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Process economics evaluation and optimization of adeno-associated virus downstream processing

Lyle, Annabel; Stamatis, Christos; Linke, Thomas; Hulley, Martyn; Schmelzer, Albert; Turner, Richard; Farid, Suzanne S; (2023) Process economics evaluation and optimization of adeno-associated virus downstream processing. Biotechnology and Bioengineering 10.1002/bit.28402. (In press). Green open access

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Abstract

Adeno-associated virus (AAV) manufacturing has traditionally focused upon lab-scale techniques to culture and purify vector products, leading to limitations in production capacity. The tool presented in this paper assesses the feasibility of using non-scalable technologies at high AAV demands and identifies optimal flowsheets at large-scale that meet both cost and purity targets. The decisional tool comprises (a) a detailed process economics model with the relevant mass balance, sizing, and costing equations for AAV upstream and downstream technologies, (b) a built-in Monte Carlo simulation to assess uncertainties, and (c) a brute-force optimization algorithm for rapid investigation into the optimal purification combinations. The results overall highlighted that switching to more scalable upstream and downstream processing alternatives is economically advantageous. The base case analysis showed the cost and robustness advantages of utilizing suspension cell culture over adherent, as well as a fully chromatographic purification platform over batch ultracentrifugation. Expanding the set of purification options available gave insights into the optimal combination to satisfy both cost and purity targets. As the purity target increased, the optimal polishing solution moved from the non-capsid purifying multimodal chromatography to anion-exchange chromatography or continuous ultracentrifugation.

Type: Article
Title: Process economics evaluation and optimization of adeno-associated virus downstream processing
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/bit.28402
Publisher version: https://doi.org/10.1002/bit.28402
Language: English
Additional information: © 2023 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: Monte Carlo simulation, adeno-associated vectors, chromatography, cost of goods modeling, optimization, ultracentrifugation
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/10168910
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