Details
| Original language | English |
|---|---|
| Pages (from-to) | 484-494 |
| Number of pages | 11 |
| Journal | Engineering in life sciences |
| Volume | 22 |
| Issue number | 7 |
| Early online date | 17 Jul 2022 |
| Publication status | Published - Jul 2022 |
Abstract
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 × 106 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.
Keywords
- ambr®, chinese hamster ovary, monoclonal antibody, process analytical technology, quality by design
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Biotechnology
- Environmental Science(all)
- Environmental Engineering
- Chemical Engineering(all)
- Bioengineering
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In: Engineering in life sciences, Vol. 22, No. 7, 07.2022, p. 484-494.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Optimization of a mAb production process with regard to robustness and product quality using quality by design principles
AU - Wohlenberg, Ole Jacob
AU - Kortmann, Carlotta
AU - Meyer, Katharina V.
AU - Schellenberg, Jana
AU - Dahlmann, Katharina
AU - Bahnemann, Janina
AU - Scheper, Thomas
AU - Solle, Dörte
N1 - Funding Information: The authors acknowledge the financial support of the research by the Federal Ministry of Education and Research, Germany (031B0744). Open access funding enabled and organized by ProjektDEAL.
PY - 2022/7
Y1 - 2022/7
N2 - 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 × 106 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.
AB - 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 × 106 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.
KW - ambr®
KW - chinese hamster ovary
KW - monoclonal antibody
KW - process analytical technology
KW - quality by design
UR - http://www.scopus.com/inward/record.url?scp=85131185899&partnerID=8YFLogxK
U2 - 10.1002/elsc.202100172
DO - 10.1002/elsc.202100172
M3 - Article
AN - SCOPUS:85131185899
VL - 22
SP - 484
EP - 494
JO - Engineering in life sciences
JF - Engineering in life sciences
SN - 1618-0240
IS - 7
ER -