Fernadez-Cerezo, L;
Rayat, A;
Chatel, A;
Pollard, J;
Lye, G;
Hoare, M;
(2020)
The prediction of the operating conditions on the permeate flux and on protein aggregation during membrane processing of monoclonal antibodies.
Journal of Membrane Science
, 596
, Article 117606. 10.1016/j.memsci.2019.117606.
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Abstract
The lack of available material during early stage bioprocess development poses numerous processing challenges such as limiting the number of full-scale experiments. Extended fundamental process understanding could be gained with the use of an ultra scale-down (USD) device using as little as 1.7 mL per experimental run. The USD system is used to predict diafiltration and ultrafiltration/diafiltration (UF/DF) performance of a pilot-scale tangential flow filtration (TFF) system, fitted with a flat-sheet cassette, operating at 500-fold larger scale. Both systems were designed by maintaining a volumetric loading of 8.1 L of feed per m2. Permeate flux was predicted for monoclonal antibody solutions with the USD system across a range of transmembrane pressure drops, feed concentrations and flow conditions during diafiltration, and desired retentate concentrations during UF/DF operations. The resulting USD data were in good agreement with the pilot-scale TFF when scaled based on similar shear rates over the membrane surface. Little change in soluble aggregates was observed in both systems but there were significantly higher increases in product turbidity in the USD system. A correlation was established to relate turbidity increase based on the volume fraction of high shear stress zone for USD systems and various pilot-scale TFF systems. The correlation was extended to encompass the processing time and concentration for a wide range of membrane processing challenges in both scales.
| Type: | Article |
|---|---|
| Title: | The prediction of the operating conditions on the permeate flux and on protein aggregation during membrane processing of monoclonal antibodies |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.memsci.2019.117606 |
| Publisher version: | https://doi.org/10.1016/j.memsci.2019.117606 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10084593 |
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