Title
Scientific solutions for regulatory guidelines: Unlocking AAV product testing
Conference Dates
February 6 – 10, 2022
Abstract
Recombinant adeno-associated virus (rAAV) represents over 65% of viral vectors being developed for gene therapy applications today. Whilst the use of rAAV is attractive as a vehicle for gene delivery, the regulatory pathway and vector manufacturing processes are complex. Through CMC guidance documents issued in 2020, the FDA recommend that characterization of gene therapy products to determine Critical Quality Attributes (CQA) is evaluated as early as possible in pre and early clinical phases. Drug Developers need high quality orthogonal analytical methods to address specific concerns for AAV products with respect to potency (titre); characterization of the capsid such as understanding Full: Empty capsid ratio and determination of aggregation and product stability, which require multiplexed assays and novel analytical technologies. For Process Developers, focus on safety, product & process impurity profiles are paramount as the traditional viral vector manufacturing methods of viral removal such as low pH or demonstration of removal of potential contaminating virus by viral clearance validation studies are not possible. Above all, the rAAV product must not be capable of replication in vitro, and the absence of replication competent AAV must be demonstrated to alleviate any safety concerns.
How then can you minimise the burden of AAV product characterization whilst maximizing the information generated? This conference talk will discuss the selection of analytical methodologies that answers this question, focusing on the development of analytic techniques to determine the critical quality attributes of aggregation and product stability.
Recommended Citation
Stuart Wright, "Scientific solutions for regulatory guidelines: Unlocking AAV product testing" in "Advancing Manufacture of Cell and Gene Therapies VII", Sharon Brownlow, Cell & Gene Therapy Catapult, UK; Sean Palecek, University of Wisconsin, USA; Damian Marshall, Achilles Therapeutics, UK; Fernanda Masri, Cell & Gene Therapy Catapult, UK Eds, ECI Symposium Series, (2022). https://dc.engconfintl.org/cellgenetherapies_vii/44