Details
| Original language | English |
|---|---|
| Pages (from-to) | 196-207 |
| Number of pages | 12 |
| Journal | Engineering in life sciences |
| Volume | 21 |
| Issue number | 3-4 |
| Early online date | 3 Dec 2020 |
| Publication status | Published - 2 Mar 2021 |
Abstract
The quality by design approach was introduced to the biopharmaceutical industry over 15 years ago. This principle is widely implemented in the characterization of monoclonal antibody production processes. Anyway, the early process phase, namely the inoculum expansion, was not yet investigated and characterized for most processes. In order to increase the understanding of early process parameter interactions and their influence on the later production process, a risk assessment followed by a design of experiments approach was conducted. The DoE included the critical parameters methotrexate (MTX) concentration, initial passage viable cell density and passage duration. Multivariate data analysis led to mathematical regression models and the establishment of a designated design space for the studied parameters. It was found that the passage duration as well as the initial viable cell density for each passage during the inoculum expansion have severe effects on the growth rate and viability of the early process phase. Furthermore, the variations during the inoculum expansion directly influenced the production process responses. This carry-over of factor effects highlights the crucial impact of early process failures and the importance of process analysis and control during the first part of mAb production processes.
Keywords
- CHO, inoculum expansion, mAb, PAT, QbD
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. 21, No. 3-4, 02.03.2021, p. 196-207.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Implementation of QbD strategies in the inoculum expansion of a mAb production process
AU - Böhl, Ole Jacob
AU - Schellenberg, Jana
AU - Bahnemann, Janina
AU - Hitzmann, Bernd
AU - Scheper, Thomas
AU - Solle, Dörte
PY - 2021/3/2
Y1 - 2021/3/2
N2 - The quality by design approach was introduced to the biopharmaceutical industry over 15 years ago. This principle is widely implemented in the characterization of monoclonal antibody production processes. Anyway, the early process phase, namely the inoculum expansion, was not yet investigated and characterized for most processes. In order to increase the understanding of early process parameter interactions and their influence on the later production process, a risk assessment followed by a design of experiments approach was conducted. The DoE included the critical parameters methotrexate (MTX) concentration, initial passage viable cell density and passage duration. Multivariate data analysis led to mathematical regression models and the establishment of a designated design space for the studied parameters. It was found that the passage duration as well as the initial viable cell density for each passage during the inoculum expansion have severe effects on the growth rate and viability of the early process phase. Furthermore, the variations during the inoculum expansion directly influenced the production process responses. This carry-over of factor effects highlights the crucial impact of early process failures and the importance of process analysis and control during the first part of mAb production processes.
AB - The quality by design approach was introduced to the biopharmaceutical industry over 15 years ago. This principle is widely implemented in the characterization of monoclonal antibody production processes. Anyway, the early process phase, namely the inoculum expansion, was not yet investigated and characterized for most processes. In order to increase the understanding of early process parameter interactions and their influence on the later production process, a risk assessment followed by a design of experiments approach was conducted. The DoE included the critical parameters methotrexate (MTX) concentration, initial passage viable cell density and passage duration. Multivariate data analysis led to mathematical regression models and the establishment of a designated design space for the studied parameters. It was found that the passage duration as well as the initial viable cell density for each passage during the inoculum expansion have severe effects on the growth rate and viability of the early process phase. Furthermore, the variations during the inoculum expansion directly influenced the production process responses. This carry-over of factor effects highlights the crucial impact of early process failures and the importance of process analysis and control during the first part of mAb production processes.
KW - CHO
KW - inoculum expansion
KW - mAb
KW - PAT
KW - QbD
UR - http://www.scopus.com/inward/record.url?scp=85097026331&partnerID=8YFLogxK
U2 - 10.1002/elsc.202000056
DO - 10.1002/elsc.202000056
M3 - Article
AN - SCOPUS:85097026331
VL - 21
SP - 196
EP - 207
JO - Engineering in life sciences
JF - Engineering in life sciences
SN - 1618-0240
IS - 3-4
ER -