Process intensification by frontal chromatography: Performance comparison of resin and membrane adsorber for monovalent antibody aggregate removal.
aggregate
antibody
frontal chromatography
membrane adsorber
resin
Journal
Biotechnology and bioengineering
ISSN: 1097-0290
Titre abrégé: Biotechnol Bioeng
Pays: United States
ID NLM: 7502021
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
25
06
2019
revised:
23
10
2019
accepted:
22
11
2019
pubmed:
4
12
2019
medline:
23
2
2021
entrez:
3
12
2019
Statut:
ppublish
Résumé
Aggregates are amongst the most important product-related impurities to be removed during the downstream processing of antibodies due to their potential immunogenicity. Traditional operations use cation-exchange resins in bind-elute mode for their separation. However, frontal analysis is emerging as an alternative. In this study, a three-step process development for a membrane adsorber and a resin material is carried out, allowing the comparison between the stationary phases. Based on a screening study, optimal loading conditions are determined, which show that weak binding is favored on the membrane and strong binding on the resin. Transfer of these findings to breakthrough experiments shows that at 99% pool purity the yield is higher for the membrane, while the resin can be loaded twice as high, exceeding yields of 85%. For the investigated antibody and based on a given regeneration protocol, the productivity of the two phases is similar, ranging around 200 g/(L·h). Due to the higher loading, the resin requires about one-third less buffer than the membrane. Furthermore, the implementation of a wash step after loading allows to further increase yield by about 5%. In comparison to a generic bind-elute process, productivity and buffer consumption are improved by an order of magnitude.
Substances chimiques
Antibodies, Monoclonal
0
Cation Exchange Resins
0
Membranes, Artificial
0
Protein Aggregates
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
662-672Subventions
Organisme : Kommission für Technologie und Innovation
ID : 19190.2 PFIW-IW
Pays : International
Informations de copyright
© 2019 Wiley Periodicals, Inc.
Références
Arosio, P., Barolo, G., Müller-Späth, T., Wu, H., & Morbidelli, M. (2011). Aggregation stability of a monoclonal antibody during downstream processing. Pharmaceutical Research, 28, 1884-1894. https://doi.org/10.1007/s11095-011-0416-7
Arosio, P., Rima, S., & Morbidelli, M. (2013). Aggregation mechanism of an IgG2 and two IgG1 monoclonal antibodies at low pH: From oligomers to larger aggregates. Pharmaceutical Research, 30, 641-654. https://doi.org/10.1007/s11095-012-0885-3
Baur, D., Angelo, J. M., Chollangi, S., Xu, X., Müller-Späth, T., Zhang, N., … Morbidelli, M. (2018). Model assisted comparison of protein A resins and multi-column chromatography for capture processes. Journal of Biotechnology, 285, 64-73. https://doi.org/10.1016/j.jbiotec.2018.08.014
Brown, A., Bill, J., Tully, T., Radhamohan, A., & Dowd, C. (2010). Overloading ion-exchange membranes as a purification step for monoclonal antibodies. Biotechnology and Applied Biochemistry, 56, 59-70. https://doi.org/10.1042/BA20090369
Carta, G., & Jungbauer, A. (2010). Downstream processing of biotechnology products, Protein Chromatography (pp. 1-55). Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA. https://doi.org/10.1002/9783527630158.ch1
Fargues, C., Bailly, M., & Grevillot, G. (1998). Adsorption of BSA and hemoglobin on hydroxyapatite support: Equilibria and multicomponent dynamic adsorption. Adsorption, 4, 5-16. https://doi.org/10.1023/A:1008822918494
Garke, G., Hartmann, R., Papamichael, N., Deckwer, W.-D., & Anspach, F. B. (1999). The influence of protein size on adsorption kinetics and equilibria in ion-exchange chromatography. Separation Science and Technology, 34, 2521-2538. https://doi.org/10.1081/SS-100100788
Hargreaves, B. (2018). Montpelier, France: William Reed. https://www.biopharma-reporter.com/Article/2018/09/11/MilliporeSigma-claims-first-of-its-kind-resin-improves-efficiency-across-the-board
