Martinez, M;
Mannall, G;
Spitali, M;
Norrant, EL;
Bracewell, DG;
(2020)
Reactor Design for Continuous Monoclonal Antibody Precipitation Based Upon Micro‐mixing.
Journal of Chemical Technology & Biotechnology
10.1002/jctb.6652.
(In press).
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Abstract
BACKGROUND: Precipitation has been applied for the processing of important therapeutics, including monoclonal antibodies (mAbs). The scale‐up has proven to be a challenging task due to the complexity of the reactions and transport processes involved. This requires a good understanding of the molecular processes underpinning precipitate formation. The aim of this study was to build a micro‐mixing model for the precipitation of a mAb in continuous tubular reactors using ammonium sulphate. The effect of micro‐mixing on precipitate formation (with respect to size, strength, and nature) was evaluated. An ultra scale‐down (USD) centrifugation methodology was applied to determine the ease of precipitate clarification. RESULTS: The results demonstrated that the final mean particle size decreased with increased micro‐mixing, and was obtained with short residence times. Antibody yields in the tubular reactors were consistently above 90% and were shown to be independent of the mixing. Similar particle sizes between a lab and pilot‐scale reactor were correlated with the average energy dissipation rate. The smaller particles obtained from improved micro‐mixing had higher fractal dimensions that correlated with minimal breakage upon exposure to turbulent shear. Precipitates were easily clarified at the USD scale (> 95% clarification), but less so at pilot‐scale (< 80% clarification). CONCLUSION: Precipitation is a rapid process where the final precipitate properties are controlled by the flow conditions. Therefore, the process can be manipulated to acquire a certain particle size range. A high‐throughput precipitation process is also possible. However, further investigation into large‐scale precipitate recovery is required. © 2020 Society of Chemical Industry
| Type: | Article |
|---|---|
| Title: | Reactor Design for Continuous Monoclonal Antibody Precipitation Based Upon Micro‐mixing |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/jctb.6652 |
| Publisher version: | https://doi.org/10.1002/jctb.6652 |
| 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/10118256 |
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