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Optimization of a mAb production process with regard to robustness and product quality using quality by design principles
Quality by Design principles are well described and widely used in biopharmaceutical industry. The characterization of a monoclonal antibody (mAb) production process is crucial for novel process development and control. Yet, the application throughout the entire upstream process was rarely demonstra...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9288990/ https://www.ncbi.nlm.nih.gov/pubmed/35865649 http://dx.doi.org/10.1002/elsc.202100172 |
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author | Wohlenberg, Ole Jacob Kortmann, Carlotta Meyer, Katharina V. Schellenberg, Jana Dahlmann, Katharina Bahnemann, Janina Scheper, Thomas Solle, Dörte |
author_facet | Wohlenberg, Ole Jacob Kortmann, Carlotta Meyer, Katharina V. Schellenberg, Jana Dahlmann, Katharina Bahnemann, Janina Scheper, Thomas Solle, Dörte |
author_sort | Wohlenberg, Ole Jacob |
collection | PubMed |
description | Quality by Design principles are well described and widely used in biopharmaceutical industry. The characterization of a monoclonal antibody (mAb) production process is crucial for novel process development and control. Yet, the application throughout the entire upstream process was rarely demonstrated. Following previously published research, this study marks the second step toward a complete process characterization and is focused on the effect of critical process parameters on the antibody production efficiency and quality of the process. In order to conduct the complex Design of Experiments approach with optimal control and comparability, the ambr®15 micro bioreactor platform was used. Investigated parameters included the pH and dissolved oxygen set points, the initial viable cell density (iVCD) as well as the N‐1 duration. Various quality attributes (e.g., growth rate, viability, mAb titer, and peak proportion) were monitored and analyzed using multivariate data analysis to evaluate the parameter effects. The pH set point and the initial VCD were identified as key process parameters with strong influence on the cell growth as well as the mAb production and its proportion to the total protein concentration. For optimization and improvement in robustness of these quality attributes the pH must be increased to 7.2, while the iVCD must be lowered to 0.2 × 10(6) cells/mL. Based on the defined design space, additional experiments verified the results and confirmed the intact bioactivity of the antibody. Thereby, process control strategies could be tuned toward high cell maintenance and mAb production, which enable optimal downstream processing. |
format | Online Article Text |
id | pubmed-9288990 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92889902022-07-20 Optimization of a mAb production process with regard to robustness and product quality using quality by design principles Wohlenberg, Ole Jacob Kortmann, Carlotta Meyer, Katharina V. Schellenberg, Jana Dahlmann, Katharina Bahnemann, Janina Scheper, Thomas Solle, Dörte Eng Life Sci Research Articles Quality by Design principles are well described and widely used in biopharmaceutical industry. The characterization of a monoclonal antibody (mAb) production process is crucial for novel process development and control. Yet, the application throughout the entire upstream process was rarely demonstrated. Following previously published research, this study marks the second step toward a complete process characterization and is focused on the effect of critical process parameters on the antibody production efficiency and quality of the process. In order to conduct the complex Design of Experiments approach with optimal control and comparability, the ambr®15 micro bioreactor platform was used. Investigated parameters included the pH and dissolved oxygen set points, the initial viable cell density (iVCD) as well as the N‐1 duration. Various quality attributes (e.g., growth rate, viability, mAb titer, and peak proportion) were monitored and analyzed using multivariate data analysis to evaluate the parameter effects. The pH set point and the initial VCD were identified as key process parameters with strong influence on the cell growth as well as the mAb production and its proportion to the total protein concentration. For optimization and improvement in robustness of these quality attributes the pH must be increased to 7.2, while the iVCD must be lowered to 0.2 × 10(6) cells/mL. Based on the defined design space, additional experiments verified the results and confirmed the intact bioactivity of the antibody. Thereby, process control strategies could be tuned toward high cell maintenance and mAb production, which enable optimal downstream processing. John Wiley and Sons Inc. 2022-06-03 /pmc/articles/PMC9288990/ /pubmed/35865649 http://dx.doi.org/10.1002/elsc.202100172 Text en © 2022 The Authors. Engineering in Life Sciences published by Wiley‐VCH GmbH. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Wohlenberg, Ole Jacob Kortmann, Carlotta Meyer, Katharina V. Schellenberg, Jana Dahlmann, Katharina Bahnemann, Janina Scheper, Thomas Solle, Dörte Optimization of a mAb production process with regard to robustness and product quality using quality by design principles |
title | Optimization of a mAb production process with regard to robustness and product quality using quality by design principles |
title_full | Optimization of a mAb production process with regard to robustness and product quality using quality by design principles |
title_fullStr | Optimization of a mAb production process with regard to robustness and product quality using quality by design principles |
title_full_unstemmed | Optimization of a mAb production process with regard to robustness and product quality using quality by design principles |
title_short | Optimization of a mAb production process with regard to robustness and product quality using quality by design principles |
title_sort | optimization of a mab production process with regard to robustness and product quality using quality by design principles |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9288990/ https://www.ncbi.nlm.nih.gov/pubmed/35865649 http://dx.doi.org/10.1002/elsc.202100172 |
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