Towards advanced bioprocess optimization: A multiscale modelling approach.

Mammalian cells produce up to 80 % of the commercially available therapeutic proteins, with Chinese Hamster Ovary (CHO) cells being the primary production host. Manufacturing involves a train of reactors, the last of which is typically run in fed-batch mode, where cells grow and produce the required protein. The feeding strategy is decided a priori, from either past operations or the design of experiments and rarely considers the current state of the process. This work proposes a Model Predictive Control (MPC) formulation based on a hybrid kinetic-stoichiometric reactor model to provide optimal feeding policies in real-time, which is agnostic to the culture, hence transferable across CHO cell culture systems. The benefits of the proposed controller formulation are demonstrated through a comparison between an open-loop simulation and closed-loop optimization, using a digital twin as an emulator of the process.