Development of control strategy for bioreactor and refill strategy of feeding system

The progressive acceleration of continuous bioprocessing method has become the focal point of advanced research and study for the biotech companies in recent years. Implementation of this method is a tedious and lengthy process but has been proven beneficial down the line. Advancement of this methodology is initiated by the U. S. Food and Drug Administration (FDA) through introduction of Quality by Design (QbD) approach. In parallel, sophisticated bioreactors are now available in the market with various applications to support the continuous upstream process. In motion, monoclonal antibodies (mAb’s) are produced by studying the behavior of CHO cell culture, affected by different media and controlled variables. Focus of this thesis is to demonstrate a systematic approach towards developing a control strategy for the critical process parameters (CPPs) of the bioreactor. Based on the study of bioreactor, control relevant process models have been developed using experimental data. Feedback control architecture has been developed in silico using proportional integral derivative (PID) controller. Further, on using advanced model predictive control (MPC) algorithm, the performance of these feedback-control loops has been investigated and compared with the performance of the PID controller. Framework for the integration of bioreactor with the control platform has been explained. As the industry is shifting towards the development of continuous process, it becomes important to make sure that these continuous processes never run short on the material. For the success of such processes, timely refilling of the required material to the feeding system becomes necessary. To illustrate this idea, refill strategy for the feed tank has been developed by mathematical modelling approach. Case studies have been conducted to investigate the impact of ambient temperature on fluid inside the feed tank during refill period.M.S.Includes bibliographical reference