UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Hybrid optimization of preparative chromatography for a ternary monoclonal antibody mixture

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. Green open access

[thumbnail of Fischer_et_al-2019-Biotechnology_Progress.pdf]
Preview
Text
Fischer_et_al-2019-Biotechnology_Progress.pdf - Accepted Version

Download (3MB) | Preview

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
Downloads since deposit
129Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item