Université Clermont Auvergne, CHU Clermont Ferrand, CNRS, Sigma Clermont, ICCF, F-63000 Clermont-Ferrand, France.
Université Clermont Auvergne, CHU Clermont Ferrand, CNRS, Sigma Clermont, ICCF, F-63000 Clermont-Ferrand, France.
J Pharm Sci. 2020 Jan;109(1):169-190. doi: 10.1016/j.xphs.2019.08.009. Epub 2019 Aug 26.
Monoclonal antibodies (mAbs) are subject to instability issues linked to their protein nature. In this work, we review the different mechanisms that can be linked to monoclonal antibodies instability, the parameters, and conditions affecting their stability (protein structure and concentration, temperature, interfaces, light exposure, excipients and contaminants, and agitation) and the different analytical methods used for appropriate physicochemical stability studies: physical stability assays (aggregation, fragmentation, and primary, secondary, and tertiary structure analysis), chemical stability assays and quantitative assays. Finally, data from different published stability studies of mAbs formulations, either in their reconstituted form, or in diluted ready to administer solutions, was compiled. Overall, the physicochemical stability of mAbs is linked to numerous factors such as formulation, environment, and manipulations, and must be thoroughly investigated using several complementary analytical techniques, each of which allowing specific characterization information to be harvested. Several stability studies have been published, some of them showing possibilities of extended stability. However, those data should be questioned due to potential lacks in study methodology.
单克隆抗体（mAbs）存在与其蛋白质性质相关的不稳定性问题。在这项工作中，我们综述了可能与单克隆抗体不稳定性相关的不同机制、影响其稳定性的参数和条件（蛋白质结构和浓度、温度、界面、光照、赋形剂和污染物以及搅拌），以及用于适当物理化学稳定性研究的不同分析方法：物理稳定性测定（聚集、碎片化以及一级、二级和三级结构分析）、化学稳定性测定和定量测定。最后，编译了不同已发表的 mAbs 制剂稳定性研究的数据，无论是在其重构形式还是在稀释的即用型溶液中。总体而言，mAbs 的物理化学稳定性与制剂、环境和操作等诸多因素有关，必须使用几种互补的分析技术进行彻底研究，每种技术都可以获取特定的特征信息。已经发表了一些稳定性研究，其中一些显示了延长稳定性的可能性。然而，由于研究方法可能存在缺陷，这些数据应受到质疑。
