Development of an integrated and highly intensified manufacturing process for rAAV vectors using Continuous Countercurrent Tangential Chromatography

Recombinant adeno-associated virus (rAAV) vectors are spearheading the development of next generation treatments to cure life threatening diseases. However, demand for rAAV is exceeding its production capacity, threatening to become a bottleneck for pivotal clinical trials.

Current methods for capture- and polishing chromatography are limiting factors due to substantial resin costs (capture) and low step recoveries (polishing). Continuous chromatography has been shown to greatly contribute to the intensification of manufacturing processes for monoclonal antibodies. Yet, similar applications for rAAV are still lacking. As a leading CDMO, LandmarkBio aims to alleviate both the shortage in rAAV manufacturing capacity and simultaneously reduce the cost of goods by integrating ChromaTan’s BioRMBTM – a novel column-free real moving bed continuous chromatography platform into its Postmark™ ® manufacturing platform. The proposed work will focus on the design of upstream and downstream processes for pilot-scale production of rAAV, including a direct comparison of CCTC process performance and economics vs. conventional batch column chromatography. ChromaTan will additionally perform detailed development for rAAV8 and rAAV9 to demonstrate its broader applicability. Based on this data package, NIIMBL members will be in a position to similarly intensify their manufacturing processes for

a diverse array of rAAV products.

Demand for rAAV is rapidly expected to exceed its production capacity, threatening to become a bottleneck for pivotal clinical trials that may negatively impact patient outcomes. Here, an investment is proposed into the development and direct comparison of CCTC process performance vs. conventional batch column chromatography to intensify rAAV downstream processing.