Advances in modeling techniques for the production and purification of biomolecules: A comprehensive review

•Intricate modeling techniques in therapeutic enzyme production have been discussed.•Modeling of integrated process like extractive fermentation has been addressed.•Several advanced models for two-dimensional chromatography have been represented.•ANN and GA based control strategies have also been briefly discussed. In response to the growing demand for therapeutic biomolecules, there is a need for continuous and cost-effective bio-separation techniques to enhance extraction yield and efficiency. Aqueous biphasic extractive fermentation has emerged as an integrated downstream processing technique, offering selective partitioning, high productivity, and preservation of biomolecule integrity. However, the dynamic nature of this technique requires a comprehensive understanding of the underlying separation mechanisms. Unfortunately, the analysis of parameters influencing this dynamic behavior can be challenging due to limited resources and time. To address this, mathematical modeling approaches can be employed to minimize the tedious trial-and-error experimentation process. This review article presents mathematical modeling approaches for both upstream and downstream processing techniques, focusing on the production of biomolecules which can be used in pharmaceutical industries in a cost-effective manner. By leveraging mathematical models, researchers can optimize the production and purification processes, leading to improved efficiency and processing cost reduction in biomolecule production.