Rapid Fed-Batch Process Development in SimCell™

The SimCell™ overcomes many limitations seen in traditional systems for fed-batch process development. In this study, we demonstrated that SimCell is a robust automated tool for rapid platform process development. A platform feed and fed-batch process parameters were identified for three recombinant CHO cell lines using three consecutive SimCell experiments: Feasibility, Feed Screening and Feed Strategy Optimization. The microfluidic miniature bioreactor system was first calibrated and baseline performance was set up for each cell line. Seven chemically-defined (CD) feeds were designed based on spent media analysis and were screened in the SimCell using 378 microbioreactors. The optimal feed improved growth substantially and increased recombinant protein titers by 2 fold compared to batch cultures for all three cell lines. SimCell fed-batch process parameters associated with the feed, such as temperature shift, pH, feed schedule and volume, were optimized using 420 microbioreactors in a Design-of-Experiment (DoE) layout. Similarities and differences in fed-batch parameters were seen across the three cell lines. Recombinant protein titers were improved by 3–4 fold compared with batch cultures. For one cell line, recombinant protein titers were doubled compared to the original control process. Statistical analysis was performed to identify the optimal production parameters for each cell line.