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Author Spotlight: Advancing Gene Therapy Research with High-Titer Adeno-Associated Virus Vector Production

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

Annabel Lyle¹, Christos Stamatis¹, Thomas Linke²

¹Department of Biochemical Engineering, The Advanced Centre for Biochemical Engineering, University College London, London, UK.

Biotechnology and Bioengineering

|April 22, 2023

Summary

This study introduces a tool to optimize large-scale adeno-associated virus (AAV) manufacturing, finding that scalable methods like suspension cell culture and chromatography are more cost-effective for meeting high AAV demands.

Keywords:

Monte Carlo simulation adeno‐associated vectors chromatography cost of goods modeling optimization ultracentrifugation

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Production, Purification, and Quality Control for Adeno-associated Virus-based Vectors

Production, Purification, and Quality Control for Adeno-associated Virus-based Vectors

Published on: January 29, 2019

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.