Multi-period scheduling of a multi-stage multi-product bio-pharmaceutical process

• We present an improved continuous time model for multi-period scheduling of bio-pharmaceutical plants.
• The specific features include better handling of changeovers, shelf life, and waste disposals.
• Effective handling of intermediate due dates, with penalties for backlogs and late deliveries.
• Improved tightening and sequencing constraints presented leading to better solution.
• The model is tested on a literature example involving multistage multiproduct production.

There have been several works in the literature for scheduling of multi-product continuous processes with significant attention laid on short-term scheduling. This work presents a continuous-time model for multi-period scheduling of a multi-stage multi-product process from bio-pharmaceutical industry. The overall model is a mixed-integer linear programming (MILP) formulation based on state-task-network (STN) representation of the process using unit-specific event-based continuous-time representation. The proposed model is an extension of model by Shaik and Floudas (2007, Industrial & Engineering Chemistry Research, 46, 1764) with several new constraints to deal with additional features such as unit and sequence dependent changeovers, multiple intermediate due dates, handling of shelf-life and waste disposal, and penalties on backlogs and late deliveries. Improved tightening and sequencing constraints have been presented. The validity of the proposed model has been illustrated through an example from the literature.