About the book

This book focuses on the application of biophysical techniques and methods in the development of biotherapeutics. Four areas, all focusing on biotherapeutics development, are emphasized (1) novel applications and new methods of traditional biophysical techniques,(2) novel and emerging technologies and their applications, (3) biophysical applications relevant to stage-wise development of a clinical biotherapeutic candidate, and (4) thermodynamic, conformational, and stabilization concepts aided by biophysical research.

The chapters are laid out in a theme based on clinical phases of development. This allows for a comprehensive view of:

• Which biophysical studies are needed for which stage and for what purpose,
• How and when to apply the techniques,
• What types of characterization regulatory agencies expect, and
• The limitations of each technique and type of application.

Overall, this book helps formulation, analytical, and bioanalytical scientists in pharma and biotech industries better understand and use biophysical methods and assess impact on quality and immunogenicity. It also provides information to help organizations develop short- and long-term strategies for resource investment in biophysical research.

Contents:

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

2 X-Ray Crystallography for Biotherapeutics 25

3 Solubility and Early Assessment of Stability for Protein Therapeutics 65

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

5 Nucleation, Aggregation, and Conformational Distortion 125

6 Utilization of Chemical Labeling and Mass Spectrometry for the Biophysical Characterization of Biopharmaceuticals 151

7 Application of Biophysical and High-Throughput Methods in the Preformulation of Therapeutic Proteins—Facts and Fictions 173

8 Bioanalytical Methods and Immunogenicity Assays 207

9 Structures and Dynamics of Proteins Probed by UV Resonance Raman Spectroscopy 243

10 Freezing- and Drying-Induced Micro- and Nano-Heterogeneity in Biological Solutions 269

Section 3 Phase III and Commercial Development

11 Late-Stage Product Characterization: Applications in Formulation, Process, and Manufacturing Development 287

12 Biophysical Analyses Suitable for Chemistry, Manufacturing, and Control Sections of the Biologic License Application (BLA) 317