Abstract Design variables of upstream and downstream process units play a significant role in the performance of monoclonal antibody (mAb) production platforms. Plantwide optimization problems in the form of mixed integer nonlinear programming (MINLP) must consider decision variables, process constraints and a suitable objective function to achieve meaningful solutions. Moreover, deterministic MINLP solvers are required to avoid simulation-based pitfalls. In this study, a deterministic branch-an