Improved clone selection by combining a manufacturability index with semi-perfusion scale-down screening systems

Abstract

Early stage cell clone screening is critical for identifying highly performing candidates in biopharmaceutical development. In this study, clone screening was carried out through miniaturisation of a semi-perfusion methodology from 24-well microwell plates (MWP) to 96-well deepwell plates (DWP). Traditional clone selection methods often rely on single-parameter metrics such as cell-specific productivity (q_P), which may not fully capture clone performance, particularly across different scales and culture formats. We evaluated a multi-parameter approach using the manufacturability index (MI_CL) to rank clones in the 96-well DWP format and compared the results with previously published data from the 24-well MWP system. The MI_CL integrates growth, viability, productivity, and metabolic parameters, providing a more comprehensive assessment than q_P alone. Our results demonstrate that MI_CL rankings offer improved robustness and greater consistency across scales compared to single-parameter q_P rankings. Notably, despite a reduced parameter set in the 96-well DWP due to volume constraints, MI_CL-based rankings aligned well with those from the more parameter-rich 24-well MWP system. These findings highlight the advantages of multi-parameter evaluation in early clone selection and underscore the limitations of relying solely on productivity metrics.