) pandemic strain to qualified laboratories (CDC rRT-PCR Swine Flu Panel G090072) under Emergency Use Authorization (EUA) from the FDA in that it has different sequences of primers and probes that are more specific to the currently circulating 2009 A(H1N1) influenza virus.

The CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel includes the following primer and probe sets and positive control:

InfA detects all influenza A strains, but does not detect influenza B strains .
pdm InfA is specific for 2009 influenza A .
pdm H1 is specific for 2009 influenza A, subtype H1 .
RNase P (RP) detects human RNase P and is used with human clinical . specimens to indicate that adequate isolation of nucleic acid resulted from the extraction of the clinical specimen
Inactivated Influenza Typing Panel Real-Time RT-PCR Positive Control is a . positive control designed to react with all the primer and probe sets including RNase P

The CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel assay is based on real-time RT-PCR technology which is used in many molecular diagnostic assays to date. The CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel influenza A primer and probe sets are designed for universal detection of type A influenza viruses. The panel also contains influenza A type and subtyping primer and probe sets designed to specifically detect human 2009 A(H1N1) influenza viruses.

One-step real-time RT-PCR assays are one-tube assays that first reverse-transcribe specific RNA templates into complementary deoxyribonucleic acid (cDNA) copies. The cDNA then serves as 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 target sequence located between the forward and reverse primers. During the extension phase of the PCR cycle, the 5' nuclease activity of Tag polymerase degrades the probe, causing the reporter dye to separate from the quencher dye, 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.

The CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel includes internal positive control materials. The human RNase P (RP) primer and probe set detects human RNase P and is used with human clinical specimens to indicate that adequate isolation of nucleic acid resulted from the extraction process 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 Influenza 2009 A(H1N1)pdm Positive Control (pdm PC) consists of influenza viruses representing 2009 A(H1N1) influenza virus and cultured human cells. The pdm PC serves as a rRT-PCR reaction control and demonstrates that the master mix and primer and probe sets for InfA, pdm InfA, pdm H1, and RP are functioning properly. All controls (HSC and pdm PC) are inactivated using beta propiolactone and are noninfectious.

The CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel components used for testing are similar to the components provided in the CDC rRT-PCR Flu Panel ([IVD] [K080570]}, following the same instructions for use on the ABI 7500 Fast Dx Real-Time PCR system.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Respiratrory tract (nasopharyngeal, nasal, throat, broncheoalveolar, tracheal, bronchial)

Indicated Patient Age Range

Not Found

Intended User / Care Setting

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.
Public health laboratories (8 U.S. public health laboratories and a Department of Defense (DoD) laboratory)

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

Analytical Performance:

Limit of Detection: Each primer and probe set was tested with two different 2009 A(H1N1) influenza virus strains.
Inclusivity of 2009 A(H1N1) Influenza Viruses: Ten 2009 A(H1N1) influenza viruses were tested at low concentrations using the CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel.
Exclusivity of Seasonal Influenza Viruses and Influenza Viruses with Pandemic Potential: Characterized seasonal influenza viruses (A/H1, A/H3, Influenza B) and 15 non-human influenza viruses that have been shown to infect humans were tested with the CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel.
Reactivity of Non-Influenza Respiratory Viral and Bacterial Pathogens: 34 non-influenza organisms (respiratory pathogens or flora) commonly present in the nasopharynx region of the human respiratory tract were tested.
Reproducibility: Evaluated at six separate laboratory sites. Each testing site assessed a panel of four simulated samples (moderate, low, "high negative" viral RNA concentration, and a negative sample). The panels and assay controls were tested at each site by two operators on 5 different days within a 10-day period.

Clinical Performance:

Sample Size: 1901 total patient specimens.
Data Source: Samples collected for routine influenza testing at 8 U.S. public health laboratories and a Department of Defense (DoD) laboratory during the 2009-2010 respiratory virus season (February-April) from individuals symptomatic with influenza-like illness (ILI). Retrospective specimens were used to supplement prospectively collected specimens due to low influenza prevalence.
Specimen Types: 1191 nasopharyngeal swabs (NPS) and nasal swabs (NS), 50 throat swabs, 519 nasal washes and nasal aspirates, 99 dual NPS/TS, and 42 lower respiratory specimens.
Annotation Protocol/Reference Methods: Virus culture with Immunofluorescent Antibody (IFA) or Direct Fluorescent Antibody (DFA) for screening and identification of influenza type. Bi-directional sequencing for confirmation of 2009 influenza A (H1N1) subtype. InfA analyte results were compared to virus culture. Pdm InfA and pdm H1 analyte results were compared to bidirectional sequencing. Sequencing was performed only on specimens identified as positive for influenza A by virus culture.

