Countercurrent staged diafiltration for formulation of high value proteins

Area of Science:

• Biotechnology
• Chemical Engineering
• Bioprocessing

Background:

• Continuous biomanufacturing aims to integrate bioreactors and chromatography.
• Protein formulation is a critical downstream processing step.
• Reducing buffer consumption is essential for cost-effective bioprocessing.

Purpose of the Study:

• To evaluate a countercurrent staged diafiltration process for continuous protein formulation.
• To assess the feasibility of reducing buffer requirements using this method.
• To model product yield, impurity removal, and buffer needs.

Main Methods:

• Utilized a polyclonal immunoglobulin (IgG) model system.
• Employed Cadence™ Inline Concentrators for experiments.
• Developed mathematical models for yield, purity, and buffer usage based on stage parameters.

Main Results:

• Experimental data from a two-stage system closely matched model predictions.
• Countercurrent staging significantly impacts buffer exchange efficiency and volume.
• The process demonstrated potential for reduced buffer consumption per unit of product.

Conclusions:

• Countercurrent staged diafiltration is a feasible method for continuous protein formulation.
• This approach offers substantial reductions in buffer requirements.
• The process can decrease the number of pump passes in biomanufacturing workflows.