Quality-targeting Dynamic Optimization of Monoclonal Antibody Production

Abstract Compliance with Quality by Design (QbD) constitutes a major challenge in biopharmaceuticals. Monoclonal antibodies (mAbs) represent a significant biopharmaceutical product class, typically produced in mammalian cell cultures. A key quality attribute for mAb production is glycosylation. We examine how process intensification affects glycosylation via dynamic optimization using different problem formulations. We maximize process performance with simultaneous control of product quality. For these, we utilize a mechanistic dynamic model for mAb production in mammalian cell cultures including glycosylation presented by Ehsani et al. in Computer Aided Chemical Engineering (2017). To achieve target glycan distribution in the final product, we incorporate constraints for the acceptable glycosylation ranges into the dynamic optimization problem. As a result, we derive optimal supplementation profiles of nutrients and/or nucleotide sugars. This work successfully illustrates an example of how model-based dynamic optimization can be employed for implementation of the QbD approach in biopharmaceutics.