Applying intensified design of experiments to mammalian cell culture processes.

Autor: Nold V; Development Biologicals Boehringer Ingelheim Pharma GmbH & Co KG Biberach an der Riß Germany., Junghans L; Development Biologicals Boehringer Ingelheim Pharma GmbH & Co KG Biberach an der Riß Germany., Bisgen L; University of Ulm Ulm Germany., Drerup R; Development Biologicals Boehringer Ingelheim Pharma GmbH & Co KG Biberach an der Riß Germany., Presser B; Development Biologicals Boehringer Ingelheim Pharma GmbH & Co KG Biberach an der Riß Germany., Gorr I; Development Biologicals Boehringer Ingelheim Pharma GmbH & Co KG Biberach an der Riß Germany., Schwab T; Development Biologicals Boehringer Ingelheim Pharma GmbH & Co KG Biberach an der Riß Germany., Knapp B; Development Biologicals Boehringer Ingelheim Pharma GmbH & Co KG Biberach an der Riß Germany., Wieschalka S; Development Biologicals Boehringer Ingelheim Pharma GmbH & Co KG Biberach an der Riß Germany.
Jazyk: angličtina
Zdroj: Engineering in life sciences [Eng Life Sci] 2021 Nov 24; Vol. 22 (12), pp. 784-795. Date of Electronic Publication: 2021 Nov 24 (Print Publication: 2022).
DOI: 10.1002/elsc.202100123
Abstrakt: 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.
Competing Interests: Raphael Drerup, Ingo Gorr, Lisa Junghans, Bettina Knapp, Verena Nold, Beate Presser, Thomas Schwab and Stefan Wieschalka have been employees of Boehringer Ingelheim during this study. Lorenzo Bisgen declares no conflict of interest.
(© 2021 The Authors. Engineering in Life Sciences published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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