[Federal Register: March 27, 2008 (Volume 73, Number 60)]
[Notices]               
[Page 16313-16314]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr27mr08-62]                         


[[Page 16313]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2008-N-0174]

 
Identification of Drug and Biological Products Deemed to Have 
Risk Evaluation and Mitigation Strategies for Purposes of the Food and 
Drug Administration Amendments Act of 2007

AGENCY:  Food and Drug Administration, HHS.

ACTION:  Notice.

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SUMMARY:  The Food and Drug Administration (FDA) is issuing this notice 
to notify holders of certain prescription new drug and biological 
license applications that they will be deemed to have in effect an 
approved risk evaluation and mitigation strategy (REMS) under the Food 
and Drug Administration Amendments Act of 2007 (FDAAA). Holders of 
applications deemed to have in effect an approved REMS are required to 
submit a proposed REMS to FDA.

DATES:  Submit proposed REMSs to FDA by September 21, 2008.

ADDRESSES:  Written communications regarding the applicability of this 
notice to a specific product should be identified with Docket Number 
FDA-2008-N-0174 and submitted to the Division of Dockets Management 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852. Submit electronic communications to http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.regulations.gov. Information about FDA implementation of FDAAA is 
available on the Internet at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/oc/initiatives/advance/fdaaa.html.

FOR FURTHER INFORMATION CONTACT:  Mary Dempsey, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, rm. 4326, Silver Spring, MD 20993-0002, 301-
796-0147.

SUPPLEMENTARY INFORMATION:

I. Introduction

    On September 27, 2007, the President signed into law FDAAA (Public 
Law 110-85). Title IX, subtitle A, section 901 of FDAAA created new 
section 505-1 of the Federal Food, Drug, and Cosmetic Act (the act) (21 
U.S.C. 355-1). Section 505-1(a) of the act authorizes FDA to require 
persons submitting certain applications\1\ to submit and implement a 
REMS if FDA determines that a REMS is necessary to ensure that the 
benefits of a drug outweigh the risks of the drug and informs the 
holder of the application for the drug of the determination. Section 
909 of FDAAA provides that Title IX, subtitle A takes effect 180 days 
after its enactment, which is March 25, 2008.
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    \1\ Section 505(p)(1) of the act (21 U.S.C. 355(p)(1)) states 
that section 505-1 of the act applies to applications for 
prescription drugs approved under section 505(b) or (j) of the act 
and applications approved under section 351 of the Public Health 
Service Act (42 U.S.C. 262).
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    FDAAA also contains REMS requirements for drug and biological 
products approved before the effective date of Title IX, subtitle A. 
Section 909(b)(1) of FDAAA specifies that a ``drug that was approved 
before the effective date of this Act is * * * deemed to have in effect 
an approved risk evaluation and mitigation strategy under section 505-1 
of the Federal Food, Drug, and Cosmetic Act * * * if there are in 
effect on the effective date of this Act elements to assure safe use--
(A) required under section 314.520 or section 601.42 of title 21, Code 
of Federal Regulations; or (B) otherwise agreed to by the applicant and 
the Secretary [of Health and Human Services] for such drug.''
    Section 909(b)(3) of FDAAA states: ``Not later than 180 days after 
the effective date of this Act, the holder of an approved application 
for which a risk evaluation and mitigation strategy is deemed to be in 
effect * * * shall submit to the Secretary a proposed risk evaluation 
and mitigation strategy. Such proposed strategy is subject to section 
505-1 of the Act as if included in such application at the time of 
submission of the application to the Secretary.''\2\
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    \2\ Title IX, subtitle A of FDAAA, which includes section 909, 
takes effect March 25, 2008; 180 days after that date is September 
21, 2008.
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    Section 909(b)(2) of FDAAA states that a REMS for a drug deemed to 
have a REMS consists of the timetable required under section 505-1(d) 
of the act and any additional elements under section 505-1(e) and (f) 
of the act in effect for the drug on the effective date of FDAAA.
    The purpose of this notice is to identify those drugs that FDA has 
determined will be deemed to have in effect an approved REMS and to 
notify holders of applications for such drugs that they are required to 
submit a proposed REMS by September 21, 2008. FDA is developing 
guidance on the preferred content and format of a proposed REMS 
required to be submitted under section 909(b) of FDAAA and will issue 
it as soon as possible.

