Uchiyama Susumu
Graduate School of Engineering, Osaka University.
Exploratory Research Center on Life and Living Systems, National Institute of Natural Sciences.
Yakugaku Zasshi. 2018;138(12):1503-1507. doi: 10.1248/yakushi.18-00020-4.
Biopharmaceuticals are often formulated as liquid dosage forms. During manufacturing and storage, protein molecules and active pharmaceutical ingredients form aggregates due to various stresses, including shaking and agitation, as well as by contact with silicone oils coated on pre-fillable syringes. The diameter of protein aggregates ranges from 15-20 nm, and that of dimers comprising a large number of antibody molecules can be up to 100 μm. Among these aggregates, those with a diameter of <100 nm are called nanometer aggregates, while those ranging between 100 nm and 1 μm are called sub-micron aggregates, and those ranging between 1 and 100 μm are called micron aggregates. In the last ten years, aggregates have been studied to determine their physical characteristics and their impact on immunogenicity. As a result, novel analytical methods and instruments for such characterizations have been established for a majority of aggregates, including those that are difficult to evaluate. Here, the biophysical features of protein aggregates are explained, followed by an introduction to the different methods for aggregate characterization, including their advantages and actual results. Finally, future perspectives and expectations regarding the characterization of protein aggregates are proposed.
生物制药通常被制成液体制剂。在生产和储存过程中，蛋白质分子和活性药物成分会由于各种应力（包括摇晃和搅拌）以及与预填充注射器上涂覆的硅油接触而形成聚集体。蛋白质聚集体的直径范围为15 - 20纳米，而由大量抗体分子组成的二聚体的直径可达100微米。在这些聚集体中，直径小于100纳米的被称为纳米聚集体，直径在100纳米至1微米之间的被称为亚微米聚集体，直径在1至100微米之间的被称为微米聚集体。在过去十年中，人们对聚集体进行了研究，以确定其物理特性及其对免疫原性的影响。因此，针对大多数聚集体，包括那些难以评估的聚集体，已经建立了用于此类表征的新型分析方法和仪器。在此，解释了蛋白质聚集体的生物物理特征，随后介绍了聚集体表征的不同方法，包括其优点和实际结果。最后，提出了关于蛋白质聚集体表征的未来展望和期望。