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

Analytical Performance

Limit of Detection (LoD):
- Study Type: Analytical sensitivity study.
- Sample Size: Not explicitly stated as "sample size" but involved testing each primer and probe set with two different 2009 A(H1N1) influenza virus strains.
- Key Results:
  - A/California/07/2009: LoD of 10^1.6^ EID50/mL for InfA, pdm InfA, and pdm H1.
  - A/New York/18/2009: LoD of 10^1.3^ EID50/mL for InfA and pdm H1, and 10^0.6^ EID50/mL for pdm InfA, with a final LoD of 10^1.3^ EID50/mL.
Inclusivity of 2009 A(H1N1) Influenza Viruses:
- Study Type: Analytical specificity study.
- Sample Size: Ten 2009 A(H1N1) influenza viruses.
- Key Results: 100% concordance with all primer and probe sets, indicating high specificity for detecting 2009 A(H1N1) influenza viruses.
Exclusivity of Seasonal Influenza Viruses and Influenza Viruses with Pandemic Potential:
- Study Type: Analytical specificity study (cross-reactivity).
- Sample Size: Characterized seasonal influenza viruses (various H1N1, H3N2, Inf B strains) and ten avian A/H5 influenza viruses.
- Key Results: Demonstrates ability to detect influenza type A viruses other than 2009 A(H1N1) viruses without a subtype as expected. 100% concordance with expected results for H5N1 strains.
Reactivity of Non-Influenza Respiratory Viral and Bacterial Pathogens:
- Study Type: Analytical specificity study (cross-reactivity).
- Sample Size: 34 non-influenza organisms (respiratory pathogens or flora).
- Key Results: 100% concordance with expected results for all primer and probe sets, indicating no cross-reactivity with these biological organisms.
Reproducibility:
- Study Type: Reproducibility and precision evaluation.
- Sample Size: Six separate laboratory sites, each testing a panel of four simulated samples (moderate, low, "high negative" viral RNA concentration, and a negative sample) by two operators across 5 days for 10 tests per sample type per site.
- Key Results:
  - No Template Control: 60/60 agreement (100%).
  - Sample 1 (moderate): InfA, pdm InfA, pdm H1, RP all showed 60/60 agreement (100%). %CV ranged from 1.48 to 4.23.
  - Sample 2 (low): InfA showed 58/60 agreement, pdm InfA showed 58/60, pdm H1 showed 54/60. RP showed 60/60. %CV varied more for low concentration samples, as expected.
  - Sample 3 ("high negative"): InfA showed 54/60 agreement, pdm InfA showed 57/60, pdm H1 showed 58/60. RP showed 60/60.
  - Sample 4 (A549 cells): RP showed 60/60 agreement.
  - HSC (Human Specimen Control): RP showed 60/60 agreement.
  - 2009 A(H1N1) Positive Control: InfA, pdm InfA, pdm H1, RP all showed 60/60 agreement (100%). %CV ranged from 1.19 to 4.78.

Clinical Performance

Study Type: Prospective clinical study with retrospective specimens.
Sample Size: 1901 total patient specimens.
Key Results:
- Overall performance call rate: >99%.
- Upper respiratory specimens (NPS/NS, NA/NW, NPS/TS):
  - Clinical sensitivity: >96% for all markers.
  - Clinical specificity: >96% for all markers.
  - Positive percent agreement: >96% for all markers.
- Lower respiratory specimens (BAL, TA, BW):
  - Clinical sensitivity: >83% for all markers (compared to culture).
  - Clinical specificity: >83% for all markers (compared to culture).
  - Positive percent agreement: 100%.

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

Clinical Performance Metrics:

Specimen Type	Marker	Sensitivity % (95% CI)	Specificity % (95% CI)	Positive Percent Agreement Retrospective
NPS/NS	InfA	96.8 (89.1-99.1)	96.2 (94.6-97.3)	99.4 (97.7-99.8)
	2009 H1N1	100 (93.7-100)	96.7 (95.3-97.7)	99.7 (98.1-99.9)
NA/NW	InfA	100 (83.2-100)	99.3 (97.5-99.8)	97.7 (94.6-99.0)
	2009 H1N1	100 (80.6-100)	98.6 (96.5-99.5)	99.0 (96.5-99.7)
NPS/TS	InfA	100 (61.0-100)	100 (93.9-100)	100 (89.0-100)
	2009 H1N1	100 (56.6-100)	98.3 (91.1-99.7)	100 (88.3-100)
BAL, TA, BW	InfA	83.3 (43.6-97.0)	83.3 (64.1-93.3)	100 (72.3-100)
	2009 H1N1	100 (56.6-100)	84.0 (65.3-93.6)	100 (72.3-100)

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.

K0100148, K080570

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

§ 866.3332 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.

Summary

0

7. 510(k) Summary

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

Assigned 510(k) number: K101564

Submitted by:

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

Contact Person:

Hve-Joo Kim, Pharm.D. Associate Director, Regulatory Affairs Office of the Director National Center for Emerging and Zoonotic Infectious Diseases (proposed) 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

June 22, 2010

Device Name

CDC Influenza 2009 A(H1N1)pdm Real-Time RT-PCR Panel

Common or Usual Name

CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel

Classification Name

Reagents for detection of specific novel influenza A viruses (21 CFR 866.3332, Product Code NXD)

Predicate devices

No predicate devices have been determined

Device Description

The CDC Influenza 2009 A(H1N1)pdm Real-time RT-PCR Panel (CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel) is a panel of oligonucleotide primers and dual-labeled hydrolysis (TaqMan®) probes which may be used in real-time RT-PCR (rRT-PCR) assays for the in vitro qualitative detection and characterization of human influenza

1

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.

The influenza A primer and probe sets are designed for universal detection of type A influenza viruses, Influenza A subtyping primer and probe sets are designed to specifically detect 2009 A (H1N1) influenza virus.

