Mechanistic modeling of minute virus of mice surrogate removal by anion exchange chromatography in micro scale.

Autor: Döring L; Process Science, Rentschler Biopharma SE, Erwin-Rentschler-Str. 21 88471 Laupheim, Germany; Karlsruhe Institute of Technology (KIT), Institute of Engineering in Life Sciences, Section IV: Biomolecular Separation Engineering, Fritz-Haber-Weg 2 76131 Karlsruhe, Germany., Winderl J; Process Science, Rentschler Biopharma SE, Erwin-Rentschler-Str. 21 88471 Laupheim, Germany., Kron M; Process Science, Rentschler Biopharma SE, Erwin-Rentschler-Str. 21 88471 Laupheim, Germany., Hubbuch J; Karlsruhe Institute of Technology (KIT), Institute of Engineering in Life Sciences, Section IV: Biomolecular Separation Engineering, Fritz-Haber-Weg 2 76131 Karlsruhe, Germany. Electronic address: juergen.hubbuch@kit.edu.
Jazyk: angličtina
Zdroj: Journal of chromatography. A [J Chromatogr A] 2024 Oct 11; Vol. 1734, pp. 465261. Date of Electronic Publication: 2024 Aug 17.
DOI: 10.1016/j.chroma.2024.465261
Abstrakt: Biopharmaceutical products are often produced in Chinese hamster ovary (CHO) cell cultures that are vulnerable to virus infections. Therefore, it is a regulatory requirement that downstream purification steps for biopharmaceuticals can remove viruses from feedstocks. Anion exchange chromatography (AEX) is one of the downstream unit operations that is most frequently used for this purpose and claimed for its capability to remove viruses. However, the impact of various process parameters on virus removal by AEX is still not fully understood. Mechanistic modeling could be a promising way to approach this gap, as these models require comparatively few experiments for calibration. This makes them a valuable tool to improve understanding of viral clearance, especially since virus spiking studies are costly and time consuming. In this study, we present how the virus clearance of a MVM mock virus particle by Q Sepharose FF resin can be described by mechanistic modeling. A lumped kinetic model was combined with a steric mass action model and calibrated at micro scale using three linear gradient experiments and an incremental step elution gradient. The model was subsequently verified for its capability to predict the effect of different sodium chloride concentrations, as well as residence times, on virus clearance and was in good agreement with the LRVs of the verification runs. Overall, models like this could enhance the mechanistic understanding of viral clearance mechanisms and thereby contribute to the development of more efficient and safer biopharmaceutical downstream processes.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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