Truly continuous low pH viral inactivation for biopharmaceutical process integration.

Area of Science:

• Biotechnology
• Process Engineering
• Viral Safety

Background:

• Continuous biomanufacturing requires efficient viral inactivation (VI) methods.
• Current VI strategies often lack integration into continuous processes.
• Ensuring adequate viral incubation time is critical for effective inactivation.

Purpose of the Study:

• To develop and evaluate a packed bed continuous viral inactivation reactor (CVIR) for low pH incubation.
• To assess the reactor's performance regarding residence time distribution (RTD) and stability.
• To demonstrate the efficacy of continuous low pH VI using model viruses.

Main Methods:

• Implementation of a packed bed CVIR designed for narrow RTD.
• Testing RTD stability across varying linear flow velocities.
• Assessing bed stability under prolonged acidic pH exposure.
• Evaluating viral inactivation using xenotropic murine leukemia virus and pseudorabies virus at low and neutral pH.

Main Results:

• The packed bed CVIR demonstrated a narrow RTD that remained consistent over a wide range of flow velocities.
• Prolonged acidic pH exposure did not compromise bed stability or RTD.
• Significant viral inactivation was achieved at low pH within 15 minutes, comparable to batch processes.
• No system-induced VI was observed at neutral pH.

Conclusions:

• The packed bed CVIR is a robust and flexible system for continuous low pH viral inactivation.
• This technology effectively guarantees the required minimum incubation time for VI.
• The study establishes a viable concept for continuous VI, showcasing the versatility of packed bed reactors.