Impact of next-generation high productivity perfusion cell culture
process on host cell protein profile and a comparison with fed-batch
cultures.
Abstract
Fed-batch culture currently represents the typical choice for the
production of monoclonal antibodies (mAbs) in the biopharmaceutical
industry. However, the implementation of perfusion culture process
combined with continuous manufacturing has gained attention due to
increased productivity and resource savings. In this paper, we compared
the host cell protein (HCP) production and profile of mAb1 between
fed-batch and perfusion culture processes. Our work demonstrated
differences in HCP production based on the type of cell culture process
for the first time. We focused on HCPs that get carried through the
purification process and are present in the final drug substance at
levels impacting antibody quality and stability. Perfusion process had
lower HCP levels and enabled higher clearance of problematic HCPs
compared to fed-batch suggesting a viable alternative process.
Furthermore, our work demonstrates proof of concept of the impact of
cell culture process on specific product quality and help to navigate
the process design when we move from traditional fed-batch to
next-generation perfusion cell culture.