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.

バイオ医薬品の製造には，動物細胞や微生物に目的遺伝子を導入して樹立された細胞基材が用いられる。細胞基材の特性は，産生物である製品の品質及び安全性に影響することから，適切な細胞基材を樹立して製造に用いることが，最終製品の品質を確保する上で極めて重要である。細胞基材については，ICH Q5B及びQ5Dガイドラインにおいて，遺伝子発現構成体の解析やセルバンクの調製と特性解析等に関して基本的な指針が示されているが，両ガイドラインが作成されてから20年以上が経過し，その間にも様々な技術革新や知見の蓄積があった。本稿では，次世代抗体医薬品等のバイオ医薬品の開発・製造の効率化に貢献することを目的に，バイオ医薬品製造に用いられる細胞基材に関して，細胞基材の樹立・特性解析・管理に関する既存のICHガイドラインの概略を説明すると共に，これまでの海外での議論やAMED研究班での検討に基づき，細胞基材のクローナリティ及び産生物のシークエンスバリアントの評価方法及び管理の考え方を紹介した。