Model-based control for column-based continuous viral inactivation of biopharmaceuticals

Area of Science:

• Biopharmaceutical Manufacturing
• Process Engineering
• Viral Safety

Background:

• Batch low-pH hold is a standard method for viral inactivation in biologics.
• Transitioning to continuous biopharmaceutical manufacturing requires adapting viral inactivation steps.
• Control challenges in continuous viral inactivation systems have been a significant hurdle.

Purpose of the Study:

• To develop and validate a low-cost, column-based continuous viral inactivation system.
• To implement advanced control strategies for pH and residence time.
• To address the control challenges in continuous viral inactivation processes.

Main Methods:

• Construction of a continuous system using off-the-shelf components.
• Implementation of a model-based, reaction-invariant pH controller with Bayesian estimation.
• Modeling residence time distribution using plug flow reactor with axial dispersion in series with a CSTR, estimated via inverse tracer experiments.

Main Results:

• Successful demonstration of pH and minimum residence time setpoint tracking and disturbance rejection.
• Achieved fast, accurate responses with no instability during controller validation.
• Consistent viral inactivation, evidenced by tight control of logarithmic reduction values over extended operation.

Conclusions:

• The developed system provides a viable solution for continuous viral inactivation.
• The control strategies ensure robust performance and consistent viral reduction.
• This work offers tools to enhance biopharmaceutical manufacturing productivity, quality, and patient safety.