(366f) Design Method for Injectable Manufacturing Processes Considering Continuous and Batch Compounding

We present a process design method considering continuous and batch modes in the compounding unit for injectable manufacturing. The method can economically optimize the design variables such as the compounding mode, the lot size, and the number of filling needles. The method integrates two types of models. One is “process-oriented models” which captures the continuous nature of the process by residence time distribution (RTD), among others. The other is “discrete-oriented models” which describes the aspects such as failure events, operating shifts, and inventory by discrete and stochastic modeling. Know-how at the manufacturing shopfloors are fully used to estimate important model parameters such as the trend of failure events happening in the process. Net present value (NPV) is used as the objective function, considering pharma-specific costs such as change control and quality control. This economic evaluation model is an extension of our previously presented model for lot-sizing in the injectable manufacturing [1].

We applied the this method in an industrial case study. Using the parameters obtained in an actual injectable manufacturing process, the design variable, especially the choice between continuous and batch compounding, could be optimized. Furthermore, a generalized map was also created by varying the specified parameters in the possible ranges of products, process, and the market characteristics. The map provided quantitative insights on the cases where continuos compounding could be economically advantageous than batch compounding. The result could be useful for both retrofitting and grassroot design for injectable manufacturing processes.

[1] M. Yamada, S. Badr, S. Fukuda, M. Nakaya, Y. Yoshioka, H. Sugiyama, Journal of Pharmaceutical Innovation, accepted