II. List of Drug and Biological Products Deemed to Have a REMS

    Drug and biological products deemed to have in effect an approved 
REMS are those that on March 25, 2008 (the effective date of Title IX, 
subtitle A of FDAAA), had in effect ``elements to assure safe use.'' 
``Elements to assure safe use'' include the following: (1) Health care 
providers who prescribe the drug have particular training or 
experience, or are specially certified; (2) pharmacies, practitioners, 
or health care settings that dispense the drug are specially certified; 
(3) the drug is dispensed to patients only in certain health care 
settings, such as hospitals; (4) the drug is dispensed to patients with 
evidence or other documentation of safe use conditions, such as 
laboratory test results; (5) each patient using the drug is subject to 
certain monitoring; or (6) each patient using the drug is enrolled in a 
registry (see section 505-1(f)(3) of the act).
    Some applications approved before the effective date of FDAAA Title 
IX, subtitle A contain these elements to assure safe use.\3\ Some of 
these applications were approved under Sec.  314.520 (21 CFR 314.520) 
or Sec.  601.42 (21 CFR 601.42). Others were not approved under part 
314, subpart H or part 601, subpart E, but still contain elements to 
assure safe use that were agreed to by the applicant and the Secretary 
for such drug. Since 2005, these elements typically appeared in 
approved risk minimization action plans (RiskMAPs) (see the guidance 
for industry entitled ``Development and Use of Risk Minimization Action 
Plans'' (70 FR 15866, March 29, 2005)).
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    \3\ These plans sometimes contain other elements to minimize 
risk such as a Medication Guide (21 CFR part 208) or a 
communication/educational plan for health care providers or 
patients. A drug will not be deemed to have a REMS if it has only a 
Medication Guide, patient package insert, and/or communication plan 
(see section 505-1(e)(2) and (e)(3) of the act).
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    FDA has reviewed its records to identify applications that were 
approved before the effective date of Title IX of FDAAA with elements 
to assure safe use and has identified the drug and biological products 
listed in table 1 of this document as those that will be deemed to have 
in effect an approved REMS.

[[Page 16314]]



      Table 1.--Products Deemed to Have in Effect an Approved REMS
------------------------------------------------------------------------
Generic or Proper                        Application         Date of
       Name            Brand Name         Number\1\        Approval\2\
------------------------------------------------------------------------
Abarelix           Plenaxis\3\        NDA 21-320        11/25/2003
------------------------------------------------------------------------
Alosetron          Lotronex           NDA 21-107        02/09/2000
------------------------------------------------------------------------
Ambrisentan        Letairis           NDA 22-081        06/15/2007
------------------------------------------------------------------------
Bosentan           Tracleer           NDA 21-290        11/20/2001
------------------------------------------------------------------------
Clozapine          Clozaril           NDA 19-758        09/26/1989
                                       ANDA 74-949       11/26/97
                                       ANDA 75-417       5/27/99
                                       ANDA 75-713       11/15/02
                                       ANDA 75-162       4/26/05
                                       ANDA 76-809       12/16/05
                   Fazaclo ODT        NDA 21-590        02/09/2004
------------------------------------------------------------------------
Dofetilide         Tikosyn            NDA 20-931        10/01/1999
------------------------------------------------------------------------
Eculizumab         Soliris            BLA 125166        03/16/2007
------------------------------------------------------------------------
Fentanyl PCA       Ionsys\3\          NDA 21-338        05/22/2006
------------------------------------------------------------------------
Fentanyl citrate   Actiq              NDA 20-747        11/04/1998
------------------------------------------------------------------------
Isotretinoin       Accutane           NDA 18-662        05/07/1982
                   Amnesteem          ANDA 75-945       11/2002
                   Claravis           ANDA 76-135       04/2003
                                       ANDA 76-356       04/2003
                   Sotret             ANDA 76-041       12/2002
                                       ANDA 76-503       06/2003
------------------------------------------------------------------------
Lenalidomide       Revlimid           NDA 21-880        12/27/2005
------------------------------------------------------------------------
Mifepristone       Mifeprex           NDA 20-687        09/28/2000
------------------------------------------------------------------------
Natalizumab        Tysabri            BLA 125104        11/23/2004
------------------------------------------------------------------------
Small pox          ACAM2000           BLA 125158        08/31/2007
 (Vaccinia)
 Vaccine, Live
------------------------------------------------------------------------
Sodium oxybate     Xyrem              NDA 21-196        07/17/2002
------------------------------------------------------------------------
Thalidomide        Thalomid           NDA 20-785        07/16/1998
                                       NDA 21-430
------------------------------------------------------------------------
\1\ New drug application (NDA), abbreviated new drug application (ANDA),
  biologics license application (BLA).
\2\ The original date of approval of the drug. FDA may have required
  elements to assure safe use at a later date.
\3\ Product is not currently marketed in the United States.

    FDA is further asking members of the public to please notify the 
agency if they are aware of applications that have not been identified 
in this document and that they believe should be deemed to have in 
effect an approved REMS. Please provide the information to Mary 
Dempsey, Risk Management Coordinator (see the FOR FURTHER INFORMATION 
CONTACT section of this document).
    Any application holder that believes its product identified in this 
notice should not be on the list of drug or biological products that 
will be deemed to have in effect an approved REMS should submit a 
letter identified with Docket Number FDA-2008-N-0174 to the Division of 
Dockets Management (see ADDRESSES) stating why the application holder 
believes its product was improperly identified in this notice. FDA will 
notify the application holder within 30 days of receipt of the letter 
of its determination.

    Dated: March 19, 2008.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E8-6201 Filed 3-26-08; 8:45 am]

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