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Development of engineering methods for the rapid evaluation of membrane filtration within bioprocesses

Eardley-Patel, R.; (2008) Development of engineering methods for the rapid evaluation of membrane filtration within bioprocesses. Doctoral thesis, University of London.

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Abstract

With the advent of high-throughput screening technologies, key constraints associated with identifying potential drug candidates are being removed - the bottleneck in the timely delivery of new drugs will inevitably shift toward process development. Conventionally, the pilot plant studies required for process design only start when there is confidence that the drug candidate will make it to market. This means that this development period is very limited, and the flowsheet that enters the manufacturing phase is often sub-optimal. Collaborative work at UCL has been developing new strategies that aim to change this paradigm. The use of scale-down experiments in the drug discovery phase, in conjunction with modelling techniques, has been shown to be capable of providing more robust process definition early on in development. Such methodologies allow the study of more process options and hence rapid identification of optimal conditions, and thus mitigate the risks associated with equipment capital investment. Further advantages are that the experiments require less material, and can be done prior to, as well as in parallel to, pilot plant development. Scale-down can also be useful for the analysis of existing processes, e.g. for validation and troubleshooting, especially where material is valuable and/or scarce. This thesis describes the design and development of a scale-down device for membrane filtration, with a focus on tangential flow microfiltration for primary clarification. The device uses a rotating disk suspended above a static membrane surface to generate surface shear, in order to mimic the global, hydrodynamic conditions found in commercial crossflow modules. Results are presented showing how filtration performance of the scale-down device (3.5xl0-4m2 membrane area) correlates well with pilot scale data (O.1m2) for a range of representative biological materials including yeast, bacterial and mammalian cell cultures. Methodologies for confident assessment of microfiltration performance are given, which are capable of dealing with different feedstocks, membrane types, and a range of operating strategies, using greatly reduced quantities of feed. The steps required to design and build the next generation of filtration scale-down device for rapid process development are also addressed, along with a discussion of the related business and regulatory issues that shape the industry.

Type:Thesis (Doctoral)
Title:Development of engineering methods for the rapid evaluation of membrane filtration within bioprocesses
Language:English
UCL classification:UCL > School of BEAMS > Faculty of Engineering Science > Biochemical Engineering

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