
[Federal Register Volume 76, Number 71 (Wednesday, April 13, 2011)]
[Notices]
[Pages 20686-20688]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-8895]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2011-D-0164]


Draft Guidance for Industry on Safety Labeling Changes; 
Implementation of the Federal Food, Drug, and Cosmetic Act; 
Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a draft guidance for industry entitled ``Safety 
Labeling Changes--Implementation of Section 505(o)(4) of the Federal 
Food, Drug, and Cosmetic Act.'' The Food and Drug Administration 
Amendments Act of 2007 (FDAAA) added new provisions to the Federal 
Food, Drug, and Cosmetic Act (the FD&C Act) authorizing FDA to require 
certain drug and biological product application holders to make safety 
related labeling changes based upon new safety information that becomes 
available after the drug or biological product is approved under the 
FD&C Act or the Public Health Service Act (the PHS Act). This draft 
guidance provides information on the implementation of the new 
provisions, including a description of the types of safety labeling 
changes that ordinarily might be required under the new legislation, 
how FDA plans to determine what constitutes new safety information, the 
procedures involved in requiring safety labeling changes, and 
enforcement of the requirements for safety labeling changes.

DATES: Although you can comment on any guidance at any time (see 21 CFR 
10.115(g)(5)), to ensure that the Agency considers your comment on this 
draft guidance before it begins work on the final version of the 
guidance, submit written or electronic comments on the draft guidance 
by July 12, 2011.

ADDRESSES: Submit written requests for single copies of this guidance 
to the Division of Drug Information, Center for Drug Evaluation and 
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 
51, Rm. 2201, Silver Spring, MD 20993-0002; or the Office of 
Communication, Outreach and Development (HFM-40), Center for Biologics 
Evaluation and Research (CBER), Food and Drug Administration, 1401 
Rockville Pike, Rockville, MD 20852-1448. The guidance may also be 
obtained by mail by calling CBER at 1-800-835-4709 or 301-827-1800. 
Send one self-addressed adhesive label to assist the office in 
processing your requests. Submit written comments on the guidance to 
the Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. 
Submit electronic comments to http://www.regulations.gov. See the 
SUPPLEMENTARY INFORMATION section for electronic access to the draft 
guidance document.

FOR FURTHER INFORMATION CONTACT: Kristen Everett, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6228, Silver Spring, MD 20993-0002, 301-
796-5400, or Stephen Ripley, Center for Biologics Evaluation and 
Research (HFM-17), Food and Drug Administration, 1401 Rockville Pike, 
Rockville, MD 20852-1448, 301-827-6210.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Safety Labeling Changes--Implementation of Section 505(o)(4) 
of the Federal Food, Drug, and Cosmetic Act.'' In the past, FDA has 
requested that holders of applications for approved products make 
labeling changes related to safety after approval to address serious 
risks. FDA learned of the potential for such serious risks from a 
variety of sources. In most cases, application holders responded to 
these requests by negotiating appropriate language with FDA staff to 
address the concerns, and then submitting a supplement or amended 
supplement to obtain approval of the change. Negotiations were often 
protracted, and FDA had few tools available at its disposal to end 
negotiations and require the changes. Congress recognized the 
limitations of FDA's authority in this area and, in FDAAA, gave FDA new 
authority to require safety labeling changes in certain circumstances.
    Title IX, section 901 of FDAAA (Pub. L. 110-85) amended the FD&C 
Act by adding new section 505(o)(4) (21 U.S.C. 355(o)(4)). Section 
505(o)(4) authorizes FDA to require, and if necessary, order labeling 
changes if FDA becomes aware of new safety information that FDA 
believes should be included in the labeling of certain prescription 
drug and biological products approved under section 505 of the FD&C Act 
or section 351 of the PHS Act (42 U.S.C. 262). Specifically, section 
505(o)(4) of the FD&C Act applies to prescription drug products with an 
approved new drug application (NDA) under section 505(b) of the FD&C 
Act, biological products with an approved biologics license application 
(BLA) under section 351 of the PHS Act, or prescription drug products 
with an approved abbreviated new drug application (ANDA) under section 
505(j) of the FD&C Act if the reference listed drug (RLD) with an 
approved NDA is not currently marketed. FDAAA imposes timeframes for 
application holders to submit and FDA staff to review such changes, and 
gives FDA new enforcement tools to bring about timely and appropriate 
labeling changes. This draft guidance provides information on the 
implementation of the new provisions, including a description of the 
types of safety labeling changes that ordinarily

[[Page 20687]]

might be required under the new legislation, how FDA plans to determine 
what constitutes new safety information, the procedures involved in 
requiring safety labeling changes, and enforcement of the requirements 
for safety labeling changes.
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will represent the Agency's current thinking on the 
implementation of section 901 of FDAAA on safety labeling changes. It 
does not create or confer any rights for or on any person and does not 
operate to bind FDA or the public. An alternative approach may be used 
if such approach satisfies the requirements of the applicable statutes 
and regulations.

II. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) either electronic or written comments regarding this 
document. It is only necessary to send one set of comments. It is no 
longer necessary to send two copies of mailed comments. Identify 
comments with the docket number found in brackets in the heading of 
this document. Received comments may be seen in the Division of Dockets 
Management between 9 a.m. and 4 p.m., Monday through Friday.

III. Paperwork Reduction Act of 1995

    Under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 
3501-3520), Federal agencies must obtain approval from the Office of 
Management and Budget (OMB) for each collection of information that 
they conduct or sponsor. ``Collection of information'' is defined in 44 
U.S.C. 3502(3) and 5 CFR 1320.3(c) and includes Agency requests or 
requirements that members of the public submit reports, keep records, 
or provide information to a third party. Section 3506(c)(2)(A) of the 
PRA, 44 U.S.C. 3506(c)(2)(A), requires Federal agencies to provide a 
60-day notice in the Federal Register for each proposed collection of 
information before submitting the collection to OMB for approval. To 
comply with this requirement, FDA is publishing this notice of the 
proposed collection of information set forth in this document.
    With respect to the collections of information associated with this 
draft guidance that were not previously approved by OMB, described 
below, FDA invites comments on the following topics: (1) Whether the 
proposed information collected is necessary for the proper performance 
of FDA's functions, including whether the information will have 
practical utility; (2) the accuracy of FDA's estimated burden of the 
proposed information collected, including the validity of the 
methodology and assumptions used; (3) ways to enhance the quality, 
utility, and clarity of the information collected; and (4) ways to 
minimize the burden of information collected on the respondents, 
including through the use of automated collection techniques, when 
appropriate, and other forms of information technology.
    This draft guidance provides information on the implementation of 
section 901 of FDAAA, which authorizes FDA to require certain drug and 
biological product application holders to make safety related labeling 
changes based upon new safety information that becomes available after 
the drug or biological product is approved under the FD&C Act or the 
PHS Act. FDA plans to request safety labeling changes by sending a 
notification letter to the application holder. Under section 
505(o)(4)(B), the application holder must respond to FDA's notification 
by submitting a labeling supplement or notifying FDA that the applicant 
does not believe the labeling change is warranted and submitting a 
statement detailing the reasons why the application holder does not 
believe a change is warranted (a rebuttal statement).
    The submission of rebuttal statements may result in the collection 
of information that is not already approved by OMB. Based on FDA's 
experience thus far with safety labeling changes requirements under 
section 505(o)(4), FDA estimates that approximately six application 
holders will elect to submit approximately one rebuttal statement each 
year and that each rebuttal statement will take approximately 6 hours 
to prepare.
    In addition, in the draft guidance, the agency states that new 
labeling prepared in response to a safety labeling change notification 
should be available on the application holder's Web site within 10 
calendar days of approval, which may result in the collection of 
information that is not already approved by OMB. FDA estimates that 
approximately 197 application holders will post new labeling one time 
each year in response to a safety labeling change notification and that 
the posting of the labeling will take approximately 4 hours to prepare.
    FDA estimates the burden of the collections of information that 
have not already been approved by OMB, is as follows:

                                                     Table 1--Estimated Annual Reporting Burden \1\
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                                                                                         Number of
                                                                        Number of      responses per        Total          Hours per       Total hours
                                                                       respondents       respondent       responses         response
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Rebuttal statement.................................................               6                1                6                6               36
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    Total..........................................................  ...............  ...............  ...............  ...............              36
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\1\ There are no capital costs or operating and maintenance costs associated with this information collection.


                                               Table 2--Estimated Annual Third Party Disclosure Burden \1\
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                                                                                           Annual
                         Type of submission                             Number of      frequency per     Total annual      Hours per       Total hours
                                                                       respondents       disclosure      disclosures       disclosure
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Post approved labeling on application holder's Web site............             197                1              197                4              788
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\1\ There are no capital costs or operating and maintenance costs associated with this information collection.

    This draft guidance also refers to previously approved collections 
of information. Specifically, the draft guidance describes: Labeling 
supplements for NDAs, ANDAs, and BLAs submitted under 21 CFR 314.70,

[[Page 20688]]

314.71, 314.97 and 601.12; and the content and format of prescription 
drug labeling submitted under 21 CFR 201.56 and 201.57. These 
collections of information are subject to review by OMB under the PRA 
act and are approved under OMB control numbers 0910-0001, 0910-0338, 
and 0910-0572. Section V of the draft guidance refers to the guidance 
entitled ``Formal Dispute Resolution: Appeals Above the Division 
Level,'' which describes collections of information approved under OMB 
control number 0910-0430.

IV. Electronic Access

    Persons with access to the Internet may obtain the document at 
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or 
http://www.regulations.gov.

    Dated: April 7, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-8895 Filed 4-12-11; 8:45 am]
BILLING CODE 4160-01-P


