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Guidance for Industry on Medication Guides-Adding a Toll-Free Number for Reporting Adverse Events; Availability

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Information about this document as published in the Federal Register.

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Food and Drug Administration, HHS.




The Food and Drug Administration (FDA) is announcing the availability of a guidance for industry entitled “Medication Guides—Adding a Toll-Free Number for Reporting Adverse Events.” Beginning July 1, 2009, manufacturers of prescription drug products approved under the Federal Food, Drug, and Cosmetic Act (the act) that are required to have a Medication Guide must add a verbatim statement to their Medication Guides containing FDA's toll-free number for reporting side effects. These manufacturers are also required to report to FDA that they have complied with this requirement. This guidance explains what statement to add to Medication Guides, where to add it, and how to notify the agency that such a statement has been added.


Submit written or electronic comments on agency guidances at any time.


Submit written requests for single copies of this draft guidance to the Division of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm. 2201,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. Send one self-addressed adhesive label to assist that office in processing your requests. Submit written comments on the draft guidance to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.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 See the SUPPLEMENTARY INFORMATION section for electronic access to the guidance document.

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Nancy Clark, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993, 301-796-5400,

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I. Background

FDA is announcing the availability of a guidance for industry entitled “Medication Guides—Adding a Toll-Free Number for Reporting Adverse Events.” On September 27, 2007, the President signed into law the Food and Drug Administration Amendments Act (FDAAA) (Public Law 110-85). Among other things, FDAAA reauthorized the Best Pharmaceuticals for Children Act (BPCA) (Public Law 107-109). When enacted in 2001, the BPCA directed FDA to issue a final rule requiring the labeling of each human drug product for which an application is approved under section 505 of the act (21 U.S.C. 355) to include: (1) A toll-free number maintained by FDA for the purpose of receiving reports of adverse events regarding drugs and (2) a statement that the number is to be used for reporting purposes only, not to receive medical advice. The BPCA stated that the final rule must reach the broadest consumer audience and minimize the cost to the pharmacy profession. As required, FDA issued a proposed rule entitled “Toll-Free Number for Reporting Adverse Events on Labeling for Human Drug Products” (69 FR 21778, April 22, 2004), which would require, among other things, that a side effects statement be included in FDA-approved Medication Guides for drug products approved under section 505 of the act.

FDA received 22 comments on this proposed rule and was in the process of analyzing the comments and conducting research on consumer comprehension of the side effects statement when FDAAA was enacted. Section 502(f) of FDAAA stated that “the proposed rule * * * entitled ‘Toll-Free Number for Reporting Adverse Events on Labeling for Human Drug Products’ * * * shall take effect on January 1, 2008,” unless FDA issues a final rule before that date. FDA did not issue a final rule by January 1, 2008, so Start Printed Page 27153as mandated by FDAAA, the provisions of the proposed rule went into effect on that date.

FDAAA mandated one change to the proposed rule. Section 502(f)(2) of FDAAA stated that the toll-free number proposed rule shall not apply to over-the-counter (OTC) drugs marketed with an application approved under section 505 of the act (application OTC drug products) if these application OTC drug products meet certain labeling requirements. Because the agency's rulemaking process was ongoing on January 1, 2008, an interim final rule was issued on January 3, 2008 (73 FR 402) that codified the provisions of the proposed rule as modified by FDAAA. The interim final rule stated that FDA anticipated that affected entities would need time to update labeling and systems to comply with the new requirements and that FDA intended to exercise its enforcement discretion and not take action to enforce the toll-free number requirements in the interim final rule until January 1, 2009. The interim final rule also stated that the agency planned to complete research begun on the proposed labeling statements and would issue a final rule taking into account the results of that research. In the Federal Register of October 28, 2008 (73 FR 63886), FDA issued a final rule with an effective date of November 28, 2008, and a compliance date of July 1, 2009. The agency is publishing this guidance to assist manufacturers in complying with the final rule.

This level 1 guidance is being issued for immediate implementation consistent with FDA's good guidance practices regulation (21 CFR 10.115). FDA has determined that prior public participation is not feasible or appropriate because the side effects statement is required by Congress and the compliance deadline for its inclusion in Medication Guides is July 1, 2009 (21 CFR 10.115(g)(2)). If comments are received on this level 1 guidance, FDA will review the comments and revise the guidance if appropriate. The guidance represents the agency's current thinking on adding a toll-free number to Medication Guides and reporting this to the agency. 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. The Paperwork Reduction Act of 1995

The required side effects statement is not subject to the Office of Management and Budget (OMB) review under the Paperwork Reduction Act (PRA) (44 U.S.C. 3501-3520) because it is “originally supplied by the Federal Government to the recipient for the purpose of disclosure to the public” and is not considered a collection of information under the PRA (5 CFR 1320.3(c)(2)). The guidance on notifying FDA in the drug's annual report that the side effects statement has been added to the drug's Medication Guide is covered by previously approved collections of information found in FDA regulations. The collections of information in 21 CFR 314.70(d) (changes to an approved application to be described in an annual report) and 314.81(b)(2)(iii)(c) (a summary of labeling changes that have been made since the last annual report) have been approved under OMB control number 0910-0001 for human drugs.

III. Comments

Interested persons may submit to the Division of Dockets Management (see ADDRESSES) written or electronic comments regarding this document. Submit a single copy of electronic comments or two paper copies of any mailed comments, except that individuals may submit one paper copy. Comments are to be identified 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.

IV. Electronic Access

Persons with access to the Internet may obtain the document at either​Drugs/​GuidanceComplianceRegulatoryInformation/​Guidances/​default.htm or

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Dated: June 1, 2009.

Jeffrey Shuren,

Associate Commissioner for Policy and Planning.

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[FR Doc. E9-13273 Filed 6-5-09; 8:45 am]