The CDC rRT-PCR 2009 A(H1N1)ødm Flu Panel is an updated version of the assay distributed by CDC. during the 2009 A(H1N1) pandemic strain to qualified laboratories (CDC rRT-PCR Swine Flu Panel G090072) under Emergency Use Authorization (EUA) from the FDA in that it has different sequences of primers and probes that are more specific to the currently circulating 2009 A(H1N1) influenza virus.

The CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel includes the following primer and probe sets and positive control:

InfA detects all influenza A strains, but does not detect influenza B strains .
pdm InfA is specific for 2009 influenza A .
pdm H1 is specific for 2009 influenza A, subtype H1 .
RNase P (RP) detects human RNase P and is used with human clinical . specimens to indicate that adequate isolation of nucleic acid resulted from the extraction of the clinical specimen
Inactivated Influenza Typing Panel Real-Time RT-PCR Positive Control is a . positive control designed to react with all the primer and probe sets including RNase P

Assay principle

The CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel assay is based on real-time RT-PCR technology which is used in many molecular diagnostic assays to date. The CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel influenza A primer and probe sets are designed for universal detection of type A influenza viruses. The panel also contains influenza A type and subtyping primer and probe sets designed to specifically detect human 2009 A(H1N1) influenza viruses.

One-step real-time RT-PCR assays are one-tube assays that first reverse-transcribe specific RNA templates into complementary deoxyribonucleic acid (cDNA) copies. The cDNA then serves as 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 target sequence located between the forward and reverse primers. During the extension phase of the PCR cycle, the 5' nuclease activity of Tag polymerase degrades the probe, causing the reporter dye to separate from the quencher dye, generating a fluorescent signal. With each cycle,

2

additional reporter dye molecules are cleaved from their respective probes, increasing the fluorescence intensity. Fluorescence intensity is monitored at each PCR cycle.

The CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel includes internal positive control materials. The human RNase P (RP) primer and probe set detects human RNase P and is used with human clinical specimens to indicate that adequate isolation of nucleic acid resulted from the extraction process 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 Influenza 2009 A(H1N1)pdm Positive Control (pdm PC) consists of influenza viruses representing 2009 A(H1N1) influenza virus and cultured human cells. The pdm PC serves as a rRT-PCR reaction control and demonstrates that the master mix and primer and probe sets for InfA, pdm InfA, pdm H1, and RP are functioning properly. All controls (HSC and pdm PC) are inactivated using beta propiolactone and are noninfectious.

The CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel components used for testing are similar to the components provided in the CDC rRT-PCR Flu Panel ([IVD] [K080570]}, following the same instructions for use on the ABI 7500 Fast Dx Real-Time PCR system.

Intended use

The CDC Influenza 2009 A(H1N1)pdm Real-Time RT-PCR Panel (CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel) is intended for use in real-time RT-PCR assays on an Applied Biosystems (ABI) 7500 Fast Dx Real-Time PCR Instrument in conjunction with clinical and epidemiological information:

For the qualitative detection of influenza virus type A viral RNA from . nasopharyngeal swabs (NPS), nasal swabs (NS), nasal aspirates (NA), nasal washes (NW), dual nasopharyngeal / throat swabs (NPS/TS), broncheoalveolar. lavage (BAL), tracheal aspirate (TA), and bronchial wash (BW), collected from the respiratory tract of human patients with signs and symptoms of respiratory infection and/or from viral culture.
For differentiation of 2009 H1N1 influenza virus RNA from nasopharyngeal . swabs (NPS), nasal swabs (NS), nasal aspirates (NA), nasal washes (NW) .dual nasopharyngeal / throat swabs (NPS/TS), broncheoalveolar lavage (BAL), tracheal aspirate (TA), and bronchial wash (BW) collected from the respiratory tract of human patients with signs and symptoms of respiratory infection and/or from viral culture.
To provide epidemiologic information for surveillance of the 2009 H1N1 influenza virus.

3

Performance characteristics for influenza A were established during the 2009-2010 influenza season when 2009 H1N1 influenza virus was the predominant influenza A virus in circulation. Performance characteristics may vary against other emerging influenza A viruses.

A negative test result for the broncheoalveolar lavage (BAL), tracheal aspirate (TA), and bronchial wash (BW) is presumptive and it is recommended these results be confirmed by viral culture.

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

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 in these cases 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

4

Substantial Equivalence Comparison:

Predicate device name(s): Focus Simplexa™ Influenza A H1N1 (2009) assay and CDC Human Influenza Virus Real-Time RT- PCR Detection and Characterization Panel
Predicate 510(k) number(s):_ K0100148 and K080570 respectively
Comparison with predicate:

