Document ID: FDA-2009-N-0277-0001
Agency: fda
Document Type: Notice
Title: Authorization of Emergency Use of Certain In Vitro Diagnostic Devices; Availability
Posted Date: 2009-08-04T04:00Z

[Federal Register: August 4, 2009 (Volume 74, Number 148)]
[Notices]               
[Page 38636-38644]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr04au09-55]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2009-N-0277]

 
Authorization of Emergency Use of Certain In Vitro Diagnostic 
Devices; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
issuance of two Emergency Use Authorizations (EUAs) (the 
Authorizations), one of which was amended, for certain in vitro 
diagnostic devices. FDA is issuing the Authorizations under the Federal 
Food, Drug, and Cosmetic Act (the act), as requested by the Centers for 
Disease Control and Prevention (CDC). The Authorizations contain, among 
other things, conditions on the emergency use of the authorized in 
vitro diagnostics. The Authorizations follow the determination by the 
Acting Secretary of the Department of Health and Human Services, 
Charles E. Johnson (the Acting Secretary), that a public health 
emergency exists involving Swine Influenza A (now known as 2009 H1N1 
Influenza A or 2009 H1N1 flu) that affects, or has the significant 
potential to affect, national security. On the basis of such 
determination, the Acting Secretary declared an emergency justifying 
the authorization of the emergency use of certain in vitro diagnostics, 
accompanied by emergency use information subject to the terms of any 
authorization issued under the act.

[[Page 38637]]

The Authorizations, which include an explanation of the reasons for 
issuance, are reprinted in this document. Elsewhere in this issue of 
the Federal Register, FDA is announcing the issuance of EUAs for 
certain antiviral drug products and the issuance of an EUA for certain 
personal respiratory protection devices.

DATES: The authorization for the Swine Influenza Virus Real-time RT-PCR 
Detection Panel (rRT-PCR Swine Flu Panel) is effective as of April 27, 
2009. The Authorization for the previously-cleared CDC Human Influenza 
Virus Real-time RT-PCR Detection and Characterization Panel for 
Respiratory Specimens (NPS, NS, TS, NPS/TS, NA2) and Viral Culture is 
effective as of May 2, 2009.

ADDRESSES: Submit written requests for single copies of the EUAs to the 
Office of Counterterrorism and Emerging Threats (HF-29), Food and Drug 
Administration, 5600 Fishers Lane, rm. 14C-26, Rockville, MD 20857. 
Send one self-addressed adhesive label to assist that office in 
processing your request or include a fax number to which the 
Authorization(s) may be sent. See the SUPPLEMENTARY INFORMATION section 
for electronic access to the Authorizations.

FOR FURTHER INFORMATION CONTACT: Boris Lushniak, Office of 
Counterterrorism and Emerging Threats (HF-29), Food and Drug 
Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-827-4067.

SUPPLEMENTARY INFORMATION:

