Towards robust cell culture processes — Unraveling the impact of media preparation by spectroscopic online monitoring
| Autor: | Fabian Stiefel, Matthias Brunner, Amandine Calvet, Monika Losing, Jan Bechmann, Jochen Schaub, Andreas Unsoeld, Philipp Brosig, Marco Kunzelmann |
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| Rok vydání: | 2019 |
| Předmět: |
0106 biological sciences
Environmental Engineering Process (engineering) Computer science media_common.quotation_subject Bioengineering Troubleshooting 01 natural sciences process robustness 03 medical and health sciences scale‐up 010608 biotechnology Quality (business) media preparation Process engineering Research Articles 030304 developmental biology media_common cell culture 0303 health sciences Potential impact media quality business.industry Manufacturing process Biopharmaceutical manufacturing Analytics SCALE-UP business PAT Research Article Biotechnology |
| Zdroj: | Engineering in Life Sciences |
| ISSN: | 1618-2863 1618-0240 |
| DOI: | 10.1002/elsc.201900050 |
| Popis: | Biopharmaceutical manufacturing processes can be affected by variability in cell culture media, e.g. caused by raw material impurities. Although efforts have been made in industry and academia to characterize cell culture media and raw materials with advanced analytics, the process of industrial cell culture media preparation itself has not been reported so far. Within this publication, we first compare mid‐infrared and two‐dimensional fluorescence spectroscopy with respect to their suitability as online monitoring tools during cell culture media preparation, followed by a thorough assessment of the impact of preparation parameters on media quality. Through the application of spectroscopic methods, we can show that media variability and its corresponding root cause can be detected online during the preparation process. This methodology is a powerful tool to avoid batch failure and is a valuable technology for media troubleshooting activities. Moreover, in a design of experiments approach, including additional liquid chromatography–mass spectrometry analytics, it is shown that variable preparation parameters such as temperature, power input and preparation time can have a strong impact on the physico‐chemical composition of the media. The effect on cell culture process performance and product quality in subsequent fed‐batch processes was also investigated. The presented results reveal the need for online spectroscopic methods during the preparation process and show that media variability can already be introduced by variation in media preparation parameters, with a potential impact on scale‐up to a commercial manufacturing process. |
| Databáze: | OpenAIRE |
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