(634e) Application of Continuous Manufacturing to Upstream Cell Culture Process with Focus to Speed to Clinic

Most of the biologics are manufactured using Chinese Hamster Ovary cells. Pharmaceutical industries use different modes of operations like Fed-batch and Continuous Manufacturing to increase their productivity. Traditionally many companies implement Fed-batch process as it is more well-known process with less operational complexity and involve shorter duration of time. However, in the recent times, focus is being shifted to enable Continuous Manufacturing in biomanufacturing to meet market demands with smaller footprint and facilitate in cost saving. With that mindset, CM was implemented to one of the cell lines with focus on speed to clinic for First-in-human clinical trials. Irrespective of which process of manufacturing is used, same quality control strategies are followed.

While developing CM process for this mAb, an initial hurdle involved choosing the best clone from top 6 selected clones based on CM modality. In addition, other challenges faced during establishing of CM process involved choice of perfusion media, gassing strategies for the bioreactors and bleeding strategies for the chosen cell line clones. The titer and the quality of the protein generated during upstream processes were assessed using established analytical assays. The CM process yielded a 2.7-fold higher volumetric productivity compared to fed-batch for this project.