Hari, S. B., Lau, H., Razinkov, V. I., Chen, S., & Latypov, R. F. (2010). Acid-induced aggregation of human monoclonal IgG1 and IgG2: Molecular mechanism and the effect of solution composition. Biochemistry, 49, 9328-9338. https://doi.org/10.1021/bi100841u
Hunter, A. K., & Carta, G. (2001). Effects of bovine serum albumin heterogeneity on frontal analysis with anion-exchange media. Journal of Chromatography A, 937, 13-19. https://doi.org/10.1016/S0021-9673(01)01301-2
Ichihara, T., Ito, T., & Gillespie, C. (2019). Polishing approach with fully connected flow-through purification for therapeutic monoclonal antibody. Engineering in Life Sciences, 19, 31-36. https://doi.org/10.1002/elsc.201800123
Ichihara, T., Ito, T., Kurisu, Y., Galipeau, K., & Gillespie, C. (2018). Integrated flow-through purification for therapeutic monoclonal antibodies processing. mAbs, 10, 325-334. https://doi.org/10.1080/19420862.2017.1417717
Jagschies, G., Lindskog, E., Lacki, K. & Galliher, P. (Eds.), 2018). Biopharmaceutical Processing (1st ed., pp. 3-31). Amsterdam: Elsevier. https://doi.org/10.1016/C2014-0-01092-1
Karst, D., Steinebach, F., & Morbidelli, M. (2018). Continuous integrated manufacturing of therapeutic proteins. Current Opinion in Biotechnology, 53, 76-84. https://doi.org/10.1016/j.copbio.2017.12.015
Knudsen, H. L., Fahrner, R. L., Xu, Y., Norling, L. A., & Blank, G. S. (2001). Membrane ion-exchange chromatography for process-scale antibody purification. Journal of Chromatography A, 907, 145-154. https://doi.org/10.1016/S0021-9673(00)01041-4
Liu, H. F., Ma, J., Winter, C., & Bayer, R. (2010). Recovery and purification process development for monoclonal antibody production. mAbs, 2, 480-499. https://doi.org/10.4161/mabs.2.5.12645
Liu, H. F., McCooey, B., Duarte, T., Myers, D. E., Hudson, T., Amanullah, A., … Kelley, B. D. (2011). Exploration of overloaded cation exchange chromatography for monoclonal antibody purification. Journal of Chromatography A, 1218, 6943-6952. https://doi.org/10.1016/j.chroma.2011.08.008
Reck, J., Pabst, T., Hunter, A., & Carta, G. (2017). Separation of antibody monomer-dimer mixtures by frontal analysis. Journal of Chromatography A, 1500, 96-104. https://doi.org/10.1016/j.chroma.2017.04.014
Stone, M. T., Cotoni, K. A., & Stoner, J. L. (2019). Cation exchange frontal chromatography for the removal of monoclonal antibody aggregates. Journal of Chromatography A, 1599, 152-160. https://doi.org/10.1016/j.chroma.2019.04.020
Tao, Y., Chen, N., Carta, G., Ferreira, G., & Robbins, D. (2012). Modeling multicomponent adsorption of monoclonal antibody charge variants in cation exchange columns. AIChE Journal, 58, 2503-2511. https://doi.org/10.1002/aic.13718
Vlasak, J., & Ionescu, R. (2011). Fragmentation of monoclonal antibodies. mAbs, 3, 253-263. https://doi.org/10.4161/mabs.3.3.15608
Vogg, S., Wolf, M. K. F., & Morbidelli, M. (2018). Continuous and integrated expression and purification of recombinant antibodies. Methods in Molecular Biology, 1850, 147-178. https://doi.org/10.1007/978-1-4939-8730-6_11
Weinbrenner, W. F., & Etzel, M. R. (1994). Competitive adsorption of α-lactalbumin and bovine serum albumin to a sulfopropyl ion-exchange membrane. Journal of Chromatography A, 662, 414-419. https://doi.org/10.1016/0021-9673(94)80530-X
Wolf, M. K. F., Closet, A., Bzowska, M., Bielser, J.-M., Souquet, J., Broly, H., & Morbidelli, M. (2019). Improved performance in mammalian cell perfusion cultures by growth inhibition. Biotechnology Journal, 14, 1700722. https://doi.org/10.1002/biot.201700722
Wollacott, R., Roth, L., Sears, T., Sharpe, R., Jiang, M., & Ozturk, S. (2015). The development of a flow-through mode cation exchange process for the purification of a monoclonal antibody. Bioprocessing Journal, 14, 5-13. https://doi.org/10.12665/J142.Wollacott
Wrzosek, K., & Polakovič, M. (2011). Effect of pH on protein adsorption capacity of strong cation exchangers with grafted layer. Journal of Chromatography A, 1218, 6987-6994. https://doi.org/10.1016/j.chroma.2011.07.097
Zhou, J. X., & Tressel, T. (2006). Basic concepts in Q membrane chromatography for large-scale antibody production. Biotechnology Progress, 22, 341-349. https://doi.org/10.1021/bp050425v