A two-step procedure for the design of perfusion bioreactors

Wolf, Marco; Pechlaner, Anna; Lorenz, Veronika; Karst, Daniel J.; Souquet, Jonathan; Broly, Hervé; Morbidelli, Massimo

doi:10.1016/j.bej.2019.107295

Cited by 23 publications

(7 citation statements)

References 42 publications

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“…The presented model-based approach represents a reliable alternative to existing experimental procedure such as the ones presented in Janoschek et al 19 and Wolf et al 20 . These protocols rely on the evaluation and optimization of different feed, harvest and bleed strategies similar to a Design of Experiments (DoE) approach.…”

Section: Design and Analysis Of Perfusion Process Conditionsmentioning

confidence: 98%

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

Richelle¹,

Corbett²,

Agarwal³

et al. 2022

Preprint

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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 CHO cells using only the knowledge captured during small-scale fed-batch experiments. The novelty of the proposed model 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.

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Section: Design and Analysis Of Perfusion Process Conditionsmentioning

confidence: 98%

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

Richelle¹,

Corbett²,

Agarwal³

et al. 2022

Preprint

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“…Comparative evaluation of fed-batch and perfusion platforms for IgG1-and IgG4-producing cell lines was carried out with ATF filtration, and perfusion was found to have 7.5 times greater average productivity (Walther et al, 2019). In another study, a two-step procedure [first, finding a suitable minimum value of the cellspecific perfusion rate (CSPR) at constant perfusion rate (P) or constant viable cell density (VCD) and second, investigating steady states at constant CSPR but elevated values of VCD and P] was developed for the design and development of CHO cell perfusion cultures and enabled high product yield and improved process performance with minor change in product quality (Wolf et al, 2019c).…”

Section: Perfusion Culture Processmentioning

confidence: 99%

Recent Developments in Bioprocessing of Recombinant Proteins: Expression Hosts and Process Development

Tripathi

Shrivastava

2019

Front. Bioeng. Biotechnol.

366

243

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Infectious diseases, along with cancers, are among the main causes of death among humans worldwide. The production of therapeutic proteins for treating diseases at large scale for millions of individuals is one of the essential needs of mankind. Recent progress in the area of recombinant DNA technologies has paved the way to producing recombinant proteins that can be used as therapeutics, vaccines, and diagnostic reagents. Recombinant proteins for these applications are mainly produced using prokaryotic and eukaryotic expression host systems such as mammalian cells, bacteria, yeast, insect cells, and transgenic plants at laboratory scale as well as in large-scale settings. The development of efficient bioprocessing strategies is crucial for industrial production of recombinant proteins of therapeutic and prophylactic importance. Recently, advances have been made in the various areas of bioprocessing and are being utilized to develop effective processes for producing recombinant proteins. These include the use of high-throughput devices for effective bioprocess optimization and of disposable systems, continuous upstream processing, continuous chromatography, integrated continuous bioprocessing, Quality by Design, and process analytical technologies to achieve quality product with higher yield. This review summarizes recent developments in the bioprocessing of recombinant proteins, including in various expression systems, bioprocess development, and the upstream and downstream processing of recombinant proteins.

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“…The presented model-based approach enabled to drastically improves the process performance (Table 4). This represents a reliable alternative to existing experimental procedure such as the ones presented in Janoschek et al (Janoschek et al, 2018) and Wolf et al (Wolf et al, 2019). These protocols rely on the evaluation and optimization of different feed, harvest and bleed strategies similar to a Design of Experiments (DoE) approach.…”

Section: Design and Analysis Of Perfusion Process Conditionsmentioning

confidence: 99%

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

Richelle¹,

Corbett²,

Agarwal³

et al. 2022

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

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 model 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.

show abstract

A two-step procedure for the design of perfusion bioreactors

Cited by 23 publications

References 42 publications

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

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

Recent Developments in Bioprocessing of Recombinant Proteins: Expression Hosts and Process Development

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

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