(26 days)
Not Found
No
The summary describes a standard RT-PCR diagnostic panel and its performance characteristics. There is no mention of AI or ML in the intended use, device description, or performance studies.
No
This device is a diagnostic panel used for the qualitative detection and characterization of human influenza viruses, which aids in diagnosis and surveillance, rather than providing therapy.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device is "intended for use in real-time RT-PCR (rRT-PCR) assays... For qualitative detection of influenza virus type A or B... For determination of the subtype of seasonal human influenza A virus... For the presumptive identification of virus in patients...". These are all diagnostic purposes aimed at identifying or characterizing a medical condition.
No
The device is a diagnostic panel consisting of oligonucleotide primers and probes, which are physical reagents used in a laboratory setting. It is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states "For qualitative detection of influenza virus type A or B from viral RNA in upper respiratory tract clinical specimens... and lower respiratory tract specimens... from human patients..." and "For determination of the subtype of seasonal human influenza A virus... from viral RNA in upper respiratory tract clinical specimens... and lower respiratory tract specimens... from human patients...". These are all diagnostic purposes performed in vitro (outside the body) on clinical specimens.
- Device Description: The description states the panel is used "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 phrase "in vitro" is a key indicator of an IVD.
- Clinical Specimen Testing: The performance studies describe testing on "human respiratory specimens," which are clinical samples.
- Diagnostic Panel: The name of the device itself, "CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel," includes the word "Diagnostic."
All of these points align with the definition of an In Vitro Diagnostic device, which is a medical device intended for use in the collection, preparation, and examination of specimens taken from the human body to provide information for diagnostic purposes.
N/A
Intended Use / Indications for Use
The CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel is intended for use in real-time RT-PCR (rRT-PCR) assays on an Applied Biosystems (ABI) 7500 Fast Dx Real-Time PCR Instrument in conjunction with clinical and epidemiological information:
- For qualitative detection of influenza virus type A or B from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], nasal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS], and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture;
- For determination of the subtype of seasonal human influenza A virus as seasonal A/H1, A/H3, and/or A/H1pdm09 from viral RNA in upper respiratory tract clinical specimens (including NPS, NS, TS, NA, NW and NPS/TS) and lower respiratory tract specimens (including BAL, BW, TA, sputum and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture;
- 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 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 epidemiologic criteria for testing suspect A/H5 specimens. The definitive identification of influenza A/H5 (Asian lineage) either directly from patient specimens or from virus cultures requires additional laboratory testing, along with clinical and epidemiological assessment in consultation with national influenza surveillance experts.
Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions. Conversely, positive results do not rule out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease.
If infection with a novel influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent influenza viruses and sent to state or local health department for testing. Viral culture should not be attempted 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)
OQW, NSU, NXD, OEP
Device Description
The CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel is used in real-time RT-PCR (rRT-PCR) assays on the ABI 7500 Fast Dx Real-Time PCR Instrument. The panel 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 CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel is based on technology which is used in many molecular diagnostic assays. rRT-PCR assays are one-tube assays that first reversetranscribe 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.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Upper respiratory tract clinical specimens (including nasopharyngeal swabs, 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)
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 a training course provided by CDC instructors or designees.
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Analytical Sensitivity - Limit of Detection (LOD)
The analytical sensitivity of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel for influenza A(H3N2)variant ((H3N2)v) virus was evaluated with two recent isolates by determining the lowest concentration of virus as measured by 50% egg infectious dose (EID55/ml) where the InfA, pdmInfA, and H3 primer and probe sets demonstrated a uniform detection rate of ≥ 95%.
Results for A/West Virginia/06/2011: InfA $10^{0.7}$ EID50/mL, pdmInfA $10^{1.4}$ EID50/mL, H3 $10^{2.1}$ EID50/mL, Final LOD $10^{2.1}$ EID50/mL.
Results for A/Indiana/12/2012: InfA $10^{0.6}$ EID50/mL, pdmInfA $10^{1.3}$ EID50/mL, H3 $10^{2.0}$ EID50/mL, Final LOD $10^{2.0}$ EID50/mL.
