Stepwise cell culture process intensification for high-productivity and cost-effective commercial manufacturing of a Mabcalin™ bispecifics

Abstract

Process intensification and media optimization, as a crucial step for improving productivity and manufacturing cost of goods (COG), set the stage for commercialization readiness and redefine the landscape for patient access. This study described a stepwise approach to explore different intensified fed-batch processes along with optimized cell culture media for the production of a Mabcalin™ bispecifics. Initially, by leveraging perfusion expansion, intensified fed-batch (IFB) with an inoculation density of 10.3 × 10⁶ cells/mL was developed to produce 6.1 g/L of products, compared to 3.9 g/L from the original traditional fed-batch (TFB). Following the IFB conversion, a high-performing production medium, MagniCHO™, was chosen to substitute the original one, which further boosted the titer to 9.1 g/L. The result underscored the significance of developing an optimized cell culture media for intensified cultivation. Furthermore, the approach of ultra-intensified intermittent-perfusion fed-batch was utilized, raising the seeding density to 73.6 × 10⁶ cells/mL. A final harvest titer of 24.5 g/L was recorded. Additionally, manufacturing COG was calculated to evaluate how process intensification could lead to improved manufacturing cost-effectiveness, with up to 71 % COG reduction attainable with the UI-IPFB process. This study demonstrated that even for difficult-to-express modalities, applying a strategic development approach including process intensification and media optimization could effectively improve manufacturing efficiency and COG competitiveness.