1st Edition
Pharmaceutical Industry Practices on Genotoxic Impurities
A great deal of confusion and uncertainty over genotoxic impurity (GTI) identification, assessment, and control exists in the pharmaceutical industry today. Pharmaceutical Industry Practices on Genotoxic Impurities strives to facilitate scientific and systematic consensus on GTI management by presenting rationales, strategies, methods, interpretations, practices, and case studies from the pharmaceutical industry. Featuring the contributions of industry leaders from nine major pharmaceutical companies, this authoritative text:
- Explores the safety, quality, and regulatory aspects of GTIs
- Provides an overview of the latest FDA and EMEA guidelines
- Explains the how and why of various GTI control tactics and practices
- Describes genotoxicity evaluation, acceptable exposure calculation, and analytical methods for testing
- Includes real-life examples of GTI control in drug substance and drug product development processes
Containing case studies from large and small pharmaceutical firms in multiple geographical regions, Pharmaceutical Industry Practices on Genotoxic Impurities supplies an overview of—and a current framework for—GTI control in the pharmaceutical industry, demonstrating how proper management of GTIs can occur with the appropriate guidance, a firm grasp of the practical implications, and effective information sharing between disciplines.
Preface
Editor
List of Contributors
Overview of Regulatory Guidelines on Impurities and Genotoxic Impurities, Heewon Lee and Debie Hoivik
Structural Alerts for Genotoxicity and Carcinogenicity, Heewon Lee
Acceptable Exposure Calculations for Impurities and Selected Compounds from the Carcinogenic Potency Database, Heewon Lee
Genotoxic Impurities from Toxicology Perspectives Including Cancer Risk Assessment, In Silico, In Vitro/In Vivo Testings, and Regulatory Aspects, Esther Vock
In Silico/Computational Assessment for the Evaluation of Genotoxic Impurities, Alexander Amberg, Andreas Czich, and Véronique Thybaud
Preclinical Assessment of Genotoxic Impurities: An Overview of Current Regulatory Guidance, Available Assays, and Data Interpretation, Todd J. Page, Vincent L. Reynolds, and J. Barry Phelps
Purification of Lead Compounds for Early Toxicology Profiling such as Ames and Short-Term Nongood Laboratory Practice Toxicology Tests, Zheng Hua, Wesley W. Barnhart, and Kyung H. Gahm
Analysis of Genotoxic Impurities in Pharmaceuticals by Gas Chromatography–Mass Spectrometry, Jie Zheng and Adam P. Schellinger
Control of Chloroethane in Raw Materials and Drug Substances Using Headspace/Gas Chromatography Analysis, Johanna Ubben and Bing-Shiou Yang
Quantification of Genotoxic Impurities in Active Pharmaceutical Ingredients, Roy Helmy, Sophie Strickfuss, Mohammad Al-Sayah, Simon Hamilton, Xiaodong Bu, Claire Lee, Tiebang Wang, and Christopher Welch
Analytical Testing and Control for Genotoxic Impurities in Drug Substances, Jane Li and Larry Wigman
Approaches to Assess, Analyze, and Control Genotoxic Impurities in Drug Substance Development, Heewon Lee
Control and Analysis of Genotoxic Impurities in Drug Substance Development, Zhi Chen, Jianbing Zhang, Shan Xiao, Qin Ji, and Frances Liu
Salt Formation of Pharmaceutical Compounds and Associated Genotoxic Risks, Soojin Kim
Identification and Control of Genotoxic Degradation Products, Fenghe Qiu
Identification and Qualification of Genotoxic Impurities as Leachables in Drug Products, Douglas J. Ball, William P. Beierschmitt, Krista L. Dobo, and Cynthia J. Magee
Pharmaceutical Industry Survey on Genotoxic Impurities and Related Topics, William A. Yakush and Heewon Lee
Index
Biography
Heewon Lee is Senior Associate Director of the Chemical Development Department at Boehringer-Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA. She is also leader of the Analytical Research Group, an active participant in the Genotoxic Impurity Council, and a member of the Pharmaceutical IQ Consortium Working Group. She holds a BS and a MS from Seoul National University, South Korea, as well as a Ph.D from the University of Michigan, Ann Arbor, USA. Previously, she worked at ArQule, a biotechnology company located in Woburn, Massachusetts, USA. After ArQule, she joined the Medicinal Chemistry Department at Boehringer-Ingelheim before moving to her current position.