How to Produce mAbs in a Cube-Shaped Stirred Single-Use Bioreactor at 200 L Scale

Schirmer, Cedric; Müller, Jan; Steffen, Nina; Werner, Sören; Eibl, Regine; Eibl, Dieter

doi:10.1007/978-1-0716-0191-4_10

Cited by 7 publications

(2 citation statements)

References 13 publications

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“…Using the Allegro TM STR platform, PALL (now Cytiva, Marlborough, MA, USA) has already shown that a stirred bioreactor does not always need to be cylindrical. The HyPerforma DynaDrive bioreactor has a rectangular footprint, but a significantly higher bioreactor fill height (H) to bioreactor diameter (D) ratio of 2.9 [22] compared to Cytiva's Allegro STR with an H/D of 1.0 [23]. Previously, the range of H/D ratios for commercially available cylindrical stirred single-use bioreactors was limited to between 1.5 and 2.2 [21].…”

Section: Introductionmentioning

confidence: 99%

Scaling Fed-Batch and Perfusion Antibody Production Processes in Geometrically Dissimilar Stirred Bioreactors

Ott,

Eibl

et al. 2024

Processes

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Modern production processes for biopharmaceuticals often work with very high cell densities. Moreover, there is a trend towards moving from fed-batch to continuous perfusion processes; a development that is influencing the requirements for bioreactor design and process control. In this study, the transfer of fed-batch and perfusion experiments between different cylindrical stirred lab-scale bioreactors and Thermo Scientific’sTM (Waltham, MA, USA) cubical HyPerformaTM DynaDriveTM Single-Use Bioreactor was investigated. Different scaling parameters were used, which were selected based on the requirements of the respective processes. Peak cell densities of up to 49 × 106 cells mL−1 and antibody titers of up to 5.2 g L−1 were achieved in 15- to 16-day fed-batch experiments. In 50-day perfusion cultivations, a viable cell volume of >100 mm3 mL−1 was maintained and more than 1 g L−1 d−1 of antibodies were harvested. The perfusion processes were automated with both cell bleed control and glucose concentration control. Cell retention was performed using Repligen’s (Waltham, MA, USA) XCell® ATF perfusion systems and single-use devices. In summary, approaches for successfully scaling highly productive fed-batch and perfusion processes between geometrically dissimilar lab and pilot scale bioreactors were demonstrated. The advantages of perfusion in comparison to fed-batch processes were also observed.

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Section: Introductionmentioning

confidence: 99%

Scaling Fed-Batch and Perfusion Antibody Production Processes in Geometrically Dissimilar Stirred Bioreactors

Ott,

Eibl

et al. 2024

Processes

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“…microorganisms, plant, animal or human cells) (Eibl et al, 2009;Chmiel et al, 2018). Bioreactors are used in numerous applications, including environmental biotechnology (biogas production Duarte et al (2021)), the production of plant cell culture extracts for the cosmetics industry (Georgiev et al, 2018), as well as the production of monoclonal antibodies, vaccines (Schirmer et al, 2020;Maschke et al, 2022) and cell therapeutics (Jossen et al, 2020). A variety of different mechanically, hydraulically and pneumatically driven bioreactor systems exist, with stirred bioreactors being the most widely used type (Seidel and Eibl, 2021;Jossen et al, 2019;Schirmer et al, 2021;Seidel et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Laboratory-independent exploration of stirred bioreactors and their fluid dynamics

Seidel

Eibl-Schindler

Eibl

2023

Education for Chemical Engineers

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Production of Modified Vaccinia Ankara Virus by Intensified Cell Cultures: A Comparison of Platform Technologies for Viral Vector Production

Gränicher

Tapia

Behrendt

et al. 2020

Biotechnology Journal

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Modified Vaccinia Ankara (MVA) virus is a promising vector for vaccination against various challenging pathogens or the treatment of some types of cancers. Because this vector is unable to replicate in human recipients, a high amount of virions per dose is required for vaccination and gene therapy. Upstream process intensification combining perfusion technologies, the avian suspension cell line AGE1.CR.pIX and the virus strain MVA‐CR19 is an option to obtain very high MVA yields. Here we compared different options for cell retention in perfusion mode using conventional stirred‐tank bioreactors including an alternating tangential flow filtration system, an acoustic settler and an inclined settler. The last two options allowed continuous MVA virus harvesting. Furthermore, we studied hollow‐fiber based bioreactors and an orbital‐shaken bioreactor in perfusion mode, both available for single‐use. Productivity for the virus strain MVA‐CR19 was compared to results from batch and continuous production reported in literature. Our results demonstrate that MVA virus is highly stable at 37°C in cell culture so that cell retention devices are only required to maximize cell concentration but not for continuous harvesting. Using a stirred‐tank bioreactor, a perfusion strategy during the whole run with working volume expansion after virus infection resulted in the highest yields. Overall, infectious MVA virus titers of 2.1–16.5 × 10 9 virions/mL were achieved in these intensified processes. Taken together, the study shows a novel perspective on high‐yield MVA virus production in conventional bioreactor systems linked to various cell retention devices and addresses options for process intensification including fully single‐use perfusion platforms. This article is protected by copyright. All rights reserved

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How to Produce mAbs in a Cube-Shaped Stirred Single-Use Bioreactor at 200 L Scale

Cited by 7 publications

References 13 publications

Scaling Fed-Batch and Perfusion Antibody Production Processes in Geometrically Dissimilar Stirred Bioreactors

Scaling Fed-Batch and Perfusion Antibody Production Processes in Geometrically Dissimilar Stirred Bioreactors

Laboratory-independent exploration of stirred bioreactors and their fluid dynamics

Production of Modified Vaccinia Ankara Virus by Intensified Cell Cultures: A Comparison of Platform Technologies for Viral Vector Production

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