An ultra scale-down approach to the rapid evaluation of pleated membrane cartridge filter performance

摘要

Pleated membrane cartridge filters are used extensively throughout a typicaludbioprocess. They are exposed to a range of operating conditions and feedstocks.udDiscrepancies between the performance of the flat sheet membrane and pleatedudmembrane have previously been identified, although little has been done to fullyudcharacterise the effects of pleating. As current scale-up techniques use the flatudsheet membrane to predict the performance of the large-scale pleated cartridge,udthe discrepancy in performance between flat sheet and pleated cartridge leads toudinaccuracy in scale-up. This inaccuracy is accounted for by over-sizing of theudequipment. In turn this reduces the efficiency of the bioprocess and increasesudcapital costs. At the present time no accurate and reliable scale-up methodologyudexists that accounts for the effects of pleating.udA systematic investigation into the effect of pleating has been conducted. Byudvarying the key pleat characteristics: pleat height, type and packing density, theudimpact upon cartridge performance of these characteristics has been determined.udUsing this knowledge, new scale-down cartridge filters have been developed,udfabricated and tested. When faced with both clean water and a pepsin proteinudsolution, performance was within 10% of the large-scale 10” counterpart, whilstudoperating with a 1000 fold reduction in feed volume. This compares well to flatudsheet membrane which showed up to 53% variation in performance to the pleatedudcartridge filter.udThe scale-down cartridge is limited to the degree in which reduction of feedstockudcan be achieved. So as to reduce feed volume requirements further, a ultra scaledownudmethodology has been developed that uses experimental models to accountudfor the effect that pleating has upon cartridge performance. When coupled withudexperimental data derived from flat sheet discs, the scale-up performanceudimproves predictions with flat sheet membrane however discrepancies still existudbetween the two scales, suggesting that the method is not yet robust. Based upon the work of this thesis the close performance between the scaledownudcartridges and the large-scale cartridges, coupled with the low feedudrequirement, make the device an excellent method by which rapid scale-up canudbe achieved during the process development of biopharmaceutical products.udHowever, it is recommended that the ultra scale-down approach is developedudfurther, so as to build a robust method to predict the performance of industrialudscale pleated filter cartridges using significantly reduced areas of flat sheetudmembrane.