Development of an automated, multiwell plate based screening system for suspension cell culture

Abstract

The automation of cell culture processes becomes more important in the pharmaceutical industry due to compressed timelines and the need to develop more products more efficiently. This drive to develop new processes faster and more efficient requires a streamlined workflow. Resource intensive approaches like the use of shake flasks limit the accessible design space for the development of highly productive processes or the characterization of established processes. Process automation provides the appropriate tools to address the following key points: Increasing experimental throughput ⇨ “Design of Experiments” using full factorial designs Increasing process information ⇨ improve process understanding (“Quality by Design”) Automate repetitive manual work ⇨ gain efficiency, focus on high value tasks Improve reproducibility ⇨ ensure robust processes A robotic plate handler based system was selected to meet the demands of a flexible, fast and modular screening system as presented in figure ​figure11. Figure 1 Schematic illustration of the developed robotic screening system prototype. Only the core system is shown with a robotic plate handler as key device connecting shaken cultivation, processing and analytical components. Results Scale-up prediction The comparability of results obtained with this new multiwell plate based culture system for suspension adapted cell lines plates and bioreactors had to be verified. It could be shown that 6-well plates were predictive for a scale-up to a 1000 L stirred tank reactor. The parameter profiles of viable cell density, lactate and antibody concentration were comparable in multiwell plates and bioreactors (2 L, 10 L and 1000 L). The plates can be used for process scale-up prediction.