(200l) Multi-Stage and Multi-Objective Design Tool for Process Design in Sterile Filling of Biopharmaceuticals

Authors: 
Shirahata, H., The University of Tokyo
Zürcher, P., ETH Zurich
Badr, S., The University of Tokyo
Sugiyama, H., The University of Tokyo
Sterile filling is a process within biopharmaceutical manufacturing, where compounded drug solutions are filled into vials or syringes. The strict consideration of product quality necessitates that manufacturing equipment be kept clean and sterile. The conventional use of fixed stainless steel equipment, termed multi-use technology (MUT), conducts multiple cleaning procedures following every batch of pharmaceutical products. Recently, a set of resin-made pre-sterilized equipment have been introduced as disposable alternatives, known as single-use technology (SUT). Introduction of SUT offers a large number of alternatives regarding possible combinations of SUT or MUT per unit operation and the relative sizes in a production line. A few tools have been already developed to support the decision-making process concerning SUT alternatives. Such tools however, are based on the economic evaluation of the alternatives and offer limited functionalities for generating process alternatives or understanding sensitivity to process parameters.

In this work, we present a multi-objective decision-making tool for sterile filling of biopharmaceuticals that can be used across multiple design stages. The basis of the work is the evaluation models developed by the authors to compare SUT and MUT in terms of the economic performance, environmental impacts, product quality, and supply robustness. The weighting factors of design objectives were defined for aggregating multi-objective evaluation results, where sensitivity analysis of the factors were conducted within the possible combinations. We will conduct a questionnaire survey to industrial practitioners, and the results can be used to set the weighting factors and provide a solution that best fits the users. Also, the tool will provide rigorous and tailored solutions across design stages by varying underlying model complexities in accordance to user requirements and available data at each design stage. The tool will be supported by data collected through industrial databases and expert knowledge. We aim to implement the tool in the form of a web-based application to enhance the practicability of the design tool for the users.