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The graphical determination of operating conditions for chromatographic sequences

Salisbury, RS; (2007) The graphical determination of operating conditions for chromatographic sequences. Doctoral thesis , UCL (University College London). Green open access

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Abstract

Multiple step chromatography sequences are necessary in biopharmaceutical downstream processing to achieve the desired levels of purity for products such as therapeutic proteins. Traditional methods of process design deal with each step individually, but this can result in a sequence that does not achieve best overall performance. This project proposes a graphical methodology for the identification of operating conditions for a two-step chromatography sequence. The method uses Windows of Operation to incorporate the tradeoffs between yield, purity, and productivity. A tie-line procedure is developed that separates the Window of Operation for the first chromatographic step into two zones. One zone contains those operating conditions that combine to produce a material which can be purified successfully by the second step to produce a product that meets the desired specifications. The second zone consists of operating conditions which will not yield a material that can be adequately purified by a second chromatographic stage to yield a product of the predetermined specifications. The methodology is valuable in that it helps in achieving the rapid design of a two-step chromatography sequence, and aids in choosing the optimum operating conditions for the first step which are highly dependent upon the operation and specifications of the second chromatographic step. Simulations carried out using a software package based on the general rate model depict the construction and use of the method applied to a sequence of ion exchange and hydrophobic interaction chromatography separating a three component protein mixture. The methodology is verified successfully using an experimental system that purifies Fab antibody fragments from a three-component system consisting also of Ribonuclease A and Cytochrome C, with a two-stage chromatography sequence, ion exchange followed by hydrophobic interaction chromatography.

Type: Thesis (Doctoral)
Title: The graphical determination of operating conditions for chromatographic sequences
Identifier: PQ ETD:593409
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.
URI: https://discovery.ucl.ac.uk/id/eprint/1446080
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