Performance benchmark of different cell clones in discontinuous and continuous bioprocesses reveals critical impact of cellular diameter

Abstract

Therapeutic proteins such as monoclonal antibodies are usually manufactured either in continuous processes such as steady-state perfusion or in discontinuous processes like fed-batch (FB). Thereby, both process formats have fundamentally different requirements for the utilized cell factories. This poses a problem as common cell line development programs are designed to select cell clones to perform well in FB cultivation. The aim of this study was to identify critical and easy to access cell line attributes for each process format and with that for the transfer of clones from fed-batch to perfusion. As a result, increased cell-volume specific productivity could be identified as beneficial within the FB not only impacting performance but as well diminishing media utilization and host-cell-proteins level. Within the perfusion, a stable cell diameter was identified as major beneficial characteristic, positively influencing cell viability, metabolite and glycan profile, as well as equipment utilization. Consistent with this, our data suggest that the inclusion of cell volume in the screening parameters is important for clone selection for both process formats and can lead to improved process design and robust cell line process transfer. Overall, this work gives valuable new insights in cell behaviour across discontinuous and continuous process formats to improve clone cell selection for both process strategies and streamline the process transfer from discontinuous towards continuous.