Analytical Sensitivity - Inclusivity
Recent isolates of influenza A(H3N2)v virus from 2009-2012 were evaluated with the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel at virus concentrations of approximately 10-0 EID50/ml. The inclusivity testing verifies that the device can detect contemporary influenza A (H3N2)v viruses near the LOD.
Clinical Specimen Testing
From July 2012-August 2012, a total of 165 human respiratory specimens that tested positive for InfA, H3, and pdmInfA markers and negative for H1 and pdmH1 markers with the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel were transferred from U.S. public health laboratories to the CDC for confirmatory testing. The specimens were retested upon arrival with the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel following the instructions for use provided in the package insert. Results were confirmed through genetic sequence analysis.
Comparison of the results obtained with the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel to the genetic sequencing analysis demonstrate a positive percent agreement of 97.6% with a 95% confidence interval of 93.9-99.1 % for the detection of influenza A(H3N2)v virus.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Positive Percent Agreement: 97.6% (95% CI: 93.9 - 99.1)
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.
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
§ 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.
0
JAN 1 4 2013
3. 510(k) Summary
The 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
CAPT Hye-Joo Kim, 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) 639-4643 (office) (404) 639-1275 (fax) hek6@cdc.gov
Proprietary Name
CDC Human Influenza Virus Real-time RT-PCR Diagnostic Panel
Common or Usual Name
Human Influenza Virus Real-time RT-PCR Diagnostic Panel
Regulatory Information
Classification Regulation Section: 866.3332- Reagents for detection of specific novel influenza A viruses Subsequent Regulation Sections: 866.3980- Respiratory viral panel multiplex nucleic acid assay 862.2570- Instrumentation for clinical multiplex test systems
Classification: Class II Classification Product Code: OQW Subsequent Product Codes: NSU, NXD, OEP Panel: Microbiology
Predicate Device CDC Human Influenza Virus Real-time RT-PCR Diagnostic Panel (K111507)
Device Description
The CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel is used in real-time RT-PCR (rRT-PCR) assays on the ABI 7500 Fast Dx Real-Time PCR Instrument. The panel 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).
1
The CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel is based on technology which is used in many molecular diagnostic assays. rRT-PCR assays are one-tube assays that first reversetranscribe 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.
Intended Use
The CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel is intended for use in rRT-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 viral RNA in upper respiratory tract . clinical specimens (including nasopharyngeal swabs [NPS], throat swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture.
- For determination of the subtype of seasonal human influenza A virus as seasonal A/H1, A/H3, . and/or A/H1pdm09 from viral RNA in upper respiratory tract clinical specimens (including NPS, NS, TS, NA, NW, and NPS/TS) and lower respiratory tract specimens (including BAL, BW, TA, sputum and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture.
- 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 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
2
laboratory testing, along with clinical and epidemiological assessment in consultation with national influenza surveillance experts.
Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions. Conversely, positive results do not rule out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease.
If infection with a novel influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent influenza viruses and sent to state or local health department for testing. Viral culture should not be attempted unless a BSL 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.
Indications for Use
The CDC Human Influenza Virus Real-Time PCR Diagnostic 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 qualitative detection of influenza virus type A or B from viral RNA in upper respiratory . 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 patients with signs and symptoms of respiratory infection and/or from viral culture
- . For determination of the subtype of seasonal human influenza A virus as seasonal A/H1, A/H3, and/or A/H1pdm09 from viral RNA in upper respiratory 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 patients with signs and symptoms of respiratory infection and/or from viral culture
- . 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, and 4) to provide epidemiologic information for surveillance of the circulating influenza viruses
Technological Characteristics
The change proposed to the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel subject to this special 510{k) will not alter the device's design or technological attributes.
