Genotoxic Impurities: Strategies for Identification and Control

A one–stop reference to genotoxic impurities in pharmaceuticals
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.

Spis treści:
Foreword.
Preface.
Section I: Development of GI Guidelines and the TTC Concept.
Chapter 1. Historical Overview of the Development of Genotoxic Impurities Guidelines and their Impact (R. Og ilvie and A. Teasdale).
Chapter 2. Development of the Threshold of Toxicological Concern Concept (TTC) and its Relationship to Duration of Exposure (A. Brigo and L. Muller).
Section 2: Evaluation of Genotoxic Risk from a Pre–clinical Perspective.
Chapter 3. Genetic Toxicity Testing to Qualify Alerting Impurities (M. O’Donovan).
Chapter 4. Use of Structure Activity Relationship (SAR) Evaluation as a Critical Tool in the Evaluation of the Genotoxic Potential of Impurities (S. Glowienke and C. Hasselgren).
Chapter 5. Compound–Specific Risk Assessments for Genotoxic Impurities: Examples and Issues (A. Teasdale and C. Humfrey).
Chapter 6. Human Genotoxic Metabolites: Identification and Risk (K. Dobo, D. Walker and A. Teasdale).
  Section 3. Perspective on Risk Posed by Genotoxic Impurities.
Chapter 7. Genotoxic Thresholds (G. Jenkins, G. Johnson, J. Parry and S. Doak).
Chapter 8. Genotoxic Impurities a Risk in Perspective? (D. Elder).
Section 4. Assessment of Genotoxic Risk: Quality Perspective.
Chapter 9. Strategies for the Evaluation of Genotoxic Impurity Risk (A. Teasdale, S. Fenner and D. Elder).
Chapter 10. Analysis of Genotoxic Impurities: Review of Approaches (D. Elder).
Chapter 11. Development of a Strategy for Analysis of Genotoxic Impurities (Andrew Baker).
Chapter 12. Strategic Approaches to the Chromatograpic Analysis of Genotoxic Impurities (Frank David, Karine Jacq, Gerd Canhoenacker and Pat Sandra).
Chapter 13. Analysis of Genotoxic Impurities by Nuclear Resonance (NMR) Spectroscopy (Andrew Philips).
Chapter 14. Mechanism and Processing Parameters Affecting the Formation of Sulfonate Esters: Summary of the PQRI Studies – PQRI Working Group (Andrew Teasdale).
Chapter 15. Aspects to Consider when Devising a Strategy to Understand if Low Level API/DP Degradants have the Potential for Genotoxicity (Alan P. McKeown and Andrew Teasdale). 

Nota bio graficzna:
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.

Okładka tylna:
A one–stop reference to genotoxic impurities in pharmaceuticals
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.