I. Background

    Section 564 of the act (21 U.S.C. 360bbb-3), as amended by the 
Project BioShield Act of 2004 (Public Law 108-276), allows FDA to 
strengthen the public health protections against biological, chemical, 
nuclear, and radiological agents. Among other things, section 564 of 
the act allows FDA to authorize the use of an unapproved medical 
product or an unapproved use of an approved medical product during a 
public health emergency that affects, or has a significant potential to 
affect, national security, and that involves biological, chemical, 
radiological, or nuclear agent or agents, or a specified disease or 
condition that may be attributable to such agent or agents. With this 
EUA authority, FDA can help assure that medical countermeasures may be 
used in an emergency to diagnose, treat, or prevent serious or life-
threatening diseases or conditions caused by such agents, when there 
are no adequate, approved, and available alternatives.
    Section 564(b)(1) of the act provides that, before an EUA may be 
issued, the Secretary must declare an emergency justifying the 
authorization based on one of the following grounds: ``(A) a 
determination by the Secretary of Homeland Security that there is a 
domestic emergency, or a significant potential for a domestic 
emergency, involving a heightened risk of attack with a specified 
biological, chemical, radiological, or nuclear agent or agents; (B) a 
determination by the Secretary of Defense that there is a military 
emergency, or a significant potential for a military emergency, 
involving a heightened risk to United States military forces of attack 
with a specified biological, chemical, radiological, or nuclear agent 
or agents; or (C) a determination by the Secretary of a public health 
emergency under section 319 of the Public Health Service Act 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 agent or agents.''
    Once the Secretary has declared an emergency justifying an 
authorization under section 564 of the act, FDA may authorize the 
emergency use of a drug, device, or biological product if the agency 
concludes that the statutory criteria are satisfied. Under section 
564(h)(1) of the act, FDA is required to publish, in the Federal 
Register, a notice of each authorization, and each termination or 
revocation of an authorization, and an explanation of the reasons for 
the action. Section 564 of the act permits FDA to authorize the 
introduction into interstate commerce of a drug, device, or biological 
product intended for use in a declared emergency. Products appropriate 
for emergency use may include products and uses that are not approved, 
cleared, or licensed under sections 505, 510(k), and 515 of the act (21 
U.S.C. 355, 360(k), and 360e) or section 351 of the PHS Act (42 U.S.C. 
262). FDA may issue an EUA only if, after consultation with the 
National Institutes of Health and CDC (to the extent feasible and 
appropriate given the circumstances of the emergency), FDA\1\ 
concludes: (1) That an agent specified in a declaration of emergency 
can cause a serious or life-threatening disease or condition; (2) that, 
based on the totality of scientific evidence available to FDA, 
including data from adequate and well-controlled clinical trials, if 
available, it is reasonable to believe that: (A) the product may be 
effective in diagnosing, treating, or preventing--(1) such disease or 
condition; or (2) a serious or life-threatening disease or condition 
caused by a product authorized under Section 564, approved or cleared 
under this Act, or licensed under Section 351 of the Public Health 
Service Act (PHS Act), for diagnosing, treating, or preventing such a 
disease or condition caused by such an agent; and (B) the known and 
potential benefits of the product, when used to diagnose, prevent, or 
treat such disease or condition, outweigh the known and potential risks 
of the product; (3) that there is no adequate, approved, and available 
alternative to the product for diagnosing, preventing, or treating such 
disease or condition; and (4) that such other criteria as the Secretary 
may by regulation prescribe are satisfied.
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    \1\ The Secretary has delegated his authority to issue an EUA 
under section 564 of the act to the Commissioner of Food and Drugs.
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    No other criteria of issuance have been prescribed by regulation 
under section 564(c)(4) of the act. Because the statute is self-
executing, FDA does not require regulations or guidance to implement 
the EUA authority. However, in the Federal Register of July 26, 2007 
(72 FR 41083), FDA announced the availability of a guidance entitled 
``Emergency Use Authorization of Medical Products.'' The guidance 
provides more information for stakeholders and the public about the EUA 
authority and the agency's process for the consideration of EUA 
requests.

II. EUA Request for Certain In Vitro Diagnostic Products

    On April 26, 2009, under section 564(b)(1)(C) of the act, the 
Acting Secretary determined that a public health emergency exists 
involving Swine Influenza A (now known as 2009 H1N1 Influenza A or 2009 
H1N1 flu) that affects, or has the significant potential to affect, 
national security. On April 26, 2009, under section 564(b) of the act, 
and on the basis of such determination, the Acting Secretary declared 
an emergency justifying the authorization of certain in vitro 
diagnostics for detection of Swine Influenza A (2009 H1N1 flu virus), 
accompanied by emergency use information subject to the terms of any 
authorization issued under 21 U.S.C. 360bbb-3(a). Notice of the 
determination and the declaration of the Acting Secretary is published 
elsewhere in this issue of the Federal Register.
    On April 27, 2009, in response to a CDC request, FDA issued an EUA 
for the Swine Influenza Virus Real-time RT-PCR Detection Panel (rRT-PCR 
Swine Flu Panel) with certain written

