Improving process efficiency to reduce cost-of-goods per dose in manufacturing of recombinant AAVs

Cell & Gene Therapy Insights 2024; 10(3), 479–499

DOI: 10.18609/cgti.2024.061

Published: 3 May
Expert Insight
Garima Thakur, Sheldon Mink, Hanne Bak, Andrew D Tustian

AAV have emerged as a leading platform for in vivo gene delivery due to their robust safety profile and ability to effectively deliver therapeutic genes to a range of tissue and organ targets. However, a key challenge limiting access to AAV therapies is the high cost of treatment of up to US$3.5 million per dose. Reasons for high cost-of-goods (COGs) per dose include low bioreactor production yields, significant product loss during purification, limited process scalability, and expensive raw materials. Notably, even a two- to three-fold reduction in costs can bring gene therapy treatments financially in-line with well-established biologics such as mAbs. For example, recurring costs for regular doses of mAbs can range from US$10,000–50,000 per year, equivalent to US$0.3–1.5 million over a lifetime usage of 30 years. Thus, there is significant opportunity to intensify gene therapy manufacturing processes to enable these curative treatments to become the most compelling option for patients both socially and financially. In this article, we discuss several manufacturing-related approaches to lower COGs/dose of AAV-based gene therapies by improving process efficiencies.