Real-Time Adaptive Inline Acidification Enhances Continuous pH Control for Viral Inactivation

Area of Science:

• Biotechnology
• Biopharmaceutical Manufacturing
• Process Engineering

Background:

• Continuous downstream processing for biologics often relies on predictive models for viral inactivation.
• Current methods face challenges during process development due to dynamic chromatography outputs (e.g., protein titer variations).
• Accurate control of critical process parameters (CPPs) like pH is essential for consistent product quality.

Purpose of the Study:

• To introduce and evaluate an inline viral inactivation system (IVIS) for continuous bioprocessing.
• To demonstrate precise, real-time pH control for inline viral inactivation.
• To integrate IVIS with capture chromatography for a fully continuous downstream process.

Main Methods:

• Development and implementation of an inline viral inactivation system (IVIS) with real-time adaptive control.
• Integration of IVIS, including a coiled flow inversion reactor (CFIR), with a multicolumn capture chromatography system.
• Utilizing inline sensor readings for precise pH regulation during continuous processing.

Main Results:

• Achieved precise inline pH manipulation within ±0.15.
• Demonstrated a narrow residence time distribution of 13.5 min with a relative width of 0.7.
• Successfully integrated IVIS with chromatography for a fully continuous downstream workflow.

Conclusions:

• The IVIS enables accurate, real-time pH control for continuous viral inactivation.
• This advancement improves management of CPPs and ensures consistent product quality in biopharmaceutical manufacturing.
• The system offers a robust solution for continuous downstream bioprocessing, adaptable to production variations.