The Advanced Centre of Biochemical Engineering, Department of Biochemical Engineering, University College London, Bernard Katz Building, Gower Street, London, WC1E 6BT, UK.
Purification Process Sciences, Biopharmaceuticals Development, R&D, AstraZeneca, Cambridge, UK.
J Chromatogr A. 2021 Feb 22;1639:461914. doi: 10.1016/j.chroma.2021.461914. Epub 2021 Jan 15.
Recent advances in process analytical technologies and modelling techniques present opportunities to improve industrial chromatography control strategies to enhance process robustness, increase productivity and move towards real-time release testing. This paper provides a critical overview of batch and continuous industrial chromatography control systems for therapeutic protein purification. Firstly, the limitations of conventional industrial fractionation control strategies using in-line UV spectroscopy and on-line HPLC are outlined. Following this, an evaluation of monitoring and control techniques showing promise within research, process development and manufacturing is provided. These novel control strategies combine rapid in-line data capture (e.g. NIR, MALS and variable pathlength UV) with enhanced process understanding obtained from mechanistic and empirical modelling techniques. Finally, a summary of the future states of industrial chromatography control systems is proposed, including strategies to control buffer formulation, product fractionation, column switching and column fouling. The implementation of these control systems improves process capabilities to fulfil product quality criteria as processes are scaled, transferred and operated, thus fast tracking the delivery of new medicines to market.
近年来，过程分析技术和建模技术的进步为改进工业层析控制策略提供了机会，以提高工艺稳健性、提高生产力并朝着实时放行测试的方向发展。本文对用于治疗性蛋白纯化的批处理和连续工业层析控制系统进行了批判性的综述。首先，概述了使用在线 UV 光谱和在线 HPLC 的传统工业分级控制策略的局限性。接下来，对在研究、工艺开发和制造中显示出前景的监测和控制技术进行了评估。这些新型控制策略将快速的在线数据采集（例如 NIR、MALS 和可变光程 UV）与通过机理和经验建模技术获得的增强的工艺理解相结合。最后，提出了工业层析控制系统的未来状态的总结，包括控制缓冲液配方、产品分级、柱切换和柱污染的策略。这些控制系统的实施提高了工艺能力，以满足产品质量标准，因为工艺在放大、转移和运行，从而快速将新药推向市场。
