Evaluation of Continuous Membrane Chromatography Concepts with an Enhanced Process Simulation Approach

Area of Science:

• Biopharmaceutical Manufacturing
• Separation Science
• Process Engineering

Background:

• Continuous chromatography is key for small-scale, cost-effective biopharmaceutical production, improving capacity, purity, yield, and reducing facility footprint.
• Membrane chromatography presents a disposable, low-cost alternative to bead-based methods, with potential for continuous processing despite capacity considerations.

Purpose of the Study:

• To develop and validate a novel process modeling approach for continuous membrane chromatography.
• To evaluate the feasibility of integrated Counter Current Chromatography (iCCC) and sequential chromatography concepts using membrane adsorber modules.
• To assess the efficiency of continuous membrane chromatography for biopharmaceutical production in a fed-batch reactor case study.

Main Methods:

• A new modeling approach was developed, combining the general rate model with advanced fluid dynamic distribution, specifically for membrane chromatography modules.
• Model parameters were determined and validated using industrial cell cultures producing Immunoglobulin G (IgG).
• The validated model was applied to evaluate iCCC and sequential chromatography concepts and a fed-batch reactor case study (20–2000 L).

Main Results:

• The new model accurately represented membrane chromatography processes, enabling efficient analysis of various process setups.
• The validated model confirmed the feasibility of continuous membrane chromatography concepts for IgG purification.
• Compared to batch operations, continuous processes achieved a 71% higher capacity, 48.5% higher productivity, and 38% lower eluent consumption.

Conclusions:

• Continuous membrane chromatography, supported by advanced process modeling, is a highly efficient technology for biopharmaceutical manufacturing.
• The developed modeling approach facilitates rapid evaluation of continuous processes, optimizing performance and resource utilization.
• This technology offers significant advantages in capacity, productivity, and cost-effectiveness over traditional batch chromatography methods.