Biophysical Methods for Biotherapeutics

With a focus on practical applications of biophysical techniques, this book links fundamental biophysics to the process of biopharmaceutical development. • Helps formulation and analytical scientists in pharma and biotech better understand and use biophysical methods • Chapters organized according to the sequential nature of the drug development process • Helps formulation, analytical, and bioanalytical scientists in pharma and biotech better understand and usestrengths and limitations of biophysical methods • Explains how to use biophysical methods, the information obtained, and what needs to be presented in a regulatory filing, assess impact on quality and immunogenicity • With a focus on practical applications of biophysical techniques, this book links fundamental biophysics to the process of biopharmaceutical development.

Preface vii About the Editor ix Contributors xi Section 1 Early Discovery Stages and Biotherapeutic Candidate Selection 1 Biophysical Methods Applied in Early Discovery of a Biotherapeutic: Case Study of an EGFR-IGF1R Bispecific Adnectin 3 Michael L. Doyle, James W. Bryson, Virginie Lafont, Zheng Lin, Paul E. Morin, Lumelle A. Schneeweis, Aaron P. Yamniuk, and Joseph Yanchunas Jr. 2 X-Ray Crystallography for Biotherapeutics 25 Glen Spraggon 3 Solubility and Early Assessment of Stability for Protein Therapeutics 65 Sheng-Jiun Wu, Gary L. Gilliland, and Yiqing Feng Section 2 First-in-Human and up to Proof-of-Concept Clinical Trials 4 Biophysical and Structural Characterization Needed Prior to Proof of Concept 95 Angela W. Blake-Haskins, Yen-Huei Lin, Zhuchun Wu, Melissa D. Perkins, and Thomas M. Spitznagel 5 Nucleation, Aggregation, and Conformational Distortion 125 Christopher J. Roberts 6 Utilization of Chemical Labeling and Mass Spectrometry for the Biophysical Characterization of Biopharmaceuticals 151 Justin B. Sperry and Lisa M. Jones 7 Application of Biophysical and High-Throughput Methods in the Preformulation of Therapeutic Proteins—Facts and Fictions 173 Ahmad M. Abdul-Fattah and Hanns-Christian Mahler 8 Bioanalytical Methods and Immunogenicity Assays 207 Bonita Rup, Corinna Krinos-Fiorotti, Boris Gorovits, and Hendrik Neubert 9 Structures and Dynamics of Proteins Probed by UV Resonance Raman Spectroscopy 243 Brian S. Leigh, Diana E. Schlamadinger, and Judy E. Kim 10 Freezing- and Drying-Induced Micro- and Nano-Heterogeneity in Biological Solutions 269 Alptekin Aksan, Vishard Ragoonanan, and Carol Hirschmugl Section 3 Phase III and Commercial Development 11 Late-Stage Product Characterization: Applications in Formulation, Process, and Manufacturing Development 287 Christine P. Chan and Li Shi 12 Biophysical Analyses Suitable for Chemistry, Manufacturing, and Control Sections of the Biologic License Application (BLA) 317 Zahra Shahrokh, Nazila Salamat-Miller, and John J. Thomas Index 355