Analysis and optimal design of batch and two-column continuous chromatographic frontal processes for monoclonal antibody purification
| Autor: | Mattia Sponchioni, Massimo Morbidelli, Dong-Qiang Lin, Sebastian Vogg, Ce Shi |
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| Rok vydání: | 2021 |
| Předmět: |
0106 biological sciences
0301 basic medicine Optimal design biochromatography Computer science medicine.drug_class Bioengineering Monoclonal antibody 01 natural sciences Applied Microbiology and Biotechnology Multi-objective optimization Chromatography Affinity Constant linear velocity 03 medical and health sciences Robustness (computer science) protein purification 010608 biotechnology Genetic algorithm Protein purification medicine Staphylococcal Protein A Downstream processing Chromatography Chemistry Process (computing) Antibodies Monoclonal continuous chromatography Chromatography Ion Exchange 030104 developmental biology Yield (chemistry) Batch processing Biotechnology |
| Zdroj: | Biotechnology and bioengineeringREFERENCES. 118(9) |
| ISSN: | 1097-0290 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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