[[Page 38638]]

information, including fact sheets for healthcare providers and 
patients and adequate directions for use, which are authorized under 
the EUA. On May 2, 2009, in response to a CDC request to allow use of 
the rRT-PCR Swine Flu Panel for different sample types and different 
reagents, FDA amended the rRT-PCR Swine Flu Panel Authorization letter 
and reissued the Authorization letter in its entirety, with amended 
written information, including adequate directions for use. In 
addition, on May 2, 2009, in response to a CDC request, FDA issued an 
EUA with certain written information, including adequate directions for 
use, to allow the use of the FDA-cleared in vitro diagnostic device, 
CDC Human Influenza Virus Real-time RT-PCR Detection and 
Characterization Panel for Respiratory Specimens (NPS, NS, TS, NPS/TS, 
NA2) and Viral Culture) (CDC rRT-PCR flu panel), for patient specimen 
types and reagents in addition to those of the cleared CDC rRT-PCR flu 
panel.

III. Electronic Access

    An electronic version of this document and the full text of the 
Authorizations are available on the Internet at http://
www.regulations.gov.

IV. The Authorizations

    Having concluded that the criteria for issuance of the 
Authorizations, one as amended, under section 564(c) of the act are 
met, FDA has authorized the emergency use of certain in vitro 
diagnostic devices.
    The Authorization for the rRT-PCR Swine Flu Panel, as amended and 
reissued in its entirety on May 2, 2009, follows and provides an 
explanation of the reasons for its issuance, as required by section 
564(h)(1) of the act:

 Richard E. Besser, MD
 Acting Director
 Centers for Disease Control and Prevention
 1600 Clifton Road, MS C-12
 Atlanta, GA 30333
 Clifton, Bldg. 1, Room 6430

 Dear Dr. Besser:

 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) for the presumptive diagnosis of
 swine influenza A (H1N1), pursuant to section 564 of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. Sec.   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. In response to that request, 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, incorporated.\1\

 On April 26, 2009, pursuant to section 564(b)(1)(C) of the Act (21 U.S.C. Sec.   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. Sec.   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, swine influenza A (H1N1).\2\ Pursuant to
 section 564(b) of the Act (21 U.S.C. Sec.   360bbb-3(b)), and on the basis of such determination, the Secretary of the Department of Health and Human Services then declared an emergency
 justifying the authorization of the emergency use of the Swine Influenza Virus Real-time RT-PCR Detection Panel (rRT-PCR Swine Flu Panel) subject to the terms of any authorization issued
 under 21 U.S.C. Sec.   360bbb-3(a).

 Having concluded that the criteria for issuance of this authorization under section 564(c) of the Act (21 U.S.C. Sec.   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)\3\ for the presumptive diagnosis of swine influenza A (H1N1) virus infection in human individuals who have been
 diagnosed with influenza A caused by a virus not subtypeable by currently available FDA-cleared devices, 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 presumptive diagnosis of swine influenza A (H1N1) virus infection for human individuals who are diagnosed with
 influenza A caused by a virus that is not subtypeable by currently available FDA-cleared devices meets the criteria for issuance of an authorization under section 564(c) of the Act, because I
 have concluded that:

    (1) The recently isolated novel 2009 influenza A (H1N1), or swine flu, 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 in the presumptive diagnosis of swine
     influenza A (H1N1) virus infection, and that the known and potential benefits of the rRT-PCR Swine Flu Panel, when used in the presumptive diagnosis of swine influenza A (H1N1) 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 presumptive diagnosis of swine influenza A (H1N1) virus
     infection.\4\

 Therefore, I have concluded that the emergency use of the rRT-PCR Swine Flu Panel for the presumptive diagnosis of swine influenza A (H1N1) virus infection in human individuals who are
 diagnosed with influenza A infections not subtypeable by currently available FDA-cleared devices meets the above criteria for issuance of an authorization.

 II. Scope of Authorization

[[Page 38639]]

 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 presumptive diagnosis
 of 2009 H1N1 influenza A virus infection for individuals who are diagnosed with influenza A caused by a virus not subtypeable by currently available FDA-cleared devices.

