Multiobjective Design Method for the Use Processes of Pharmaceutical Excipients Considering Quality and Cost-Effectiveness

Purpose Achieving cost-effectiveness while maintaining strict quality regulations is an emerging topic in pharmaceutical manufacturing. With a focus on the use process of excipients, e.g., reception, storage, testing, and actual usage, this paper presents a multiobjective design method for determining the optimal process setup. Method The method consists of setup of the problem, creation of models for quality and economic evaluation, and finally multiobjective optimization. A case study was performed using benzyl alcohol, an oxidation-sensitive material; we designated the amount of oxidized impurities and the costs associated with testing as the quality and economic objectives, respectively. The process was simulated, considering container volume and purchase frequency as the design variables, and also the use of Raman spectroscopy as an alternative to conventional identification testing. Results The multiobjective evaluation indicated options on the Pareto frontier, i.e., the set of non-dominant options. Here, the process with larger containers and less frequent purchases resulted in reduced testing costs but more impurities and vice versa for the opposite combination. The use of Raman spectroscopy was more effective in reducing the cost of identification testing than in preventing the degree of oxidation by not opening the container. Conclusions Through the case study, we showed that the method was capable of identifying the promising process settings, especially with the aid of graphical analysis on the Pareto frontier. The method, which is currently focused on excipients, could be extended to similar design cases using raw materials for pharmaceutical manufacturing.