摘要
近年来,包括治疗类抗体在内的治疗类蛋白产品已成为现代生物制药的主力军。然而,此类产品具有复杂的产品质量属性,在一定程度上限制了产品的研发与质控(quality control,QC)。随着高分辨质谱技术的发展,基于质谱的多属性分析(multi-attribute method,MAM)具有多种产品质量属性的直接检测以及杂质的鉴别能力,其在产品的研发及QC中的重要作用逐渐显现。鉴于MAM有助于促进药品质量及QC水平提升、生产成本降低,为了探索MAM在研发和QC中的应用,本文从MAM的基本流程、在生物制药领域研发与QC中的应用、FDA对MAM在QC中应用的考量以及面临的机遇与挑战进行了介绍。以期为MAM在我国治疗类抗体药物中的应用提供思路,并为其在QC中更好的开发、使用、替代传统方法奠定基础。
In recent years therapeutic proteins products including therapeutic antibodies have become a major driving force for the modern biopharmaceutical industry.However,they have complex product quality attributes(PQAs)which limit product development and quality control(QC).Recent advances in high resolution mass spectrometry(MS)have led to the use of an MS-based multi-attribute method(MAM)for quality control testing of therapeutic proteins,which allows for direct measurement of multiple PQAs and identification of impurities.MAM helps to promote the improvement of product quality and QC and a reduction in manufacturing cost.To explore the application of MAM in QC,we discuss generic MAM workflow,the current state of MAM application in product development and QC,identify points to consider for use of MAM as a QC test,and summarize MAM’s advantages and challenges in this article.The future application of MAM for therapeutic antibodies and the opportunities for its further development,use,and substitution for conventional methods is presented.
作者
汪泓
徐进
尹红锐
徐明明
凌今
郭怀祖
邵泓
陈钢
WANG Hong;XU Jin;YIN Hong-rui;XU Ming-ming;LING Jin;GUO Huai-zu;SHAO Hong;CHEN Gang(Shanghai Institute for Food and Drug Control,NMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies,Shanghai 201203,China;State Key Laboratory of Antibody Medicine and Targeted Therapy,NMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies,Shanghai 201203,China)
出处
《药学学报》
CAS
CSCD
北大核心
2020年第9期2092-2098,共7页
Acta Pharmaceutica Sinica
基金
国家自然科学基金青年科学基金资助项目(81803422)
上海市科委技术标准项目(18DZ2202000)
上海市科委技术标准项目(18DZ2200700)
上海科技创新行动计划(17431905400,17431901800)。
