Cargando…

Boosting Productivity for Advanced Biomanufacturing by Re-Using Viable Cells

Monoclonal antibodies (mAb) have gained enormous therapeutic application during the last decade as highly efficient and flexible tools for the treatment of various diseases. Despite this success, there remain opportunities to drive down the manufacturing costs of antibody-based therapies through cos...

Descripción completa

Detalles Bibliográficos
Autores principales: Reger, Lucas Nik, Saballus, Martin, Matuszczyk, Jens, 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/PMC9978186/
https://www.ncbi.nlm.nih.gov/pubmed/36873352
http://dx.doi.org/10.3389/fbioe.2023.1106292
_version_ 1784899462578044928
author Reger, Lucas Nik
Saballus, Martin
Matuszczyk, Jens
Kampmann, Markus
Wijffels, Rene H.
Martens, Dirk E.
Niemann, Julia
author_facet Reger, Lucas Nik
Saballus, Martin
Matuszczyk, Jens
Kampmann, Markus
Wijffels, Rene H.
Martens, Dirk E.
Niemann, Julia
author_sort Reger, Lucas Nik
collection PubMed
description Monoclonal antibodies (mAb) have gained enormous therapeutic application during the last decade as highly efficient and flexible tools for the treatment of various diseases. Despite this success, there remain opportunities to drive down the manufacturing costs of antibody-based therapies through cost efficiency measures. To reduce production costs, novel process intensification methods based on state-of-the-art fed-batch and perfusion have been implemented during the last few years. Building on process intensification, we demonstrate the feasibility and benefits of a novel, innovative hybrid process that combines the robustness of a fed-batch operation with the benefits of a complete media exchange enabled through a fluidized bed centrifuge (FBC). In an initial small-scale FBC-mimic screening, we investigated multiple process parameters, resulting in increased cell proliferation and an elongated viability profile. Consecutively, the most productive process scenario was transferred to the 5-L scale, further optimized and compared to a standard fed-batch process. Our data show that the novel hybrid process enables significantly higher peak cell densities (163%) and an impressive increase in mAb amount of approximately 254% while utilizing the same reactor size and process duration of the standard fed-batch operation. Furthermore, our data show comparable critical quality attributes (CQAs) between the processes and reveal scale-up possibilities and no need for extensive additional process monitoring. Therefore, this novel process intensification strategy yields strong potential for transfer into future industrial manufacturing processes.
format Online
Article
Text
id pubmed-9978186
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-99781862023-03-03 Boosting Productivity for Advanced Biomanufacturing by Re-Using Viable Cells Reger, Lucas Nik Saballus, Martin Matuszczyk, Jens Kampmann, Markus Wijffels, Rene H. Martens, Dirk E. Niemann, Julia Front Bioeng Biotechnol Bioengineering and Biotechnology Monoclonal antibodies (mAb) have gained enormous therapeutic application during the last decade as highly efficient and flexible tools for the treatment of various diseases. Despite this success, there remain opportunities to drive down the manufacturing costs of antibody-based therapies through cost efficiency measures. To reduce production costs, novel process intensification methods based on state-of-the-art fed-batch and perfusion have been implemented during the last few years. Building on process intensification, we demonstrate the feasibility and benefits of a novel, innovative hybrid process that combines the robustness of a fed-batch operation with the benefits of a complete media exchange enabled through a fluidized bed centrifuge (FBC). In an initial small-scale FBC-mimic screening, we investigated multiple process parameters, resulting in increased cell proliferation and an elongated viability profile. Consecutively, the most productive process scenario was transferred to the 5-L scale, further optimized and compared to a standard fed-batch process. Our data show that the novel hybrid process enables significantly higher peak cell densities (163%) and an impressive increase in mAb amount of approximately 254% while utilizing the same reactor size and process duration of the standard fed-batch operation. Furthermore, our data show comparable critical quality attributes (CQAs) between the processes and reveal scale-up possibilities and no need for extensive additional process monitoring. Therefore, this novel process intensification strategy yields strong potential for transfer into future industrial manufacturing processes. Frontiers Media S.A. 2023-02-16 /pmc/articles/PMC9978186/ /pubmed/36873352 http://dx.doi.org/10.3389/fbioe.2023.1106292 Text en Copyright © 2023 Reger, Saballus, Matuszczyk, 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
Matuszczyk, Jens
Kampmann, Markus
Wijffels, Rene H.
Martens, Dirk E.
Niemann, Julia
Boosting Productivity for Advanced Biomanufacturing by Re-Using Viable Cells
title Boosting Productivity for Advanced Biomanufacturing by Re-Using Viable Cells
title_full Boosting Productivity for Advanced Biomanufacturing by Re-Using Viable Cells
title_fullStr Boosting Productivity for Advanced Biomanufacturing by Re-Using Viable Cells
title_full_unstemmed Boosting Productivity for Advanced Biomanufacturing by Re-Using Viable Cells
title_short Boosting Productivity for Advanced Biomanufacturing by Re-Using Viable Cells
title_sort boosting productivity for advanced biomanufacturing by re-using viable cells
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9978186/
https://www.ncbi.nlm.nih.gov/pubmed/36873352
http://dx.doi.org/10.3389/fbioe.2023.1106292
work_keys_str_mv AT regerlucasnik boostingproductivityforadvancedbiomanufacturingbyreusingviablecells
AT saballusmartin boostingproductivityforadvancedbiomanufacturingbyreusingviablecells
AT matuszczykjens boostingproductivityforadvancedbiomanufacturingbyreusingviablecells
AT kampmannmarkus boostingproductivityforadvancedbiomanufacturingbyreusingviablecells
AT wijffelsreneh boostingproductivityforadvancedbiomanufacturingbyreusingviablecells
AT martensdirke boostingproductivityforadvancedbiomanufacturingbyreusingviablecells
AT niemannjulia boostingproductivityforadvancedbiomanufacturingbyreusingviablecells