Continuous In-Line Virus Inactivation for Next Generation Bioprocessing

Area of Science:

• Biotechnology
• Pharmaceutical Manufacturing
• Process Engineering

Background:

• Viral inactivation is crucial for the safety of monoclonal antibody (mAb) therapeutics.
• Traditional methods use large batch tanks with extended hold times (30-60 min) at low pH.
• Continuous processing offers potential for improved efficiency and facility utilization.

Purpose of the Study:

• To develop and characterize a lab-scale continuous viral inactivation system for mAb therapeutics.
• To identify optimal incubation chamber designs for narrow residence time distributions in continuous flow.
• To compare the viral inactivation kinetics of the continuous system with traditional batch methods.

Main Methods:

• Design, construction, and characterization of a lab-scale continuous viral inactivation prototype.
• Evaluation of multiple incubation chamber designs for optimal flow characteristics.
• Inactivation studies using multiple viruses under various conditions (pH, buffer, mAb concentration, temperature).
• Comparison of continuous in-line system performance against traditional batch-mode viral inactivation.

Main Results:

• Successful development and characterization of a continuous viral inactivation system.
• Identification of incubation chamber designs promoting narrow residence time distributions.
• Demonstration of rapid low pH viral inactivation kinetics in the continuous system.
• Comparable viral inactivation kinetics between the continuous and batch methods were observed.

Conclusions:

• The developed continuous viral inactivation system is a viable alternative to traditional batch processing.
• The system enables efficient viral inactivation for monoclonal antibody therapeutics.
• Continuous processing offers comparable safety assurance to batch methods, supporting advanced manufacturing strategies.