Notice: Establishing Timeframes for Implementation of Product Safety 
Labeling Changes; Request for Comments

Federal Register: Volume 76, Number 244 (Tuesday, December 20, 2011)
                  Pages 78929-78930

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice; request for comments.

SUMMARY: The Food and Drug Administration (FDA) is seeking comments on 
specific issues related to its authority under the Federal Food, Drug, 
and Cosmetic Act (the FD&C Act) to require or order safety labeling 
changes for approved prescription drug products based on new safety 
information that becomes available after a drug product is approved. 
The FD&C Act specifies the timeframes within which a safety labeling 
change must be submitted when required or ordered by the FDA, and 
timeframes for FDA to conclude its review and take regulatory action 
regarding safety labeling changes. FDA's regulations also provide 
procedures by which labeling changes that do not qualify as changes 
based on new safety information can be requested by FDA or by the 
holder of the drug approval. FDA is seeking public input to assist the 
Agency in establishing specific timeframes for implementing both types 
of labeling changes.

DATES: Submit either electronic or written comments by February 21, 
2012.

ADDRESSES: Submit electronic comments on this document to http://www.regulations.gov. 
Submit written comments to the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852. All comments should be identified with 
the docket number found in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: Kristen Miller, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6226, Silver Spring, MD 20993-0002, (301) 
796-0762, Fax: (301) 847-8440.

SUPPLEMENTARY INFORMATION:

I. Background

    On September 27, 2007, the Food and Drug Administration Amendments 
Act of 2007 (FDAAA) was enacted. Title IX, Subtitle A, section 901 of 
FDAAA added to the FD&C Act new section 505(o) (21 U.S.C. 355(o)), 
which authorizes FDA to require labeling changes when the Agency 
becomes aware of new safety information it believes should be included 
in the labeling of an approved drug product.\1\
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    \1\ For purposes of this notice, drug product means a human drug 
product including a biological drug product. Labeling includes the 
carton or other container or packaging labels, the prescribing 
information, patient package inserts, and Medication Guides.
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    Before the enactment of FDAAA, if FDA believed that a labeling 
change was necessary to address safety information newly identified 
after approval of a drug product, the Agency would ask the application 
holder to make the appropriate labeling changes. In most cases, 
application holders responded to FDA's requests for labeling changes by 
negotiating appropriate language with FDA staff to address the concern, 
and then submitting a supplement or amended supplement to obtain 
approval of the changes. FDA routinely asked applicants to submit 
supplemental applications to revise the labeling of approved products, 
but the Agency lacked the authority to compel changes to product 
labeling based on new safety information. At times, FDA and application 
holders discussed the appropriate timeframe by which new labeling would 
be made available. Typically products that had already moved beyond the 
manufacturing line were not withdrawn from distribution to change 
existing labeling under the timeframes.
    Under FDAAA, FDA is now authorized to require and, if necessary, 
order application holders to implement safety labeling changes to 
reflect new safety information (section 505(o)(4) of the FD&C Act). 
Although the statute provides specific and relatively short timelines 
for submission and review of FDAAA-required safety labeling changes 
following a notification or order from FDA, the statute does not 
include specific deadlines for how soon the revised labeling must be 
incorporated into the packaging of the product that is offered for 
sale, or into other labeling (section 505(o)(4) of the FD&C Act).
    In an effort to make revised safety labeling available as soon as 
possible after the changes required under FDAAA are approved, FDA has 
recommended that application holders post the revised labeling on their 
Web sites within 10 days of approval. (See draft guidance for industry 
entitled ``Safety Labeling Changes--Implementation of Section 505(o)(4) 
of the Federal Food, Drug, and Cosmetic Act'' (76 FR 20686, April 13, 
2011)). In letters approving supplements with safety labeling changes, 
FDA has also recommended that revised labeling accompany the product 
within ``a reasonable amount of time'' and has occasionally suggested 
specific timeframes when this could occur. However, we have not yet 
announced general timeframes in which we expect new labeling to be 
disseminated nor have we established the timeframe for when product 
packaging needs to reflect the revised label.
    In addition to safety labeling changes that may be required under 
FDAAA, FDA may continue to request safety labeling changes under 
existing regulations and application holders may continue to propose 
labeling changes on their own initiative (Sec. Sec.  314.70 and 601.12 
(21 CFR 314.70 and 601.12)). Existing regulations in Sec. Sec.  314.70 
and 601.12 describe several mechanisms for effecting proposed labeling 
changes to approved drug applications including the following: (1) A 
prior approval supplement (PAS) is used for changes that must receive 
approval before being implemented; (2) a changes-being-effected 
supplement (CBE) is used for other kinds of labeling revisions that 
must be received by the Agency prior to distribution of the drug with 
the revised labeling; and (3) the annual report for the drug product is 
used for certain minor changes that need only be described in the next 
annual report.
    Current labeling regulations do not provide specific timeframes for 
implementing other safety labeling changes--changes not required under 
FDAAA--that are made by submitting a PAS or CBE, or by reporting the 
change in the annual report.

