生物制药
生物过程
过程分析技术
设计质量
计算机科学
关键质量属性
工艺工程
采样(信号处理)
工艺验证
过程(计算)
下游(制造业)
生化工程
工程类
生物技术
操作系统
运营管理
滤波器(信号处理)
生物
化学工程
计算机视觉
作者
Yang Liu,Chi Zhang,Jiangchao Chen,Janice Fernandez,Pragna Vellala,Tanmay Kulkarni,Isaiah Aguilar,Diana Ritz,Kevin Lan,Pramthesh Patel,Aston Liu
标识
DOI:10.1016/j.xphs.2021.09.011
摘要
In response to FDA's call for Quality by Design (QbD) in biopharmaceutical product development, the biopharmaceutical industry has been developing highly sensitive and specific technologies in the monitoring and controlling of product quality attributes for bioprocesses. We previously published the successful application of an off-line multi-attribute method (MAM) to monitor more than 20 critical quality attributes (CQA) with superior sensitivity for the upstream process. To further remove the hurdles of laborious process sampling and sample preparation associated with the offline method, we present here a fully integrated MAM based online platform for automated real time online process monitoring. This integrated system includes Modular Automated Sampling Technology (MAST) based aseptic sampling, multi-function Sequential Injection Analysis (SIA) sample preparation, UHPLC separation and high-resolution mass spectrometry (HRMS) analysis. Continuous automated daily monitoring of a 17-day cell culture process was successfully demonstrated for a model monoclonal antibody (mAb) molecule with similar specificity and sensitivity as we reported earlier. To the best of our knowledge, this is the first report of an end-to-end automated online MAM system, which would allow the MAM to be applied to routine bioprocess monitoring, potentially replacing multiple conventional low resolution and low sensitivity off-line methods. The online HPLC or HPLC/MS platform could be easily adapted to support other processing steps such as downstream purification with minimal software re-configuration.
科研通智能强力驱动
Strongly Powered by AbleSci AI