Computational fluid dynamics (CFD) insights into agitation stress methods in biopharmaceutical development

Area of Science:

• Biopharmaceutical development
• Protein science
• Process engineering

Background:

• Agitation of small liquid volumes is routine in biopharmaceutical process, formulation, and packaging.
• Protein degradation during agitation is common but poorly understood.
• Characterizing agitation stress is crucial for identifying degradation mechanisms and sensitivities.

Purpose of the Study:

• To model and compare fluid stresses generated by four common laboratory agitation instruments.
• To identify and quantify stresses in bulk liquid and near interfaces.
• To inform selection of agitation methods for better understanding protein degradation.

Main Methods:

• Computational fluid dynamics (CFD) was used to model the agitation of 1 mL of fluid.
• Four common laboratory agitation instruments were simulated: rotator, orbital shaker, magnetic stirrer, and vortex mixer.
• Fluid stresses were identified, quantified, and compared in bulk liquid and near interfaces.

Main Results:

• The vortex mixer generated the most intense overall stresses.
• The magnetic stirrer system exhibited locally intense shear near the stir bar.
• The rotator produced gentler stresses but higher air-water interfacial stresses.
• The orbital shaker offered intermediate stresses with good vial-to-vial homogeneity.

Conclusions:

• Different laboratory agitators impart distinct types and intensities of fluid stress.
• Targeted selection of agitation methods based on stress profiles can improve understanding of protein degradation.
• This approach enhances predictability for real-world biopharmaceutical applications.