Chapter 9. Physicochemical Data Requirements for the Design of Fine Chemical Processes: Acquisition and Application

Abstract

Process design is an essential precursor to the introduction of a pharmaceutical product into the market. Discovery chemists require a rapid synthesis of their target molecules; process efficiency is unimportant at that stage. It is rare that the synthesis process used in discovery is adequate for manufacture; even if it were, much additional information would be required before a product could be safely and economically manufactured. So once a new product has been selected for development, the next task for the process scientists is to select a route and design a process. Design of a good manufacturing process requires much more understanding and information than is provided in a typical laboratory process description. A majority of pharmaceutical manufacturing processes are multiphase in nature, and good process design and scale-up require consideration of a variety of interactions between chemistry and the physical environment in which the chemistry takes place. This chapter outlines the scope of the data requirements and the understanding of the science required to support adequate design of optimised laboratory and manufacturing processes. The amount and nature of the information required depends strongly on the complexity of the process, and an approach to identifying critical data requirements is described. This approach to process development makes for more efficient processes and leads to less failures on scale-up. Numerous examples are provided of the application of the acquired data to the optimisation of laboratory processes and to scale-up.