Modeling retention time distribution in continuous Protein A affinity capture for materials traceability and...

Area of Science:

• Biopharmaceutical Manufacturing
• Chemical Engineering
• Process Analytical Technology

Background:

• The biopharmaceutical industry is transitioning from batch to continuous manufacturing, driven by efficiency and regulatory guidelines like ICH Q13.
• Material traceability is a key regulatory consideration in continuous manufacturing, yet it is underexplored in Protein A continuous capture processes.
• Existing methods lack robust solutions for real-time material traceability and diversion in continuous bioprocessing.

Purpose of the Study:

• To develop a retention time distribution (ReTD) model for a twin-column continuous capture process to enable material traceability.
• To simulate and validate ReTD behavior during different operational steps of continuous capture.
• To propose a practical method for material traceability and diversion based on the ReTD model for real-time product release.

Main Methods:

• Developed a retention time distribution (ReTD) model for a twin-column continuous capture process, extending a single-column model.
• Simulated ReTD behavior during startup, interconnected load, and disconnected load steps.
• Validated simulations using tracer experiments with fluorescently labeled proteins.

Main Results:

• The ReTD model accurately predicted material distribution in elution peaks across process switches.
• Experimental validation confirmed good agreement between model predictions and tracer experiment results.
• The study identified breakthrough dynamics, exchange effects, and operational step changes as key factors influencing ReTD behavior.

Conclusions:

• A novel ReTD model provides a method for material traceability and diversion in continuous capture processes.
• The periodic nature of continuous capture allows extrapolation of ReTD behavior for extended durations.
• This ReTD-based approach supports real-time product release by enabling tracking and diversion of non-conforming materials, meeting regulatory requirements.