 The authorized rRT-PCR Swine Flu Panel is as follows:

 The Swine Influenza Virus Real-time RT-PCR Detection Panel is a panel of oligonucleotide primers and dual-labeled hydrolysis (Taqman[reg]) probes for use in the real-time RT-PCR assay on the
 ABI 7500 Fast Dx Real-Time PCR instrument for the in vitro qualitative detection of 2009 H1N1 influenza viral RNA in nasopharyngeal swabs (NPS), nasal swabs (NS), throat swabs (TS), dual NPS/
 TS swab, or nasal aspirate (NA) specimens from patients with signs and symptoms of respiratory infection and viral culture. The universal 2009 H1N1 influenza swInfA (NP gene) and swH1 (HA
 gene) primer and probe sets are designed for detection of 2009 A/H1N1 influenza viruses. In addition rRT-PCR Flu Panel (NPS, NS, TS, NPS/TS, NA) authorized for emergency use utilizes the
 AgPath-ID\TM\ One-Step RT-PCR Kit Human amplification reagents.

 The rRT-PCR Swine Flu Panel includes the following primer and probe sets:
     InfA detects universal influenza A strains in nasopharyngeal swabs (NPS), nasal swabs (NS), throat swabs (TS), dual NPS/TS swab, or nasal aspirate (NA) specimens from patients
     with signs and symptoms of respiratory infection, and virus culture.
     swInfA specifically detects swine influenza A strains (NP gene) in nasopharyngeal swabs (NPS), nasal swabs (NS), throat swabs (TS), dual NPS/TS swab, or nasal aspirate (NA)
     specimens from patients with signs and symptoms of respiratory infection, and virus culture.
     swH1 is specific for swine influenza A, subtype H1 (HA gene) in nasopharyngeal swabs (NPS), nasal swabs (NS), throat swabs (TS), dual NPS/TS swab, or nasal aspirate (NA) specimens
     from patients with signs and symptoms of respiratory infection, and viral culture.

 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 consistent with the attached template is authorized to be distributed to public health and other qualified laboratories\5\ under this EUA,
 despite the fact that it does not meet certain requirements otherwise required by federal law.

 The following written information pertaining to the emergency use of the authorized rRT-PCR Swine Flu Panel is authorized to be made available to health care providers and patients:

     Fact Sheet For Healthcare Providers: Interpreting Swine Influenza Rt-Pcr Detection Panel Test Results
     Fact Sheet For Patients: Understanding Swine Influenza Kit Test Results

 See attached. 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 in the presumptive diagnosis of swine influenza A (H1N1) 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 presumptive diagnosis of swine influenza A (H1N1) virus infection pursuant to section 564(c)(2)(A) of the Act. 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 presumptively diagnose
 swine influenza A (H1N1) 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's determination under section 564(b)(1)(C) described above and
 the Secretary of HHS's corresponding declaration under section 564(b)(1), the rRT-PCR Swine Flu Panel described above is authorized to presumptively diagnose swine influenza A (H1N1) virus
 infection in human individuals who are diagnosed with influenza A caused by a virus not subtypeable by currently available FDA cleared devices.
 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;
     registration and listing requirements under section 510 of the Act;
     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);

[[Page 38640]]

     investigational device requirements, including requirements under 21 CFR Part 812; and
     reporting requirements that apply to cleared or approved devices, including requirements under 21 CFR Parts 803 and 806.

 IV. Conditions of Authorization

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

 CDC
  A. CDC will distribute the rRT-PCR Swine Flu Panel labeled with the intended use statement, adequate directions for use, any appropriate limitations on the use of the device, and any
   available information regarding performance of the device only to qualified laboratories.

  C. CDC will provide to the qualified 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.

  D. 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.

  E. CDC will ensure that the state and/or local public health authority(ies) are informed of this EUA, including the terms and conditions herein.

  F. CDC will ensure qualified laboratories have a process in place for reporting test results to health care providers and federal, state and/or local public health authorities, as
   appropriate.

  G. CDC will track adverse events.

  H. Through a process of inventory control, CDC will maintain records of device usage.

  I. CDC will collect information on the performance of the assay, to include the incidence of false positive and negative results.

 Public Health and Other Qualified Laboratories

  J. Qualified 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 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).

  K. 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.

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

  M. 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.

  N. 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.

  O. CDC and the appropriate state/and or local public health authority(ies) will ensure that 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.

