Automation of Integrated Perfusion Control Simplifying Process Intensification of Mammalian Biomanufacturing in Single‐Use Bioreactors

Abstract

AbstractProduction of biopharmaceuticals needs to become faster, more flexible, and efficient. Perfusion processes allow to operate cell cultivations at higher cell concentrations, shorten their process time and increase their productivity. Still, either customized software solutions or third‐party stand‐alone control devices are often used for perfusion control. Its integration into a bioreactor automation platform will simplify the implementation and application of perfusion processes in the future. In this study, the automation of an integrated perfusion control strategy for a scalable single‐use bioreactor family is demonstrated. The control strategy is illustrated by means of a CHO cell N–1 perfusion process in a 50‐L bioreactor. Accurate control allowed to achieve 80 · 106 c mL−1 within five days. Furthermore, also DO and pH setpoints were precisely controlled throughout the N–1 perfusion process. Finally, the advantage of this process strategy is exemplified by comparing fed‐batch processes inoculated from N–1 perfusion vs. N–1 batch processes.