Mutagenic Impurities (eBook, ePUB)

Strategies for Identification and Control
Redaktion: Teasdale, Andrew

• Format: ePub

Produktbeschreibung

Learn to implement effective control measures for mutagenic impurities in pharmaceutical development In Mutagenic Impurities: Strategies for Identification and Control, distinguished chemist Andrew Teasdale delivers a thorough examination of mutagenic impurities and their impact on the pharmaceutical industry. The book incorporates the adoption of the ICH M7 guideline and focuses on mutagenic impurities from both a toxicological and analytical perspective. The editor has created a primary reference for any professional or student studying or working with mutagenic impurities and offers readers a definitive narrative of applicable guidelines and practical, tested solutions. It demonstrates the development of effective control measures, including chapters on the purge tool for risk assessment. The book incorporates a discussion of N-Nitrosamines which was arguably the largest mutagenic impurity issue ever faced by the pharmaceutical industry, resulting in the recall of Zantac and similar drugs resulting from N-Nitrosamine contamination. Readers will also benefit from the inclusion of: * A thorough introduction to the development of regulatory guidelines for mutagenic and genotoxic impurities, including a historical perspective on the development of the EMEA guidelines and the ICH M7 guideline * An exploration of in silico assessment of mutagenicity, including use of structure activity relationship evaluation as a tool in the evaluation of the genotoxic potential of impurities * A discussion of a toxicological perspective on mutagenic impurities, including the assessment of mutagenicity and examining the mutagenic and carcinogenic potential of common synthetic reagents Perfect for chemists, analysts, and regulatory professionals, Mutagenic Impurities: Strategies for Identification and Control will also earn a place in the libraries of toxicologists and clinical safety scientists seeking a one-stop reference on the subject of mutagenic impurity identification and control.

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Produktdetails

• Verlag: John Wiley & Sons
• Seitenzahl: 544
• Erscheinungstermin: 1. Februar 2022
• Englisch
• ISBN-13: 9781119551256
• Artikelnr.: 63397976

Autorenporträt

Andrew Teasdale, PhD, is a senior principal scientist with AstraZeneca and a member of ICH Q3C, Q3D, Q3E Expert working groups as well as an industry advisor to ICH M7. He received his doctorate in organic chemistry from Durham University. He is the inventor of the purge factor concept applied to risk assessment of mutagenic impurities and has authored over 30 papers on that subject.

Inhaltsangabe

List of Contributors xix

Preface xxi

Section 1 The Development of Regulatory Guidelines for Mutagenic/Genotoxic Impurities - Overall Process 1

1 Historical Perspective on the Development of the EMEA Guideline and Subsequent ICH M7 Guideline 3
Andrew Teasdale

1.1 Introduction 3

1.1.1 CPMP - Position Paper on the Limits of Genotoxic Impurities -2002 4

1.1.1.1 Scope/Introduction 4

1.1.1.2 Toxicological Background 4

1.1.1.3 Pharmaceutical (Quality) Assessment 4

1.1.1.4 Toxicological Assessment 4

1.1.2 Guideline on the Limits of Genotoxic Impurities - Draft June 2004 5

1.1.3 PhRMA (Mueller) White Paper 6

1.1.4 Finalized EMA Guideline on the Limits of Genotoxic Impurities - June 2006 8

1.1.4.1 Issues Associated with Implementation 9

1.1.4.2 Control Expectations for Excipients 11

1.1.4.3 Control Expectations for Natural/Herbal Products 12

1.1.4.4 Identification of Potential Impurities 12

1.1.4.5 The Principle of Avoidance 12

1.1.4.6 The ALARP Principle 14

1.1.4.7 Overall 14

1.1.5 SWP Q&A Document 14

1.1.5.1 The Application of the Guideline in the Investigational Phase and Acceptable Limits for GIs Where Applied to Studies of Limited Duration 14

1.1.5.2 Application of the Guideline to Existing Products 15

1.1.5.3 Avoidance and ALARP 17

1.1.5.4 ICH Identification Threshold and its Relation to MI Assessment 17

1.1.6 FDA Draft Guideline 17

1.1.7 Other Relevant Guidance 17

1.1.7.1 Excipients 18

1.1.8 Herbals 18

1.1.9 ICH S9 18

1.1.10 Conclusions 19

References 19

2 ICH M7 - Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk 21
Andrew Teasdale and Raphael Nudelman

2.1 Introduction 21

2.2 ICH M7 22

2.2.1 Introduction 22

2.2.2 Scope 22

2.2.2.1 Established Products 22

2.2.2.2 Anticancer Treatments 23

2.2.2.3 Nature of Therapeutic Agent/Excipients 23

2.2.3 General Principles 24

2.2.4 Considerations for Marketed Products 25

2.2.4.1 Post-approval Changes to Drug Substance, Chemistry, and Manufacturing Controls 26

2.2.4.2 Post-approval Changes to Drug Product Chemistry, Manufacturing, and Controls 26

2.2.4.3 Changes to the Clinical Use of Drug Products 26

2.2.5 Other Considerations for Marketed Products 27

2.2.6 Drug Substance and Drug Product Impurity Assessment 27

2.2.6.1 Synthetic Impurities 28

2.2.6.2 Degradation Products 28

2.2.7 Hazard Assessment 29

2.2.8 Risk Characterization 32

2.2.8.1 Acceptable Intakes Based on Compound-specific Risk Assessments 32

2.2.8.2 Acceptable Intakes for Class 2 and Class 3 Compounds 33

2.2.8.3 Multiple Impurities 34

2.2.8.4 Exceptions and Flexibility in Approaches 35

2.2.9 Control Strategy 35

2.2.9.1 Considerations for Control Approaches 37

2.2.9.2 Considerations for Periodic Testing 37

2.2.9.3 Control of Degradation Products 38

2.2.10 Lifecycle Management 38

2.2.11 Documentation 38

2.2.11.1 Clinical Trail Applications 38

2.2.11.2 Common Technical Document (Marketing Application) 39

2.2.12 Other Aspects 39

2.2.12.1 Relationship Between ICH M7 and ICH Q3A 39

2.3 Conclusions 40

2.4 Commentary on ICH M7 Questions and Answers 40

2.4.1 Section 1 - Introduction 41

2.4.1.1 Questio