Process Intensification Using a One-Step Inoculum Production and High-Seeded Fed-Batch Processes

Various approaches to process intensification are currently being investigated to ensure time and cost savings when producing biopharmaceuticals. In the present study, a one-step inoculum production was established based on an ultra-high cell density working cell bank with immunoglobulin G producing Chinese hamster ovary cells. Cryovials were used for direct inoculation of 1-L wave-mixed perfusion bioreactors. When reaching around 180 center dot 10(6) cells mL(-1) in N-1 perfusion mode, low-seed and high-seed fed-batch experiments in shake flasks were inoculated, as was the case for 250-mL stirred single-use bioreactors. Additionally, proof-of-concept runs at 50-L and 200-L scale were successfully performed. The intensification approach presented allows manufacturing capacity to be increased by up to 50 %.