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The accelerated study of bioprocess purification sequences for improved bioprocessing discovery

Reynolds, Tommy Sean; (2005) The accelerated study of bioprocess purification sequences for improved bioprocessing discovery. Doctoral thesis , UCL (University College London). Green open access

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Abstract

In the biopharmaceutical industry being first to market is often key to product success. However process development still needs to deliver an economic, regulatory compliant and effective process. Scale-down studies are commonly used for this purpose since they are quicker and cheaper than pilot plant work. However it is necessary that scale-down methods be created which not only examine the conditions of process stages but also allow production of realistic output streams. These output streams can then be used in the development of subsequent purification operations and facilitate rapid and efficient process development while minimising early investment and risk. Scale-down techniques were used to predict the effects of process changes in a plasma fractionation operation. These predictions were compared to pilot plant data and the full- scale process to assess their accuracy. The scale-down techniques used did not predict the performance of full-scale operations reliably despite being in close agreement with pilot plant results. This is due to the limitations of current scale-down techniques, which focus on a few core parameters and fail to examine engineering and operational details of larger processes. Traditionally, predicting filtration operations is via a bench-top pressure filter, using constant pressure tests to examine the effect of pressure on filtrate flux rate and filter cake dewatering. Interpretation of the results into cake resistance at unit applied pressure (?) and compressibility (n) is used to predict the pressure profile required to maintain a constant, predetermined flux rate. This thesis reports on the operation of a continuous mode laboratory filter in such a way as to prepare filter cakes and filtrate similar to those produced at the industrial scale. Analysis of the filtration rate profile indicated the filter cake to have changing properties (compressibility) with time. Using the insight gained from the new scale-down method gave predictions of the flux profile in a pilot-scale candle filter superior to those obtained from the traditional laboratory batch filter. Very small chromatography columns can be useful tools for narrowing down the myriad of process options involved with this operation, but operational practicalities mean that traditional scale-down rules must be broken. Additionally a number of factors make their operation and subsequent interpretation of results problematic. By identifying and then quantifying the effects of these phenomena it is possible to compensate for their impact. By making several calculated adjustments to the outputs from a small column it was possible to predict the performance of much larger laboratory columns.

Type: Thesis (Doctoral)
Title: The accelerated study of bioprocess purification sequences for improved bioprocessing discovery
Identifier: PQ ETD:602479
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest. Third party copyright material has been removed from the ethesis. Images identifying individuals have been redacted or partially redacted to protect their identity.
UCL classification: UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/1446554
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