Towards a Digital Bioprocess Replica: Computational Approaches in Biopharmaceutical Development and Manufacturing

Abstract

Quantitative unit operation models for the optimization and refinement of modern late-stage biopharmaceutical drug manufacturing processes have recently attracted increasing attention. The supplementary benefits of these models include increased process robustness and control in combination with a more stringent design of the bioprocess due to a reduced number of exploratory experiments. In addition to unit operations, further efforts also focus on digital bioprocess replicas, which are straightforward combinations of unit operation and process models from inoculum to the fill and finish phase. In this review, we shed more light on digital bioprocess replicas in addition to standard unit operation models and discuss their strengths and weaknesses. We comment on the current usage of these approaches for late stage processes and outline the associated benefits, challenges and limitations.

Keywords: digital bioprocess replicas; holistic process models; machine learning and statistical approaches; molecular and mechanistic models; quality by design; unit operation models.