Specification of Drug Substances and Products. Development and Validation of Analytical Methods. Edition No. 2

Table of Contents

PART 1�INTRODUCTION 1.�Introduction 2.�General Principles and Regulatory Considerations: Specifications and Shelf Life Setting 3.�General Principles and Regulatory Considerations: Method Development and Validation 4.�Application of Quality by Design (QbD) to the Development and Validation of Analytical Methods 5.�Analytical Methods in the Clinical Phase of Development 6. Method Transfer 7. Process Analytical Technology

PART 2�UNIVERSAL TESTS 8.�Description and Identification 9. Assay and Impurities: Specifications 10.�Assay and Impurities: Method Development and Life-Cycle Management 11.�Assay and Impurities: Method Validation 12.�Mutagenic Impurities 13.�Residual Solvents 14.�Inorganic Impurities (Elemental Impurities)

PART 3�SPECIFIC TESTS: DRUG SUBSTANCES 15.�Solid State Characterization 16.�Chiral Methods 17.�Water Determination

PART 4�SPECIFIC TESTS DRUG PRODUCT 18.�Drug Release: Oral Products 19.�Topical Products 20.�Extractables and Leachables

PART 5�BIOTECHNOLOGY PRODUCTS 21. Regulatory Requirements for Setting Drug Substance and Drug Product Specifications� 22. Validation of Analytical Methods for Biotechnology Products

PART 6�PHARMACOPEIAL METHODS 23.�Pharmacopeial Methods and Test (Updated)

PART 7�BIOLOGICAL FLUIDS 24.�Biological Fluids

Authors

Christopher M. Riley President of Riley and Rabel Consulting Services, Maryville, MO, USA. Dr Riley is President, Riley and Rabel Consulting Services, Inc. He received a bachelor's degree in pharmacy (1977) and PhD degree in Pharmaceutical Chemistry (1980) from the University of Bath, England. He was a post-doctoral fellow at the University of Kansas in the Department of Pharmaceutical Chemistry (1981-1982) before joining the faculty of the Department of Pharmaceutics at the University of Florida. He returned to the University of Kansas as faculty member in 1986 where he remained until 1994. He was Vice President and Head of Analytical R&D at Dupont Pharmaceuticals (previously Dupont Merck) from 1994 to 2001. He joined ALZA 2001, a subsidiary of Johnson & Johnson, where he had positions of increasing responsibility up to Vice President and West Coast Site Head ChemPharm Development. He left ALZA in May 2007 to form Riley and Rabel Consulting Services, Inc., which provides consulting services to the Pharmaceutical and Biotechnology Industries, specializing in Analytical and Pharmaceutical Development, CMC Strategy, Organizational and Managerial Effectiveness and Patent Litigation. He has co-authored more than 140 book chapters and papers in peer-reviewed journals, as well as five books. He was awarded the Conference Science Award of the Royal Pharmaceutical Society of Great Britain and the Jubilee Medal of the Chromatographic Society. He was elected Fellow of the American Association of Pharmaceutical Scientists (AAPS) and served as the chair of the Analysis and Pharmaceutical Quality Section of AAPS and a Member of the AAPS Executive Committee. Dr. Riley has served as member and chair of the PhRMA Analytical Technical Committee (ATC), as well as a member and chair of the PhRMA Technical Leadership Committee (TLC). Dr. Riley represented PhRMA on the ICH Expert Working Group on Impurities in Drug Substances (Q3A) and Drug Products (Q3B) and was Chair of the PhRMA Working Group on Genotoxic Impurities. Thomas W. Rosanske Consultatnt, Lee's Summit, MO, USA. Former Director of Business Development at Acceleration Laboratory Services, Incorporated. He has previously held scientific and senior management positions at The Upjohn Company, Marion Laboratories, Marion Merrell Dow, Hoechst Marion Roussel, Quintiles, Eli Lilly, Beckloff Associates, and PPD. He currently serves on a Small Molecule USP Expert Committee. George L. Reid Principal Consultant, Cardinal Health, Kansas City, MO, USA.