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U.S. Department of Health and Human Services

Medical Devices

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Letter of Authorization: Focus Diagnostics Influenza A H1N1 (2009) Real-Time RT-PCR

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 As of June 23, 2010, the EUAs have been terminated and this information is no longer current.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

John G. R. Hurrell, Ph.D.
Vice President and General Manager
Focus Diagnostics, Inc.
11331 Valley View Street
Cypress, CA 90630

Dear Dr. Hurrell:

On July 23, 2009 FDA issued a letter authorizing the emergency use of the Focus Diagnostics Influenza A H1N1 (2009) Real-Time RT-PCR (Flu A H1N1 (2009) rRT-PCR ) for the 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 laboratories certified under the Clinical Laboratory Improvement Amendments of 1988, 42 U.S.C. §263a, to perform high complexity tests (CLIA High Complexity Laboratories). On November 20, 2009, Focus submitted a request for an amendment to the Emergency Use Authorization. In response to that request, the letter authorizing emergency use of the Flu A H1N1 (2009) rRT-PCR is being reissued in its entirety with the amendments incorporated.1

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.2 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 Flu A H1N1 (2009) rRT-PCR 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 Flu A H1N1 (2009) rRT-PCR 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 und er 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 Flu A H1N1 (2009) rRT-PCR may be effective for the diagnosis of 2009 H1N1 influenza virus infection, and that the known and potential benefits of the Flu A H1N1 (2009) rRT-PCR, when used in the diagnosis of 2009 H1N1 influenza virus infection, outweigh the known and potential risks of such product; and
  3. There is no adequate, approved, and available alternative to the emergency use of the Flu A H1N1 (2009) rRT-PCR for the diagnosis of 2009 H1N1 influenza virus infection.3

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 Flu A H1N1 (2009) rRT-PCR for the diagnosis of 2009 H1N1 influenza virus infection in individuals with signs and symptoms of respiratory infection.

The Authorized Flu A H1N1 (2009) rRT-PCR:

The Focus Diagnostics Influenza A H1N1 (2009) Real Time RT-PCR test is a real-time RT-PCR assay that utilizes fluorogenic hydrolysis (Taqman ®) probes for use on the ABI 7500 Real-Time PCR instrument for thein vitroqualitative detection of 2009 H1N1 influenza viral RNA in upper respiratory tract specimens (such as 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 (such as broncheoalveolar lavage (BAL), bronchial aspirate (BA); bronchial wash (BW); endotracheal aspirate (EA); endotracheal wash (EW); tracheal aspirate (TA), and lung tissue) from patients with signs and symptoms of respiratory infection. The assay is composed of two principal steps: (1) extraction of RNA from patient specimens, (2) one-step reverse transcription and PCR amplification with human influenza A virus and the 2009 H1N1 influenza virus-specific primers and real-time detection with influenza A and 2009 H1N1 influenza virus-specific probes.

The Flu A H1N1 (2009) rRT-PCR includes the following primer and probe sets:

  • FLU A detects a well-conserved region of the matrix gene from influenza A viruses in both human influenza A virus and 2009 H1N1 influenza virus.
  • SWINE 1 and SWINE 2 specifically detect two separate regions of the 2009 H1N1 influenza virus strain’s HA gene. The SWINE 1 and SWINE 2 reactions are not multiplexed and are performed in parallel in separate wells.

The Flu A H1N1 (2009) rRT-PCR also includes control materials :

  • Internal Positive Amplification Control (IPC): Exogenous IPC Reagent available separately from Applied Biosystems (Catalog No. 4308323). An internal positive control is included to confirm the absence of PCR inhibition.
  • External Positive Control: Swine influenza virus stock (ATCC VR-897) diluted at 1:800.
  • External Negative Control: Nuclease free water.

The above described Flu A H1N1 (2009) rRT-PCR test, when labeled consistently with the labeling authorized by FDA, entitled Influenza A H1N1 (2009) Real-Time RT-PCR Package Insert, (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 and used by CLIA High Complexity Laboratories under this EUA, despite the fact that it does not meet certain requirements otherwise required by federal law.

The above described Flu A H1N1 (2009) rRT-PCR testis authorized to be accompanied by the following information pertaining to the emergency use, which is authorized to be made available to healthcare providers and patients:

  • Fact Sheet For Healthcare Providers: Interpreting Focus Diagnostics Influenza A H1N1 (2009) Real-Time RT-PCR Test Results
  • Fact Sheet For Patients: Understanding The Focus Diagnostics Influenza A H1N1 (2009) Real-Time RT-PCR Test Results

As described in section IV below, Focus Diagnostics and CLIA High Complexity Laboratories are also authorized to make available additional information relating to the emergency use of the authorized Flu A H1N1 (2009) rRT-PCR 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 Flu A H1N1 (2009) rRT-PCR in the specified population, when used for diagnosis of 2009 H1N1 influenza virus infection, outweigh the known and potential risks of such a 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 Flu A H1N1 (2009) rRT-PCR 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 Flu A H1N1 (2009) rRT-PCR 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 Flu A H1N1 (2009) rRT-PCR 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's determination under section 564(b)(1)(C) described above and the Secretary of HHS's corresponding declaration under section 564(b)(1), the Flu A H1N1 (2009) rRT-PCR 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 Flu A H1N1 (2009) rRT-PCR 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 Flu A H1N1 (2009) rRT-PCR.
  • 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:

