Advances in process control strategies for mammalian fed-batch cultures

Advanced process monitoring in biologics manufacturing has been an important utility for enhancing process consistency to generate desirable and consistent product quality. The integration of Process Analytical Technology (PAT) in real-time monitoring of bioprocesses has been a focus of process research in the past decade to meet the paradigm of quality by design (QbD). This review article describes how at-line sampling devices, and in-line/on-line spectroscopic sensors are making headway in bioprocess monitoring, highlighting successful examples of feed process control that makes use of real-time data for feedback decisions. Coupled with rational feed media design, feed control strategies can be based on real-time bioreactor input parameters such as cell density, substrate levels, pH, and oxygen consumption. The rationale behind these control strategies and the impact to process performance and product quality are also discussed.