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U.S. Department of Health and Human Services

Medical Devices

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Letter of Authorization: IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay

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 As of June 23, 2010, the EUAs have been terminated and this information is no longer current.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 22, 2010

 

Dr. Phillip T. Moen, Jr.
Director, Product Development
IntelligentMDx
19 Blackstone Street
Cambridge, MA 02139

Dear Dr. Moen:

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 IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay 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 IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay (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 IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay 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 IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay may be effective for the diagnosis of 2009 H1N1 influenza virus infection, and that the known and potential benefits of the IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay, 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 IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay 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 IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay for the diagnosis of 2009 H1N1 influenza virus infection in individuals with signs and symptoms of respiratory infection.

The Authorized IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay:

The IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay is a real-time reverse transcriptase PCR (rRT-PCR) for the in vitro qualitative detection and differentiation 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)) from patients with signs and symptoms of respiratory infection. The testing procedure consists of nucleic acid extraction with the Qiagen QIAamp Viral RNA Mini Kit followed by rRT-PCR on the Applied Biosystems 7500 Real-Time PCR System, 7500 Fast Real-Time PCR System, or the 7500 Fast Dx Real-Time PCR Instrument.

IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay includes the following primer and probe sets:

  • INFA: detects a conserved region of the matrix (M) gene that is present in both seasonal and 2009 H1N1 influenza A viruses.
  • 2009 H1N1: detects a region of the hemagglutinin (HA) gene found in the 2009 H1N1 influenza virus.  
  • Extraction/Process Control: detects an RNA sequence in whole bacteriophage MS2 that is noncompetitive with the INFA and 2009 H1N1 2009 targets. 

The IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay also includes the following control materials:

  • Bacteriophage MS2 Extraction/Process Control is added to every patient sample and is carried through all steps of the procedure from nucleic acid isolation and purification through amplification to ensure that effective nucleic acid extraction is achieved and to monitor for inhibition of RT-PCR.
  • Negative Control consists of viral transport media containing MS2 bacteriophage and is taken through both nucleic acid extraction and RT-PCR processes to demonstrate that all extraction and amplification reagents are free of target influenza RNA and amplicons and to ensure that detection of target genes is not due to false positive results.
  • No Template Control consists of nuclease free water and is included in each RT-PCR run to demonstrate that amplification reagents are free of target influenza and MS2 RNA and amplicons.
  • Positive Controls consist of separate in vitro transcribed RNAs containing targets recognized by the INF A and 2009 H1N1 detection systems and are included in each RT-PCR run to demonstrate that these detection systems are operating at the required level of sensitivity.

The IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay requires the following Applied Biosystems hardware with corresponding software:

  • 7500 Real-Time PCR System (SDS v1.4 Software or 7500 Software v2.01), or
  • 7500 Fast Real-Time PCR System (SDS v1.4 Software or 7500 Software v2.01), or
  • 7500 Fast Dx Real-Time PCR Instrument (SDS v1.4 Software)

The IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay requires the use of the following additional reagents/materials:

  • Qiagen QIAamp Viral RNA Mini Kit

The above described IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay, when labeled consistently with the labeling authorized by FDA, entitled IntelligentMDx IMDx 2009 Influenza A H1N1 Real-Time RT-PCR 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 High Complexity Laboratories under this EUA, despite the fact that it does not meet certain requirements otherwise required by federal law.

The above described IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay 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 IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay Results
  • Fact Sheet for Patients: Understanding IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay Results

As described in section IV below, IntelligentMDX is also authorized to make available additional information relating to the emergency use of the authorized IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay 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 IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay 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 IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay 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 IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay, 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 IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay 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 IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay 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 IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay 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 IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay.
  • 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:

IntelligentMDx

A.  IntelligentMDx will distribute the authorized IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay with the authorized labeling, as may be revised with written permission of FDA, only to CLIA High Complexity Laboratories.

B.  IntelligentMDx will provide to the CLIA High Complexity Laboratories the authorized IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay Fact Sheet for Healthcare Providers and the authorized IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay Fact Sheet for Patients.

C.  IntelligentMDx will make available on its website the authorized IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay Fact Sheet for Healthcare Providers and the authorized IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay Fact Sheet for Patients.

D.  IntelligentMDx will inform state and/or local public health authority(ies) of this EUA, including the terms and conditions herein.

E.  All advertising and promotional descriptive printed matter relating to the use of the authorized IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay 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.

F.  All advertising and promotional descriptive printed matter relating to the use of the IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay 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 the 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.

G.  No advertising or promotional descriptive printed matter relating to the use of the authorized IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay may represent or suggest that this test is safe or effective for the diagnosis of 2009 H1N1 influenza virus.

H.  IntelligentMDx will ensure that CLIA High Complexity Laboratories using the authorized IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay have a process in place for reporting test results to healthcare providers and federal, state and/or local public health authorities, as appropriate.

I.  IntelligentMDx will track adverse events and report to FDA as required under 21 CFR part 803.

J.  Through a process of inventory control, IntelligentMDx will maintain records of device usage.

K.  IntelligentMDx 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 IntelligentMDx becomes aware.

L.  IntelligentMDx is authorized to make available additional information relating to the emergency use of the authorized IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay that is consistent with, and does not exceed, the terms of this letter of authorization.

M.  Only IntelligentMDx may request changes to the authorized IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay Fact Sheet for Healthcare Providers or the authorized IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay Fact Sheet for Patients. Such requests will be made by contacting FDA concerning FDA review and approval.

CLIA High Complexity Laboratories

N.  CLIA High Complexity Laboratories will include with reports of the results of the IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay the authorized Fact Sheet for Healthcare Providers and the authorized Fact Sheet for Patients.

O.  CLIA High Complexity Laboratories will perform the assay on an Applied Biosystems 7500 Real-Time PCR System, 7500 Fast Real-Time PCR System, or the 7500 Fast Dx Real-Time PCR Instrument with the appropriate software.

P.  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.

Q.  CLIA High Complexity Laboratories will collect information on the performance of the assay, and report to IntelligentMDx any suspected occurrence of false positive or false negative results of which CLIA High Complexity Laboratories become aware.

R.  CLIA High Complexity Laboratories will clearly and conspicuously state on reports of the results of the IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay 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.

IntelligentMDx and CLIA High Complexity Laboratories

S.  IntelligentMDx 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 IMDx 2009 Influenza A H1N1 Real-Time RT-PCR Assay 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.