A predictive modular approach to constraint satisfaction under uncertainty -- with application to glycosylation in continuous monoclonal antibody biosimilar production

TL;DR

This paper introduces a modular predictive filter for constraint satisfaction in process control, effectively reducing violations under uncertainty, demonstrated through a glycosylation case in monoclonal antibody production.

Contribution

It presents a novel, computationally efficient constraint handling module that can be integrated with existing controllers for real-time bioprocess optimization under uncertainty.

Findings

Constraint violation cost reduced by over 60%

Method is suitable for real-time applications

Effective in complex bioprocess scenarios

Abstract

The paper proposes a modular-based approach to constraint handling in process optimization and control. This is partly motivated by the recent interest in learning-based methods, e.g., within bioproduction, for which constraint handling under uncertainty is a challenge. The proposed constraint handler, called predictive filter, is combined with an adaptive constraint margin and a constraint violation cost monitor to minimize the cost of violating soft constraints due to model uncertainty and disturbances. The module can be combined with any controller and is based on minimally modifying the controller output, in a least squares sense, such that constraints are satisfied within the considered horizon. The proposed method is computationally efficient and suitable for real-time applications. The effectiveness of the method is illustrated through a realistic case study of glycosylation constraint satisfaction in continuous monoclonal antibody biosimilar production using Chinese hamster ovary cells, employing a metabolic network model consisting of 23 extracellular metabolites and 126 reactions. In the case study, the average constraint-violation cost is reduced by more than 60% compared to the case without the proposed constraint-handling method.