In this paper, the application of a robust nonlinear model predictive control (NMPC) framework to mammalian cell cultures is proposed, dealing with possible large kinetic parameter uncertainties. Industrial constraints formulated in view of good manufacturing practice and quality-by-design approach are also considered, namely the assurance that all state trajectories are contained within a corridor defined by lower and upper safety bounds. The latter are assimilated to the well-known tube-based paradigm which is used to formulate the corresponding robust NMPC problem. Both classical and tube-based NMPC performances are assessed in numerical simulations where specific key-species are regulated while dealing with an uncertain plant model. The capability of the tube-based method to reduce the impact of the parameter variations on the state trajectories and the violation of the constraints is highlighted, suggesting the transfer of the method on a real pharmaceutical process.

在本文中，提出了将稳健的非线性模型预测控制（NMPC）框架应用于哺乳动物细胞培养，以处理可能存在的较大动力学参数不确定性。还考虑了根据良好制造实践和质量设计方法制定的工业约束，即确保所有状态轨迹都包含在由安全下限和上限定义的走廊内。后者被同化为众所周知的基于管的范例，用于制定相应的鲁棒 NMPC 问题。经典和基于管的 NMPC 性能均在数值模拟中进行评估，其中在处理不确定的植物模型时对特定关键物种进行调节。强调了基于管的方法减少参数变化对状态轨迹的影响和违反约束的能力，表明该方法可以转移到真实的制药过程中。