This article provides a perspective on control and operations for biopharmaceutical manufacturing. Challenges and opportunities are described for (1) microscale technologies for high-speed continuous processing, (2) plug-and-play modular unit operations with integrated monitoring and control systems, (3) dynamic modeling of unit operations and entire biopharmaceutical manufacturing plants to support process development and plant-wide control, and (4) model-based control technologies for optimizing startup, changeover, and shutdown. A challenge is the ability to simultaneously address the uncertainties, nonlinearities, time delays, non-minimum phase behavior, constraints, spatial distributions, and mixed continuous-discrete operations that arise in biopharmaceutical operations. The design of adaptive and hybrid control strategies is discussed. Process data analytics and grey-box modeling methods are needed to deal with the heterogeneity and tensorial dimensionality of biopharmaceutical data. Novel bioseparations as discussed as a potential cost-effective unit operation, with a discussion of challenges for the widespread application of crystallization to therapeutic proteins.

本文提供了有关生物制药生产的控制和操作的观点。针对以下挑战和机遇进行了描述：（1）高速连续处理的微型技术；（2）具有集成监视和控制系统的即插即用模块化单元操作；（3）单元操作和整个生物制药生产工厂的动态建模支持过程开发和全厂范围内的控制，以及（4）基于模型的控制技术，用于优化启动，转换和关闭。一个挑战是能够同时解决生物制药操作中出现的不确定性，非线性，时间延迟，非最小相位行为，约束，空间分布以及混合连续离散操作的能力。讨论了自适应和混合控制策略的设计。需要处理数据分析和灰盒建模方法来处理生物制药数据的异质性和张量维度。新型生物分离技术被认为是一种潜在的具有成本效益的单元操作，同时还讨论了将结晶技术广泛应用于治疗性蛋白质所面临的挑战。