Virus study for continuous low pH viral inactivation inside a coiled flow inverter

Area of Science:

• Biopharmaceutical Manufacturing
• Viral Clearance
• Process Engineering

Background:

• Continuous processing is increasingly important for monoclonal antibody (mAb) production.
• Low pH viral inactivation is a standard step in mAb manufacturing.
• The coiled flow inverter (CFI) enables continuous low pH viral inactivation, but experimental validation is lacking.

Purpose of the Study:

• To develop and execute a virus study for continuous low pH viral inactivation using a CFI.
• To validate the effectiveness of the CFI for viral clearance in mAb production.
• To demonstrate the adaptability of the concept for other continuous viral clearance steps.

Main Methods:

• Development of a technical rationale for experimental setup, spiking, and sampling.
• Execution of a virus study using xenotropic murine leukemia virus.
• Testing two protein A chromatography setups at different pH levels and comparing with a batch experiment.

Main Results:

• Sufficient low pH viral inactivation (decadic logarithm reduction value >4) was achieved in all tested conditions.
• Complete viral inactivation occurred within 14.5 minutes for both continuous and batch experiments.
• The CFI demonstrated effective viral clearance, comparable to batch processes.

Conclusions:

• The study presents a successful virus study concept and experiment for continuous viral inactivation using a CFI.
• The CFI effectively inactivates viruses, supporting its use in continuous biopharmaceutical manufacturing.
• Transferability of batch results to continuous processes is feasible due to the CFI's plug-flow characteristics.