(299e) Selection Support Method of Single-Use Vs. Multi-Use Technologies in Parenterals Manufacturing

Authors: 
Shirahata, H., The University of Tokyo
Hirao, M., The University of Tokyo
Sugiyama, H., The University of Tokyo

The objective of this study is to create a decision supporting method for the choice between single-use and multi-use technologies in Parenterals manufacturing. There are two different manufacturing technologies for Parenterals, i.e., multi-use system (MU) and single-use system (SU). MU is a conventional technology using stainless steel, the equipment of which is cleaned with water for injection and sterilized with pure steam before and after batch production. In contrast, SU is a new technology using plastic-resin, the components of which are assembled and disposed by every batch. The choice of these two technologies is critical regarding quality, cost-effectiveness or environmental impacts, and there have been various case studies reported mainly for the drug substance manufacturing. However, a general decision-support tool is still in its infancy, and Parenterals manufacturing, a step after drug substance manufacturing to produce injectables, has not been investigated extensively.

This work presents a selection support method of SU vs. MU technologies in Parenterals manufacturing. The methodology consists of three steps. First, the manufacturing process is modeled and evaluated in terms of operating cost and life cycle CO2 emissions as monetary and environmental objectives, respectively. Evaluation models were created that can reflect main features of each technology, such as preparation time, number of required operators or the area of the isolator. Second, in order to simulate the effects of input parameters, what-if analysis is performed. Among various parameters to be analyzed, pump speed can also influence the filling accuracy of the product, one of the most important quality attribute of Parenterals. This finding is based on an experiment, where coefficient of variations (CV) of the filling volume were measured with varying liquid viscosity, inner tube diameter, and pump speed. The result showed that the pump speed was the only parameter that caused significant difference on the CV, i.e., what-if analysis of pump speed can also be an evaluation on the product quality. Lastly, the results derived from above two processes are interpreted in terms of economy, environmental impact, and quality.

The methodology was demonstrated with considering the following cases: (a) different batch size in one batch production, (b) different production patterns under a fixed scale. As for case (a), SU is more cost-effective than MU when the batch size is small, and as the batch size increases, this tendency changes at certain point. Regarding CO2 emissions, SU was found to be preferable regardless of the batch size. By performing what-if analysis on pump speed, the interval of batch size was obtained where the choice will differ depending on the priority of the filling accuracy. As for case (b), the operating cost of SU is smaller than that of MU in the pattern of “small-scale production of numerous products”, and the other way round in the pattern of “large-scale production of small number of products”. Similar to case (a), SU was found to be environmentally friendlier regardless of the production pattern, and the what-if analysis indicated the interval where the priority of the quality makes difference in the choice of the technology.