Genotoxic Impurities: Strategies for Identification and Control

“This book is a valuable resource when dealing with genotoxic impurities. Its publication is timely considering the new ICH M7 guideline under discussion. I highly recommend the book to toxicology and CMC professionals and to anyone with a general interest in genotoxic impurities.” (Drug Information Journal, 1 March 2012)

“This is an unmatched resource for understanding current regulations that guide the development of pharmaceuticals with respect to genotoxic substances, including the foundational principles upon which these guidelines were established. Armed with this knowledge, readers will appreciate the assessment of analytical techniques to control genotoxic impurities to a level that preserves both drug safety and quality throughout the development process.” (Doody’s, 26 August 2011)

“This is a very good book and addresses the issue in a very sensible, dare I say it, pragmatic approach.” (The British Toxicology Society Journal, 1 May 2011)

“Overall, a valuable addition to a pharmaceutical scientists’ library. The topics covered are relevant and of interest to various ‘stake-holders’ in the drug development arena, including chemists, analysts and programme managers. I can recommend it.” (Journal of Organic Process Research & Development, 2011)

“The style throughout is easy to read and content readily digested, especially those chapters [on] chemical process development and early-phase API development … From a more practical point of view, the contents are well set out, and indexing appeared appropriate. … Overall, a valuable addition to a pharmaceutical scientist’s library. The topics covered are relevant and of interest to various ‘stake-holders’ in the drug development arena, including chemists, analysts, and programme managers. I can recommend it.” (American Chemical Society, 2011)

This volume examines the full range of issues the pharmaceutical industry faces when seeking to ensure control over the levels of genotoxic impurities in pharmaceuticals. It offers comprehensive practical guidance on how to both assess and control genotoxic impurities (GIs) through all phases of drug development.

Featuring contributed chapters by experts from both the quality assurance and toxicology fields, Genotoxic Impurities covers all topics from the ground up, using real-world examples and case studies to help readers meet the challenges of regulatory compliance. Other important features include:

• A detailed review of current regulatory guidelines relating to GIs, including discussion of their implications and the thinking behind their development

• A thorough evaluation of the threshold of toxicological concern (TTC) concept, along with an examination of the emerging evidence supporting the existence of thresholds even for DNA-reactive mutagens.

• Step-by-step instructions , including both analytical and safety strategies, on how to evaluate risks posed by GIs

• Discussion of the risks posed by GIs from other sources, i.e., dietary exposure and the endogenous production of genotoxins.

• Specific advice on chromatographic strategy and other key analyticaltechniques, including the innovative use of NMR

The first comprehensive resource of its kind, Genotoxic Impurities is an indispensable reference for researchers and professionals in the pharmaceutical industry. It is also useful for regulatory professionals who need to interpret the regulatory guidelines covering GIs.