The project addresses the industry's need for standardized and optimized protocols for rAAV production, critical for consistent and scalable gene therapy manufacturing. It focuses on validating robust analytical methods like TEM, AUC, and AEX-HPLC to ensure capsid quality and process reliability. By improving comparability across labs and enhancing documentation, it supports regulatory compliance and accelerates transitions from research to clinical applications. These advancements meet the growing demand for efficient, high-quality rAAV processes in gene therapy.
The solution is to develop and validate standardized, reproducible protocols for rAAV production and analysis across multiple academic and industry labs. This includes implementing robust analytical techniques like TEM, AUC, and AEX-HPLC for comprehensive capsid characterization. Optimizing processes through Design of Experiments (DOE) ensures scalability, consistency, and efficiency. These efforts create a reliable framework that addresses regulatory requirements and advances the scalability of gene therapy manufacturing.
Development of an analytical approach for improved separation of full, partial, and empty AAV capsid contents.
Rapid and at-line identification and accurate quantification each capsid variation in AAV products.
Development of an automated approach for robustness and reproducibility while sparing buffer and sample.
Implementing the N-Rich continuous chromatography method for AAV capsid analysis reduces analytical cycle time and minimizes resource-intensive manual steps, enabling faster batch release. This improvement can cut manufacturing costs by an estimated 15–20% through reduced batch failures, lower consumable usage, and improved process efficiency, while accelerating time-to-market for gene therapy products.
Development and validation of a new analytical method: A fluorescence-based continuous chromatography approach (N-Rich) for accurate quantification and separation of full, empty, and partial AAV capsids.
System integration: Complete integration of the Contichrom Cube system with dual FL detectors, UV detectors, and optimized flow cells for improved analytical capability.
Advancement of BRL from 4 to 5: Demonstrated technology readiness through documented results meeting acceptance criteria for integration and robustness studies.
Yoon, S., Lee, K., McNally, D., Cattaneo, M., & Regalado, E., PC4.1-138_Developing a Fluorescence-based Multi-step IEX-HPLC Method for Quantification of Full, Partial and Empty Capsid in AAV products, NIIMBL National Meeting, Washington, DC, July 26, 2022.
Yoon, S., Presenter, PC4.1-138: Developing a Fluorescence-based Multi-step IEX-HPLC Method for Quantification of Full, Partial and Empty Capsid in AAV products, NIIMBL National Meeting, Washington, D.C., July 27, 2022.
Lee, K., NIIMBL Member Forum 2022 PC4.1-138 Yoon Discussion, NIIMBL Member Forum, Virtual, June 30, 2022.
Lee, K., PC4.1-138 Yoon Lightning Talk, NIIMBL National Meeting, Virtual, June 26, 2022.
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University of Massachusetts Lowell
Artemis Biosystems Inc.
MassBiologics of the University of Massachusetts Medical School
Massachusetts Life Sciences Center
Merck Sharp & Dohme LLC
