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U.S. Department of Health and Human Services

Medical Devices

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Letter of Authorization: Qiagen artus® Inf. A H1N1 2009 LC RT-PCR Kit

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 As of June 23, 2010, the EUAs have been terminated and this information is no longer current.

March 11, 2010

Kim Davis
Manager - Regulatory and Clinical Sciences North America
QIAGEN
1201 Clopper Road
Gaithersburg, MD 20878

Dear Ms. Davis:

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 artus® Inf. A H1N1 2009 LC RT-PCR Kit 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 CLIA High Complexity Laboratories, which are laboratories certified under the Clinical Laboratory Improvement Amendments of 1988, 42 U.S.C. §263a, to perform high complexity tests.

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.1 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 artus Inf. A H1N1 2009 LC RT-PCR Kit (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 artus Inf. A H1N1 2009 LC RT-PCR Kit 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 artus Inf. A H1N1 2009 LC RT-PCR Kit may be effective for the diagnosis of 2009 H1N1 influenza virus infection, and that the known and potential benefits of the artus Inf. A H1N1 2009 LC RT-PCR Kit, 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 artus Inf. A H1N1 2009 LC RT-PCR Kit for the diagnosis of 2009 H1N1 influenza virus infection.2

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 artus Inf. A H1N1 2009 LC RT-PCR Kit for the diagnosis of 2009 H1N1 influenza virus infection in individuals with signs and symptoms of respiratory infection.

The Authorized artus Inf. A H1N1 2009 LC RT-PCR Kit Test:

The artus Inf. A H1N1 2009 LC RT-PCR Kit test is a real-time reverse transcription polymerase chain reaction (rRT-PCR) test for the in vitro qualitative detection and differentiation of 2009 H1N1 influenza viral RNA in nasopharyngeal swabs (NPS) from patients with signs and symptoms of respiratory infection. The artus Inf. A H1N1 2009 LC RT-PCR Kit is to be used in combination with the LightCycler ® 2.0 Real Time PCR system and the EZ1 DSP Virus System. The assay is composed of two principal steps: (1) extraction of RNA from patient specimens, (2) one-step reverse transcription and PCR amplification using fluorogenic probes for detection.

The artus Inf. A H1N1 2009 LC RT-PCR Kit includes the following primer and probe sets:

  • H1F and H1C: two primer-probe sets designed to detect the presence of two regions of the hemagglutinin (HA) gene specifically found in the 2009 H1N1 influenza virus. Probes specific to each amplicon are labeled with the same fluorophore for the direct detection in fluorescence channel 530.
  • InfA: a one-primer pair-three-probes set designed to detect the presence of a well conserved region of the matrix (M) gene found in influenza A virus. The inclusion of three probes provides increased assurance that the assay will still detect influenza A in the event of a mutation occurring in the targeted region. Detection of InfA also occurs through fluorescence channel 530.
  • Internal Control (IC): a primer-probe set designed to detect an artificial sequence with no homologies to influenza sequences. The IC serves as extraction control and is detected in fluorescence channel 610.

The artus Inf. A H1N1 2009 LC RT-PCR Kit also includes the following control materials:

  • Influenza A Matrix Positive Control and 2009 H1N1 Positive Control.

A Positive Control for the influenza A matrix gene is included in the Influenza AMaster and a positive control for the 2009 H1N1 HA gene is included in the Influenza H1N1 Master to ensure that the assay reagents and instruments are functioning as intended for the detection of influenza A virus and 2009 H1N1 influenza virus. Both controls must generate a positive response in order for the run to be considered valid.

  • Negative (no template) Control.
  • A Negative Control (“no template”) is needed to control for sample-to-sample carryover or contamination of reagents with target sequences. Nuclease-free PCR grade water is provided with the artus kit as a negative (no-template) control.

The artus Inf. A H1N1 2009 LC RT-PCR Kit requires the following hardware with corresponding software:

  • EZ1 Advanced Instrument (QIAGEN, cat. no. 9001410) with the EZ1 DSP Virus Card v. 2.0 (QIAGEN, cat. no. 9018306).
  • LightCycler® 2.0 instrument with software v. 4.1 (Roche Diagnostics).

The artus Inf. A H1N1 2009 LC RT-PCR Kit requires the use of the following additional reagents/materials:

  • EZ1 DSP Virus Kit (QIAGEN, cat. no. 62724).
  • LightCycler® Multicolor Demo Set (Roche Applied Science, cat. no. 03 624 854 001).
  • LightCycler® Capillaries , 20 μl (Roche Applied Science, cat. no. 04 929 292 001) .
  • LightCycler® Cooling Block and centrifuge adaptors (Roche Applied Science, cat. no. 11 909 312 001).
  • LightCycler® Capping Tool (Roche Applied Science, cat. no. 03 357 317 001)

The above described artus Inf. A H1N1 2009 LC RT-PCR Kit, when labeled consistently with the labeling authorized by FDA, entitled artus® Inf. A H1N1 2009 LC RT-PCR Kit Protocol, (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 High Complexity Laboratories under this EUA, despite the fact that it does not meet certain requirements otherwise required by federal law.

