ABSTRACT
Won’t Happen to Us” ........................................................................224 10.1.3 Potential Risk for Everyone: The Cost of Failure .............................225
10.2 Developability and Quality by Design (QbD) ..............................................226 10.2.1 Developability: Another Word for Quality ......................................226 10.2.2 Developability: A Three-Stage Process to Implementing a
Holistic QbD .....................................................................................228 10.2.3 Developability Toolkit: Different Methodologies for Early
De-Risking ........................................................................................230 10.2.3.1 Computational Methodologies ...........................................230 10.2.3.2 Surrogate/Proxy Analytical Methodologies ...................... 231
10.3 Manufacturability of Biological Drugs: Aggregation, Chemical Stability, and Productivity ............................................................................ 232 10.3.1 Physical Stability and Aggregation: Computational Approaches..... 233 10.3.2 Chemical Instability and Post-Translational Modications.............. 235 10.3.3 Productivity and Yield ...................................................................... 238 10.3.4 Importance of Formulation: Formulability Assessment ................... 239
10.4 Safety in Biopharmaceuticals: Immunogenicity and Immunotoxicology .... 241 10.4.1 Need for Preclinical Immunogenicity Assessment .......................... 241 10.4.2 Alternatives to Animal Tests for Preclinical Immunogenicity ......... 243 10.4.3 In Silico Prediction of Immunogenicity ........................................... 243 10.4.4 In Vitro and Ex Vivo Cell-Based Assays ..........................................245
