关键质量属性
工作流程
化学
产品(数学)
鉴定(生物学)
数据挖掘
计算机科学
质量(理念)
生化工程
设计质量
数据库
工程类
数学
物理化学
哲学
几何学
认识论
粒径
生物
植物
作者
Zhiqi Hao,Benjamin Moore,Chengfeng Ren,Monica Sadek,Frank Macchi,Lindsay Yang,Jack Harris,Laura M. Yee,Emily Liu,Vanessa Tran,Milady R. Niñonuevo,Yan Chen,Christopher Yu
标识
DOI:10.1016/j.jpba.2021.114330
摘要
Multi-attribute method (MAM) using peptide map analysis with high resolution mass spectrometry is increasingly common in product characterization and the identification of critical quality attributes (CQAs) of biotherapeutic proteins. Capable of providing structural information specific to amino acid residues, quantifying relative abundance of product variants or degradants, and detecting profile changes between product lots, a robust MAM can replace multiple traditional methods that generate profile-based information for product release and stability testing. In an effort to provide informative and efficient analytical monitoring for monoclonal antibody (mAb) products, from early development to manufacturing quality control, we describe the desired MAM performance profile and address the major scientific challenges in MAM method validation. Furthermore, to support fast speed investigational product development, we describe a platform method validation strategy and results of an optimized MAM workflow. This strategy is applied to support the use of MAM for multiple mAb products with similar structures and physicochemical properties, requiring minimal product-specific method validation activities. Three mAb products were used to demonstrate MAM performance for common and representative product quality attributes. Method validation design and acceptance criteria were guided by the Analytical Target Profile concept, as well as relevant regulatory guidelines to ensure the method is fit-for-purpose. A comprehensive system suitability control strategy was developed, and reported here, to ensure adequate performance of the method including sample preparation, instrument operation, and data analysis. Our results demonstrated sufficient method performance for the characteristics required for quantitative measurement of product variants and degradants.
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