Development of robust expanded bed adsorption processes for CGMP manufacture of biopharmaceutical products

Ewert, Stephanie (2017). Development of robust expanded bed adsorption processes for CGMP manufacture of biopharmaceutical products. University of Birmingham. Ph.D.

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Abstract

Expanded Bed Adsorption (EBA) is a form of liquid fluidized bed adsorption chromatography employing dense chromatographic media of defined size distribution. EBA's main advantage stems from its ability to perform chromatographic separations with crude feedstocks, thereby combining three separate tasks - clarification, concentration and initial capture/purification - in one single unit operation. Still, understanding of support particle movement (solid phase dispersion) is limited, impairing the process' robustness. In this work, the technique of Positron Emission Particle Tracking (PEPT) was employed extensively to study solid phase motion and dispersion in expanded beds of commercial media. In addition to providing evidence of classification and non-uniform bed expansion in all fluidised beds under study, PEPT was used to determine kinetics of bed stabilisation and identify changes in tracer position and speed along the length of the bed in response to variations in flow rate, degree of column misalignment, and means of fluid distribution. Furthermore, adsorbent particle motion was investigated under 'real process' conditions, i.e. during the application of a porcine serum feedstock.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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