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U.S. Department of Health and Human Services

Medical Devices

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Letter of Authorization: Cepheid Xpert® Flu A Panel for the Diagnosis of 2009 H1N1 Influenza Virus Infection

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 As of June 23, 2010, the EUAs have been terminated and this information is no longer current.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 24, 2009

Russel K. Enns, Ph.D.
Senior Vice President
Regulatory, Clinical & Government Affairs and Quality Systems
Cepheid
904 Caribbean Drive
Sunnyvale, CA 94089

Dear Dr. Enns:

This letter is in response to your request that the Food and Drug Administration (FDA) issue an Emergency Use Authorization (EUA) for emergency use of the Cepheid Xpert ® Flu A Panel for the diagnosis of 2009 H1N1 influenza virus infection in patients with signs and symptoms of respiratory 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 (CLIA), 42 U.S.C. §263a, to perform moderate complexity tests and by laboratories certified under CLIA to perform high complexity tests.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 Xpert ® Flu A 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 Xpert ® Flu A 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 Xpert ® Flu A Panel may be effective for the diagnosis of 2009 H1N1 influenza virus infection, and that the known and potential benefits of the Xpert ® Flu A Panel , 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 Xpert ® Flu A Panel 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 Xpert ® Flu A Panel for the diagnosis of 2009 H1N1 influenza virus infection in individuals with signs and symptoms of respiratory infection.

The Authorized Xpert ® Flu A Panel:

The Cepheid Xpert Flu A Panel is a rapid, automatedin vitrodiagnostic test for qualitative detection and differentiation of 2009 H1N1 influenza virus RNA. The assay is performed on the Cepheid GeneXpert Dx System. The system automates and integrates sample purification, nucleic acid amplification, and detection of the target viral RNA sequences using real-time reverse transcriptase polymerase chain reaction (rRT-PCR). The system consists of an instrument, personal computer, and preloaded software for running tests and viewing the results.

The assay detects specific viral gene sequences for the Flu A matrix (Flu A target), and the hemagglutinin gene of 2009 H1N1 influenza virus (2009 H1N1 target). The specimen types for which analytical and method comparison in clinical samples performance data are provided include nasal aspirates/washes (NA/W) and nasopharyngeal (NP) swab specimens in viral transport media (VTM) or universal transport media (UTM) collected from patients suspected of having influenza.

Components of the Test:

The Xpert Flu A Panel includes the following assays:

  • Flu A Matrix: four forward primer sequences, three reverse primers and one probe sequence for detecting the matrix gene in Flu A
  • 2009 H1: two forward primer sequences, one reverse primer and one probe sequence for detecting the hemagglutinin gene in 2009 Flu A H1.

The Xpert Flu A Panel also includes the following controls:

  • SPC: Armored RNA in the form of a dry bead that is included in each cartridge to verify adequate processing of the sample virus.
  • PCC: The Probe Check Control PCC indicates that the probes and dyes are present and intact

The Xpert Flu A Panel requires the following hardware with corresponding software:

  • Cepheid GeneXpert Dx System and software package

The above described Xpert Flu A Panel , when labeled consistently with the labeling authorized by FDA, entitled Xpert Flu A Panel Assay Package Insert, (available at 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 Moderate and High Complexity Laboratories under this EUA, despite the fact that it does not meet certain requirements otherwise required by federal law.

The above described Xpert ® Flu A Panelis 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 Cepheid ® Xpert ® Flu A Panel Test Results
  • Fact Sheet For Patients: Understanding Cepheid ® Xpert ® Flu A Panel Test Results

As described in section IV below, Cepheid is also authorized to make available additional information relating to the emergency use of the authorized Xpert ® Flu A 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 Xpert ® Flu A Panel 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 Xpert ® Flu A 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 Xpert ® Flu A 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 Xpert ® Flu A 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's determination under section 564(b)(1)(C) described above and the Secretary of HHS's corresponding declaration under section 564(b)(1), the Xpert ® Flu A 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 Xpert ® Flu A 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 Xpert ® Flu A 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:

Cepheid

  1. Cepheid will distribute the authorized Xpert ® Flu A Panel with the authorized labeling, as may be revised with written permission of FDA, only to CLIA Moderate and High Complexity Laboratories.
  2. Cepheid will provide to the CLIA Moderate and High Complexity Laboratories the authorized Xpert ® Flu A Panel Fact Sheet for Healthcare Providers and the authorized Xpert ® Flu A Panel Fact Sheet for Patients.
  3. Cepheid will make available on its website the authorized Xpert ® Flu A Panel Fact Sheet for Healthcare Providers and the authorized Xpert ® Flu A Panel Fact Sheet for Patients.
  4. Cepheid 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 Xpert ® Flu A Panel 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 authorized Xpert ® Flu A Panel shall clearly and conspicuously state that:
    • This test has not been FDA cleared or approved;
    • FDA has not determined that this test may be performed in settings with certificates of waiver under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. § 263a;
    • 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 Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3(b)(1), unless the authorization is revoked sooner; and
    • The declaration of emergency will expire on April 26, 2010, unless it is terminated sooner or renewed.
  7. No advertising or promotional descriptive printed matter relating to the use of the authorized Xpert ® Flu A Panel may represent or suggest that this test is safe or effective for the diagnosis of 2009 H1N1 influenza virus.
  8. Cepheid will ensure that CLIA Moderate and High Complexity Laboratories using the authorized Xpert ® Flu A Panel have a process in place for reporting test results to healthcare providers and federal, state and/or local public health authorities, as appropriate.
  9. Cepheid will track adverse events and report to FDA as required under 21 CFR part 803.
  10. Through a process of inventory control, Cepheid will maintain records of device usage.
  11. Cepheid 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 Cepheid becomes aware.
  12. Cepheid is authorized to make available additional information relating to the emergency use of the authorized Xpert ® Flu A Panel that is consistent with, and does not exceed, the terms of this letter of authorization.
  13. Only Cepheid may request changes to the authorized Xpert ® Flu A Panel Fact Sheet for Healthcare Providers or the authorized Xpert ® Flu A Panel Fact Sheet for Patients. Such requests will be made by contacting FDA concerning FDA review and approval.

CLIA Moderate and High Complexity Laboratories

  1. CLIA Moderate and High Complexity Laboratories will include with reports of the results of the Xpert ® Flu A Panel the authorized Fact Sheet for Healthcare Providers and the authorized Fact Sheet for Patients.
  2. CLIA Moderate and High Complexity Laboratories will perform the assay on the Cepheid GeneXpert Dx System.
  3. CLIA Moderate and 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 Moderate and High Complexity Laboratories will collect information on the performance of the assay, and report to Cepheid any suspected occurrence of false positive or false negative results of which CLIA Moderate and High Complexity Laboratories become aware.
  5. CLIA Moderate and High Complexity Laboratories will clearly and conspicuously state on reports of the results of the Xpert Flu A that this test is only authorized for the diagnosis of 2009 H1N1 influenza virus and not for seasonal influenza A, B, or any other pathogen.

Cepheid and CLIA Moderate and High Complexity Laboratories

  1. Cepheid and CLIA Moderate and High Complexity Laboratories 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 Xpert ® Flu A 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.

____________________________
Joshua M. Sharfstein, M.D.
Principal Deputy Commissioner of Food and Drugs


1 For ease of reference this letter will refer to these two types of laboratories together as “CLIA Moderate and High Complexity Laboratories.”

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

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