Opportunities to implement continuous processing in production of recombinant adeno-associated viral vectors

Cell & Gene Therapy Insights 2023 9(3), 563–579

DOI: 10.18609/cgti.2023.082

Published: 5 June
Garima Thakur, Sheldon Mink, Hanne Bak, Andrew Tustian

Shifting from batch to continuous manufacturing is a promising way of lowering manufacturing costs by 60–80%. This is because continuous processing allows upstream and downstream unit operations to run simultaneously with reduced downtime, higher productivity, and at several-fold smaller scale via a range of enabling technologies including perfusion bioreactors, single pass filtration modules, and multi-column chromatography systems. Most advancements in continuous processing have been made in the context of monoclonal antibody processes, but no end-to-end continuous process has yet been implemented at scale. This is in part due to a lack of business case supporting the creation of new continuous manufacturing facilities and processes versus utilization of existing legacy batch processing infrastructure with well-established norms. However, the business case for continuous processing is stronger for production of recombinant adeno-associated viral vectors (rAAV) due to high treatment costs and a paucity of existing manufacturing facilities. Gene therapy treatments based on rAAV currently cost up to USD 3 million per patient and have high cost-of-goods ranging up to USD 1 million per dose. Thus, continuous processing can play a critical role in making rAAV treatments more affordable and accessible. In this article, we explore recent developments in continuous processing for rAAV and provide an overview of some of the major opportunities for intensification of rAAV processes by applying continuous processing tools, many of which were originally developed for monoclonal antibodies but can be equally well or even better suited for rAAV production.