title: Overview of genotoxic impurities in pharmaceutical development.
abstract: This symposium focuses on the management of genotoxic impurities in the synthesis of pharmaceuticals. Recent developments in both Europe and United States require sponsors of new drug applications to develop processes to control the risks of potential genotoxic impurities. Genotoxic impurities represent a special case relative to the International Conference on Harmonisation Q3A/Q3B guidances, because genotoxicity tests used to qualify the drug substance may not be sufficient to demonstrate safety of a potentially genotoxic impurity. The default risk management approach for a genotoxic impurity is the threshold of toxicological concern unless a more specific risk characterization is appropriate. The symposium includes descriptions of industry examples where impurities are introduced and managed in the synthesis of a pharmaceutical. It includes recent regulatory developments such as the "staged threshold of toxicological concern" when administration is of short duration (eg, during clinical trials).
authors: Eli Lilly and Company, Lilly Research Laboratories, Health Safety and Environmental, Indianapolis, IN 46285, USA. jpbercu@lilly.com
authors: Joel P
authors: JP
authors: Bercu
authors: Krista L
authors: KL
authors: Dobo
authors: Elmar
authors: E
authors: Gocke
authors: Timothy J
authors: TJ
authors: McGovern
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D002626:Chemistry, Pharmaceutical; D004247:DNA / Q000187:drug effects / Q000235:genetics; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004340:Drug Contamination; D055808:Drug Discovery; D005020:Ethyl Methanesulfonate / Q000633:toxicity; D005062:European Union; D006801:Humans; D007880:Legislation, Drug; D009153:Mutagens / Q000633:toxicity*; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000138:chemical synthesis* / Q000737:chemistry; D018570:Risk Assessment; D014481:United States
chemical_list: D002273:Carcinogens; D009153:Mutagens; D004364:Pharmaceutical Preparations; D004247:DNA; D005020:Ethyl Methanesulfonate