Production and maintenance planning optimisation in biopharmaceutical processes under performance decay using a continuous-time formulation: A multi-objective approach

This work addresses the optimal planning of biopharmaceutical continuous manufacturing processes under performance decay, modelling its operational constraints in a mixed integer linear programing (MILP) model, based on a Resource Task Network (RTN) continuous single-time grid formulation. The model assesses the manufacturing constraints for the determination of the production schedule while defining the appropriate maintenance planning timing in downstream units to assure optimal process performance. An improved model approach is discussed and compared with the application results to literature-based industrial cases. In order to evaluate different solutions towards the multiple decision maker's strategic and operational objectives, the definition of the Pareto sets for three bi-objective analyses is performed with the augmented ε-constraint method, using the profit maximisation: with the minimisation of the number of intermediate maintenance operations, the maximisation of average service level, and the maximisation of the utilisation rate of processing units.