Cell Line Development: Accelerating Process Optimization By Combining Ambr® 15 Cell Culture With Octet® Titer Measurements

By Jonathan Kirby, Alison Rees-Manley, David Apiyo, Lukas Klein, Eva Diem, Tim Dale

Cell line development involves the screening of thousands of clones to find those that are stable, produce high yields of the bioproduct and exhibit desired critical quality attributes (CQAs). Typically screening and process optimization activities will be carried out at the small scale in bioreactor cultures to ensure that results translate up to larger bioreactor scales. Performance data is primarily based on cell growth, cell viability, metabolite analysis and product titer, and assessed over the entire culture process duration. Often product titer data will have a longer turn-around time where samples are submitted to analytical groups for analysis. Introducing analytical technology into the cell culture process development workflow can greatly speed up the time to results. The Octet® platform is an analytical instrument that can easily be implemented in cell line development labs to facilitate rapid determination of product yield. This capability allows informed decisions directly at the end of the process, for example which samples need to be sent off for quality analysis, reducing overall sample numbers. It also enables the next experiments to be planned based on all of the performance data, rather than waiting days or weeks for product yield results to be available. Here we show the power of using the Ambr® 15 Cell Culture system with an integrated Vi-CELL XR and Ambr® Analysis Module together with an Octet® to identify optimum yield conditions in media screening and process optimization experiments.