Evaluation of challenges to the ubiquitous nature of chromatography.
Doctoral thesis, UCL (University College London).
Packed bed chromatography is the workhorse of the majority of downstream purification processes used for the manufacture of biopharmaceutical therapeutics. This high dependence upon chromatography has lead to concerns being raised regarding the manufacturing costs and also the potential constraints on plant productivity imposed by packed bed processes, particularly in light of advances seen in upstream operations. This has not unsurprisingly generated a significant degree of discussion amongst the bioprocessing community on how best to deal with these challenges. Amongst the proposed strategies, is the adoption of what may be termed \alternative" bioseparation techniques, which may potentially offer higher processing capacities at a lower cost. In this study a Multi-Attribute Decision Making MADM) based framework was used to evaluate these bioseparation techniques being considered as potential alternatives to packed bed chromatography. This evaluation included consideration of a wide range of process characteristics, beyond just performance and cost related attributes, but also considering areas such as the ease of process development, operation and scalability. The use of this framework not only allows the most promising technologies to be identified, but manipulation of the non-deterministic outputs of this framework permitted indications to be obtained as to the most productive directions for further technology development. Using the indicators provided by this framework, experimental studies were carried out in order to study the performance of these most promising alternatives, when used as part of a whole downstream processing train. These studies yielded information upon the interactions between these different bioseparation technologies and allowed the impact on process productivity and process economy to be evaluated. The collective findings from this study reinforce the generally held opinion that none of these alternative bioseparation techniques can currently be considered the key to overcoming the challenges faced by downstream processing. Indeed evaluations of the techniques imply that the ubiquitous nature of packed bed chromatography is likely to remain for the foreseeable future. However the tools which have been developed allow for a rational explanation of what exact factors are the barriers to adoption for these techniques, and as a consequence provide guidance as to the areas in which future development is most required.
|Title:||Evaluation of challenges to the ubiquitous nature of chromatography|
|Open access status:||An open access version is available from UCL Discovery|
|UCL classification:||UCL > School of BEAMS > Faculty of Engineering Science > Biochemical Engineering|
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