Techno-Economic Analysis of Membrane-Based Purification Platforms for AAV Vector Production.

Area of Science:

• Biotechnology
• Process Engineering
• Gene Therapy Manufacturing

Background:

• Viral vector manufacturing for gene therapies is scaling up.
• Techno-economic analysis (TEA) is crucial for optimizing early-stage process development.
• Membrane-based purification technologies are key for large-scale production.

Purpose of the Study:

• To adapt a TEA framework for adeno-associated viral vector (AAV) purification.
• To identify critical membrane properties impacting large-scale manufacturing performance.
• To explore the design space for optimizing viral vector purification processes.

Main Methods:

• Adapted a TEA framework from monoclonal antibody capture for AAV purification.
• Incorporated mechanistic models for flux decline and capsid separation.
• Developed graphical user interfaces for design space exploration.
• Performed sensitivity analyses on key process variables.

Main Results:

• Increasing module capacity in tangential flow filtration (TFF) reduced cost of goods more than increasing operational flux.
• Membrane chromatography with low dynamic binding capacity (DBC) and short residence time (RT) showed comparable or better economics than high DBC/long RT.
• Salt concentration significantly influences the separation of full and empty capsids, affecting purity.

Conclusions:

• Module capacity is a primary driver for cost reduction in TFF harvesting of viral vectors.
• Optimizing DBC and RT in membrane chromatography is essential for economic and purity goals.
• Understanding salt concentration effects is critical for achieving high purity in viral vector purification.