(692f) Model Predictive Control: A Process Development Tool for Mammalian Cell Culture Processes

In recent years, there has been a growing necessity to increase the speed, efficacy and information content associated to the development and scale-up of biopharmaceutical processes, particularly given the regulatory authorities current shift in philosophy towards quality-by-design (QbD). This QbD requirement for increased process understanding intensifies the work involved in the earlier phases of the drug-product lifecycle. The benefit, however, is that the increased process knowledge can speed the technical transfer from development into manufacturing, deliver a more optimised, robust process with higher titres and greater reproducibility and aid in troubleshooting and root-cause analysis of deviations during production.

A model predictive control (MPC) technology platform incorporating Raman spectroscopy was developed as a tool to streamline upstream bioprocess development and applied to a fed-batch CHO culture. In this talk, the core elements of the MPC will be discussed, namely the development of the Raman PAT method for the online quantification of cell density, substrate and metabolite concentrations, the process model and the MPC control algorithm.

The application of the MPC to process development will be demonstrated through a case study of its application to a CHO fed-batch culture. The MPC enabled the transition from traditional bolus to a PAT-enabled continuous feeding strategy in order to prevent nutrient depletion and deliver a stable macro-environment for the cells. Overall, application of the glucose set-point control strategy resulted in a 1.5 fold increase in peak viable cell density (VCD) and the integral of the viable cell density (IVC) which is directly related to increased titre.