Hybrid modeling in bioprocess dynamics: Structural variabilities, implementation strategies, and practical challenges

Hybrid modeling, with an appropriate blend of the mechanistic and data-driven framework, is increasingly being adopted in bioprocess modeling, model-based experimental design (digital-twin), identification of critical process parameters, and optimization. However, the development of a hybrid model from experimental data is an inherently complex workflow, involving designed experiments, selection of the data-driven process, identification of model parameters, assessment fitness, and generalization capability. Depending on the complexity of the process system and purpose, each piece of these modules can flexibly be incorporated into the puzzle. However, this extra flexibility can be a cause of concern to trace an "optimal" model structure. In this paper, the development of hybrid models in a common bioprocess system, selection of data-driven components and their mapping to states, choice of parameter identification techniques, and model quality assurance are revisited. The challenges associated with hybrid-model development, and corrective actions have also been reviewed. The review also suggests the lack of data, and code sharing in communal repositories can be a hurdle in the exploration, and expansion of those tools in a bioprocess system.