Genotoxic and Carcinogenic Impurities in Drug Substances and Products Recommended Approaches.pdf

Guidance for Industry Genotoxic and Carcinogenic Impurities in Drug Substances and Products: Recommended Approaches DRAFT GUIDANCE This guidance document is being distributed for comment purposes only. Comments and suggestions regarding this draft document should be submitted within 60 days of publication in the Federal Register of the notice announcing the availability of the draft guidance. Submit 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 listed in the notice of availability that publishes in the Federal Register. For questions regarding this draft document contact David Jacobson-Kram at 301-796-0175. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) December 2008 Pharmacology and Toxicology I:\7834dft.doc 12/03/08 Guidance for Industry Genotoxic and Carcinogenic Impurities in Drug Substances and Products: Recommended Approaches Additional copies are available from: Office of Communications 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 E-mail: druginfo@ Fax: 301-847-8714 (Tel) 301-796-3400 /cder/guidance/index.htm U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) December 2008 Pharmacology and Toxicology TABLE OF CONTENTS I. INTRODUCTION 1 II. BACKGROUND 2 A. ICH Guidances for Industry Relating to Drug Impurities and Residual Solvents 3 B. EMEA Proposed Guideline on Limits of Genotoxic Impurities 4 III. RECOMMENDED APPROACHES FOR INITIAL ASSESSMENT OF GENOTOXIC POTENTIAL OF IMPURITIES 6 IV. RECOMMENDED AP