Rigorous approach to scheduling of sterile drug product manufacturing

Abstract

Abstract Optimizing the scheduling of liquid drug product manufacturing is paramount for pharmaceutical companies in their increasingly competitive environment and requires the modelling of industry-specific constraints. Such constraints include: (i) changing sequence-dependent setup times; (ii) maintaining a sterile production environment (e.g., through sterile holding times); (iii) periods with limited or no plant activity (e.g., no workforce during weekends); and (iv) demand timing (i.e., delivery deadline and release date constraints). In this work, an immediate precedence model is formulated to optimize the scheduling of liquid drug product manufacturing, considering the industry-specific constraints. The primary objective is to minimize the production makespan. Four case studies comprising up to 38 batches from a real multi-product facility illustrate the performance of the rigorous optimization approach. The makespan could be reduced by up to 7.9% compared to expert schedules.