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

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Abstract

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 × 1019 vg/year. Economic analysis is used to analyze the cost and provide a breakdown into specific categories and unit operations. The Benzonase® 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 × 1019 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 × 1019 vg/year whereas batch operation is more cost-effective to supply AAV products that are less than 0.5 × 1019 vg/year.

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Funding

This work received technical support from Eli Lilly and Company and financial support from U.S. Food and Drug Administration, grant number DHHS-FDA-R01FD006588, and NSF, grant number 1933584.

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Authors and Affiliations

  1. Department of Chemical and Biochemical Engineering, Rutgers—The State University of New Jersey, 98 Brett Road, NJ, 08854-8058, Piscataway, USA

    Ou Yang

  2. Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA

    Yinying Tao

  3. CSL Behring, 1201 N Kinzie Ave, Bradley, IL, 60915, USA

    Maen Qadan

  4. Department of Chemical and Biomolecular Engineering, University of Delaware, 150 Academy St, Newark, DE, 19716-3196, USA

    Marianthi Ierapetritou

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  1. Ou Yang
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Correspondence to Marianthi Ierapetritou.

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Yang, O., Tao, Y., Qadan, M. et al. Process Design and Comparison for Batch and Continuous Manufacturing of Recombinant Adeno-Associated Virus. J Pharm Innov 18, 275–286 (2023). https://doi.org/10.1007/s12247-022-09645-x

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