Proteins, which are the active ingredients of biopharmaceuticals, have large molecular weights and complex structures compared to chemical substances. Various physical and chemical changes of proteins occur in the process of manufacturing, storage, transportations and medical practice, which may lead to decrease of biological activity and aggregate formation, ultimately affecting the efficacy and safety of the products. Stability data are essential information for determining key elements of control strategies, such as molecular design, formulation design, primary packaging, and manufacturing processes, and are the basis for establishing product shelf-life. Developing next-generation antibodies with high medical importance and revolutionary properties tends to be required to shorten the development period. Thus, it is necessary to accumulate data on stability as early as possible in the development stage, and to understand possible physical and chemical changes quantitatively and qualitatively. However, the accumulation of stability data requires mush resources and time. Particularly it takes years to acquire stability data for setting the shelf-life, which is one of obstacles to rapid development. Therefore, it is highly expected that new technologies will be developed and utilized, such as methods for predicting stability of proteins using statistical analysis and predicting models from existing data and/or data obtained in a short period of time during accelerated tests. In this paper, we review the background, current situation, and general issues regarding stability evaluation of biopharmaceuticals, and discuss future issues.
