Instability of drug does not impact only the potency, purity and safety of the protein formulation, but can also lead to formation of toxic impurities. Stability of the protein formulations is the critical quantity, playing an essential role as performance attributes, that needs to be evaluated during formulation development, shipping, handling, and marketing. Thus, stability assessment of proteins since early phase of product development throughout the post-marketing is significant in providing the quality and safety evidence. Similar to the small molecules, instability of macromolecules can be separated into two common types: chemical and physical instability. Chemical stability relates to the processes of forming or breaking the covalent bonds, which create new compounds. Various chemical degradation processes are such as deamidation, hydrolysis, oxidation, proteolysis, racemization, beta-elimination, disulfide exchange, and DKP formation. While physical instability means the process that changes physical state of the protein but the chemical composition does not. This article will focus on only physical instability pathways including four major processes: denaturation, aggregation, precipitation, and adsorption.

protein, aggregates, denaturation, precipitation, surface-induced interface