PDF(Pubmed)
Abstract：
Therapeutic mAbs show a specific \"charge fingerprint\" that may affect safety and efficacy, and, as such, it is often identified as a critical quality attribute (CQA). Capillary iso-electric focusing (cIEF), commonly used for the evaluation of such CQA, provides an analytical tool to investigate mAb purity and identity across the product lifecycle. Here, we discuss the results of an analysis of a panel of antibody products by conventional and whole-column imaging cIEF systems performed as part of European Pharmacopoeia activities related to development of \"horizontal standards\" for the quality control of monoclonal antibodies (mAbs). The study aimed at designing and verifying an independent and transversal cIEF procedure for the reliable analysis of mAbs charge variants. Despite the use of comparable experimental conditions, discrepancies in the charge profile and measured isoelectric points emerged between the two cIEF systems. These data suggest that the results are method-dependent rather than absolute, an aspect known to experts in the field and pharmaceutical industry, but not suitably documented in the literature. Critical implications from analytical and regulatory perspectives, are herein thoughtfully discussed, with a special focus on the context of market surveillance and identification of falsified medicines.
摘要：
治疗性单克隆抗体显示特定的“电荷指纹”，可能会影响安全性和有效性，and,因此，它通常被确定为关键质量属性(CQA)。毛细管等电聚焦(cIEF),通常用于评估这样的CQA，提供了一种分析工具来调查整个产品生命周期中的mAb纯度和身份。这里,我们讨论了通过常规和全柱成像cIEF系统分析一组抗体产品的结果,该系统是欧洲药典活动的一部分,与单克隆抗体(mAb)质量控制"水平标准"的开发相关.该研究旨在设计和验证用于可靠分析mAb电荷变体的独立和横向cIEF程序。尽管使用了可比的实验条件，两个cIEF系统之间出现了电荷分布和测量等电点的差异。这些数据表明，结果是方法依赖的，而不是绝对的，该领域和制药行业专家已知的一个方面，但在文献中没有适当的记载。从分析和监管的角度来看，关键的影响，在这里进行了深思熟虑的讨论，特别关注市场监督和伪造药品识别的背景。
