Genotoxic Impurities

Strategies for Identification and Control

Buch | Hardcover

448 Seiten

2011
John Wiley & Sons Inc (Verlag)
978-0-470-49919-1 (ISBN)

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This 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.

This book examines genotoxic impurities and their impact on the pharmaceutical industry. Specific sections examine this from both a toxicological and analytical perspective. Within these sections, the book defines appropriate strategies to both assess and ultimately control genotoxic impurities, thus aiding the reader to develop effective control measures. An opening section covers the development of guidelines and the threshold of toxicological concern (TTC) and is followed by a section on safety aspects, including safety tests in vivo and vitro, and data interpretation. The second section addresses the risk posed by genotoxic impurities from outside sources and from mutagens within DNA. In the final section, the book deals with the quality perspective of genotoxic impurities focused on two critical aspects, the first being the analysis and the second how to practically evaluate the impurities.

ANDREW TEASDALE, PhD, is a senior QA executive with AstraZeneca and chairs the company's internal genotoxic impurities advisory group. With over fifteen years of experience in analytical chemistry and quality assurance, Dr. Teasdale has published a number of papers relating to GIs and has been a speaker on genotoxic impurities at a number of conferences. Dr. Teasdale has also led two expert groups working in the field of genotoxic impurities, including an analytical group in the UK and a Project Quality Research Institute (PQRI) working group, which focused on the critical area of sulfonate ester formation and control.

Foreword 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

Erscheint lt. Verlag	1.3.2011
Verlagsort	New York
Sprache	englisch
Maße	163 x 241 mm
Gewicht	758 g
Themenwelt	Medizin / Pharmazie ► Medizinische Fachgebiete ► Pharmakologie / Pharmakotherapie
	Studium ► 2. Studienabschnitt (Klinik) ► Humangenetik
	Naturwissenschaften ► Chemie
ISBN-10	0-470-49919-2 / 0470499192
ISBN-13	978-0-470-49919-1 / 9780470499191
Zustand	Neuware