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Title: Ultra scale-down technologies for membrane processing using high monoclonal antibody concentrates
Author: Fernandez Cerezo, Lara
ISNI:       0000 0004 7964 9207
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2019
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The availability of material is a key constraint in the development of full-scale bioprocesses. Using a combination of critical flow regime analysis, modelling and experimentation, ultra scale-down (USD) methods can yield bioprocess information using only millilitre quantities. A USD device comprising a stirred cell with 1.7 mL capacity is presented. This device resulted from a redesign of an existing device using computational fluid dynamics. The distance between the edge of the rotating disc and membrane surface is critical to reduce the presence of high shear regions. In addition, areas identified as being of low shear, ~ 40% of the membrane area, were blanked. The resulting design has an effective membrane area of 2.1 cm² with a rotating disc mounted 2.0 mm from the membrane surface leading to an approximately uniform shear rate (+/- 17% of average) in a defined layer above the membrane surface. The performance of the USD device was compared with tangential flow filtration (TFF) systems of the same ratio of feed volume to membrane area. The pilot-scale TFF system was characterised in terms of the shear rate using flow rate-pressure drop relationships for the cassette. It operates with ~500-fold larger feed volume and membrane area than the USD system. For a monoclonal antibody diafiltration stage, good agreement was attained in the performance between the two scales at equivalent average shear rates. This resulted in a methodology to predict flux using the USD device as a function of transmembrane pressure, concentration, flow conditions, and volume concentration factors. These predictions are compared to measured flux at pilot-scale. One difference between the systems is the processed sample turbidity. This is possibly due to high shear zones in the presence of membrane and metal surfaces. Mechanisms are described to help define the effect on the process material. A preliminary study of the USD methodology for the processing of nanobodies is used to explore the wider application of the thesis findings.
Supervisor: Hoare, M. ; Lye, G. J. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available