                   Joshua M. Sharfstein, MD
                   Principal Deputy Commissioner
                   Acting Commissioner

 \1\ The amendments 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\ Memorandum, Determination Pursuant to Sec.   564 of the Federal Food, Drug, and Cosmetic Act (April 26, 2009).
\3\ FDA is 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 ease of reference, this letter will use the term the ``rRT-PCR Swine Flu Panel.''
\4\ No other criteria of issuance have been prescribed by regulation under section 564(c)(4) of the Act.
\5\ 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.

[[Page 38641]]

    The Authorization for the cleared CDC rRT-PCR flu panel follows and 
provides an explanation of the reasons for its issuance, as required by 
section 564(h)(1) of the act:

 Richard E. Besser, MD
 Acting Director
 Centers for Disease Control and Prevention
 1600 Clifton Road, MS C-12
 Atlanta, GA 30333
 Clifton, Bldg. 1, Room 6430

 Dear Dr. Besser:
 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 CDC\1\ Human Influenza Virus Real-
 time RT-PCR Detection and Characterization Panel for Respiratory Specimens (NPS, NS, TS, NPS/TS, NA\2\) and Viral Culture (rRT-PCR Flu Panel (NPS, NS, TS, NPS/TS, NA)) as a first tier test
 for the qualitative detection of influenza virus type A or B and subtype determination of seasonal human influenza A virus (seasonal A/H1 or A/H3) for individuals suspected of having a 2009
 H1N1 influenza virus infection, pursuant to section 564 of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. Sec.   360bbb-3) by public health and other qualified laboratories.

 The CDC Human Influenza Virus Real-time RT-PCR Detection and Characterization Panel (rRT-PCR Flu Panel) was cleared by FDA on September 30, 2008 for use with nasopharyngeal and/or nasal swab
 specimens. Because of issues of availability and adequacy of the cleared test associated with the need for testing additional specimen types, this letter authorizes the emergency use of the
 rRT-PCR Flu Panel (NPS, NS, TS, NPS/TS, NA) with specimen types and reagents in addition to those of the cleared test, as described below. The rRT-PCR Flu Panel (NPS, NS, TS, NPS/TS, NA) is
 authorized as a first tier test for patient specimens with suspected 2009 H1N1 influenza virus and is an integral component of the testing algorithm for the rRT-PCR Swine Flu Panel authorized
 for use under an April 27, 2009 Emergency Use Authorization.

 On April 26, 2009, pursuant to section 564(b)(1)(C) of the Act (21 U.S.C. Sec.   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. Sec.   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.\3\ Pursuant to
 section 564(b) of the Act (21 U.S.C. Sec.   360bbb-3(b)), and on the basis of such determination, the Secretary of the Department of Health and Human Services then declared an emergency
 justifying the authorization of the emergency use of the CDC Human Influenza Virus Real-time RT-PCR Detection and Characterization Panel for Respiratory Specimens (NPS, NS, TS, NPS/TS, NA)
 and Viral Culture subject to the terms of any authorization issued under 21 U.S.C. Sec.   360bbb-3(a).

 Having concluded that the criteria for issuance of this authorization under section 564(c) of the Act (21 U.S.C. Sec.   360bbb-3(c)) are met, I am authorizing the emergency use of the CDC
 Human Influenza Virus Real-time RT-PCR Detection and Characterization Panel for Respiratory Specimens (NPS, NS, TS, NPS/TS, NA) and Viral Culture (rRT-PCR Flu Panel (NPS, NS, TS, NPS/TS,
 NA))\4\ as a first tier test for the qualitative detection of influenza virus type A or B and subtype determination of seasonal human influenza A virus (seasonal A/H1 or A/H3) in individuals
 suspected of having a 2009 H1N1 influenza virus infection. The rRT-PCR Flu Panel (NPS, NS, TS, NPS/TS, NA) is a first tier test because it should be used to test specimens from such
 individuals first. If the test result of the rRT-PCR Flu Panel (NPS, NS, TS, NPS/TS, NA) is positive for influenza A and negative for H1 (seasonal) and H3 subtypes, then the laboratory should
 test the specimen with the rRT-PCR Swine Flu Panel.

