Protein aggregation, particle formation, characterization & rheology

In this review, we attempt to give a concise overview of recent progress made in mechanistic understanding of protein aggregation, particulate formation and protein solution rheology. Recent advances in analytical techniques and methods for characterizing protein aggregation and the formed protein particles as well as advancements, technique limitations and controversies in the field of protein solution rheology are discussed. The focus of the review is primarily on biotherapeutics and proteins/antibodies that are relevant to that area. As per the remit of Current Opinion in Colloid and Interface Science, here we attempt to stimulate interest in areas of debate. While the field is certainly not mature enough that all problems may be considered resolved and accepted by consensus, we wish to highlight some areas of controversy and debate that need further attention from the scientific community. Aggregation increases the low shear rate viscosity for this particular mAb solution during incubation at 40°C over 41days. Adapted from Castellanos et al. (ref. 84). [Display omitted] •Advances in characterization techniques for protein particle sizing are reviewed.•Advances in scattering techniques for elucidating aggregation mechanism are reviewed.•Multiple aggregation mechanisms exist, resulting in different aggregate properties.•Aggregate properties influence which technique(s) are best for characterization.•The effects of aggregation and sub-visible particle formation on antibody solution rheology are discussed.