| Device
Characteristics | CDC rRT-PCR 2009
A(H1N1)pdm Flu Panel
(New Device) | Simplexa™ Influenza
A H1N1 (2009)
(K100148) | CDC Human Influenza Virus
Real-Time RT-PCR Detection
and Characterization Panel
(K080570) |
|----------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The CDC rRT-PCR 2009
A(H1N1)pdm Flu Panel is
intended for use in real-time
RT-PCR assays on the
Applied Biosystems (ABI)
7500 Fast Dx Real-Time
PCR instrument for the in
vitro qualitative detection of
influenza virus type A and
2009 A(H1N1) viral RNA
from nasopharyngeal
swabs (NPS), nasal swabs
(NS), throat swabs (TS),
nasal aspirates (NA), nasal
washes (NW), dual
nasopharyngeal / throat
swabs (NPS/TS) and lower
respiratory tract specimens
(LRTS) from human
patients with signs and
symptoms of respiratory
infection and/or from viral
culture, in conjunction with
clinical and epidemiological
risk factors. | The Focus Diagnostics
Simplexa™ Influenza A
H1N1 (2009) assay is
intended for use on the
3M Integrated Cycler as
part of the Microfluidic
Molecular System for
the in vitro qualitative
detection and
differentiation of
influenza A and 2009
H1N1 influenza viral
RNA in nasopharyngeal
swabs (NPS), nasal
swabs (NS), and
nasopharyngeal
aspirates (NPA) from
human patients with
signs and symptoms of
respiratory infection in
conjunction with clinical
and epidemiological risk
factors. | 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/HI 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. |
| Identification of
Inf A | Yes (Universal A) | Yes | Yes |
| Assay Results | Qualitative | Qualitative | Qualitative |
| Nucleic Acid
Extraction | Yes | Yes | Yes |
| Device
Characteristics | CDC rRT-PCR 2009
A(H1N1)pdm Flu
Panel (New Device) | Simplexa™ Influenza A
H1N1 (2009) (New
Device) | CDC Human Influenza Virus
Real-Time RT- PCR Detection
and Characterization Panel
(Predicate Device #2) |
| Sample types | NPS, NS, NPS/TS,
NA, NW, BAL, BW,
TA, and/or virus
culture | NPS, NS, NPA | NPS, NS |
| Extraction Methods | • QIAamp® Viral RNA
Mini Kit, Qiagen Inc.
• MagNA Pure
Compact -Total
Nucleic Acid Kit.
Roche Applied
Science
• MagNA Pure
Compact - RNA
Isolation Kit, Roche
Applied Science
• MagNA Pure LC -
RNA Isolation Kit II,
Roche Applied
Science
• Qiagen QIAcube
with QIAamp® Viral
RNA Mini Kit,
Qiagen Inc.
• NucliSENS®
easyMAG®,
bioMerieux | • QIAamp® Viral RNA
Mini Kit, Qiagen Inc.
• MagNA Pure Total
Nucleic Acid Isolation
Kit (Roche)
• MagNA Pure LC
Instrument (Roche) | • QIAamp® Viral RNA Mini Kit,
Qiagen Inc.
• RNeasy® Mini Kit, Qiagen, Inc.
• MagNA Pure LC RNA Isolation
Kit II, Roche Applied Science
• MagNA Pure Total Nucleic Acid
Kit, Roche Applied Science |
| Assay Type | Real-time RT-PCR | Real-time RT-PCR | Real-Time RT-PCR |
| ldentification of
2009 H1N1 Subtype | Yes | Yes | No |
| Required
Instrumentation | Applied Biosystems
7500 Fast Dx Real-
Time PCR Instrument | Integrated cycler with
Integrated Cycler Studio
software v. 2.0 | Applied Biosystems 7500 Fast Dx
Real- Time PCR Instrument with
SDS software version 1.4 |
| Multiplex Capability | No
(Modular Use with
CDC rRT-PCR Flu
Panel (K08570) | Yes | No |

Similarities

5

Differences

Analytical Performance

1. Limit of Detection

Analytical sensitivity was demonstrated by determining the limit of detection (LoD) of each primer and probe set in the CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel. Each primer and probe set was tested with two different 2009 A(H1N1) influenza virus

6

strains. The limit of detection for each primer and probe set was calculated to indicate the range of lowest detectable concentration of influenza virus (EID50/mL) with a 95.0 percent or greater positivity. The lowest concentration of influenza virus detected was determined to be the end-point concentration where the type and subtype primer and probe sets had uniform detection. If the two end-points differ in concentration the higher (or limiting) concentration was used.

	Limit of Detection (EID50/mL)
2009 H1N1 Virus	InfA	pdm InfA	pdm H1	Final LoD
A/California/07/2009	10 1.6	10 1.6	10 1.6	10 1.6
A/New York/18/2009	10 1.3	10 0.6	10 1.3	10 1.3

2. Inclusivity of 2009 A(H1N1) Influenza Viruses

The CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel analytical specificity was demonstrated by inclusivity testing. To demonstrate the specificity of the primer and probe sets to detect a diverse population of 2009 A(H1N1) influenza viruses, ten 2009 A(H1N1) influenza viruses were tested at low concentrations using the CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel. The CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel analytical specificity inclusivity data indicated 100% concordance with all primer and probe sets included in the device. These data indicate that the CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel is highly specific for detecting 2009 A(H1N1) influenza viruses.

