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U.S. Department of Health and Human Services

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Letter of Authorization: CDC Swine Influenza Virus Real-time RT-PCR Detection Panel

The information previously contained on these webpages were authorized under the 2009 H1N1 Influenza Emergency Use Authorizations (EUAs). As of June 23, 2010, the EUAs have been terminated and this information is no longer current.

December 18, 2009

Thomas R. Frieden, MD, MPH
Director
Centers for Disease Control and Prevention
1600 Clifton Rd, MS D-14
Atlanta, GA 30333
December 18, 2009

Dear Dr. Frieden:

On April 27, 2009, FDA issued a letter authorizing the emergency use of the Swine Influenza Virus Real-time RT-PCR Detection Panel (rRT-PCR Swine Flu Panel) assay for the presumptive diagnosis of 2009 H1N1 influenza virus infection, pursuant to section 564 of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. § 360bbb-3) by public health and other qualified laboratories . On May 1, 2009, CDC submitted a request for an amendment to the Emergency Use Authorization.1 On August 31, 2009 CDC submitted a request for a second amendment2 and on November 30, 2009 CDC submitted a request for a third amendment3 to the Emergency Use Authorization G090072. In response to those requests, the letter authorizing emergency use of the rRT-PCR Swine Flu Panel is being reissued in its entirety with the amendments, as requested by CDC.

On April 26, 2009, pursuant to section 564(b)(1)(C) of the Act (21 U.S.C. § 360bbb-3(b)(1)(C)), the Secretary of the Department of Health and Human Services (HHS) determined that there is a public health emergency under 42 U.S.C. § 247d that affects, or has a significant potential to affect, national security, and that involves a specified biological, chemical, radiological, or nuclear agent or agents, or a specified disease or condition that may be attributable to such an agent or agents -- in this case, 2009 H1N1 influenza virus.4 Pursuant to section 564(b) of the Act (21 U.S.C. § 360bbb-3(b)), and on the basis of such determination, the Secretary of HHS then declared an emergency justifying the authorization of the emergency use of certain in vitro diagnostics for the detection of 2009 H1N1 influenza virus, subject to the terms of any authorization issued under 21 U.S.C. § 360bbb-3(a).

Having concluded that the criteria for issuance of this authorization under section 564(c) of the Act (21 U.S.C. § 360bbb-3(c)) are met, I am authorizing the emergency use of the Swine Influenza Virus Real-time RT-PCR Detection Panel (rRT-PCR Swine Flu Panel) (as described in the scope section of this letter (Section II)) for the diagnosis of 2009 H1N1 influenza virus infection in individuals with signs and symptoms of respiratory infection, subject to the terms of this authorization.

I. Criteria for Issuance of Authorization

I have concluded that the emergency use of the rRT-PCR Swine Flu Panel for the diagnosis of 2009 H1N1 influenza virus infection in individuals with signs and symptoms of respiratory infection meets the criteria for issuance of an authorization under section 564(c) of the Act, because I have concluded that:

  1. The 2009 H1N1 influenza virus can cause influenza, a serious or life threatening disease or condition to humans infected by this virus;
  2. Based on the totality of scientific evidence available to FDA, it is reasonable to believe that the rRT-PCR Swine Flu Panel may be effective for the diagnosis of 2009 H1N1 influenza virus infection, and that the known and potential benefits of the rRT-PCR Swine Flu Panel, when used in the diagnosis of 2009 H1N1influenza virus infection, outweigh the known and potential risks of such products; and
  3. There is no adequate, approved, and available alternative to the emergency use of the rRT-PCR Swine Flu Panel for the diagnosis of 2009 H1N1 influenza virus infection.5

II. Scope of Authorization

I have concluded, pursuant to section 564(d)(1) of the Act, that the scope of this authorization is limited to the use of the authorized rRT-PCR Swine Flu Panel for the diagnosis of 2009 H1N1 influenza virus infection in individuals  with signs and symptoms of respiratory infection.

The Authorized rRT-PCR Swine Flu Panel :

The Swine Influenza Virus Real-time RT-PCR Detection Panel is a panel of oligonucleotide primers and dual-labeled hydrolysis (Taqman®) probes for use in the real-time RT-PCR assay on the Roche LightCycler ® 2.0, and the Applied Biosystems (ABI) 7500 Fast Dx Real-time PCR, and the RUO marketed 7500 Fast Real-time PCR instruments for the in vitro qualitative detection of 2009 H1N1 influenza viral RNA in upper respiratory tract specimens (such as nasopharyngeal swabs (NPS), nasal swabs (NS), throat swabs (TS), dual NPS/TS swabs, or nasal aspirates (NA)) and the lower respiratory tract specimens (such as bronchoalveolar lavage (BAL), bronchial aspirate (BA); bronchial washes (BW), endotracheal aspirates (EA) and endotracheal wash (EW), tracheal aspirates (TA), and lung tissue) from patients with signs and symptoms of respiratory infection and from viral culture. The universal influenza A (Matrix gene), 2009 H1N1 influenza swInfA (NP gene), and swH1 (HA gene) primer and probe sets are designed for detection of 2009 H1N1 influenza viruses.

