ProfessorBrian Glennon

Bioprocess Scale-up; Pharmaceutical Crystallization; Modelling of bioprocessing operations; Distillation Design Methods Research As part of the effort to produce new therapeutic treatments, it is necessary to ensure that these innovative products can be safely and reliably produced on a large-scale at a reasonable cost, and with minimum environmental impact. Throughout the chemical and biochemical manufacturing industries, one of the greatest technical challenges is the scale-up of processes from the laboratory to production-scale. For many operations, this is straightforward, with the system obeying well-defined and well-established scale-up rules. This is especially true for large-scale continuous processing (e.g. distillation, extraction, filtration, etc.). However, for batch processing, scale-up is generally far more empirical, with heavy emphasis placed on the use of pilot-plant studies to provide a technological bridge between the laboratory and the production plant. Our research group is interested in developing better ways to more reliably facilitate such transfer. In particular, the scale-up of biological processes has proved problematic. The response of a micro-organism to the processing environment in a production operation often proves to be significantly different from that observed in the laboratory. This variation in response is understandable when the different environments are considered in any detail. In laboratory equipment, typically shake-flasks, mixing, aeration and substrate distribution are all quite uniform. Pressure and temperature gradients are essentially non-existent, or present over such small scales as to be negligible. In production-scale systems, which may range from 100 litres up to 200 m 3 in size, the extent of the variation in local values for all of these parameters may, by comparison, be very significant. A similar problem faces the production of bulk pharmaceuticals, whether produced through chemical or biological synthesis. In particular, almost all pharmaceuticals are purified using batch crystallization in large stirred tanks (geometrically similar to bioreactors), which are poorly mixed due to the limitations of the vessel design. The crystallization process is governed by kinetic transport phenomena, which are complex functions of the prevailing non-equilibrium conditions within the vessel. Thus, heterogeneities in the distribution of, for example, solute concentration or temperature will significantly alter the performance of the process-scale crystalliser compared to a well-mixed system, such as may typically prevail in the laboratory-scale vessel from which the process has been developed. As with bioreactor scale-up, the challenge is to determine the interactions between identifiable stages of the crystallisation system, in which different transport activities prevail. A variety of technologies are employed as part of these investigations, ranging from pilot-scale bioreactors, to in-line imaging systems.