Fischer, V;
Kucia-Tran, R;
Lewis, W;
Velayudhan, A;
(2019)
Hybrid optimization of preparative chromatography for a ternary monoclonal antibody mixture.
Biotechnology Progress
, 35
(5)
, Article e2849. 10.1002/btpr.2849.
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Abstract
In the purification of monoclonal antibodies, ion‐exchange chromatography is typically used among the polishing steps to reduce the amount of product‐related impurities such as aggregates and fragments, whilst simultaneously reducing HCP, residual Protein A and potential toxins and viruses. When the product‐related impurities are difficult to separate from the products, the optimization of these chromatographic steps can be complex and laborious. In this paper, we optimize the polishing chromatography of a monoclonal antibody from a challenging ternary feed mixture by introducing a hybrid approach of the simplex method and a form of local optimization. To maximize the productivity of this preparative bind‐and‐elute cation‐exchange chromatography, wide ranges of the three critical operational parameters – column loading, the initial salt concentration and gradient slope – had to be considered. The hybrid optimization approach is shown to be extremely effective in dealing with this complex separation that was subject to multiple constraints based on yield, purity and product breakthrough. Furthermore, it enabled the generation of a large knowledge space that was subsequently used to study the sensitivity of the objective function. Increased design space understanding was gained through the application of Monte Carlo simulations. Hence, this work proposes a powerful hybrid optimization method, applied to an industrially relevant process development challenge. The properties of this approach and the results and insights gained, make it perfectly suited for the rapid development of biotechnological unit operations during early‐stage bioprocess development.
Type: | Article |
---|---|
Title: | Hybrid optimization of preparative chromatography for a ternary monoclonal antibody mixture |
Location: | United States |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1002/btpr.2849 |
Publisher version: | https://doi.org/10.1002/btpr.2849 |
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. |
Keywords: | antibody purification, constrained experimental simplex optimization, design space, early-stage bioprocess development, preparative scale polishing chromatography |
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/10075034 |
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