 I. Criteria for Issuance of Authorization

 I have concluded that the emergency use of the rRT-PCR Flu Panel (NPS, NS, TS, NPS/TS, NA) as a first tier test for the qualitative detection of influenza virus type A or B and subtype
 determination of seasonal human influenza A virus (seasonal A/H1 or A/H3) for individuals suspected of having a 2009 H1N1 influenza virus infection meets the criteria for issuance of an
 authorization under section 564(c) of the Act, because I have concluded that:
    (1) The recently isolated novel 2009 influenza A (H1N1), or swine flu, 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 Flu Panel (NPS, NS, TS, NPS/TS, NA) may be effective as a first tier test
     for the qualitative detection of influenza virus type A or B and subtype determination of seasonal human influenza A virus (seasonal A/H1 or A/H3) in nasopharyngeal swabs (NPS), nasal
     swabs (NS), throat swabs (TS), and/or dual NPS/TS swab specimens and nasal aspirates (NA) from patients with signs and symptoms of respiratory infection suspected of having a 2009 H1N1
     influenza virus infection and/or from viral culture, and that the known and potential benefits of the rRT-PCR Flu Panel (NPS, NS, TS, NPS/TS, NA), when used as a first tier test in the
     qualitative detection of influenza virus type A or B and subtype determination of seasonal human influenza A virus (seasonal A/H1 or A/H3), 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 Flu Panel (NPS, NS, TS, NPS/TS, NA) as a first tier test for the qualitative detection of
     influenza virus type A or B and subtype determination of seasonal human influenza A virus (seasonal A/H1 or A/H3) in nasopharyngeal swabs (NPS), nasal swabs (NS), throat swabs (TS), and/
     or dual NPS/TS swab specimens and nasal aspirates (NA) from patients with signs and symptoms of respiratory infection and/or from viral culture specimens suspected of having a 2009 H1N1
     influenza virus infection.\5\

 Therefore, I have concluded that the emergency use of the rRT-PCR Flu Panel (NPS, NS, TS, NPS/TS, NA) as a first tier test for the qualitative detection of influenza virus type A or B and
 subtype determination of seasonal human influenza A virus (seasonal A/H1 or A/H3) for individuals suspected of having a 2009 H1N1 influenza virus infection meets the above criteria for
 issuance of an authorization.

[[Page 38642]]

 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 Flu Panel (NPS, NS, TS, NPS/TS, NA) for the
 qualitative detection of influenza virus type A or B and subtype determination of seasonal human influenza A virus (seasonal A/H1 or A/H3) for individuals suspected of having a 2009 H1N1
 influenza virus infection.

 The authorized rRT-PCR Flu Panel (NPS, NS, TS, NPS/TS, NA):

 CDC Human Influenza Virus Real-time RT-PCR Detection and Characterization Panel for Respiratory Specimens (NPS, NS, TS, NPS/TS, NA) and Viral Culture is a panel of oligonucleotide primers and
 dual-labeled hydrolysis probes for use in the real-time RT-PCR assay on the ABI 7500 Fast Dx Real-Time PCR instrument for the in vitro qualitative detection of human influenza viral RNA in
 nasopharyngeal swabs (NPS), nasal swabs (NS), throat swabs (TS), and/or dual NPS/TS swab specimens and nasal aspirates (NA) from patients with signs and symptoms of respiratory infection and/
 or from viral culture.\6\

 The rRT-PCR Flu Panel (NPS, NS, TS, NPS/TS, NA) uses the same primer and probe sequences as the CDC Human Influenza Virus Real-time RT-PCR Detection and Characterization Panel as the device
 cleared under K080570 except that the rRT-PCR Flu Panel (NPS, NS, TS, NPS/TS, NA) authorized for emergency use also utilizes the AgPath-ID\TM\ One-Step RT-PCR Kit Human amplification
 reagents.

 Assay principle

     The rRT-PCR Flu Panel (NPS, NS, TS, NPS/TS, NA) is used in real-time RT-PCR assays on the ABI 7500 Fast instruments. The primer and probe sets are designed for detection and
     subtyping of influenza A viruses.

