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Christina Fuentes PhD1*, Jacob Staudhammer2*,
J. Fraser Wright PhD3, Nicole Paulk PhD4, Scott Cross MS5
1Senior Consultant, Dark Horse Consulting Group; 2Principal, Dark Horse Consulting Group; 3Department of Pediatrics, Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Center for Definitive and Curative Medicine, Stanford University School of Medicine, Stanford, CA, USA; 4Assistant Professor of AAV Gene Therapy, Department of Biochemistry and Biophysics Dept, UCSF, San Francisco, CA, USA; 5Senior Principal, Dark Horse Consulting Group.
*Authors contributed equally
Several recombinant adeno-associated virus (rAAV)-based gene therapies are now approved in the US and abroad, with many others soon to follow. Advancements in the field, including the development of novel and improved analytical techniques, have enabled an increased understanding of these complex biological products. As the field matures, so should characterization of rAAV products to ensure consistent quality, safety, and efficacy. Empty, full, and partial capsid ratios, and the inherent product heterogeneity that occurs in rAAV products is one area receiving increased attention. This document describes topics around heterogeneity and product-related impurities associated with rAAV products, and how these attributes can contribute to the product’s overall quality profile. Additionally, this document summarizes several leading analytical techniques available to characterize heterogeneity and provides recommendations to sponsors for advanced rAAV characterization.