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Title: An ultra scale-down approach to the rapid evaluation of pleated membrane cartridge filter performance
Author: Brown, A. I.
ISNI:       0000 0004 2729 159X
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2011
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Pleated membrane cartridge filters are used extensively throughout a typical bioprocess. They are exposed to a range of operating conditions and feedstocks. Discrepancies between the performance of the flat sheet membrane and pleated membrane have previously been identified, although little has been done to fully characterise the effects of pleating. As current scale-up techniques use the flat sheet membrane to predict the performance of the large-scale pleated cartridge, the discrepancy in performance between flat sheet and pleated cartridge leads to inaccuracy in scale-up. This inaccuracy is accounted for by over-sizing of the equipment. In turn this reduces the efficiency of the bioprocess and increases capital costs. At the present time no accurate and reliable scale-up methodology exists that accounts for the effects of pleating. A systematic investigation into the effect of pleating has been conducted. By varying the key pleat characteristics: pleat height, type and packing density, the impact upon cartridge performance of these characteristics has been determined. Using this knowledge, new scale-down cartridge filters have been developed, fabricated and tested. When faced with both clean water and a pepsin protein solution, performance was within 10% of the large-scale 10” counterpart, whilst operating with a 1000 fold reduction in feed volume. This compares well to flat sheet membrane which showed up to 53% variation in performance to the pleated cartridge filter. The scale-down cartridge is limited to the degree in which reduction of feedstock can be achieved. So as to reduce feed volume requirements further, a ultra scaledown methodology has been developed that uses experimental models to account for the effect that pleating has upon cartridge performance. When coupled with experimental data derived from flat sheet discs, the scale-up performance improves predictions with flat sheet membrane however discrepancies still exist between the two scales, suggesting that the method is not yet robust. Based upon the work of this thesis the close performance between the scaledown cartridges and the large-scale cartridges, coupled with the low feed requirement, make the device an excellent method by which rapid scale-up can be achieved during the process development of biopharmaceutical products. However, it is recommended that the ultra scale-down approach is developed further, so as to build a robust method to predict the performance of industrial scale pleated filter cartridges using significantly reduced areas of flat sheet membrane.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available