Integrated Design of Process Configuration and Scheduling for Hydrogen Peroxide Decontamination in Biopharmaceutical Injectable Manufacturing

摘要

We present integrated process design and scheduling for hydrogen peroxide decontamination,a time-intensive change-over in biopharmaceutical injectable manufacturing.Models were developed that can(i)configure process parameters,e.g.,loading amount of hydrogen peroxide in the isolator,and(ii)deal with the scheduling of filling and change-over of multiple batches/products under shift-and weekend-constraints.Sterility assurance level(SAL)of products and the required time for producing all batches were defined as the objective functions for quality and productivity,respectively.The models were applied to multiobjective optimization of process configuration and scheduling for producing 15 batches consisting of different product numbers,characteristics,and batch sizes.Pareto optimal solutions could be obtained that minimized both objectives.The trade-off became more significant when the product became more vulnerable to the residual hydrogen peroxide after decontamination and the product change-over became more frequent,which is the trend in the industry.Thus,the study motivates collaborative design of process and scheduling for the decontamination process in biopharmaceutical manufacturing.