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CFD Supported Investigation of Shear Induced by Bottom-Mounted Magnetic Stirrer in Monoclonal Antibody Formulation

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Abstract

Purpose

Biological pharmaceutical unit operations like homogenization or pooling of liquids are often performed in stirred vessels. Bottom-mounted magnetic stirrers are usually the system of choice in drug product manufacturing, because bottom-mounted magnetic stirrers are considered to be gentle mixing systems. Nevertheless, magnetic stirrers can cause shear stress and, thus, lead to protein damage.

Methods

This study uses computational fluid dynamics (CFD), because flow and shear rates cannot easily be measured at the spot of interest. The investigation utilizes CFD models, which were checked for plausibility by comparing experimental results and model outcome. The investigators first modeled macroscopic flow across a range of vessel volume capacities. Subsequently, detailed models focusing on two locations (bearing gap (2 mm - 3.5 mm) and spigot gap (40 μm - 80 μm)) were developed.

Results

The macroscopic flow modeling showed that the direction of flow varies based on the vessel volume capacity. The detailed CFD model estimated significant flow through the bearing gap. However, the calculated shear rates in the bearing gap were always lower than the shear rates which occur directly next to the impeller tip. The CFD model calculated significantly higher shear rates in the spigot gap and flow in the lower microliter range.

Conclusions

Shear rates at the impeller tip are typically used as parameter to characterize stirred mixing systems. Although higher shear rates were found in the spigot gap, these higher shear rates can most likely be neglected for most applications due to non-significant flow through the spigot gap.

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Abbreviations

ρ :

Density of the fluid

ε max :

Maximum local energy dissipation rate

μ :

Viscosity

τ :

Shear stress

τ max :

Maximum shear stress

\( \dot{\gamma} \) :

Mean shear rate

API:

Active Pharmaceutical Ingredient

CFD:

Computational Fluid Dynamics

c homo :

Concentration (final value) in steady state

D :

Impeller diameter

D inho :

Degree of inhomogeneity

h :

Impeller height

h G :

Cylinder height

n :

Stirrer rotation frequency

N p :

Power number

r:

Radius

t homo :

Time for one measurement sensor to reach homogeneity

u tip :

Impeller tip speed

V :

Volume of the fluid

v max :

Maximum liquid velocity

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors would like to thank Michael Bigalke for conducting the experiments and Natalie Rakel for initiating the study. Furthermore, we thank Michael Barkhudarov and Frieder Semler from Flow Science for their technical help and useful discussion on numerical topics.

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Authors and Affiliations

  1. Roche Diagnostics Deutschland GmbH, Sandhofer Str. 116, 68305, Mannheim, Germany

    Tobias Ladner, Sebastian Odenwald, Kevin Kerls, Gerald Zieres & Julien Bœuf

  2. F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, 4070, Basel, Switzerland

    Adeline Boillon

Authors
  1. Tobias Ladner
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  2. Sebastian Odenwald
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  3. Kevin Kerls
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  4. Gerald Zieres
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  5. Adeline Boillon
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  6. Julien Bœuf
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Correspondence to Julien Bœuf.

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Ladner, T., Odenwald, S., Kerls, K. et al. CFD Supported Investigation of Shear Induced by Bottom-Mounted Magnetic Stirrer in Monoclonal Antibody Formulation. Pharm Res 35, 215 (2018). https://doi.org/10.1007/s11095-018-2492-4

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  • DOI: https://doi.org/10.1007/s11095-018-2492-4

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