| 2009 A/H1N1 Virus | ID50/mL
Tested | Average
InfA Ct
Value
(N=3) | Average
pdm InfA
Ct Value
(N=3) | Average
pdm H1
Ct Value
(N=3) |
|--------------------------|-------------------|--------------------------------------|------------------------------------------|----------------------------------------|
| A/MEXICO/4108/2009 | 102.5 | 33.46 | 36.20 | 32.86 |
| A/CALIFORNIA/8/2009 | 102.2 | 29.75 | 31.57 | 28.80 |
| A/CALIFORNIA/7/2009 | 102.4 | 34.16 | 35.28 | 33.78 |
| A/CALIFORNIA/04/2009 | 101.9 | 32.26 | 33.54 | 32.13 |
| A/TEXAS/48/2009 | 102.0 | 32.20 | 33.14 | 32.06 |
| A/WASHINGTON/29/2009 | 102.5 | 30.58 | 32.35 | 30.10 |
| A/SOUTH CAROLINA/18/2009 | 102.6 | 25.44 | 24.55 | 26.90 |
| A/NEW YORK/18/2009 | 102.7 | 27.95 | 26.42 | 28.23 |
| A/ENGLAND/195/2009 | 102.0 | 26.92 | 27.03 | 29.36 |

7

A/NORTH CAROLINA/39/2009	$10^{2.7}$	27.23	26.47	27.96
--------------------------	------------	-------	-------	-------

3. Exclusivity of Seasonal Influenza Viruses and Influenza Viruses with Pandemic Potential

Characterized seasonal influenza viruses representing various geographical locations (A/H1, A/H3, Influenza B) were tested with the CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel to demonstrate the specificity of the primer and probe sets. To demonstrate the ability of the influenza A primer and probe sets to detect influenza A/H5 viruses with pandemic potential, the reactivity of the CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel was tested with ten avian A/H5 influenza viruses that have been shown to infect humans. The CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel demonstrates the ability to detect influenza type A viruses other than 2009 A(H1N1) viruses without a subtype as expected.

| Type | Virus | Titer
(log
TCID50/mL) | InfA | pdm
InfA | pdm H1 |
|------------------------------|---------------------------|-----------------------------|------|-------------|--------|
| H1N1 | A/JIANGXI/160/2005 | 5.6 | + | - | - |
| | A/SOLOMON ISLANDS/03/2006 | 6.2 | + | - | - |
| | A/TAIWAN/42/2006 | 4.7 | + | - | - |
| | A/FUKUSHIMA/141/2006 | 5.7 | + | - | - |
| | A/MEXICO/1744/2007 | 5.3 | + | - | - |
| | A/MEXICO/1729/2007 | 4.8 | + | - | - |
| | A/MEXICO/1677/2007 | 5.7 | + | - | - |
| | A/MEXICO/949/2007 | 5.1 | + | - | - |
| | A/BANGLADESH/7286/2007 | 6.1 | + | - | - |
| | A/MEXICO/2010/2007 | 5.1 | + | - | - |
| | A/BRISBANE/59/2007 | 8.4 (EID50/mL) | + | - | - |
| | A/PARAGUAY/61/2009 | 7.2 | + | - | - |
| | A/HAWAII/08/2006 | 7.8 | + | - | - |
| | A/WISCONSIN/03/2007 | 8.2 | + | - | - |
| | A/HENAN/JINSHUI/147/2007 | 8.1 | + | - | - |
| | A/BRISBANE/10/2007 | 6.8 | + | - | - |
| | A/MEXICO/922/2007 | 7.8 | + | - | - |
| H3N2 | A/AFGHANISTAN/2903/2008 | 5.0 | + | - | - |
| | A/MEXICO/1938/2007 | 5.1 | + | - | - |
| | A/MEXICO/1995/2007 | 4.3 | + | - | - |
| | A/ANHUI/1239/2005 | 8.1 | + | - | - |
| | A/MEXICO/1842/2007 | 6.1 | + | - | - |
| | A/PERTH/16/2009 | 8.2 (EID50/mL) | + | - | - |
| | A/WISCONSIN/15/2009 | 8.1 (EID50/mL) | + | - | - |
| | Inf B | B/FLORIDA/04/2006 | 5.7 | - | - |
| B/CHONGQING/YONGCHUAN18/2007 | | 7.7 | - | - | - |
| B/FLORIDA/02/2006 | | 6.0 | - | - | - |
| B/PENNSYLVANIA/05/2007 | | 6.6 | - | - | - |
| B/BANGLADESH/5972/2007 | | 4.7 | - | - | - |
| B/BANGLADESH/3461/2007 | | 3.7 | - | - | - |

8

B/BANGLADESH/7110/2007	4.2	-	-
A/MEXICO/1819/2007	5.1	-	-
B/TEXAS/17/2007	5.7	-	-
B/TEXAS/03/2007	5.6	-	-
B/BRISBANE/60/2008	8.5 (EID50/mL)	-	-
B/TEXAS/26/2008	8.2 (EID50/mL)	-	-

| Type | Virus | Clade | Titer
(log
EID50/mL) | InfA | pdm
InfA | pdm
H1 |
|------|------------------------------------------|-------|----------------------------|------------|-------------|-----------|
| H5N1 | A/Japanese white eye/Hong Kong/1038/2006 | 2.3.4 | 9.2 | +
(3/3) | - | - |
| | A/Duck/Hunan/795/2002 | 2.1 | 9.9 | +
(3/3) | - | - |
| | A/Chicken/Yunnan/1251/2003 | 1 | 9.3 | +
(3/3) | - | - |
| | A/Common magpie/Hong Kong/645/2006 | 2.3.2 | 9.2 | +
(3/3) | - | - |
| | A/Vietnam/1194/2004 | 1 | 9.3 | +
(3/3) | - | - |
| | A/Egypt/321/2007 | 2.2 | 9.2 | +
(3/3) | - | - |
| | A/Anhui/1/2005 | 2.3.4 | 9.3 | +
(3/3) | - | - |
| | A/Chicken/India/NIV3487/2006 | 2.2 | 9.3 | +
(3/3) | - | - |
| | A/Chicken/Vietnam/NCVD-016/2008 | 7 | 9.1 | +
(3/3) | - | |
| | A/Cambodia/R040505/2007 | 1 | 8.5 | +
(3/3) | - | - |

