Examining the implications and practical implementation of multi-disciplinary International Conference on Harmonization (ICH) topics, this book gives an integrated view of how the guidelines inform drug development strategic planning and decision-making, together with impact on marketed products.

List of Contributors ix An Introduction to ICH Quality Guidelines: Opportunities and Challenges 1 1 ICHQ1A(R2) Stability Testing of New Drug Substance and Product and ICHQ1C Stability Testing of New Dosage Forms 3 Andy Rignall 2 Stability Testing: Photostability Testing of New Drug Substances and Products ICH Q1B 45 David Clapham 3 ICH Q1D: Bracketing and Matrixing Designs for Stability Testing of New Drug Substances and Products 73 Raymond Peter Munden 4 ICH Q1E Evaluation for Stability Data 89 Garry Scrivens 5 Q2(R1) Validation of Analytical Procedures: Text and Methodology 127 Phillip Borman and David Elder 6 Impurities in New Drug Substances and New Drug Products: ICH Q3A/B: Key Guidelines in the General Impurity Management Process 167 Andrew Teasdale, David Elder, James Harvey, and Steven Spanhaak 7 ICH Q3C Impurities: Guideline for Residual Solvents 199 John Connelly 8 ICH Q3D Elemental Impurities 233 Andrew Teasdale and Sarah Thompson 9 ICH Q4: Pharmacopeial Harmonization and Evaluation and Recommendation of Pharmacopeial Texts for Use in the ICH Regions 281 David Elder 10 ICH Q5A: Viral Safety of Biotechnology Products 311 Daniel Galbraith 11 ICH Q5B Analysis of the Expression Construct in Cell Lines Used for Production of Recombinant DNA‐Derived Protein Products 337 Jianxin Ye, Zhong Liu, and David Pollard 12 ICH Q5C Stability Testing of Biotechnological/Biological Products 345 John G. Davies, Di Gao, Yoen Joo Kim, Richard Harris, Patricia W. Cash, Timothy L. Schofield, Roujian Zhang, and Qiang Qin 13 Q5D Derivation and Characterization of Cell Substrates Used for Production ofBiotechnological/Biological Products 375 Mark Plavsic 14 Conduct of Risk Assessments: An Integral Part of Compliance with ICH Q5A and ICH Q5D 395 Raymond W. Nims 15 ICH Q5E Comparability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing Processes: Summary and Analysis of ICH Q5E Guideline 409 Ramani R. Raghavan and Robert McCombie 16 ICH Q6A Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances 433 David Elder 17 ICH Q6B Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products 467 Scott R. Rudge and Raymond W. Nims 18 Process‐Related Impurities in Biopharmaceuticals: A Deeper Dive into Ich Q6b 487 Anil Raghani, Kim Li, Jeanine L. Bussiere, Joel P. Bercu, and Jinshu Qiu 19 ICH Q7 Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients (APIs) 509 Gordon Munro 20 Q8(R2): Pharmaceutical Development 535 Per Holm, Morten Allesø, Mette C. Bryder, and René Holm 21 ICH Q9 Quality Risk Management 579 David Elder and Andrew Teasdale 22 ICH Q10 Quality Systems: ICH Q10 Implementation at Genentech/Roche 611 Larry Wigman and Danny Ooi 23 ICH Q11: Development and Manufacture of Drug Substance 639 Ronald Ogilvie 24 ICH M7: Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk 667 Andrew Teasdale Index 701 

In 1989, global regulatory authorities in the United States, Europe, and Japan – together with pharmaceutical trade associations from the same regions – established an International Conference on Harmonization (ICH) to standardize the quality and safety requirements for drug product registration. Through the ICH process, more than fifty guidelines have been produced covering quality, non-clinical safety, clinical efficacy and safety, and multi-disciplinary topics. While the guidelines provide a clear framework in terms of requirements, there remains the necessity to interpret how compliance can be achieved practically. Interpreting and implementing the ICH quality guidelines from a practical point of view is thus a challenge facing the entire pharmaceutical industry. Motivated by the pressing need for a consistent and integrated view of how the guidelines inform drug development strategic planning and decision-making, ICH Quality Guidelines: An Implementation Guide focuses on the quality guidelines and requirements along with their implications and practical implementation. Featuring chapters by authors who were involved in the development of the guidelines and subject matter experts, the book offers a succinct and definitive text with practical case study examples. Topics include stability testing, analytical method validation, impurities, biotechnology drugs and products, and good manufacturing practice (GMP). The book provides a primary reference point for practitioners addressing the dual challenge of interpretation and practical implementation of the guidelines, giving not only a definitive narrative, but also actual solutions to effectively manage the associated identified issues. Encompassing both R&D and marketing environments, ICH Quality Guidelines details the appropriate application during the phases of drug development – a truly global issue and thus valuable to anyone involved in the pharma industry throughout the world.