Automation of Cell Line Development Using the OptiCHO Expression System

Abstract

An automated platform concept for production of therapeutic monoclonal antibodies in suspension-adapted CHO cells has previously been established. This allows colony detection, screening and expansion of a large number of clones. Regulatory aspects required for generation of biopharma production cell lines have been considered. The automated platform was adapted for generation of cell lines for production of therapeutic monoclonal antibodies based on a dhfr-expression system, OptiCHO (Invitrogen) in CHO DG44 cells. A limiting dilution was performed and >1300 clones were expanded and screened for titer in overgrown batch cultures in 24-well plates. The 167 best producing clones were further expanded and evaluated in a second titer screen of overgrown batch cultures in shake flasks. As generally seen for several mammalian expression systems there was a poor correlation between titer in first and second screen. We address this by using an automated platform, allowing screening and expansion of a high number of clones to increase the likelihood of finding high producing cell lines.