3
Substantial Equivalence Comparison
The CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel (K111507) will serve as the predicate for the intended change. Please see Table 1 for a detailed comparison.
| CDC Human Influenza Virus Real-time PCR Diagnostic Panel (K111507) | Modified CDC Human Influenza Virus Real-time PCR Diagnostic Panel | |
|---|---|---|
| Intended Use | The CDC Human Influenza Virus Real-Time PCR Diagnostic 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 qualitative detection of influenza virus type A or B from viral RNA in upper respiratory 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 patients with signs and symptoms of respiratory infection and/or from viral culture for determination of the subtype of seasonal human influenza A virus as seasonal A/H1, A/H3, and/or A/H1pdm09 from viral RNA in upper respiratory 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 patients with signs and symptoms of respiratory infection and/or from viral culture 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 the circulating influenza viruses. | Same |
| Table | 1: Device | Comparison | ||||
|---|---|---|---|---|---|---|
4
| Specimen Types | Nasopharyngeal swabs, nasal swabs, throat swabs,
nasal aspirates, nasal washes and dual
nasopharyngeal/throat swabs, bronchoalveolar
lavages, bronchial aspirates, bronchial washes,
tracheal aspirates, sputum, and lung tissue and virus
culture. | Same |
|-----------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| CDC Human Influenza Virus Real-time PCR
Diagnostic Panel (K111507) | Modified CDC Human Influenza Virus
Real-time PCR Diagnostic Panel | Same |
| Technology | Real-time RT-PCR | Same |
| Required
Instrumentation | Applied Biosystems 7500 Fast Dx Real- Time PCR
Instrument | Same |
| Organism
Detected | Universal influenza A viruses (animal and human),
Swine-origin influenza A viruses, Influenza B
viruses, and Influenza A subtypes: seasonal A/H1,
A/H3, A/H1pdm09, and A/H5 | Same |
| Nucleic Acid
Extraction | Yes | Same |
| Extraction
Method | · 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® easy MAG®, bioMerieux | Same |
| Enzyme Master
Mix | 'Invitrogen SuperScript™ III Platinum® One-Step
Quantitative RT-PCR Kits (with or without ROX) | Same |
| Non Standard
Results Guidance | Results positive for InfA, H3, and pdmInfA
markers and negative for H1 and pdmH1 markers
are reported as inconclusive and referred to CDC.
for further testing. | Results positive for InfA, H3, and
pdmInfA markers and negative for HI and
pdmH1 markers are interpreted as a
presumptive positive for influenza A
(H3N2) variant virus and referred to CDC
for further testing. |
Performance Summary
Analytical Sensitivity - Limit of Detection (LOD)
The analytical sensitivity of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel for influenza A(H3N2) variant ((H3N2)v) virus was evaluated with two recent isolates by determining the lowest concentration of virus as measured by 50% egg infectious dose (EID55/ml) where the InfA, pdmInfA, and H3 primer and probe sets demonstrated a uniform detection rate of ≥ 95%. The results are summarized in Table 2.
| Influenza A(H3N2)v
| virus | Limit of Detection (EID50/mL) | |||
|---|---|---|---|---|
| InfA | pdm InfA | H3 | Final LOD | |
| A/West Virginia/06/2011 | $10^{0.7}$ | $10^{1.4}$ | $10^{2.1}$ | $10^{2.1}$ |
Table 2: (H3N2)v LOD Summary
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| A/Indiana/12/2012 | $10^{0.6}$ | $10^{1.3}$ | $10^{2.0}$ | $10^{2.0}$ |
|---|---|---|---|---|
| ------------------- | ------------ | ------------ | ------------ | ------------ |
Analytical Sensitivity - Inclusivity
Recent isolates of influenza A(H3N2)v virus from 2009- 2012 were evaluated with the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel at virus concentrations of approximately 10-0 EIDsoml. The inclusivity testing verifies that the device can detect contemporary influenza A (H3N2)v viruses near the LOD. The results are summarized in Table 3.
| Strain designation | EID50/mL | Average InfA
Ct Value (n=3) | Average pdm InfA
Ct Value (n=3) | Average H3
Ct Value (n=3) |
|-------------------------|------------|--------------------------------|------------------------------------|------------------------------|
| A/Kansas/13/2009 | $10^{2.0}$ | 33.4 | 32.6 | 33.9 |
| A/Indiana/08/2011 | $10^{2.3}$ | 33.0 | 33.5 | 35.6 |
| A/Wisconsin/12/2011 | $10^{2.1}$ | 28.9 | 26.9 | 28.9 |
| A/West Virginia/06/2011 | $10^{2.9}$ | 28.1 | 28.3 | 30.1 |
| A/Indiana/12/2012 | $10^{2.1}$ | 31.7 | 32.8 | 36.0 |
Table 3: Inclusivity Testing
Clinical Specimen Testing
From July 2012-August 2012, a total of 165 human respiratory specimens that tested positive for InfA, H3, and pdmInfA markers and negative for H1 and pdmH1 markers with the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel were transferred from U.S. public health laboratories to the CDC for confirmatory testing.
