Process Design and Comparison for Batch and Continuous Manufacturing of Recombinant Adeno-Associated Virus

Recombinant adeno-associated virus (rAAV) is one of the most widely used viral vectors that has been used for gene therapy to treat a variety of human diseases. As a newly developed product type with growing demand, understanding process performance is critical. In this study, flowsheet modeling is used to design a rAAV drug manufacturing process operating in batch and continuous mode. The designed plant has the capability to reach an annual production rate close to 2.7 x 10(19) vg/year. Economic analysis is used to analyze the cost and provide a breakdown into specific categories and unit operations. The Benzonase (R) nuclease used in the primary clarification contributes the highest amount among the overall costs for both batch and continuous processes. For batch operation, the most cost-effective production rate is 2.6 x 10(19) vg/year which is obtained by applying process debottlenecking method. To understand the process flexibility, different manufacturing scales are compared for batch and continuous operation. The analysis illustrated that the continuous operation becomes advantageous for production above 0.5 x 10(19) vg/year whereas batch operation is more cost-effective to supply AAV products that are less than 0.5 x 10(19) vg/year.