Gene Therapy
Regulatory & Standards
Viral/Non-Viral Vectors

FDA to Discuss Toxicity Risks of AAV Vector-Based Gene Therapy Products

Georgi Makin
5 August 2021

The FDA has announced a meeting of the Cellular, Tissue and Gene Therapies Advisory Committee (CTGTAC) to consider the toxicity of AAV vector-based gene therapy products.

UPDATE: The event information and materials have been updated ahead of the meeting, with Advisory Committee members Roland Herzog (Indiana University), Kenneth Berns (University of Florida) and Charles Vite (University of Pennsylvania) declaring conflicts in financial interest.

As the date for the meeting draws closer, more and more commentaries on high dosage AAVs are surfacing as members of the community postulate on what the outcome of these discussions might be. 

 Ahead of our upcoming meeting reaction Phacilitate Talks episode, Nicole Paulk from UC San Francisco, commented: 

 “I’m hopeful that this Advisory Committee provides clarity for investigators on several key issues that are top of mind for all of us in the field. Given the fantastic ASGCT Roundtable event on AAV Integration held August 18th, I feel confident that Day 1 Session 1 will be much of the same and a continuation of that conversation. The remaining four sessions will be where most of the more intriguing science will be covered. I’m confident that with Drs. Herzog, Vite, and Berns leading the conversations, we’ve got strong scientific voices guiding the compass in the right direction.”

In other news, Victoria Dohnal, Director of Science and Regulatory Affairs at the Biotechnology Innovation Organization (BIO) has signed a letter calling for a 60-day comment extension post-meeting, suggesting that stakeholders will value the opportunity to examine the event materials, listen to the discussion in full and provide ‘substantive’ commentary to the FDA.

If you will be joining the meetings and would like to contribute to a dedicated, collaborative reaction piece with Phacilitate, please email me via:

The announcement document states that matters for consideration include oncogenicity risks due to vector genome integration, as well as safety issues identified during preclinical and/or clinical evaluation.

 The meeting, spanning two consecutive days from 2–3 September 2021 at 10:00–18:00 [ET], will be open to the public (virtually) and the FDA has stated that a docket for public comment is currently being established (FDA-2021-N-0651).

 More information for providing comment can be found here, via the official FDA document published with the Federal Register.

Joining information, via YouTube:  


The agenda will be as follows:

2nd September 2021  

  • Session 1: Vector integration and oncogenicity risks
  • Session 2: Hepatotoxicity issues

3rd September 2021  

  • Session 3: Thrombotic microangiopathy issues
  • Session 4: Non-clinical findings of neurotoxicity, especially related to dorsal root ganglion toxicity issues
  • Session 5: Clinical findings of neurotoxicity, based on brain magnetic resonance imaging studies

Background material will reportedly be provided by the FDA no later than 2 business days ahead of the meeting, here.

 You can find more information about the sessions via the official FDA document, here.

Source: FDA Document, Docket No. FDA-2021-N-0651, via the Federal Register