Applying intensified design of experiments to mammalian cell culture processes
Abstract The analysis of data collected using design of experiments (DoE) is the current gold standard to determine the influence of input parameters and their interactions on process performance and product quality. In early development, knowledge on the bioprocess of a new product is limited. Many...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley-VCH
2022-12-01
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| Series: | Engineering in Life Sciences |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/elsc.202100123 |
| _version_ | 1811301550085111808 |
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| author | Verena Nold Lisa Junghans Lorenzo Bisgen Raphael Drerup Beate Presser Ingo Gorr Thomas Schwab Bettina Knapp Stefan Wieschalka |
| author_facet | Verena Nold Lisa Junghans Lorenzo Bisgen Raphael Drerup Beate Presser Ingo Gorr Thomas Schwab Bettina Knapp Stefan Wieschalka |
| author_sort | Verena Nold |
| collection | DOAJ |
| description | Abstract The analysis of data collected using design of experiments (DoE) is the current gold standard to determine the influence of input parameters and their interactions on process performance and product quality. In early development, knowledge on the bioprocess of a new product is limited. Many input parameters need to be investigated for a thorough investigation. For eukaryotic cell cultures, intensified DoE (iDoE) has been proposed as efficient tool, requiring fewer bioreactor runs by introducing setpoint changes during the bioprocess. We report the first successful application of iDoE to mammalian cell culture, performing sequential setpoint changes in the growth phase for the selected input parameters temperature and dissolved oxygen. The process performance data were analyzed using ordinary least squares regression. Our results indicate iDoE to be applicable to mammalian bioprocesses and to be a cost‐efficient option to inform modeling early on during process development. Even though only half the number of bioreactor runs were used in comparison to a classical DoE approach, the resulting models revealed comparable input‐output relations. Being able to examine several setpoint levels within one bioreactor run, we confirm iDoE to be a promising tool to speed up biopharmaceutical process development. |
| first_indexed | 2024-04-13T07:10:50Z |
| format | Article |
| id | doaj.art-214cddb197b148198da9e2ac1224ccff |
| institution | Directory Open Access Journal |
| issn | 1618-0240 1618-2863 |
| language | English |
| last_indexed | 2024-04-13T07:10:50Z |
| publishDate | 2022-12-01 |
| publisher | Wiley-VCH |
| record_format | Article |
| series | Engineering in Life Sciences |
| spelling | doaj.art-214cddb197b148198da9e2ac1224ccff2022-12-22T02:56:52ZengWiley-VCHEngineering in Life Sciences1618-02401618-28632022-12-01221278479510.1002/elsc.202100123Applying intensified design of experiments to mammalian cell culture processesVerena Nold0Lisa Junghans1Lorenzo Bisgen2Raphael Drerup3Beate Presser4Ingo Gorr5Thomas Schwab6Bettina Knapp7Stefan Wieschalka8Development Biologicals Boehringer Ingelheim Pharma GmbH & Co KG Biberach an der Riß GermanyDevelopment Biologicals Boehringer Ingelheim Pharma GmbH & Co KG Biberach an der Riß GermanyUniversity of Ulm Ulm GermanyDevelopment Biologicals Boehringer Ingelheim Pharma GmbH & Co KG Biberach an der Riß GermanyDevelopment Biologicals Boehringer Ingelheim Pharma GmbH & Co KG Biberach an der Riß GermanyDevelopment Biologicals Boehringer Ingelheim Pharma GmbH & Co KG Biberach an der Riß GermanyDevelopment Biologicals Boehringer Ingelheim Pharma GmbH & Co KG Biberach an der Riß GermanyDevelopment Biologicals Boehringer Ingelheim Pharma GmbH & Co KG Biberach an der Riß GermanyDevelopment Biologicals Boehringer Ingelheim Pharma GmbH & Co KG Biberach an der Riß GermanyAbstract The analysis of data collected using design of experiments (DoE) is the current gold standard to determine the influence of input parameters and their interactions on process performance and product quality. In early development, knowledge on the bioprocess of a new product is limited. Many input parameters need to be investigated for a thorough investigation. For eukaryotic cell cultures, intensified DoE (iDoE) has been proposed as efficient tool, requiring fewer bioreactor runs by introducing setpoint changes during the bioprocess. We report the first successful application of iDoE to mammalian cell culture, performing sequential setpoint changes in the growth phase for the selected input parameters temperature and dissolved oxygen. The process performance data were analyzed using ordinary least squares regression. Our results indicate iDoE to be applicable to mammalian bioprocesses and to be a cost‐efficient option to inform modeling early on during process development. Even though only half the number of bioreactor runs were used in comparison to a classical DoE approach, the resulting models revealed comparable input‐output relations. Being able to examine several setpoint levels within one bioreactor run, we confirm iDoE to be a promising tool to speed up biopharmaceutical process development.https://doi.org/10.1002/elsc.202100123best‐cost strategyearly stage developmentindustrial mammalian cell cultureintensified design of experimentsmodeling upstream bioprocessing |
| spellingShingle | Verena Nold Lisa Junghans Lorenzo Bisgen Raphael Drerup Beate Presser Ingo Gorr Thomas Schwab Bettina Knapp Stefan Wieschalka Applying intensified design of experiments to mammalian cell culture processes Engineering in Life Sciences best‐cost strategy early stage development industrial mammalian cell culture intensified design of experiments modeling upstream bioprocessing |
| title | Applying intensified design of experiments to mammalian cell culture processes |
| title_full | Applying intensified design of experiments to mammalian cell culture processes |
| title_fullStr | Applying intensified design of experiments to mammalian cell culture processes |
| title_full_unstemmed | Applying intensified design of experiments to mammalian cell culture processes |
| title_short | Applying intensified design of experiments to mammalian cell culture processes |
| title_sort | applying intensified design of experiments to mammalian cell culture processes |
| topic | best‐cost strategy early stage development industrial mammalian cell culture intensified design of experiments modeling upstream bioprocessing |
| url | https://doi.org/10.1002/elsc.202100123 |
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