     One-step RT-PCR assays are one-tube assays that first reverse-transcribe specific Ribonucleic acid (RNA) templates into cDNA copies. The complementary deoxyribonucleic acid (cDNA)
     then undergoes a polymerase chain reaction (PCR) that utilizes a thermocyclic heating and cooling of the reaction to logarithmically amplify a specific region of DNA. The probe anneals to
     a specific target sequence located between the forward and reverse primers. During the extension phase of the PCR cycle, the 5' nuclease activity of Taq polymerase degrades the probe,
     causing the reporter dye to separate from the quencher dye, generating a fluorescent signal. With each cycle, additional reporter dye molecules are cleaved from their respective probes,
     increasing the fluorescence intensity. Fluorescence intensity is monitored at each PCR cycle.

     No template controls (NTCs) and positive template controls for all primer and probe sets are included in each run. An extraction control (HSC) provides a secondary negative
     control that validates the extraction procedure and reagent integrity. The RNase P assay serves as a control to ensure adequate RNA resulted from extraction of each clinical specimen and
     that no inhibitors were present in the specimen. RNA extracted from clinical samples contains human RNA. The RP primer and probe set targets the human ribonuclease P gene. Therefore, the
     level of the RNase P primer and probe set reaction reflects the relative amount of human RNA recovered from the specimen and its suitability for clinical testing.

 The above rRT-PCR Flu Panel (NPS, NS, TS, NPS/TS, NA), when labeled consistent with the attached template, is authorized to be distributed to public health and other qualified laboratories\7\
 under this EUA, despite the fact that it does not meet certain requirements otherwise required by federal law.

 The following written information pertaining to the emergency use of the authorized rRT-PCR Swine Flu Panel is authorized to be made available to health care providers and patients:

     Fact Sheet For Healthcare Providers: Interpreting rRT-PCR Flu Panel (NPS, NS, TS, NPS/TS, NA) Test Results
     Fact Sheet For Patients: Understanding rRT-PCR Flu Panel (NPS, NS, TS, NPS/TS, NA) Kit Test Results

 See attached. 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 Flu Panel (NPS, NS, TS, NPS/TS, NA) 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 Flu Panel (NPS, NS, TS, NPS/TS,
 NA) in the specified population, when used as a first tier test in the qualitative detection of influenza virus type A or B and subtype determination of seasonal human influenza A virus
 (seasonal A/H1 or A/H3) for individuals suspected of having a 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 Flu
 Panel (NPS, NS, TS, NPS/TS, NA) may be effective as a first tier test in the qualitative detection of influenza virus type A or B and subtype determination of seasonal human influenza A virus
 (seasonal A/H1 or A/H3) for individuals suspected of having a 2009 H1N1 influenza virus infection pursuant to section 564(c)(2)(A) of the Act. 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 Flu Panel (NPS, NS, TS, NPS/TS, NA), when used for
 qualitative detection of influenza virus types A or B and subtype determination of seasonal human influenza A virus (seasonal A/H1 or A/H3) from individuals suspected of having a 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.

[[Page 38643]]

 The emergency use of the authorized rRT-PCR Flu Panel (NPS, NS, TS, NPS/TS, NA) 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 rRT-PCR Flu Panel (NPS, NS, TS, NPS/TS, NA) described above is authorized as a first tier
 test to qualitatively detect influenza virus types A or B and subtype seasonal human influenza A virus (seasonal A/H1 or A/H3) for individuals suspected of having a 2009 H1N1 influenza virus
 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 Flu Panel (NPS, NS, TS, NPS/TS, NA) during the duration of this emergency use authorization\8\:
     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 Flu Panel (NPS, NS, TS, NPS/TS, NA);
     registration and listing requirements under section 510 of the Act;
     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);
     investigational device requirements, including requirements under 21 CFR Part 812; and
     reporting requirements that apply to cleared or approved devices, including requirements under 21 CFR Parts 803 and 806.

