Revised Long-Term Scheduling Model for Multi-Stage Biopharmaceutical Processes

Biopharmaceuticals are therapeutic drugs engineered to target specific sites within the body. Their manufacturing process comprises two primary stages: upstream processing (USP) and downstream processing (DSP). USP primarily involves cell culture and growth, whereas DSP focuses on purifying and packaging the final product. The recent literature only reports a few studies addressing production planning and scheduling in biopharmaceutical manufacturing. In this work, we address a long-term scheduling and midterm planning problem incorporating on-time or late delivery of final products with unknown finite delivery rates. Early delivery is prohibited, and late delivery incurs a penalty cost. Published models and evolutionary algorithms exhibit key limitations in areas such as shelf-life modeling, inventory management, and product delivery. To overcome these shortcomings, we propose a revised mixed-integer linear programming (MILP) model implemented using the General Algebraic Modeling System (GAMS). When applied to two illustrative examples, the model reduces optimum event counts by two to three, improving computational efficiency through fewer binary variables, continuous variables, and constraints. Furthermore, it achieves up to 7% improvement over two published benchmarks, underscoring its potential to enhance scheduling strategies for multiproduct biopharmaceutical facilities.