Quality-targeting dynamic optimization of monoclonal antibody production
| Autor: | Andreas Schuppert, Alireza Ehsani, Sebastian Niedenführ, Chrysoula Dimitra Kappatou, Alexander Mitsos, Adel Mhamdi |
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| Rok vydání: | 2020 |
| Předmět: |
Glycosylation
Optimization problem Computer science medicine.drug_class 020209 energy General Chemical Engineering media_common.quotation_subject Final product 02 engineering and technology Monoclonal antibody Nucleotide sugar Quality by Design Computer Science Applications chemistry.chemical_compound Biopharmaceutical 020401 chemical engineering chemistry 0202 electrical engineering electronic engineering information engineering medicine Quality (business) Biochemical engineering 0204 chemical engineering media_common |
| Zdroj: | Computers & Chemical Engineering. 142:107004 |
| ISSN: | 0098-1354 |
| DOI: | 10.1016/j.compchemeng.2020.107004 |
| Popis: | Compliance with Quality by Design (QbD) constitutes a major challenge in biopharmaceuticals. Monoclonal antibodies (mAbs) represent a significant biopharmaceutical product class, typically produced in mammalian cell cultures. A key quality attribute for mAb production is glycosylation. We examine how process intensification affects glycosylation via dynamic optimization using different problem formulations. We maximize process performance with simultaneous control of product quality. For these, we utilize a mechanistic dynamic model for mAb production in mammalian cell cultures including glycosylation presented by Ehsani et al. in Computer Aided Chemical Engineering (2017). To achieve target glycan distribution in the final product, we incorporate constraints for the acceptable glycosylation ranges into the dynamic optimization problem. As a result, we derive optimal supplementation profiles of nutrients and/or nucleotide sugars. This work successfully illustrates an example of how model-based dynamic optimization can be employed for implementation of the QbD approach in biopharmaceutics. |
| Databáze: | OpenAIRE |
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