Process for Continuous Fab Production by Digestion of IgG

Area of Science:

• Bioprocessing and pharmaceutical manufacturing.
• Protein engineering and purification.
• Continuous manufacturing technologies.

Background:

• Traditional batch processing in bioprocessing faces limitations in efficiency and scalability.
• Intensified processing and continuous manufacturing offer potential advantages over batch methods.
• Post-translational modifications of therapeutic proteins can benefit from advanced manufacturing approaches.

Purpose of the Study:

• To develop an intensified process for enzymatic digestion of immunoglobulin G (IgG).
• To integrate continuous enzymatic digestion with continuous purification of the resulting Fab fragment.
• To enhance the efficiency of therapeutic protein production through continuous manufacturing.

Main Methods:

• Integration of a continuous packed-bed reactor for enzymatic digestion.
• Development of a novel three-column multicolumn countercurrent solvent gradient purification (MCSGP) process.
• Continuous loading and straight-through processing of reaction mixtures.

Main Results:

• Successful intensification of enzymatic digestion of IgG.
• Seamless integration of digestion and purification steps.
• Demonstration of continuous Fab fragment purification using the novel MCSGP process.

Conclusions:

• The developed integrated process offers a significant advancement in bioprocessing efficiency.
• Continuous manufacturing strategies are viable for complex biopharmaceutical production steps.
• The novel three-column MCSGP process enables continuous operation for protein fragment purification.