Novartis Pharma AG, Basel, Switzerland.
Heinrich Heine University, Düsseldorf, Germany.
Eur J Pharm Biopharm. 2021 Feb;159:137-142. doi: 10.1016/j.ejpb.2021.01.003. Epub 2021 Jan 9.
Pharmaceutical continuous manufacturing is considered as an emerging technology by the regulatory agencies, which have defined a framework guided by an effective quality risk management. With the understanding of process dynamics and the appropriate control strategy, pharmaceutical continuous manufacturing is able to tackle the Quality-by-Design paradigm that paves the way to the future smart manufacturing described by Quality-by-Control. The introduction of soft sensors seems to be a helpful tool to reach smart manufacturing. In fact, soft sensors have the ability to keep the quality attributes of the final drug product as close as possible to their references set by regulatory agencies and to mitigate the undesired events by potentially discard out of specification products. Within this review, challenges related to implementing these technologies are discussed. Then, automation control strategies for pharmaceutical continuous manufacturing are presented and discussed: current control tools such as the proportional integral derivative controllers are compared to advanced control techniques like model predictive control, which holds promise to be an advanced automation concept for pharmaceutical continuous manufacturing. Finally, industrial applications of model predictive control in pharmaceutical continuous manufacturing are outlined. Simulations studies as well as real implementation on pharmaceutical plant are gathered from the control of one single operation unit such as the tablet press to the control of a full direct compaction line. Model predictive control is a key to enable the industrial revolution or Industry 4.0.
制药连续制造被监管机构视为一种新兴技术，他们已经制定了一个框架，该框架以有效的质量管理为指导。通过对工艺动力学的理解和适当的控制策略，制药连续制造能够应对质量源于设计的范例，为质量源于控制的未来智能制造铺平道路。软传感器的引入似乎是实现智能制造的有用工具。事实上，软传感器有能力使最终药物产品的质量属性尽可能接近监管机构设定的参考值，并通过潜在地丢弃不符合规格的产品来减轻不良事件。在这篇综述中，讨论了实施这些技术所面临的挑战。然后，介绍并讨论了制药连续制造的自动化控制策略：当前的控制工具，如比例积分微分控制器，与先进的控制技术，如模型预测控制进行了比较，后者有望成为制药连续制造的先进自动化概念。最后，概述了模型预测控制在制药连续制造中的工业应用。从对单个操作单元（如压片机）的控制到对整个直接压缩生产线的控制，从控制模拟研究到制药工厂的实际实施，都收集了模型预测控制的应用案例。模型预测控制是实现工业革命或工业 4.0 的关键。
