Genotoxic Impurities: Strategies for Identification and Control

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. Ogilvie 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).