Generic environmental risk assessment of clinical trials with AAV vectors

Hundreds of clinical trials have been carried out worldwide in which use was made of viral vectors derived from adeno-associated viruses (AAV). In recent years COGEM has published a large number of advisory reports on such trials, and in all these trials the risks to human health and the environment proved to be negligible. Drawing on these findings, COGEM has prepared a generic environmental risk assessment for clinical applications of AAV vectors. This generic environmental risk assessment can simplify and streamline the authorisation process.
AAVs are non-pathogenic viruses that can only replicate in the presence of a helper virus. AAV vectors are stripped of all viral genes except the viral sequences at the ends of the genome, the inverted terminal repeats (ITRs). As a result, the vectors are unable to replicate even in the presence of a helper virus. COGEM therefore concludes that, given the characteristics of the AAV vectors used, the risks to human health and the environment posed by clinical trials with these vectors are negligible.
The Commission notes that as AAV vectors used in clinical trials cannot spread further in the environment, there are no environmental risk grounds for refusing applications for these clinical trials if they are conducted under contained use conditions. The attached report contains COGEM’s advice on this topic and a discussion of the underlying reasoning.