Analysis and optimal design of batch and two-column continuous chromatographic frontal processes for monoclonal antibody purification.
biochromatography
continuous chromatography
protein purification
Journal
Biotechnology and bioengineering
ISSN: 1097-0290
Titre abrégé: Biotechnol Bioeng
Pays: United States
ID NLM: 7502021
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
revised:
09
02
2021
received:
04
12
2020
accepted:
12
03
2021
pubmed:
24
3
2021
medline:
3
3
2022
entrez:
23
3
2021
Statut:
ppublish
Résumé
The increasing demand for efficient and robust processes in the purification of monoclonal antibodies (mAbs) has recently brought frontal chromatography to the forefront. Applied during the polishing step, it enables the removal of high molecular weight aggregates from the target product, achieving high purities. Typically, this process is operated in batch using a single column, which makes it intrinsically subjected to a purity-yield tradeoff. This means that high purities can only be achieved at the cost of lowering the product yield and vice versa. Recently, a two-column continuous implementation of frontal chromatography, referred to as Flow2, was developed. Despite being able of alleviating the purity-yield tradeoff typical of batch operations, the increase in the number of process parameters complicates its optimal design, with the risk of not exploiting its full potential. In this study, we developed an ad hoc design procedure (DP) suitable for the optimization of both batch frontal chromatography and Flow2 in terms of purity, yield, and productivity. This procedure provided similar results as a multiobjective optimization based on genetic algorithm but with lower computational effort. Then, batch and Flow2 operated at their optimal conditions were compared. Besides showing a more favorable Pareto front of yield and productivity at a specified purity, the Flow2 process demonstrated improved robustness compared to the batch process with respect to modifications in the loading linear velocity, washing buffer ionic strength and loading time, thus providing an appealing operation for integrated processes.
Substances chimiques
Antibodies, Monoclonal
0
Staphylococcal Protein A
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3420-3434Informations de copyright
© 2021 Wiley Periodicals LLC.
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