Recombinant adeno-associated virus (AAV) gene therapies rely on accurate capsid titer measurements to determine dosage and assess product quality. Capsid titer is commonly measured using enzyme-linked immunosorbent assay (ELISA), the most widely adopted technique in the industry. However, significant variability among commercial ELISA kits and calibrants introduces uncertainty in reported capsid titers. This lack of consistency limits comparability of AAV9 capsid titer values across projects, products, and regulatory submissions, creating a critical need for standardized, reliable methods to ensure accuracy and precision in capsid quantification.
This study aims to address this critical gap in the field by evaluating a new AAV9 analytical reference material developed by the United States Pharmacopeia (USP, catalog #1800241), which can be used as an ELISA calibrant. By quantifying test articles relative to this new USP standard, it may be possible to improve the accuracy and precision of AAV9 capsid titer measurements across commercial ELISA kits. If found to be the case, this study has the potential to advance analytical harmonization and support regulatory confidence in gene therapy manufacturing and testing.
Establish the USP AAV9 calibrant as a universal reference by quantifying and correcting offsets between the USP standard and individual kit standards, enabling consistent normalization and reducing inter-kit variability across all participating laboratories.
This seven-lab study aims to harmonize AAV9 capsid quantification by leveraging USP reference material and multiple commercial ELISA kits, exploring sources of variability and improving precision through rigorous statistical analysis. By generating shared, high-quality data across diverse sites, the project seeks to establish robust analytical standards that reduce inconsistencies, support regulatory confidence, and advance gene therapy manufacturing practices.
Future: A white paper or peer-reviewed publication: to improve transparency, comparability, and confidence in AAV analytical methods.
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Carnegie Mellon University
Keck Graduate Institute
Landmark Bio
Michigan Technological University
North Carolina State University
PATH Center for Vaccines Innovation & Access
University of Delaware