To demonstrate the ability of the influenza A primer and probe sets to detect potential pandemic influenza A viruses, the reactivity of the CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel was also tested with 15 non-human influenza viruses that have been shown to infect humans. These data demonstrate 100% concordance with expected results and strongly supports the intended use claims of the device and demonstrates the performance specificity of the device.

Reactivity of Non-Influenza Respiratory Viral and Bacterial Pathogens

The CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel analytical specificity was further demonstrated by testing 34 non-influenza organisms (respiratory pathogens or flora) commonly present in the nasopharynx region of the human respiratory tract. The CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel analytical specificity reactivity study showed 100% concordance with the expected results for all primer and probe sets included in the device. These data indicate that the CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel primer and probe sets do not cross react with biological organisms that may be present in the human nasopharynx.

9

| Markers
Tested | Commensal
Bacteria and
Yeast
Detection | Non-Influenza
Respiratory
Virus Detection | Detection
Expected | Concordance |
|-------------------|-------------------------------------------------|-------------------------------------------------|-----------------------|-------------|
| Inf A | 0/19 | 0/15 | No | 100 % |
| pdm InfA | 0/19 | 0/15 | No | 100 % |
| pdm H1 | 0/19 | 0/15 | No | 100 % |

5. Reproducibility

The reproducibility and precision of the CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel were evaluated at six separate laboratory sites. Each testing site assessed a panel of four simulated samples at relative moderate, low (near the assay lower limit of detection range), and "high negative" viral RNA concentration, and a negative sample. The panels and assay controls were tested at each site by two operators on 5 different days within a 10-day period. Each site tested one of the six extraction methods associated with this device. Simulated samples in the qualification panel used in the reproducibility evaluation were:

Sample #1 Influenza 2009 A/H1N1 moderate viral RNA titer range Sample #2 Influenza 2009 A/H1N1 low viral RNA titer range

Sample #3 Influenza 2009 A/H1N1 "high negative" RNA titer range

Sample #4 Influenza Negative (uninfected A549 cells)

