Increasing batch-to-batch reproducibility of CHO-cell cultures using a model predictive control approach

Abstract

By means of a model predictive control strategy it was possible to ensure a high batch-to-batch reproducibility in animal cell (CHO-cell) suspensions cultured for a recombinant therapeutic protein (EPO) production. The general control objective was derived by identifying an optimal specific growth rate taking productivity, protein quality and process controllability into account. This goal was approached indirectly by controlling the oxygen mass consumed by the cells which is related to specific biomass growth rate and cell concentration profile by manipulating the glutamine feed rate. Process knowledge represented by a classical model was incorporated into the model predictive control algorithm. The controller was employed in several cultivation experiments. During these cultivations, the model parameters were adapted after each sampling event to cope with changes in the process' dynamics. The ability to predict the state variables, particularly for the oxygen consumption, led to only moderate changes in the desired optimal operational trajectories. Hence, nearly identical oxygen consumption profiles, cell and protein titers as well as sialylation patterns were obtained for all cultivation runs.

Advanced model‐based control strategies for the intensification of upstream and downstream processing in mAb production

“…The lack of more advanced online measurements hinders eventually the development of advanced process control tools that can improve the process efficiency. Despite the aforementioned obstacles, significant contributions have been reported in the control of mammalian cell cultures systems . Most of the presented studies rely either on an overwhelming amount of measurements or mathematical models and optimization procedures of excessive computational requirements.…”

Between the Poles of Data‐Driven and Mechanistic Modeling for Process Operation

“…Also seed train optimization can be an application of mechanistic models . Other applications are model‐based feeding profile optimization or model based monitoring and control of bioprocesses, e.g., by controlling the feed rate .…”

Model Predictive Feeding Rate Control in Conventional and Single-use Lab-scale Bioreactors: A Study on Practical Application

“…where J -control cost function, g; X -biomass concentration, g L -1 ; X pred -predicted biomass concentration, g L A model of the similar structure and MPC technique for Chinese hamster ovary (CHO) cell culture MPC were applied in research of Aehle et al 17 Kuprijanov et al 6 applied MPC for biomass concentration tracking. Further applications in chemical and refinery industrial processes were reported by Yüzgec et al 18 In the case investigated, the MPC non-convex problem is solved.…”