Economic and engineering aspects of disposables-based bioprocessing

Biopharmaceutical companies face a fast moving competitive market with high product failure rates. Disposables-based bioprocessing meets some of these current pressures and concerns by employing single-use, pre-sterilised, pre-validated components instead of traditional stainless-steel fixed equipment. The advantages include increased flexibility, smaller initial investments and potential reduction of time to market. This thesis provides an engineering study of the use of disposable equipment as an alternative to conventional systems. A costing framework was developed to compare disposables-based and conventional plants. The use of disposable equipment was shown to result in a 70% increase in running costs, substantially offset by a 40% reduction in the capital investment required. The production of a Fab' antibody fragment from an E. coli fermentation was used as the illustrative case study. Sensitivity analysis to different variables was made to confirm the results. The study showed a loss in yield in different unit operations in the disposable process could be compensated for by a reduction of the materials costs. It was also predicted that the use of disposables could reduce time to market by up to 1.5 years. The running costs associated with the single use of microfiltration membranes were shown to have a high impact on the overall cost indicating that minimisation of membrane area was crucial. Experimental work focused on this unit operation, aimed at controlling transmission. Transmission was shown to decrease rapidly and the causes for this decrease were explained and modelled. A strategy that maintains % transmission at high values was developed and evaluated theoretically and experimentally. The method comprises short intermediate rinsing steps, capable of restoring the membrane properties. The resulting reduced filtration areas were shown to enhance further the economic attractiveness of the disposable approach. Overall disposables-based bioprocessing was shown to be economically and technologically competitive with conventional engineering approaches.