Development of temperature-controlled batch and 3-column counter-current protein A system for improved therapeutic...

Area of Science:

• Bioprocess Engineering
• Chromatography
• Protein Purification

Background:

• Process parameters are critical for optimizing bioprocess chromatography.
• Temperature is an under-characterized parameter in Protein A chromatography.
• Understanding temperature effects is key for monoclonal antibody (mAb) purification.

Purpose of the Study:

• To investigate the mechanistic effects of temperature on Protein A chromatography for mAb purification.
• To develop and validate temperature-dependent models for optimizing chromatography processes.
• To enhance productivity in both batch and continuous chromatography systems.

Main Methods:

• Utilized a 3D-printed heating jacket for precise temperature control (10-30 °C) during various chromatography steps.
• Performed batch loading experiments and fitted data to mechanistic and correlation-based models.
• Optimized and validated a 3-column temperature-controlled periodic counter-current chromatography (TCPCC) system.

Main Results:

• Dynamic binding capacity (DBC) increased with temperature in batch loading.
• A 3-column TCPCC at 30 °C showed a 47% increase in DBC compared to 20 °C batch.
• Productivity doubled at 30 °C compared to 20 °C batch, with further increases at higher mAb feed concentrations.

Conclusions:

• Temperature is a critical, tunable parameter for Protein A chromatography optimization.
• Temperature-dependent models provide a valuable tool for optimizing batch and continuous chromatography.
• Optimized temperature control significantly enhances mAb purification efficiency and productivity.