10

Panel
L

ﺮ |
| )pdm

C

| N=10 tests | bioMerieux NucliSENS
easyMAG | | | Roche MagNA Pure LC
TNA | | | Roche MagNA Pure
Compact NA | | | Qiagen QIAcube Viral
RNA | | | Qiagen Manual Viral
RNA | | | Roche MagNA Pure
Compact RNA | | | Total
Agreeme
nt | |
|-----------------------------------------------------|------------------------------------------|---------|-------|------------------------------------------|---------|-------|------------------------------------------|---------|-------|------------------------------------------|---------|-------|------------------------------------------|---------|-------|------------------------------------------|---------|-------|------------------------|-------|
| | Agreeme
nt with
expected
result | Avg. Ct | % CV | Agreeme
nt with
expected
result | Avg. Ct | % CV | Agreeme
nt with
expected
result | Avg. Ct | % CV | Agreeme
nt with
expected
result | Avg. Ct | % CV | Agreeme
nt with
expected
result | Avg. Ct | % CV | Agreeme
nt with
expected
result | Avg. Ct | % CV | | |
| No Template
Control | 10/10 | NA | NA | 10/10 | NA | NA | 10/10 | NA | NA | 10/10 | NA | NA | 10/10 | NA | NA | 10/10 | NA | NA | 60/60 | |
| Sample 1
moderate | InfA | 10/10 | 28.52 | 2.59 | 10/10 | 30.53 | 2.55 | 10/10 | 31.99 | 4.23 | 10/10 | 27.92 | 2.06 | 10/10 | 28.85 | 2.00 | 10/10 | 30.54 | 2.12 | 60/60 |
| | pdm
InfA | 10/10 | 27.49 | 2.10 | 10/10 | 29.98 | 2.69 | 10/10 | 30.63 | 3.10 | 10/10 | 27.68 | 2.25 | 10/10 | 28.72 | 1.59 | 10/10 | 29.81 | 2.57 | 60/60 |
| | pdm
H1 | 10/10 | 30.21 | 2.12 | 10/10 | 32.23 | 3.17 | 10/10 | 32.98 | 2.31 | 10/10 | 30.63 | 1.48 | 10/10 | 31.09 | 1.69 | 10/10 | 32.38 | 2.57 | 60/60 |
| RP | 10/10 | 28.78 | 1.33 | 10/10 | 30.79 | 2.65 | 10/10 | 32.27 | 2.51 | 10/10 | 27.55 | 2.43 | 10/10 | 27.82 | 2.45 | 10/10 | 29.43 | 1.77 | 60/60 | |
| Sample 2
low | InfA | 10/10 | 33.10 | 3.26 | 8/10 | 31.75 | 35.61 | 8/10 | 36.12 | 4.11 | 10/10 | 32.95 | 1.04 | 10/10 | 33.49 | 3.14 | 10/10 | 34.48 | 2.88 | 58/60 |
| | pdm
InfA | 10/10 | 32.50 | 2.48 | 9/10 | 30.42 | 35.27 | 9/10 | 31.50 | 35.27 | 10/10 | 32.91 | 3.32 | 10/10 | 33.89 | 3.27 | 10/10 | 34.48 | 2.92 | 58/60 |
| | pdm
H1 | 10/10 | 35.19 | 3.10 | 7/10 | 28.85 | 52.94 | 7/10 | 29.34 | 52.77 | 10/10 | 34.66 | 1.27 | 10/10 | 36.12 | 2.18 | 10/10 | 36.57 | 3.70 | 54/60 |
| RP | 10/10 | 28.44 | 1.34 | 10/10 | 30.33 | 2.78 | 10/10 | 31.44 | 3.27 | 10/10 | 27.41 | 1.95 | 10/10 | 28.34 | 1.55 | 10/10 | 28.57 | 5.11 | 60/60 | |
| Sample 3
"high
negative" | InfA | 8/10 | NA | NA | 10/10 | NA | NA | 9/10 | NA | NA | 10/10 | NA | NA | 7/10 | NA | NA | 10/10 | NA | NA | 54/60 |
| | pdm
InfA | 10/10 | NA | NA | 10/10 | NA | NA | 10/10 | NA | NA | 9/10 | NA | NA | 8/10 | NA | NA | 10/10 | NA | NA | 57/60 |
| | pdm
H1 | 10/10 | NA | NA | 9/10 | NA | NA | 10/10 | NA | NA | 9/10 | NA | NA | 10/10 | NA | NA | 10/10 | NA | NA | 58/60 |
| RP | 10/10 | 28.04 | 2.13 | 10/10 | 30.08 | 4.92 | 10/10 | 31.12 | 2.60 | 10/10 | 26.89 | 2.09 | 10/10 | 28.33 | 1.41 | 10/10 | 28.45 | 3.31 | 60/60 | |
| Sample 4
A549
cells | RP | 10/10 | 28.68 | 2.75 | 10/10 | 30.20 | 5.68 | 10/10 | 32.10 | 1.74 | 10/10 | 27.06 | 2.65 | 10/10 | 28.60 | 2.29 | 10/10 | 29.33 | 4.00 | 60/60 |
| HSC | RP | 10/10 | 28.51 | 2.30 | 10/10 | 29.80 | 4.48 | 10/10 | 29.55 | 3.11 | 10/10 | 25.89 | 2.04 | 10/10 | 27.30 | 1.61 | 10/10 | 27.35 | 4.98 | 60/60 |
| Influenza
2009
A(H1N1)
Positive
Control | InfA | 10/10 | 23.71 | 2.10 | 10/10 | 21.95 | 2.97 | 10/10 | 23.54 | 4.10 | 10/10 | 21.62 | 1.39 | 10/10 | 23.66 | 2.63 | 10/10 | 24.95 | 2.21 | 60/60 |
| | pdm
InfA | 10/10 | 22.81 | 2.68 | 10/10 | 22.27 | 1.91 | 10/10 | 23.79 | 2.78 | 10/10 | 21.82 | 2.62 | 10/10 | 23.63 | 1.57 | 10/10 | 24.93 | 2.03 | 60/60 |
| | pdm
H1 | 10/10 | 25.76 | 1.55 | 10/10 | 24.35 | 4.78 | 10/10 | 26.36 | 2.42 | 10/10 | 25.31 | 1.19 | 10/10 | 25.89 | 2.13 | 10/10 | 27.52 | 2.53 | 60/60 |
| RP | 10/10 | 28.84 | 1.66 | 10/10 | 27.44 | 3.23 | 10/10 | 29.03 | 4.03 | 10/10 | 27.35 | 1.84 | 10/10 | 28.59 | 2.35 | 10/10 | 28.82 | 3.26 | 60/60 | |

.

11

Clinical Performance

Performance characteristics of the CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel were established during a prospective study at 8 U.S. public health laboratories and a Department of Defense (DoD) laboratory during the 2009-2010 respiratory virus season (February-April). Samples used for this study were collected for routine influenza testing at each site from individuals who were symptomatic with influenzalike illness (ILI) and included both upper and lower respiratory specimen types. Because of the low prevalence of influenza, retrospective specimens were used to supplement prospectively collected specimens.

The reference methods utilized in this study were virus culture with Immunofluorescent Antibody (IFA) or Direct Fluorescent Antibody (DFA) for screening and identification of influenza type and bi-directional sequencing for confirmation of 2009 influenza A (H1N1) subtype. InfA analyte results from the CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel were compared to virus culture results in the analysis. Sequencing was performed only with specimens that were first identified as positive for influenza A by virus culture. Pdm InfA and pdm H1 analyte results from the CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel were compared to bidirectional sequencing results in the analysis.

