Integrated continuous downstream process of monoclonal antibody developed by converting the batch platform process...

Area of Science:

• Biotechnology
• Chemical Engineering
• Pharmaceutical Sciences

Background:

• Monoclonal antibody (mAb) purification is critical for biopharmaceutical manufacturing.
• Traditional batch processes can be time-consuming and resource-intensive.
• Continuous processing offers potential for improved efficiency and reduced footprint.

Purpose of the Study:

• To develop and characterize a continuous downstream process for monoclonal antibody purification.
• To integrate periodic-counter current chromatography (PCCC) and flow-through chromatography (FTC) for efficient mAb isolation.
• To assess the process's flexibility, stability, and resource requirements.

Main Methods:

• Process characterization of a continuous downstream purification train.
• Utilized two Protein A columns in a periodic-counter current chromatography (PCCC) configuration for mAb capture.
• Employed a batch reactor for low pH virus inactivation (VI) and flow-through chromatography (FTC) with anion-mixed mode and cation exchange columns for polishing.
• Integrated virus filtration post-polishing.

Main Results:

• Achieved good recovery and purity values across multiple runs with varying feed rates and concentrations.
• Demonstrated process flexibility and stability in handling feed fluctuations.
• The integrated process required only three surge/pool tanks, significantly reducing buffer requirements.
• Successful scale-up to a Good Manufacturing Practice (GMP) facility was achieved.

Conclusions:

• The developed continuous downstream process is effective for monoclonal antibody purification.
• The PCCC and FTC combination offers a robust and efficient purification strategy.
• The process is scalable, flexible, and requires minimal intermediate storage, paving the way for more streamlined biomanufacturing.