II. Purpose of Request for Comments

    Because safety labeling changes may be related to serious risks, 
this information must be promptly communicated to prescribers and 
patients. Thus, it is important for FDA to clarify its expectations 
regarding the timeframes for applicants to implement safety labeling 
changes to ensure that the labeling is updated in a timely manner. FDA 
anticipates that in most cases, as in the past, it will not be 
necessary for products with existing labeling to be withdrawn from 
distribution and that under certain circumstances it may be appropriate 
for products with existing labeling to remain in distribution until the 
current product inventory is exhausted.
    FDA is interested in hearing from application holders, 
manufacturers, distributors, and other stakeholders about their 
experience with and views on the practical implementation of revised 
product labeling, including their views as to how factors in the 
following

[[Page 78930]]

three categories may affect implementation: (1) Drug manufacturing and 
packaging, and printing labels and other labeling; (2) supply chain 
issues; and, (3) other issues. FDA may use the information received to 
develop draft guidance for industry regarding timeframes for revising 
product labeling following the approval of safety labeling changes, and 
may apply these timeframes to particular safety labeling changes.

III. Questions Posed by FDA

    With this notice, FDA is soliciting comments from application 
holders, manufacturers, distributors, and other stakeholders on the 
following questions:

A. Considerations Related to Drug Manufacturing and Packaging, and to 
Printing Labeling

    1. What are the considerations related to drug manufacturing and 
packaging, of which FDA should be aware, as they relate to 
implementation of revised product labeling?
    2. What are the considerations related to printing labels and other 
types of labeling of which FDA should be aware, as they relate to 
implementation of different types of revised product labeling?

B. Supply Chain Issues

    3. What are the supply chain factors (including storage, shipping, 
and distribution factors) of which FDA should be aware that limit or 
otherwise affect how quickly a labeling change can be implemented?

C. Other Considerations

    4. What alternative labeling mechanisms (e.g., having labeling 
available on a product Web site) could be used to disseminate new 
safety information quickly to patients and health care providers?
    5. How should the relative seriousness of the new safety 
information, or whether the new safety information describes a newly 
identified risk, or strengthens a risk already identified in current 
labeling, affect timelines for implementing revised product labeling?
    6. What are the implementation considerations when the safety 
labeling change is to prescriber versus patient labeling (or both)?
    7. What would be a reasonable timeframe following approval of 
revised safety related labeling changes for applicants to implement the 
revised labeling? Please relate this timeframe to the optimal point in 
the supply chain (e.g., newly manufactured product, newly shipped 
product) and the type of labeling change.
    8. Are there other considerations or options related to 
implementing safety labeling changes of which FDA should be aware?

IV. Comments

    Interested persons may submit either electronic or written comments 
regarding this document to the Division of Dockets Management (see 
ADDRESSES). 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 at the Division of Dockets 
Management between 9 a.m. and 4 p.m., Monday through Friday, as well as 
at http://www.regulations.gov.

    Dated: December 14, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-32438 Filed 12-19-11; 8:45 am]
BILLING CODE 4160-01-P