Model-based intensification of CHO cell cultures: One-step strategy from fed-batch to perfusion

Anne Richelle, Brandon Corbett, Piyush Agarwal, Anton Vernersson, Johan Trygg, Chris McCready
2022 Frontiers in Bioengineering and Biotechnology  
There is a growing interest in continuous processing of the biopharmaceutical industry. However, the technology transfer from traditional batch-based processes is considered a challenge as protocol and tools still remain to be established for their usage at the manufacturing scale. Here, we present a model-based approach to design optimized perfusion cultures of Chinese Hamster Ovary cells using only the knowledge captured during small-scale fed-batch experiments. The novelty of the proposed
more » ... el lies in the simplicity of its structure. Thanks to the introduction of a new catch-all variable representing a bulk of by-products secreted by the cells during their cultivation, the model was able to successfully predict cellular behavior under different operating modes without changes in its formalism. To our knowledge, this is the first experimentally validated model capable, with a single set of parameters, to capture culture dynamic under different operating modes and at different scales.
doi:10.3389/fbioe.2022.948905 pmid:36072286 pmcid:PMC9443430 fatcat:qdbuevx5mvg2lhzpw35e2ypiw4