Biophysical Methods for Biotherapeutics

TAPAN K. DAS is the Director of the Mass Spectrometry and Biophysics Center of Excellence in the Analytical Development and Testing group at Bristol-Myers Squibb. He is responsible for biophysical and analytical development for biotherapeutics structure-function characterization, analytical comparability, protein particulate analysis, and support for commercial biotherapeutics products. Dr. Das is also the Chair of the Biotechnology Section of Ameri an Association of Pharmaceutical Scientists.

• Preface viiAbout the Editor ixContributors xiSection 1 Early Discovery Stages and Biotherapeutic Candidate Selection1 Biophysical Methods Applied in Early Discovery of a Biotherapeutic: Case Study of an EGFR-IGF1R Bispecific Adnectin 3Michael 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 25Glen Spraggon3 Solubility and Early Assessment of Stability for Protein Therapeutics 65Sheng-Jiun Wu, Gary L. Gilliland, and Yiqing FengSection 2 First-in-Human and up to Proof-of-Concept Clinical Trials4 Biophysical and Structural Characterization Needed Prior to Proof of Concept 95Angela W. Blake-Haskins, Yen-Huei Lin, Zhuchun Wu, Melissa D. Perkins, and Thomas M. Spitznagel5 Nucleation, Aggregation, and Conformational Distortion 125Christopher J. Roberts6 Utilization of Chemical Labeling and Mass Spectrometry for the Biophysical Characterization of Biopharmaceuticals 151Justin B. Sperry and Lisa M. Jones7 Application of Biophysical and High-Throughput Methods in the Preformulation of Therapeutic Proteins—Facts and Fictions 173Ahmad M. Abdul-Fattah and Hanns-Christian Mahler8 Bioanalytical Methods and Immunogenicity Assays 207Bonita Rup, Corinna Krinos-Fiorotti, Boris Gorovits, and Hendrik Neubert9 Structures and Dynamics of Proteins Probed by UV Resonance Raman Spectroscopy 243Brian S. Leigh, Diana E. Schlamadinger, and Judy E. Kim10 Freezing- and Drying-Induced Micro- and Nano-Heterogeneity in Biological Solutions 269Alptekin Aksan, Vishard Ragoonanan, and Carol HirschmuglSection 3 Phase III and Commercial Development11 Late-Stage Product Characterization: Applications in Formulation, Process, and Manufacturing Development 287Christine P. Chan and Li Shi12 Biophysical Analyses Suitable for Chemistry, Manufacturing, and Control Sections of the Biologic License Application (BLA) 317Zahra Shahrokh, Nazila Salamat-Miller, and John J. ThomasIndex 355