2011-8895. Draft Guidance for Industry on Safety Labeling Changes; Implementation of the Federal Food, Drug, and Cosmetic Act; Availability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.

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The Food and Drug Administration (FDA) is announcing the availability of a draft guidance for industry entitled “Safety Labeling Changes—Implementation of Section 505(o)(4) of the Federal Food, Drug, and Cosmetic Act.”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 This draft guidance provides information on the implementation of the new provisions, including a description of the types of safety labeling changes that ordinarily might be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comment on any guidance at any time (see 21 CFR 10.115(g)(5)), to ensure that the Agency considers your comment on this draft guidance before it begins work on the final version of the guidance, submit written or electronic comments on the draft guidance by July 12, 2011.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 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

	Number of respondents	Number of responses per respondent	Total responses	Hours per response	Total hours
Rebuttal statement	6	1	6	6	36
Total					36
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

Type of submission	Number of respondents	Annual frequency per disclosure	Total annual disclosures	Hours per disclosure	Total hours
Post approved labeling on application holder's Web site	197	1	197	4	788
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, 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.