Description
Book SynopsisThis book provides a primary reference point for anyone addressing the issue of genotoxic impurities, providing not only a definitive narrative of regulatory guidelines but also practical solutions to effectively manage the issue. Specific sections examine this from both a toxicological and analytical perspective.
Trade Review“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)
Table of ContentsForeword ix
Preface xi
Contributors xiii
Part 1 Development of Genotoxic Impurities Guidelines and the Threshold of Toxicological Concern Concept
Chapter 1 Historical Overview of the Development of Genotoxic Impurities Guidelines and TheirImpact 3
Ron Ogilvie and Andrew Teasdale
Chapter 2 Development of the Threshold of Toxicological Concern Concept and Its Relationship toDuration of Exposure 27
Alessandro Brigo and Lutz Müller
Part 2 Evaluation of Genotoxic Risk from a Preclinical Perspective
Chapter 3 Genetic Toxicity Testing to Qualify Alerting Impurities 67
Mike O’Donovan
Chapter 4 Use of Structure Activity Relationship (SAR) Evaluation as a Critical Tool in the Evaluation ofthe Genotoxic Potential of Impurities 97
Susanne Glowienke and Catrin Hasselgren
Chapter 5 Compound-specific Risk Assessments for Genotoxic Impurities: Examples and Issues 121
Andrew Teasdale and Charles Humfrey
Chapter 6 Human Genotoxic Metabolites: Identification and Risk Management 151
Krista Dobo, Don Walker, and Andrew Teasdale
Part 3 Perspective on Risk Posed by Genotoxic Impurities
Chapter 7 Genotoxic Thresholds 171
Gareth J.S. Jenkins, George E. Johnson, James M. Parry, and Shareen H. Doak
Chapter 8 Genotoxic Impurities: A Risk in Perspective 193
Dave Elder and Jim Harvey
Part 4 Assessment of Genotoxic Risk: Quality Perspective
Chapter 9 Strategies for the Evaluation of Genotoxic Impurity Risk 221
Andrew Teasdale, Dave Elder, and Simon Fenner
Chapter 10 Analysis of Genotoxic Impurities: Review of Approaches 249
Dave Elder
Chapter 11 Development of a Strategy for Analysis of Genotoxic Impurities 281
Andrew Baker
Chapter 12 Strategic Approaches to the Chromatographic Analysis of Genotoxic Impurities 305
Frank David, Karine Jacq, Gerd Vanhoenacker, and Pat Sandra
Chapter 13 Analysis of Genotoxic Impurities by Nuclear Magnetic Resonance Spectroscopy 351
Andrew Phillips
Chapter 14 Mechanism and Processing Parameters Affecting the Formation of Sulfonate Esters:Summary of the Product Quality Research Institute Studies 385
Andrew Teasdale
Chapter 15 Aspects to Consider When Low-level Active Pharmaceutical Ingredient/Drug ProductDegradants Have the Potential for Genotoxicity 409
Alan P. McKeown and Andrew Teasdale
Index 423