 IV. Conditions of Authorization

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

 CDC
  A. CDC will distribute the rRT-PCR Flu Panel (NPS, NS, TS, NPS/TS, NA) labeled with the intended use statement, adequate directions for use, any appropriate limitations on the use of the
   device, and any available information regarding performance of the device only to qualified laboratories.
  B. CDC will provide to the qualified state and/or local public health authority(ies) the authorized rRT-PCR Flu Panel (NPS, NS, TS, NPS/TS, NA) Fact Sheets for health care providers, and the
   authorized rRT-PCR Flu Panel (NPS, NS, TS, NPS/TS, NA) Fact Sheets for patients.
  C. CDC will make available on its website the authorized rRT-PCR Flu Panel (NPS, NS, TS, NPS/TS, NA) Fact Sheets for health care providers, and the authorized rRT-PCR Flu Panel (NPS, NS, TS,
   NPS/TS, NA) Fact Sheets for patients.
  D. CDC will ensure that the state and/or local public health authority(ies) are informed of this EUA, including the terms and conditions herein.
  E. CDC will ensure qualified laboratories have a process in place for reporting test results to health care providers and federal, state and/or local public health authorities, as
   appropriate.
  F. CDC will track adverse events.
  G. Through a process of inventory control, CDC will maintain records of device usage.
  H. CDC will collect information on the performance of the assay, to include the incidence of false positive results.

 Public Health and Other Qualified Laboratories
  I. Qualified 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 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).
  J. 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.

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

  K. 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 Flu
   Panel (NPS, NS, TS, NPS/TS, NA) that is consistent with, and does not exceed, the terms of this letter of authorization.

  L. Only CDC may request changes to the authorized Fact Sheet for health care providers or the authorized rRT-PCR Flu Panel (NPS, NS, TS, NPS/TS, NA) Fact Sheet for patients. Such requests
   will be made by contacting FDA concerning FDA review and approval.

  M. CDC and the appropriate state/and or local public health authority(ies) will ensure that 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 Flu Panel (NPS, NS, TS, NPS/TS, NA) 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.

[[Page 38644]]

                   Joshua M. Sharfstein, MD
                   Principal Deputy Commissioner
                   Acting Commissioner

 \1\ Centers for Disease Control and Prevention
\2\ Nasopharyngeal swabs, nasal swabs, throat swabs, dual nasopharyngeal swabs/throat swabs, nasal aspirates.
\3\ Memorandum, Determination Pursuant to Sec.   564 of the Federal Food, Drug, and Cosmetic Act (April 26, 2009).
\4\ FDA is authorizing the emergency use of the CDC Human Influenza Virus Real-time RT-PCR Detection and Characterization Panel for Respiratory Specimens (NPS, NS, TS, NPS/TS, NA) and Viral
  Culture (rRT-PCR Flu Panel (NPS, NS, TS, NPS/TS, NA) as described in the scope section of this letter (Section II). For ease of reference, this letter will use the term the ``rRT-PCR Flu
  Panel (NPS, NS, TS, NPS/TS, NA).''
\5\ The cleared test for in vitro qualitative detection of human influenza viral RNA (The CDC rRT-PCR Flu Panel (IVD) 510(K) 080570) is not adequate because of the need to test additional
  types of samples during this emergency and it is not sufficiently available because of limited availability of certain reagents. No other criteria of issuance have been prescribed by
  regulation under section 564(c)(4) of the Act.
\6\ The CDC rRT-PCR Flu Panel (IVD) 510(K) 080570 is indicated for the in vitro qualitative detection of human influenza viral RNA in nasopharyngeal swabs (NPS) and nasal swabs (NS) only.
\7\ 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.
\8\ These requirements are waived only for the rRT-PCR Flu Panel (NPS, NS, TS, NPS/TS, NA) that is authorized for emergency use. These requirements, and all other applicable statutory and
  regulatory requirements, continue to apply to the CDC rRT-PCR Flu Panel (IVD) 510(K) 080570.

    Dated: June 30, 2009.
Randall W. Lutter,
Deputy Commissioner for Policy.
[FR Doc. E9-18569 Filed 8-3-09; 8:45 am]

BILLING CODE 4160-01-S