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.
| Deliverable/Output | Description | Accessibility |
|---|---|---|
Assets | Receive and install all equipment (HPLC, FL detector, columns, standards, other consumables) | Available / Completed, |
Assets | Completed setup of IEX-HPLC with FL detector available for the initial run | Available / Completed, |
Material | Establishment of all reference samples and enrichment if necessary | Available / Completed, |
Procedures | Establishment of at least two different orthogonal methods in capsids characterization. Comparative assessment on Repeatability, intermediate precision, linearity, accuracy, and LOD/LOQ. (Linear correlation R2 > 0.9 & < 2SD for robustness and consistency) | Available / Completed, |
Technical Data | Completion of all different sample measurement using FL IEX-HPLC and orthogonal methods. | Under Development / In Progress, |
Procedures | Optimization Accuracy(at least 90%), resolution(Rs>2), separation time(1-5 min), sensitivity(1E11 vg/ml), LOD(~1E9 total vg injected) comparison with orthogonal methods. | Under Development / In Progress, |
Development of an analytical approach for improved separation of full, partial, and empty AAV capsid contents.
Development of an automated approach for robustness and reproducibility while sparing buffer and sample.
Rapid and at-line identification and accurate quantification each capsid variation in AAV products.
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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
