Cell and gene therapy consulting firm submits draft AAV purity guidance to FDA
Back in September, the FDA held a two-day adcomm on gene therapy. At the time, hopes were that talks and discussions could offer a clear direction for the field’s future — and people came away disappointed as no solid recommendations or conclusions were offered. Anthony Davies, the chief behind Dark House Consulting, a cell and gene therapy specialist firm, said at the time that the adcomm was “a missed opportunity.”
Now, the firm is stepping to the plate with its own recommendations for AAVs — submitting those ideas in the form of a draft guidance to the FDA.
Dark Horse Consulting announced Sunday that its draft guidance, named Testing of Adeno-Associated Viral (AAV) Vector-Based Human Gene Therapy Products for Empty Capsids During Product Manufacture, was mainly driven by former CBER veteran Donald Fink and bioengineering consultant Christina Fuentes — including the help of collaborating experts such as Nicole Paulk, a professor who runs a gene therapy lab at UC San Francisco.
The guidance hones in on the role that empty AAV vector capsids can play in product impurity, and looks to establish release criterion for full to empty (FTE) capsid ratios. From the draft submitted to the FDA:
One potential contributor to the immunotoxicity observed is the presence of empty AAV capsids in the final gene therapy product. Empty AAV capsids are considered a product impurity as they do not carry genomic material intended to provide a therapeutic effect. This guidance provides sponsors of AAV vector-based human gene therapy products with the recommendation to establish a maximum release criterion for empty AAV capsids to better control immunogenicity that may be due to empty capsid product impurity and provide for improved product safety in the context of systemic administration.
The 10-page proposed draft guidance also explains what other impurities it thinks the FDA should recognize:
“If the FDA moves forward with guidance informed by this recommendation, the result will be a reasonable, achievable impurity limit that will maximize efficacy while minimizing adverse side effects,” the firm noted. The FDA has not publicly indicated if it will accept the draft guidance for consideration.
