The stabilization of biopharmaceuticals: current understanding and future perspectives

Proteins have many therapeutic advantages over small synthetic drugs in terms of their high specificity and activity. Accordingly, the global biopharmaceutical market grows rapidly and has driven the continuous increase of R&D investment in protein-based drug products, thus the number of approved protein drugs also continuously increases. However, during their manufacture, transport, and storage, proteins are often exposed to various detrimental environments that can cause protein destabilization, resulting in undesirable drug properties such as partial or complete loss of biological activity, altered solubility, and immunogenicity. Therefore, the thorough evaluation/monitoring and optimization of process variables and product formulations are critical to ensure product quality during its appropriate shelf-life. However, because of (i) the complexity of protein structures, (ii) multiple degradation pathways, and (iii) various intrinsic and extrinsic factors that can affect the stability, protein stabilization is not straightforward and remains a big challenge in the clinical development and commercialization of protein-based drug products, although significant progress has been made. Considering that a better understanding of the various instability mechanisms and factors is important for the quality control of protein drug products and their successful clinical usage, this review briefly overviews protein destabilization pathways and deals with general issues such as controlling the factors of protein stabilization, especially during manufacturing, shipping and storage.