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A novel hybrid bioprocess strategy addressing key challenges of advanced biomanufacturing

Monoclonal antibodies (mAb) are commonly manufactured by either discontinuous operations like fed-batch (FB) or continuous processes such as steady-state perfusion. Both process types comprise opposing advantages and disadvantages in areas such as plant utilization, feasible cell densities, media co...

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Autores principales: Reger, Lucas Nik, Saballus, Martin, Kappes, Annika, Kampmann, Markus, Wijffels, Rene H., Martens, Dirk E., Niemann, Julia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10349264/
https://www.ncbi.nlm.nih.gov/pubmed/37456731
http://dx.doi.org/10.3389/fbioe.2023.1211410
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author Reger, Lucas Nik
Saballus, Martin
Kappes, Annika
Kampmann, Markus
Wijffels, Rene H.
Martens, Dirk E.
Niemann, Julia
author_facet Reger, Lucas Nik
Saballus, Martin
Kappes, Annika
Kampmann, Markus
Wijffels, Rene H.
Martens, Dirk E.
Niemann, Julia
author_sort Reger, Lucas Nik
collection PubMed
description Monoclonal antibodies (mAb) are commonly manufactured by either discontinuous operations like fed-batch (FB) or continuous processes such as steady-state perfusion. Both process types comprise opposing advantages and disadvantages in areas such as plant utilization, feasible cell densities, media consumption and process monitoring effort. In this study, we show feasibility of a promising novel hybrid process strategy that combines beneficial attributes of both process formats. In detail, our strategy comprises a short duration FB, followed by a fast media exchange and cell density readjustment, marking the start of the next FB cycle. Utilizing a small-scale screening tool, we were able to identify beneficial process parameters, including FB interval duration and reinoculation cell density, that allow for multiple cycles of the outlined process in a reproducible manner. In addition, we could demonstrate scalability of the process to a 5L benchtop system, using a fluidized-bed centrifuge as scalable media exchange system. The novel process showed increased productivity (+217%) as well as longer cultivation duration, in comparison to a standard FB with a significantly lower media consumption per produced product (−50%) and a decreased need for process monitoring, in comparison to a perfusion cultivation. Further, the process revealed constant glycosylation pattern in comparison to the perfusion cultivation and has strong potential for further scale-up, due to the use of fully scalable cultivation and media exchange platforms. In summary, we have developed a novel hybrid process strategy that tackles the key challenges of current biomanufacturing of either low productivity or high media consumption, representing a new and innovative approach for future process intensification efforts.
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spelling pubmed-103492642023-07-16 A novel hybrid bioprocess strategy addressing key challenges of advanced biomanufacturing Reger, Lucas Nik Saballus, Martin Kappes, Annika Kampmann, Markus Wijffels, Rene H. Martens, Dirk E. Niemann, Julia Front Bioeng Biotechnol Bioengineering and Biotechnology Monoclonal antibodies (mAb) are commonly manufactured by either discontinuous operations like fed-batch (FB) or continuous processes such as steady-state perfusion. Both process types comprise opposing advantages and disadvantages in areas such as plant utilization, feasible cell densities, media consumption and process monitoring effort. In this study, we show feasibility of a promising novel hybrid process strategy that combines beneficial attributes of both process formats. In detail, our strategy comprises a short duration FB, followed by a fast media exchange and cell density readjustment, marking the start of the next FB cycle. Utilizing a small-scale screening tool, we were able to identify beneficial process parameters, including FB interval duration and reinoculation cell density, that allow for multiple cycles of the outlined process in a reproducible manner. In addition, we could demonstrate scalability of the process to a 5L benchtop system, using a fluidized-bed centrifuge as scalable media exchange system. The novel process showed increased productivity (+217%) as well as longer cultivation duration, in comparison to a standard FB with a significantly lower media consumption per produced product (−50%) and a decreased need for process monitoring, in comparison to a perfusion cultivation. Further, the process revealed constant glycosylation pattern in comparison to the perfusion cultivation and has strong potential for further scale-up, due to the use of fully scalable cultivation and media exchange platforms. In summary, we have developed a novel hybrid process strategy that tackles the key challenges of current biomanufacturing of either low productivity or high media consumption, representing a new and innovative approach for future process intensification efforts. Frontiers Media S.A. 2023-06-30 /pmc/articles/PMC10349264/ /pubmed/37456731 http://dx.doi.org/10.3389/fbioe.2023.1211410 Text en Copyright © 2023 Reger, Saballus, Kappes, Kampmann, Wijffels, Martens and Niemann. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioengineering and Biotechnology
Reger, Lucas Nik
Saballus, Martin
Kappes, Annika
Kampmann, Markus
Wijffels, Rene H.
Martens, Dirk E.
Niemann, Julia
A novel hybrid bioprocess strategy addressing key challenges of advanced biomanufacturing
title A novel hybrid bioprocess strategy addressing key challenges of advanced biomanufacturing
title_full A novel hybrid bioprocess strategy addressing key challenges of advanced biomanufacturing
title_fullStr A novel hybrid bioprocess strategy addressing key challenges of advanced biomanufacturing
title_full_unstemmed A novel hybrid bioprocess strategy addressing key challenges of advanced biomanufacturing
title_short A novel hybrid bioprocess strategy addressing key challenges of advanced biomanufacturing
title_sort novel hybrid bioprocess strategy addressing key challenges of advanced biomanufacturing
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10349264/
https://www.ncbi.nlm.nih.gov/pubmed/37456731
http://dx.doi.org/10.3389/fbioe.2023.1211410
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