(678f) Process Development and Design for Greener Pharmaceutical Processes

Pharmaceuticals are particularly difficult molecules to manufacture and a number of challenges need to be addressed for effective process development and design. First the target molecule needs to be made within specification using a process developed in a very short timeline, brought about by the limited patent-life of the product and the need to recover high discovery costs. The second challenge arises from the need to integrate new technologies, and in particular biotechnology. The majority of pharmaceuticals manufactured today (and in the pipeline) are small molecules, although an increasing number have more than one chiral center and are complex multi-functional molecules. Unsurprisingly, therefore biotechnology has a role in the synthesis of such molecules via fermentation (to supply starting materials), whole-cell biocatalysis (to carry out complex conversions involving enzymes which cannot be isolated or multiple steps) and immobilized enzymes (to create chiral center(s) using reusable catalysts). In all these cases the biotechnological production methods need to be integrated with multi-step chemical synthesis and purification technology in order to obtain a greener production process. The third challenge is to design processes with integrated control such that PAT can be fully implemented and processes can be operated more efficiently. Processes will only take full advantage of PAT concepts such as ?real time release' if traditional batch-processing based production is replaced by continuous production. This will mean that processes can be controlled on the basis of suitable in-line/on-line measurements, such that real-time control can ensure that the product is within specification and can be marketed without the need for extensive laboratory testing. In this presentation tools to address each of these three challenges will be presented with specific examples.