高通量工艺开发在生物制药下游工艺中的应用  

Application of high throughput process development platform in biopharmaceutical downstream process

作　　者：周大卫 李学宁 季宇 沈黾 陆利强 汪艳文 ZHOU Da-wei;LI Xue-ning;JI Yu(BIO Downstream Purification Process Development Department,BeiGene(Suzhou)Co.,Ltd.,Suzhou 215123,China)

机构地区：[1]百济神州(苏州)生物科技有限公司生物制药下游纯化工艺开发部,215123

出　　处：《中国实用医药》2023年第14期172-180,共9页China Practical Medicine

摘　　要：随着生物医药的快速发展,生物医药进入临床前的工艺开发和生产是候选药物进入临床开发的“关键路径”。众所周知在生物制药下游工艺开发过程中,早期的层析工艺开发是非常复杂和具有挑战性的,由于工艺开发和特性描述需要大量的资源,但项目前期澄清料液有限,无法完成大量的实验以确定操作参数,即使传统的缩小规模实验在项目推进和物料方面仍然是个巨大的挑战。现在一种以自动化操作的高通量工艺开发(HTPD)方法开始被运用于下游工艺开发中,这种方法不仅平行评估大量实验参数,还能全面且系统化的完成工艺设计及优化,同时HTPD方法也可用在后期申报的缩小模型验证及工艺表征中,可大大缩短药物进入临床及商业化的时间。本文主要介绍HTPD在下游工艺开发中常见的微型色谱柱及应用,并以Tecan高通量液体工作站为例介绍了HTPD开发应用及其放大案例。With the rapid development of biomedicine,the process development and production of biomedicine before entering clinical development is the"key path"for candidate drugs.It is well known in the downstream of biopharmaceutical technology process that chromatography development is very complex and challenging.The technology development and characterization need lots of resources,while material is limited at the early stage.Not enough representative material to determine the operating parameters,even the traditional scale down experiment approach faces a huge challenge.Thus,a high throughput process development(HTPD)platform is developed and applied in downstream process development with automatically operation.This platform can not only evaluate a large number of experimental parameters in parallel,but also complete process design and optimization comprehensively and systematically.HTPD can also be used in the application of small-scale model validation and process characterization,which greatly shortens the time for drugs to enter the clinical and commercial.This paper introduces the common micro columns and applications of HTPD in downstream process development,and introduces the HTPD development application and its scale-up case with Tecan high throughput liquid workstation as an example.

关 键 词：高通量工艺开发 预填充96孔过滤板 高通量微型色谱柱 高通量工艺开发层析工艺 

分 类 号：TQ460.6[化学工程—制药化工]