Sharma Basant
Pharmaceutical Technology, Global Biologics Supply Chain LLC, HTD 6-2, Horsham, PA 19044, USA.
Biotechnol Adv. 2007 May-Jun;25(3):325-31. doi: 10.1016/j.biotechadv.2007.01.007. Epub 2007 Jan 30.
Immunogenicity of biopharmaceuticals relates to the intrinsic complexity of proteins as well as the complexities of the manufacturing process. The manufacture of biopharmaceuticals involves a number of complex processing steps designed to create a highly pure, stable, safe, and effective product. The process often lasts many months and can be divided into seven stages - host cell development, master cell bank establishment, protein production, purification, analysis, formulation, and storage and handling. Even minor variations at any of these stages can lead to clinically relevant changes in efficacy and/or safety of the end product. Due to the complexity of the process and the inherently unstable nature of proteins outside the body, compositional changes can occur, leading to decreased biological activity, alteration of molecular structure, and possible increased risk of host immune responses following administration. Examples are discussed whereby immunogenicity associated with some of these changes has occurred with potentially serious clinical consequences.
生物制药的免疫原性与蛋白质的内在复杂性以及生产过程的复杂性有关。生物制药的生产涉及许多复杂的加工步骤，旨在生产出高度纯净、稳定、安全且有效的产品。该过程通常持续数月，可分为七个阶段——宿主细胞开发、主细胞库建立、蛋白质生产、纯化、分析、制剂以及储存和处理。这些阶段中任何一个阶段的微小变化都可能导致最终产品的疗效和/或安全性出现临床相关变化。由于该过程的复杂性以及蛋白质在体外固有的不稳定性质，可能会发生成分变化，导致生物活性降低、分子结构改变，并可能增加给药后宿主免疫反应的风险。文中讨论了一些与这些变化相关的免疫原性导致潜在严重临床后果的例子。
