Chromatographic strategies for the analytical characterization of adeno-associated virus vector-based gene therapy products

Abstract

In recent years, the biopharmaceutical industry's interest in gene therapy modalities has increased dramatically. To warrant their quality during manufacturing and upstream/downstream process, fit-for-purpose analytical methods play a crucial role in the overall control strategy. However, characterization of gene therapy products remains challenging due to their large size, structural complexity, heterogeneity, potential instability, and limited sample availability. In addressing some of these challenges with innovative approaches, liquid chromatography (LC) based methods have become an integral part of the currently used analytical toolbox. This review focuses on both established methods and emerging trends in the LC analysis of adeno-associated virus (AVV) vector-based gene therapy products. Each method is discussed to highlight their advantages, drawbacks, and unique capabilities in the analysis of AAV gene transfer vehicles and their corresponding impurities. Taken together, this review provides guidance on the selection of LC-based methods for routine testing and extended characterization of gene therapy products.