关键质量属性
稳健性(进化)
计算机科学
化学
色谱法
计算生物学
生物
生物化学
基因
物理化学
粒径
作者
Lan Wang,Gang Wu,Chuanfei Yu,Qinghe Tong,Wenbo Wang,Xi Huang,Hao Li
出处
期刊:Current Pharmaceutical Biotechnology
[Bentham Science]
日期:2023-08-01
卷期号:24 (10): 1315-1325
被引量:2
标识
DOI:10.2174/1389201024666221111160403
摘要
Peptide-Fc fusion proteins are inherently heterogeneous and complex molecules. Protein post-translational modifications (PTMs) or truncation can arise during manufacturing or product storage. Some of these product attributes could potentially impact the efficacy or safety of the bio-molecule and are thus classified as critical quality attributes (CQAs). These CQAs should be controlled in order to ensure manufacturing and quality consistency.A subunit UPLC-ToF MS based MAM method was developed for identity test and quantitatively monitored two critical quality attributes (CQAs) resulting from two truncations of that fusion protein (fragment 1 and 2). Three independent laboratories are involved in the method validation according to ICH Q2(R1), ICH Q6B, FDA and NMPA guidance.This developed method fully meets the pre-defined analytical target profile (ATP), including specificity, accuracy, precision, quantitation limit, linearity, range and robustness. Three independent labs co-validate a UPLC-ToF MS based MAM method for protein drug QC release and stability testing.The experimental design of method validation can be a reference for LC-HRMS-based subunit MAM methods that have been widely used in the characterization of antibodies, ADCs and other protein-based biologics. This work paves the way for implementing MAM in QC with more targeted control of product quality.
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