Process‐aware data‐driven modelling and model predictive control of bioreactor for the production of monoclonal antibodies

Abstract This manuscript addresses the problem of controlling a bioreactor to maximize the production of a desired product while respecting the constraints imposed by the nature of the bio‐process. The approach is demonstrated by first building a data‐driven model and then formulating a model predictive controller (MPC) with the results illustrated by implementing a detailed monoclonal antibody production model (the test bed) created by Sartorius Inc. In particular, a recently developed data‐driven modelling approach using an adaptation of subspace identification techniques is utilized that enables the incorporation of known physical relationships in the data‐driven model development (constrained subspace model identification), making the data‐driven model process aware. The resultant controller implementation demonstrates a significant improvement in production compared to the existing proportional integral (PI) controller strategy used in the monoclonal antibody production. Simulation results also demonstrate the superiority of the process‐aware or constrained subspace MPC compared to traditional subspace MPC. Finally, the robustness of the controller design is illustrated via the implementation of a model developed using data from a test bed with a different set of parameters, thus showing the ability of the controller design to maintain good performance in the event of changes such as a different cell line or feed characteristics.