The specimens were retested upon arrival with the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel following the instructions for use provided in the package insert. Results were confirmed through genetic sequence analysis. Comparison of the results obtained with the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel to the genetic sequencing analysis demonstrate a positive percent agreement of 97.6% with a 95% confidence interval of 93.9-99.1 % for the detection of influenza A(H3N2)v virus.
| Comparator¹ | |||
|---|---|---|---|
| Positive² | Negative | Performance | |
| CDC Flu rRT-PCR Dx | |||
| Panel (+) | 161 | NA | 97.6% Positive Percent |
| Agreement | |||
| (93.9 - 99.1) 95% CI | |||
| CDC Flu rRT-PCR Dx | |||
| Panel (-) | 4 | NA | NA |
| Total | 165 | NA | NA |
Table 4: Clinical Performance Comparison
1The comparator is genetic sequence analysis.
A positive result for InfA, H3, and pdmInfA markers (negative for H1 and pdmH1 markers) was investigated. Any result that was not positive for all three markers InfA, and H3 was considered negative. NA = not applicable.
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Risk Analysis
The risk analysis for the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel was reviewed to verify that the change did not present increased or new risks to the user. No new risks were identified as a result of the proposed modification. As an additional mitigation, specimens containing influenza A (H3N2)v viruses will continue to be referred immediately to the CDC for further confirmation.
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 additions for use and intended use of the device will remain the same. It is only the interpretation of the results that will be modified, allowing users to report the result as a presumptive positive for influenza A (H3N2) variant virus instead of inconclusive. This information, along with the results of the performance testing, demonstrates that the modified device is substantially equivalent to the predicate.
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Image /page/7/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three lines representing its wings and tail feathers. The eagle is positioned to the right of the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA", which is arranged in a circular fashion around the left side of the logo.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-002
JAN 1 4 2013
Centers for Disease Control and Prevention c/o Hye-Joo Kim, Pharm.D. Associate Director for Regulatory Affairs Office of the Director, National Center for Emerging and Zoonotic Infectious Diseases 1600 Clifton Road, MS-C18 Atlanta, GA 30333
Re: K123905
· Trade/Device Name: CDC Human Influenza Virus Real-Time RT-PCR Diagnostic 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, NSU, NXD, OEP Dated: December 18, 2012 Received: December 19, 2012
Dear Captain 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
8
Page 2 - Hye-Joo Kim
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.
If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostics and Radiological Health at (301) 796-5450. 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 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/cdrh/industry/support/index.html.
Sincerely yours,
Sally AJHojvat
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
9
2. Indications for Use Statement
510(k) Number (if known): K123905
Device Name: CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel
The CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel is intended for use in real-time RT-PCR (rRT-PCR) assays on an Applied Biosystems (ABI) 7500 Fast Dx Real-Time PCR Instrument in conjunction with clinical and epidemiological information:
- For qualitative detection of influenza virus type A or B from viral RNA in upper . respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], nasal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS], and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture;
- For determination of the subtype of seasonal human influenza A virus as seasonal A/H1, . A/H3, and/or A/H1pdm09 from viral RNA in upper respiratory tract clinical specimens (including NPS, NS, TS, NA, NW and NPS/TS) and lower respiratory tract specimens (including BAL, BW, TA, sputum and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture;
- 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 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 epidemiologic criteria for testing suspect A/H5 specimens. The definitive identification of influenza A/H5 (Asian lineage) either directly from patient specimens or from virus cultures requires additional laboratory testing, along with clinical and epidemiological assessment in consultation with national influenza surveillance experts.
Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions. Conversely, positive results do not rule out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease.
If infection with a novel influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent influenza viruses and sent to state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
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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.
Prescription Use X (Part 21 CFR 801 Subpart D)
AND/OR
Over-The-Counter Use (21 CFR 801 Subpart C)
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