The above described artus Inf. A H1N1 2009 LC RT-PCR Kit is 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 artus ® Inf. A H1N1 2009 LC RT-PCR Kit Test Results
  • Fact Sheet for Patients: Understanding the artus ® Inf. A H1N1 2009 LC RT-PCR Kit Test Results

As described in section IV below, QIAGEN is also authorized to make available additional information relating to the emergency use of the authorized artus Inf. A H1N1 2009 LC RT-PCR Kit 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 artus® Inf. A H1N1 2009 LC RT-PCR Kit 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 artus® Inf. A H1N1 2009 LC RT-PCR Kit 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 artus® Inf. A H1N1 2009 LC RT-PCR Kit, 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 artus® Inf. A H1N1 2009 LC RT-PCR Kit 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 artus® Inf. A H1N1 2009 LC RT-PCR Kit 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 artus® Inf. A H1N1 2009 LC RT-PCR Kit 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 artus Inf. A H1N1 2009 LC RT-PCR Kit.
  • 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:

QIAGEN

  1. QIAGEN will distribute the authorized artus® Inf. A H1N1 2009 LC RT-PCR Kit with the authorized labeling, as may be revised with written permission of FDA, only to CLIA High Complexity Laboratories.
  2. QIAGEN will provide to the CLIA High Complexity Laboratories the authorized artus® Inf. A H1N1 2009 LC RT-PCR Kit Fact Sheet for Healthcare Providers and the authorized artus Inf. A H1N1 2009 LC RT-PCR Kit Fact Sheet for Patients.
  3. QIAGEN will make available on its website the authorized artus® Inf. A H1N1 2009 LC RT-PCR Kit Fact Sheet for Healthcare Providers and the authorized artus® Inf. A H1N1 2009 LC RT-PCR Kit Fact Sheet for Patients.
  4. QIAGEN 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 artus® Inf. A H1N1 2009 LC RT-PCR Kit 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 artus® Inf. A H1N1 2009 LC RT-PCR Kit 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 diagnosis of 2009 H1N1 influenza virus and not for diagnosis of 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 artus® Inf. A H1N1 2009 LC RT-PCR Kit may represent or suggest that this test is safe or effective for the diagnosis of 2009 H1N1 influenza virus.
  8. QIAGEN will ensure that CLIA High Complexity Laboratories using the authorized artus® Inf. A H1N1 2009 LC RT-PCR Kit have a process in place for reporting test results to healthcare providers and federal, state and/or local public health authorities, as appropriate.
  9. QIAGEN will track adverse events and report to FDA as required under 21 CFR part 803.
  10. Through a process of inventory control, QIAGEN will maintain records of device usage.
  11. QIAGEN 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 QIAGEN becomes aware.
  12. QIAGEN is authorized to make available additional information relating to the emergency use of the authorized artus® Inf. A H1N1 2009 LC RT-PCR Kit that is consistent with, and does not exceed, the terms of this letter of authorization.
  13. Only QIAGEN may request changes to the authorized artus® Inf. A H1N1 2009 LC RT-PCR Kit Fact Sheet for Healthcare Providers or the authorized artus® Inf. A H1N1 2009 LC RT-PCR Kit Fact Sheet for Patients. Such requests will be made by contacting FDA concerning FDA review and approval.

CLIA High Complexity Laboratories

  1. CLIA High Complexity Laboratories will include with reports of the results of the artus® Inf. A H1N1 2009 LC RT-PCR Kit the authorized Fact Sheet for Healthcare Providers and the authorized Fact Sheet for Patients.
  2. CLIA High Complexity Laboratories will use the QIAGEN EZ1 Advanced Instrument for nucleic acid extraction and perform the assay on the LightCycler® 2.0 Real Time PCR system.
  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 QIAGEN any suspected occurrence of false positive or false negative results of which CLIA High Complexity Laboratories become aware.
  5. CLIA High Complexity Laboratories will clearly and conspicuously state on reports of the results of the artus® Inf. A H1N1 2009 LC RT-PCR Kit that this test is only authorized for the diagnosis of 2009 H1N1 influenza virus and not for seasonal influenza A, B, or any other virus or pathogen.

QIAGEN and CLIA High Complexity Laboratories

  1. QIAGEN and CLIA 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 artus® Inf. A H1N1 2009 LC RT-PCR Kit 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 Memorandum, Determination Pursuant to §564 of the Federal Food, Drug, and Cosmetic Act (April 26, 2009).

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