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###### Department of Health and Human Services

###### Food and Drug Administration

          - [Docket No. 1996D-0041]

# AGENCY:

Food and Drug Administration, HHS.

# ACTION:

Notice.

# SUMMARY:

                        The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled “Addendum to E2C Clinical Safety Data Management:  Periodic Safety Update Reports for Marketed Drugs” (the ICH E2C guidance).  The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).  In the                         **Federal Register**                         of May 19, 1997 (62 FR 27470), FDA published the ICH E2C guidance, which recommends a unified standard for the format, content, and reporting frequency for postmarketing periodic safety update reports (PSURs) for drug and biological products.  This guidance, an addendum to the ICH E2C guidance, provides additional information on the content and format of PSURs, including clarification of the objectives, general principles, and model for PSURs.  This guidance is intended to help harmonize collection and submission of postmarketing clinical safety data.                    

# DATES:

You may submit written or electronic comments at any time.

# ADDRESSES:

                        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.fda.gov/​dockets/​ecomments*.  Submit written requests for single copies of the guidance to the Division of Drug Information (HFD-240), Center for Drug Evaluation and Research, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, or the Office of Communication, Training and Manufacturers Assistance (HFM-40), Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, Rockville, MD  20852-1448, 301-827-3844, FAX:   888-CBERFAX.  Send two self-addressed adhesive labels to assist the office in processing your requests.  Requests and comments should be identified with the docket number found in brackets in the heading of this document.  See the                         **SUPPLEMENTARY INFORMATION**                         section for electronic access to the guidance document.                    

# FOR FURTHER INFORMATION CONTACT:

*Regarding the guidance*:  Min Chen, Center for Drug Evaluation and Research (HFD-430), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD  20857, 301-827-3159, or Miles Braun, Center for Biologics Evaluation and Research (HFM-220), Food and Drug Administration, 1401 Rockville Pike, Rockville, MD  20852, 301-827-6090.                    

*Regarding the ICH*:  Michelle Limoli, Office of International Programs (HFG-1), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-827-4480.                    

# SUPPLEMENTARY INFORMATION:

## I.  Background

In recent years, many important initiatives have been undertaken by regulatory authorities and industry associations to promote international harmonization of regulatory requirements.  FDA has participated in many meetings designed to enhance harmonization and is committed to seeking scientifically based harmonized technical procedures for pharmaceutical development.  One of the goals of harmonization is to identify and then reduce differences in technical requirements for drug development among regulatory agencies.

                    ICH was organized to provide an opportunity for tripartite harmonization initiatives to be developed with input from both regulatory and industry representatives.  FDA also seeks input from consumer representatives and others.  ICH is concerned with harmonization of technical requirements for the registration of pharmaceutical products among three regions:   The European Union, Japan, and the United States.  The six ICH sponsors are the European Commission; the European Federation of Pharmaceutical Industries Associations; the Japanese Ministry of Health, Labour, and Welfare; the Japanese Pharmaceutical Manufacturers Association; the Centers for Drug Evaluation and Research and Biologics Evaluation and Research, FDA; and the Pharmaceutical Research and Manufacturers of America.  The ICH Secretariat, which coordinates the preparation of documentation, is                           ( print page 5552)                        provided by the International Federation of Pharmaceutical Manufacturers Associations (IFPMA).                

The ICH Steering Committee includes representatives from each of the ICH sponsors and the IFPMA, as well as observers from the World Health Organization, Health Canada, and the European Free Trade Area.

                    In the                     **Federal Register**                     of December 31, 2002 (67 FR 79939), FDA published a notice announcing the availability of a draft tripartite guidance entitled “Addendum to E2C Clinical Safety Data Management:  Periodic Safety Update Reports for Marketed Drugs.”  The notice gave interested persons an opportunity to submit comments by January 24, 2003.                

After consideration of the comments received and revisions to the draft guidance, a final draft of the guidance was submitted to the ICH steering committee and endorsed by the three participating regulatory agencies in February 2003.

This guidance provides additional information on the objectives, general principles, and model for PSURs specified in the ICH E2C guidance, including clarification of the following topics:
    - When separate PSURs will be considered appropriate,
    - Synchronization of National Birthdates with the International Birthdates,
    - Reporting frequency and time for submission changes, and
    - Use of the reference safety information.

In addition, this guidance includes information on the following topics not previously addressed in the ICH E2C guidance.
    - Summary bridging reports and addendum reports,
    - Executive summaries, and
    - Information on risk management programs and risk-benefit analyses.

The document should be used in conjunction with the ICH E2C guidance.

This guidance represents the agency's current thinking on this topic.  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, at any time, submit to the Division of Dockets Management (see                     **ADDRESSES**                    ) written comments on the guidance.  Two copies of any comments are to be submitted, except that individuals may submit one copy.  Comments are to be identified with the docket number found in brackets in the heading of this document.  The guidance and received comments may be seen in the Division of Dockets Management between 9 a.m. and 4 p.m., Monday through Friday.                

## III.  Electronic Access

                    Persons with access to the Internet may obtain the document at                     *http://www.fda.gov/​ohrms/​dockets/​default.htm*,                     *http://www.fda.gov/​cder/​guidance/​index.htm*, or                     *http://www.fda.gov/​cber/​publications.htm*.                

Dated: January 23, 2004.

Jeffrey Shuren,

Assistant Commissioner for Policy.

[FR Doc. 04-2314 Filed 2-4-04; 8:45 am]

BILLING CODE 4160-01-S