Biological performance of two different 1000 L single‐use bioreactors applying a simple transfer approach

Minow, Benjamin; Tschoepe, Susanne; Regner, Anja; Populin, Maeva; Reiser, Sven; Noack, Caroline; Neubauer, Peter

doi:10.1002/elsc.201300147

Cited by 12 publications

(5 citation statements)

References 33 publications

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“…In mammalian cell cultures, one of the commonly used criteria is similar power input per volume ( P / V , or the mean specific energy dissipation rate). Other criteria, such as impeller pumping rate per unit bioreactor volume, and a combination of P / V with O 2 volumetric mass transfer coefficient (

k_{L} a true)

have been applied in stirred‐tank bioreactors with desirable scale‐up/process transfer performance. In addition, shear stress was used for scaling‐up insect cell‐based vaccine productions .…”

Section: Introductionmentioning

confidence: 99%

A practical approach in bioreactor scale‐up and process transfer using a combination of constant P/V and vvm as the criterion

Hoshan

Jiang

et al. 2017

Biotechnology Progress

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Bioreactor scale-up is a critical step in the production of therapeutic proteins such as monoclonal antibodies (MAbs). With the scale-up criterion such as similar power input per volume or O volumetric mass transfer coefficient ( kLa), adequate oxygen supply and cell growth can be largely achieved. However, CO stripping in the growth phase is often inadequate. This could cascade down to increased base addition and osmolality, as well as residual lactate increase and compromised production and product quality. Here we describe a practical approach in bioreactor scale-up and process transfer, where bioreactor information may be limited. We evaluated the sparger kLa and kLaCO2 (CO volumetric mass transfer coefficient) from a range of bioreactor scales (3-2,000 L) with different spargers. Results demonstrated that kLa for oxygen is not an issue when scaling from small-scale to large-scale bioreactors at the same gas flow rate per reactor volume (vvm). Results also showed that sparging CO stripping, kLaCO2, is dominated by the gas throughput. As a result, a combination of a minimum constant vvm air or N flow with a similar specific power was used as the general scale-up criterion. An equation was developed to determine the minimum vvm required for removing CO produced from cell respiration. We demonstrated the effectiveness of using such scale-up criterion with five MAb projects exhibiting different cell growth and metabolic characteristics, scaled from 3 to 2,000 L bioreactors across four sites. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1146-1159, 2017.

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k_{L} a true)

Section: Introductionmentioning

confidence: 99%

A practical approach in bioreactor scale‐up and process transfer using a combination of constant P/V and vvm as the criterion

Hoshan

Jiang

et al. 2017

Biotechnology Progress

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“…The process regime can be adapted (e.g. power input, gas flow rates) based on the characterization data from this study [36].…”

Section: Discussionmentioning

confidence: 99%

Harmonization and characterization of different single‐use bioreactors adopting a new sparger design

Minow

Seidemann

Tschoepe

et al. 2014

Engineering in Life Sciences

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In mammalian cell culture, single-use bioreactors are widely used. Different hardware designs are available, ranging from stirred tank reactors to wave mixed and cubical shaken systems. Unlike in stainless steel systems, where standards exist, in singleuse bioreactors aeration devices are often predefined by the supplier. While ring sparger systems are the gold standard in stainless steel bioreactors, not all singleuse bioreactors are available with ring spargers. In this study, a comprehensive characterization of two stirred tank single-use bioreactor systems (XDR TM from Xcellerex and S.U.B. from Thermo Scientific Hyclone) was performed under GMP conditions with 200/250 L and 1000 L bioreactors. Engineering facts like mass transfer rates for oxygen k L a o2 and carbon dioxide k L a CO2 as well as mixing number were evaluated. To achieve improved similarity in key engineering parameters and in consequence cell culture performance, the submerse aeration device of the S.U.B.(to date only open tube and frit) was remodeled resulting in a drilled hole sparger design. Results of the characterization showed that k L a o2 in the S.U.B. was enhanced from 8.5 h −1 to 11.5 h −1 at the maximum, and the k L a CO2 was very similar between both bioreactor types. Knowledge of the characterization data as well as improved oxygen transfer rate in the S.U.B. allows for an interchangeable usage of the two different single-use bioreactors.

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“…Despite the already substantial amount of experimental data regarding wave mixed single-use bioreactors, given the wide interest from researchers and broad applicability in modern areas of biopharmacy, bioengineering, and novel medical therapies, characterization of rocking bioreactors is still desired, as it has been discussed in reports about, e.g., stirred single-use and multi-use reactors (10 –1 to 10 0 dm 3 volume, − 10 1 to 10 2 dm 3 volume, − and 10 3 dm 3 volume − ). Similar to other bioreactor types, such as orbitally shaken single-use bioreactors − and shake flasks − or airlift bioreactors, − it is valuable and relevant to further supplement the base of experimental data about wave mixed devices, including those regarding the mass transfer.…”

Section: Introductionmentioning

confidence: 99%

Mass Transfer in a Liter-Scale Wave Mixed Single-Use Bioreactor: Influence of Viscosity and Antifoaming Agent

Bartczak

Wierzchowski

Pilarek

2023

Ind. Eng. Chem. Res.

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Wave mixed single-use bioreactors (also called rocking bioreactors) are a group of devices in which mixing is caused by characteristic wave-like movement of liquid inside a pillow-shaped bag mounted on a continuously oscillating platform. This study aimed to investigate the influence of liquid phase viscosity and the presence of an antifoaming agent on the mass transfer in a 2 liter single-use bag used in a ReadyToProcess WAVE 25 bioreactor system. The mass transfer rate was quantified by measuring the volumetric liquid-side mass transfer coefficient k L a using a gassing-out method. Two liquid phase mixture types were independently composed of Dulbecco's modified Eagle medium or water and supplemented with fetal bovine serum (FBS). The viscosity of the liquid phases was modified with glycerin. The measurements were performed with and without the addition of a Pluronic F-68 antifoaming agent in a viscosity range of 0.9−4.2 mPa•s. It was shown that the viscosity of the liquid phase significantly impacts the values of the k L a coefficient, ranging from 0.8 to 3.7 h −1 at α = 7°and ω = 2 min −1 . The addition of the antifoaming agent caused a decrease in the mass transfer rate. A correlation has been proposed for estimating k L a values as a function of the modified Reynolds number.

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Biological performance of two different 1000 L single‐use bioreactors applying a simple transfer approach

Cited by 12 publications

References 33 publications

A practical approach in bioreactor scale‐up and process transfer using a combination of constant P/V and vvm as the criterion

A practical approach in bioreactor scale‐up and process transfer using a combination of constant P/V and vvm as the criterion

Harmonization and characterization of different single‐use bioreactors adopting a new sparger design

Mass Transfer in a Liter-Scale Wave Mixed Single-Use Bioreactor: Influence of Viscosity and Antifoaming Agent

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