1. Side‐by‐side comparability of batch and continuous downstream for the production of monoclonal antibodies
- Author
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Martin Lobedann, Klaus Kaiser, Martin Poggel, Peter Schwan, Karl Geisen, Benjamin Maiser, Tobias Thüte, Bastian Budde, Nils Weber, Kerstin Baumarth, Mike Kuerschner, Sven-Oliver Borchert, Viktorija Kistler, Francisca Maria Alberti Aguilo, Maike Temming, Gerhard Schembecker, Andreas Blank, Laura David, Felix Oehme, and Heiko Brandt
- Subjects
0106 biological sciences ,0301 basic medicine ,Imagination ,Chemical substance ,Materials science ,media_common.quotation_subject ,Pilot Projects ,Bioengineering ,CHO Cells ,01 natural sciences ,Applied Microbiology and Biotechnology ,03 medical and health sciences ,Search engine ,Process duration ,Bioreactors ,Cricetulus ,Cricetinae ,010608 biotechnology ,Animals ,Process engineering ,media_common ,business.industry ,Final product ,Antibodies, Monoclonal ,030104 developmental biology ,Pilot plant ,Batch Cell Culture Techniques ,Forced degradation ,Degradation (geology) ,Drug Contamination ,business ,Chromatography, Liquid ,Biotechnology - Abstract
Continuous processing is the future production method for monoclonal antibodies (mAbs). A fully continuous, fully automated downstream process based on disposable equipment was developed and implemented inside the MoBiDiK pilot plant. However, a study evaluating the comparability between batch and continuous processing based on product quality attributes was not conducted before. The work presented fills this gap comparing both process modes experimentally by purifying the same harvest material (side-by-side comparability). Samples were drawn at different time points and positions in the process for batch and continuous mode. Product quality attributes, product-related impurities, as well as process-related impurities were determined. The resulting polished material was processed to drug substance and further evaluated regarding storage stability and degradation behavior. The in-process control data from the continuous process showed the high degree of accuracy in providing relevant process parameters such as pH, conductivity, and protein concentration during the entire process duration. Minor differences between batch and continuous samples are expected as different processing conditions are unavoidable due to the different nature of batch and continuous processing. All tests revealed no significant differences in the intermediates and comparability in the drug substance between the samples of both process modes. The stability study of the final product also showed no differences in the stability profile during storage and forced degradation. Finally, online data analysis is presented as a powerful tool for online-monitoring of chromatography columns during continuous processing.
- Published
- 2020
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