Focus Diagnostics

  1. Focus Diagnostics will distribute the Flu A H1N1 (2009) rRT-PCR with the authorized labeling, as may be revised with written permission of FDA, only to CLIA High Complexity Laboratories.
  2. Focus Diagnostics will provide to the CLIA High Complexity Laboratories the authorized Flu A H1N1 (2009) rRT-PCR Fact Sheet for Healthcare Providers and the authorized Flu A H1N1 (2009) rRT-PCR Fact Sheet for Patients.
  3. Focus Diagnostics will make available on its website the authorized Flu A H1N1 (2009) rRT-PCR Fact Sheet for Healthcare Providers and the authorized Flu A H1N1 (2009) rRT-PCR Fact Sheet for Patients.
  4. Focus Diagnostics will inform state and/or local public health authority(ies) of this EUA, including the terms and conditions herein.
  5. All advertising and promotional descriptive printed matter relating to the use of the authorized Flu A H1N1 (2009) rRT-PCR shall be consistent with the Fact Sheets and authorized labeling, as well as the terms set forth in this EUA and other requirements set forth in the Act and FDA regulations.
  6. All advertising and promotional descriptive printed matter relating to the use of the Flu A H1N1 (2009) rRT-PCR shall clearly and conspicuously state that:
    • This test has not been FDA cleared or approved;
    • This test has been authorized by FDA under an Emergency Use Authorization;
    • This test has been authorized only for the detection of 2009 H1N1 influenza virus and not for any other viruses or pathogens;
    • This test is only authorized for the duration of the declaration of emergency under section 564(b)(1) of the Act, 21 U.S.C. §360bbb-3(b)(1); and
    • The declaration of emergency will expire on April 26, 2010, unless it is terminated or revoked sooner or renewed.
  7. No advertising or promotional descriptive printed matter relating to the use of the authorized Flu A H1N1 (2009) rRT-PCR may represent or suggest that this test is safe or effective for the diagnosis of 2009 H1N1 influenza virus.
  8. Focus Diagnostics will ensure CLIA High Complexity Laboratories using the authorized Flu A H1N1 (2009) rRT-PCR have a process in place for reporting test results to healthcare providers and federal, state and/or local public health authorities, as appropriate.
  9. Focus Diagnostics will track adverse events and report to FDA as required under 21 CFR part 803.
  10. Through a process of inventory control, Focus Diagnostics will maintain records of device usage.
  11. Focus Diagnostics will collect information on the performance of the assay, and report to FDA any suspected occurrence of false positive or false negative results of which Focus Diagnostics becomes aware.

CLIA High Complexity Laboratories

  1. CLIA High Complexity Laboratories will include with reports of the results of the Flu A H1N1 (2009) rRT-PCR the authorized Fact Sheet for Healthcare Providers and the authorized Fact Sheet for Patients.
  2. CLIA High Complexity Laboratories will perform the assay on an Applied Biosystems 7500 Fast Dx Real- time PCR instrument or the RUO marketed Applied Biosystems 7500 Real-time PCR instrument.
  3. CLIA High Complexity Laboratories will have a process in place for reporting test results to healthcare providers and federal, state and/or local public health authorities, as appropriate.
  4. CLIA High Complexity Laboratories will collect information on the performance of the assay, and report to Focus Diagnostics any suspected occurrence of false positive or false negative results of which CLIA High Complexity Laboratories become aware.

Focus Diagnostics and CLIA High Complexity Laboratories

  1. Focus Diagnostics is authorized to make available additional information relating to the emergency use of the authorized Flu A H1N1 (2009) rRT-PCR that is consistent with, and does not exceed, the terms of this letter of authorization.
  2. Only Focus Diagnostics may request changes to the authorized Fact Sheet for Healthcare Providers or the authorized Flu A H1N1 (2009) rRT-PCR Fact Sheet for Patients. Such requests will be made by contacting FDA concerning FDA review and approval.
  3. Focus Diagnostics 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 Flu A H1N1 (2009) rRT-PCR 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

1The amendments to the July 23, 2009 letter authorize use of additional upper respiratory tract samples, such as nasal swabs (NS), throat swabs (TS), nasal aspirates (NA), nasal washes (NW), and dual nasopharyngeal / throat swabs (NPS/TS), and lower respiratory tract specimens, such as broncheoalveolar lavage (BAL), bronchial aspirate (BA), bronchial wash (BW), endotracheal aspirate (EA), endotracheal wash (EW), tracheal aspirate (TA), and lung tissue. There are also corrections to the waiver section and minor wording changes made to be consistent with more recently issued Emergency Use Authorizations for in vitro diagnostic devices.

2Memorandum, Determination Pursuant to § 564 of the Federal Food, Drug, and Cosmetic Act (April 26, 2009).

3No other criteria of issuance have been prescribed by regulation under section 564(c)(4) of the Act.