Case Studies Applying Biophysical Techniques to Better Characterize Protein Aggregates and Particulates of Varying Size

Abstract

During the manufacture, storage, and administration of protein therapeutics, aggregates and particles of varying size can form. The presence of these impurities may directly affect the immunogenicity and efficacy of the protein-based drugs. The detection and characterization of protein aggregates and particles has therefore become increasingly important from a pharmaceutical perspective, especially the use of different analytical technologies to comprehensively characterize the number, size range, morphology, and composition of protein aggregates and particles over a wide size range. This review chapter evaluates recent case studies that have utilized a combination of biophysical techniques to characterize soluble protein aggregates (1–100 nm) as well as submicron-sized (100–1,000 nm), subvisible (1–100 μm), and visible (>100 μm) protein particles. The case studies not only provide interesting comparisons of different biophysical methods but also examine varying effects observed with different protein therapeutics formulated in different dosage forms.