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Evaluation of Continuous Membrane Chromatography Concepts with an Enhanced Process Simulation Approach
Modern biopharmaceutical products strive for small-scale, low-cost production. Continuous chromatography has shown to be a promising technology because it assures high-capacity utilization, purity and yield increases, and lower facility footprint. Membrane chromatography is a fully disposable low-co...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698847/ https://www.ncbi.nlm.nih.gov/pubmed/31544865 http://dx.doi.org/10.3390/antib7010013 |
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author | Zobel-Roos, Steffen Stein, Dominik Strube, Jochen |
author_facet | Zobel-Roos, Steffen Stein, Dominik Strube, Jochen |
author_sort | Zobel-Roos, Steffen |
collection | PubMed |
description | Modern biopharmaceutical products strive for small-scale, low-cost production. Continuous chromatography has shown to be a promising technology because it assures high-capacity utilization, purity and yield increases, and lower facility footprint. Membrane chromatography is a fully disposable low-cost alternative to bead-based chromatography with minor drawbacks in terms of capacity. Hence, continuous membrane chromatography should have a high potential. The evaluation of continuous processes goes often along with process modeling. Only few experiments with small feed demand need to be conducted to estimate the model parameters. Afterwards, a variety of different process setups and working points can be analyzed in a very short time, making the approach very efficient. Since the available modeling approaches for membrane chromatography modules did not fit the used design, a new modeling approach is shown. This combines the general rate model with an advanced fluid dynamic distribution. Model parameter determination and model validation were done with industrial cell cultures containing Immunoglobulin G (IgG). The validated model was used to evaluate the feasibility of the integrated Counter Current Chromatography (iCCC) concept and the sequential chromatography concept for membrane adsorber modules, starting with a laboratory-type module used for sample preparation. A case study representing a fed-batch reactor with a capacity from 20 to 2000 L was performed. Compared to batch runs, a 71% higher capacity, 48.5% higher productivity, and 38% lower eluent consumption could be achieved. |
format | Online Article Text |
id | pubmed-6698847 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-66988472019-09-05 Evaluation of Continuous Membrane Chromatography Concepts with an Enhanced Process Simulation Approach Zobel-Roos, Steffen Stein, Dominik Strube, Jochen Antibodies (Basel) Article Modern biopharmaceutical products strive for small-scale, low-cost production. Continuous chromatography has shown to be a promising technology because it assures high-capacity utilization, purity and yield increases, and lower facility footprint. Membrane chromatography is a fully disposable low-cost alternative to bead-based chromatography with minor drawbacks in terms of capacity. Hence, continuous membrane chromatography should have a high potential. The evaluation of continuous processes goes often along with process modeling. Only few experiments with small feed demand need to be conducted to estimate the model parameters. Afterwards, a variety of different process setups and working points can be analyzed in a very short time, making the approach very efficient. Since the available modeling approaches for membrane chromatography modules did not fit the used design, a new modeling approach is shown. This combines the general rate model with an advanced fluid dynamic distribution. Model parameter determination and model validation were done with industrial cell cultures containing Immunoglobulin G (IgG). The validated model was used to evaluate the feasibility of the integrated Counter Current Chromatography (iCCC) concept and the sequential chromatography concept for membrane adsorber modules, starting with a laboratory-type module used for sample preparation. A case study representing a fed-batch reactor with a capacity from 20 to 2000 L was performed. Compared to batch runs, a 71% higher capacity, 48.5% higher productivity, and 38% lower eluent consumption could be achieved. MDPI 2018-03-02 /pmc/articles/PMC6698847/ /pubmed/31544865 http://dx.doi.org/10.3390/antib7010013 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zobel-Roos, Steffen Stein, Dominik Strube, Jochen Evaluation of Continuous Membrane Chromatography Concepts with an Enhanced Process Simulation Approach |
title | Evaluation of Continuous Membrane Chromatography Concepts with an Enhanced Process Simulation Approach |
title_full | Evaluation of Continuous Membrane Chromatography Concepts with an Enhanced Process Simulation Approach |
title_fullStr | Evaluation of Continuous Membrane Chromatography Concepts with an Enhanced Process Simulation Approach |
title_full_unstemmed | Evaluation of Continuous Membrane Chromatography Concepts with an Enhanced Process Simulation Approach |
title_short | Evaluation of Continuous Membrane Chromatography Concepts with an Enhanced Process Simulation Approach |
title_sort | evaluation of continuous membrane chromatography concepts with an enhanced process simulation approach |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698847/ https://www.ncbi.nlm.nih.gov/pubmed/31544865 http://dx.doi.org/10.3390/antib7010013 |
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