The rRT-PCR Swine Flu Panel includes the following primer and probe sets:

  • InfA detects a well-conserved region of the Matrix Protein (M) gene from influenza A viruses in both seasonal human influenza A virus and 2009 H1N1 virus.
  • swInfA specifically detects the 2009 H1N1 influenza strains (NP gene).
  • sw H1 is specific for the 2009 H1N1 influenza and detects the presence of the hemagglutinin (HA) gene specifically found in the 2009 H1N1 virus.

The rRT-PCR Swine Flu Panel also includes control materials:

  • RNase P (RP) detects human RNase P and is used as a positive control with human clinical specimens to indicate that adequate isolation of nucleic acid resulted from the extraction of the clinical specimen.
  • Swine Influenza Panel Real-Time RT-PCR Positive Control (SIPC) is a positive control designed to react with all the primer and probe sets including RNase P.

The above rRT-PCR Swine Flu Panel, when labeled consistently with the labeling authorized by FDA, entitled the Swine Influenza Virus Real-time RT-PCR Detection Panel (rRT-PCR Swine Flu Panel) (see http://www.fda.gov/MedicalDevices/ Safety/EmergencySituations/ucm161496.htm), as may be revised with written permission of FDA, is authorized to be distributed to public health and other qualified laboratories6 under this EUA, despite the fact that it does not meet certain requirements otherwise required by federal law.

The above described  rRT-PCR Swine Flu Panel is authorized to be accompanied by the following information pertaining to the emergency use, which are authorized to be made available to health care providers and patients:

  • Fact Sheet For Healthcare Providers: Interpreting the Swine Influenza Virus Real-time RT-PCR Detection Panel Test Results
  • Fact Sheet For Patients: Understanding r rt-pcr Swine Influenza Detection Panel Test Results

As described in section IV below, CDC and the appropriate state and/or local public health authority(ies) are also authorized to make available additional information relating to the emergency use of the authorized rRT-PCR Swine Flu Panel that is consistent with, and does not exceed, the terms of this letter of authorization.

I have concluded, pursuant to section 564(d)(2) of the Act, that it is reasonable to believe that the known and potential benefits of the authorized rRT-PCR Swine Flu Panel in the specified population, when used for diagnosis of 2009 H1N1 influenza virus infection, outweigh the known and potential risks of such product.

I have concluded, pursuant to section 564(d)(3) of the Act, based on the totality of scientific evidence available to FDA, that it is reasonable to believe that the authorized rRT-PCR Swine Flu Panel may be effective in the diagnosis of 2009 H1N1 influenza virus infection pursuant to section 564(c)(2)(A) of the Act. The FDA has reviewed the scientific information available including the information supporting the conclusions described in Section I above, and concludes that the authorized rRT-PCR Swine Flu Panel, when used to diagnose 2009 H1N1 influenza virus infection in the specified population, meets the criteria set forth in section 564(c) of the Act concerning safety and potential effectiveness.

The emergency use of the authorized rRT-PCR Swine Flu Panel under this EUA must be consistent with, and may not exceed, the terms of this letter, including the scope and the conditions of authorization set forth below. Subject to the terms of this EUA and under the circumstances set forth in the Secretary of HHS' determination under section 564(b)(1)(C) described above and the Secretary of HHS' corresponding declaration under section 564(b)(1), the rRT-PCR Swine Flu Panel described above is authorized to diagnose 2009 H1N1 influenza virus infection in individuals with signs and symptoms of respiratory infection.

This EUA will cease to be effective when the declaration of emergency is terminated under section 564(b)(2) of the Act or when the EUA is revoked under section 564(g) of the Act.

III. Waiver of Certain Requirements

I am waiving the following requirements for the rRT-PCR Swine Flu Panel during the duration of this emergency use authorization:

  • Current good manufacturing practice requirements, including the quality system requirements under 21 CFR Part 820 with respect to the design, manufacture, packaging, labeling, storage, and distribution of the rRT-PCR Swine Flu Panel;
  • Labeling requirements for cleared, approved, or investigational devices, including labeling requirements under 21 CFR 809.10 and 809.30, except for the intended use statement (21 CFR 809.10(a)(2), (b)(2)), adequate directions for use (21 U.S.C. 352(f)), (21 CFR 809.10(b)(5) and (8)), any appropriate limitations on the use of the device including information required under 21 CFR 809.10(a)(4), and any available information regarding performance of the device, including requirements under 21 CFR 809.10(b)(12);

IV. Conditions of Authorization

Pursuant to section 564 of the Act, I am establishing the following conditions on this authorization:

