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.
The project aims to establish the technology at lab-scale for three serotypes (rAAV5, rAAV8, rAAV9) and scale up for rAAV5 to pilot scale. A detailed cost of goods assessment will be provided for production at pilot scale and extrapolated to manufacturing scale. Based on this data package, NIIMBL members are encouraged to similarly intensify their manufacturing processes.
Development of an intensified manufacturing process for rAAV will enable smaller-sized CDMO’s to produce rAAV vectors in clinically relevant quantities, thereby alleviating the imminent bottleneck in the production of clinical trial materials.
Intensified processes are characterized by both a smaller facility and environmental footprint. Through process intensification, we aim to make our manufacturing processes more sustainable.
Integrating ChromaTan’s BioRMB™ continuous chromatography into Landmarks Postmark™ platform will significantly intensify rAAV manufacturing, reducing resin costs and improving step recoveries. This innovation is projected to lower cost of goods for manufacturers while alleviating global capacity bottlenecks, enabling faster clinical trial progression and improved profitability.
Development and 3x10L pilot scale rAAV production using LMB’s Postmark™ AAV platform.
Affinity- and polishing chromatography development in BioRMBTM and batch columns.
Process confirmation at pilot scale.
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Landmark Bio
ChromaTan Corporation