There were 1901 total patient specimens evaluated at the nine clinical testing sites: 1191 nasopharyngeal swabs (NPS) and nasal swabs (NS), 50 throat swabs, 519 nasal washes and nasal aspirates, 99 dual NPS/TS, and 42 lower respiratory specimens.

The overall performance call rate for the CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel in the clinical evaluation at nine different sites was greater than 99%.

The clinical sensitivity of the CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel for all markers tested using upper respiratory specimens was greater than 96% and the clinical specificity for all markers was greater than 96%. The positive percent agreement was greater than 96% for all markers tested.

The clinical sensitivity and specificity of the CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel was also evaluated with lower respiratory specimens. The clinical sensitivity and specificity for all markers in the panel were greater than 83% when compared to culture. The positive percent agreement of the CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel was 100%.

The clinical performance of the CDC Influenza 2009 A(H1N1)pdm Real-Time RT-PCR Panel supports the intended use of this device, demonstrates a clinical utility, and meets labeling claims.

The CDC 2009 A(H1N1)pdm rRT-PCR Panel Clinical Sensitivity, Specificity, and Percent Agreement Summary

12

| Specimen

Type	InfA			2009 H1N1
	Sensitivity
% (95% CI)	Specificity
% (95% CI)	Positive
Percent
Agreement
Retrospective	Sensitivity
% (95% CI)	Specificity
% (95% CI)	Positive
Percent
Agreement
Retrospective
NPS/NS	96.8
(89.1-99.1)	96.2
(94.6-97.3)	99.4
(97.7-99.8)	100
(93.7-100)	96.7
(95.3-97.7)	99.7
(98.1-99.9)
NA/NW	100
(83.2-100)	99.3
(97.5-99.8)	97.7
(94.6-99.0)	100
(80.6-100)	98.6
(96.5-99.5)	99.0
(96.5-99.7)
NPS/TS	100
(61.0-100)	100
(93.9-100)	100
(89.0-100)	100
(56.6-100)	98.3
(91.1-99.7)	100
(88.3-100)
BAL, TA,
BW	83.3
(43.6-97.0)	83.3
(64.1-93.3)	100
(72.3-100)	100
(56.6-100)	84.0
(65.3-93.6)	100
(72.3-100)

and the comments of the comments of the comments of the comments of

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13

Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-0609 Silver Spring, MD 20993-0002

Dr. Hye-Joo Kim Associate Director, Regulatory Affairs Centers for Disease Control and Prevention 1600 Clifton Rd, N.E., Mail Stop C-12 Atlanta, Georgia 30333

UUN 2 2 2010

Re: K101564

Trade/Device Name:	CDC Influenza 2009 A (H1N1)pdm Real-time RT-PCR Panel
Regulation Number:	21 CFR §866.3332
Regulation Name:	Reagents for detection of specific novel influenza A viruses
Regulatory Class:	Class II
Product Code:	OQW
Dated:	June 02, 2010
Received:	June 04, 2010

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 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 Part 801); 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.

14

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutlFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. 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/ReportalProblem/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 Small Manufacturers, International and Consumer Assistance 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.

Sincerely yours,

Uhe Schlf for

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

15

3. Indications for Use Statement

510(k) Number: K101564

Device Name: CDC Influenza 2009 A(H1N1)pdm Real-Time RT-PCR Panel

Intended use

The CDC Influenza 2009 A(H1N1)pdm Real-Time RT-PCR Panel (CDC rRT-PCR 2009 A(H1N1)pdm Flu Panel) is intended for use in real-time RT-PCR assays on an Applied Biosystems (ABI) 7500 Fast Dx Real-Time PCR Instrument in conjunction with clinical and epidemiological information:

For the qualitative detection of influenza virus type A viral RNA from . nasopharyngeal swabs (NPS), nasal swabs (NS), nasal aspirates (NA), nasal washes (NW), dual nasopharyngeal / throat swabs (NPS/TS), broncheoalveolar lavage (BAL), tracheal aspirate (TA), and bronchial wash (BW), collected from the respiratory tract of human patients with signs and symptoms of respiratory infection and/or from viral culture.
For differentiation of 2009 H1N1 influenza virus RNA from nasopharyngeal . swabs (NPS), nasal swabs (NS), nasal aspirates (NA), nasal washes (NW) .dual nasopharyngeal / throat swabs (NPS/TS), broncheoalveolar lavage (BAL), tracheal aspirate (TA), and bronchial wash (BW) collected from the respiratory tract of human patients with signs and symptoms of respiratory infection and/or from viral culture.
To provide epidemiologic information for surveillance of the 2009 H1N1 . influenza virus.

Performance characteristics for influenza A were established during the 2009-2010 influenza season when 2009 H1N1 influenza virus was the predominant influenza A virus in circulation. Performance characteristics may vary against other emerging influenza A viruses.

A neqative test result for the broncheoalveolar lavage (BAL), tracheal aspirate (TA), and bronchial wash (BW) is presumptive and it is recommended these results be confirmed by viral culture.

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

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 in these cases unless a BSL 3+ facility is available to receive and culture specimens.

16

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

Prescription Use (Part 21 CFR 801 Subpart D)

AND/OR

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

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

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety

Uive Sch

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Office of In Vitro Diagnostic Device Evaluation and Safety

510(k)_