CDC

  1. CDC will distribute the rRT-PCR Swine Flu Panel with the authorized labeling, as may be revised with written permission of FDA only to qualified laboratories.
  2. CDC will provide to the qualified laboratories and state and/or local public health authority(ies) the authorized rRT-PCR Swine Flu Panel Fact Sheets for Health Care Providers, and the authorized rRT-PCR Swine Flu Panel Fact Sheets for Patients.
  3. CDC will make available on its website the authorized rRT-PCR Swine Flu Panel Fact Sheets for Health Care Providers, and the authorized rRT-PCR Swine Flu Panel Fact Sheets for Patients.
  4. CDC will inform state and/or local public health authority(ies) of this EUA, including the terms and conditions herein.
  5. CDC will ensure that qualified laboratories using the rRT-PCR Swine Flu Panel have a process in place for reporting test results to health care providers and federal, state and/or local public health authorities, as appropriate.
  6. CDC will track adverse events and report to FDA as required under 21 CFR part 803.
  7. Through a process of inventory control, CDC will maintain records of device usage.
  8. CDC will collect information on the performance of the assay, and report to FDA any suspected occurrence of false positive and negative results of which CDC becomes aware.

Public Health and Other Qualified Laboratories

  1. Public health and other qualified laboratories will include with reports of the results of the rRT-PCR Swine Flu Panel, the authorized Fact Sheets for Health Care Providers and the authorized Fact Sheet for Patients.
  2. Qualified laboratories will perform the assay on the Roche LightCycler ® 2.0 Real-time PCR system, or an Applied Biosystems 7500 Fast Dx Real-time PCR instrument, or the RUO marketed Applied Biosystems 7500 Real-time PCR instrument that is validated by Applied Biosystems with regard to the updated software but only partially qualified regarding its laboratory performance (proficiency testing with the CDC sample panel not performed).
  3. Qualified laboratories will have a process in place for reporting test results to health care providers and federal, state and/or local public health authorities, as appropriate.
  4. Qualified laboratories will collect information on the performance of the assay, and report to CDC any suspected occurrence of false positive or false negative results of which qualified laboratories become aware.

CDC and State and/or Local Public Health Authority(ies)

  1. CDC and the appropriate state and/or local public health authority(ies) are authorized to make available additional information relating to the emergency use of the authorized rRT-PCR Swine Flu Panel that is consistent with, and does not exceed, the terms of this letter of authorization.
  2. Only CDC may request changes to the authorized Fact Sheet for Health Care Providers or the authorized rRT-PCR Swine Flu Panel Fact Sheet for Patients. Such requests will be made by contacting FDA concerning FDA review and approval.
  3. CDC and the appropriate state/and or local public health authority(ies) will ensure that any records associated with this EUA are maintained until notified by FDA. Such records will be made available to FDA for inspection upon request.

  The emergency use of the authorized rRT-PCR Swine Flu Panel as described in this letter of authorization must comply with the conditions above and all other terms of this authorization.

V. Duration of Authorization

This EUA will be effective until the declaration of emergency is terminated under section 564(b)(2) of the Act or the EUA is revoked under section 564(g) of the Act.

____________________________
Margaret A. Hamburg, M.D.
Commissioner of Food and Drugs


1 The amendment to the April 27, 2009 letter allow use of different sample types (throat swabs (TS), dual NPS/TS swab, or nasal aspirate (NA) specimens) and different reagents.

2 The amendment to the May 2, 2009 letter allow use of the LightCycler ® 2.0 Real-time PCR system, in addition to the ABI 7500 Fast Dx system, with the CDC rRT-PCR Swine Flu Panel .

3 The amendment to the May 2, 2009 letter authorize use of nasal washes as additional upper respiratory tract specimen and use of lower respiratory tract specimens (such as bronchoalveolar lavage (BAL), bronchial aspirate (BA); bronchial wash (BW); endotracheal aspirate (EA); endotracheal wash (EW); tracheal aspirate (TA), and lung tissue) as acceptable clinical specimens with the CDC rRT-PCR Swine Flu Panel; to remove the word “presumptive” from the Intended Use; to allow the use of the CDC rRT-PCR Swine Flu Panel as a stand alone test; to include Human Specimen Control (HSC) that was previously included in the CDC rRT-PCR Flu Panel (IVD, K080570); and to update packaging by removing product from foam envelopes and segregating into boxes. There are also minor wording changes made to be consistent with more recently issued Emergency Use Authorizations for in vitro diagnostic devices.

4 Memorandum, Determination Pursuant to § 564 of the Federal Food, Drug, and Cosmetic Act (April 26, 2009).

5 No other criteria of issuance have been prescribed by regulation under section 564(c)(4) of the Act.

6 All users, analysts, and any person reporting diagnostic results from use of this device should be trained to perform and interpret the results from this procedure by a CDC instructor or designee prior to use. CDC Influenza Division will limit the distribution of this device to those users who have successfully completed training provided by CDC instructors or designees. Use is limited to designated laboratories that are qualified to receive and use the CDC rRT-PCR Flu Panel (IVD) 510(K) 080570. See "Conditions of Authorization" below.