Process economics evaluation and optimization of adeno-associated virus downstream processing.

Area of Science:

• Biotechnology
• Process Engineering
• Viral Vector Manufacturing

Background:

• Traditional adeno-associated virus (AAV) production relies on lab-scale methods, limiting large-scale manufacturing capacity.
• High demand for AAV vectors necessitates scalable and cost-effective production strategies.

Purpose of the Study:

• To develop and utilize a decisional tool for assessing the feasibility of non-scalable technologies in high-demand AAV production.
• To identify optimal large-scale manufacturing flowsheets that meet both economic and purity targets for AAV vectors.

Main Methods:

• A comprehensive process economics model incorporating mass balance, sizing, and costing for AAV upstream and downstream processes.
• Integration of Monte Carlo simulation for uncertainty assessment in AAV manufacturing.
• Application of a brute-force optimization algorithm to rapidly evaluate purification strategy combinations.

Main Results:

• Switching to scalable upstream (suspension cell culture) and downstream (chromatographic purification) processing alternatives offers significant economic advantages.
• The base case analysis confirmed the cost and robustness benefits of suspension cell culture over adherent culture and chromatography over batch ultracentrifugation.
• Increasing purity targets shifted optimal downstream polishing strategies from multimodal chromatography to anion-exchange chromatography or continuous ultracentrifugation.

Conclusions:

• Scalable manufacturing processes are crucial for meeting the growing demand for adeno-associated virus (AAV) vectors.
• The developed decisional tool effectively identifies cost-effective and high-purity AAV production strategies.
• Process optimization, particularly in downstream purification, is key to achieving desired AAV vector quality and economic viability.