Generic environmental risk assessment of replication-deficient adenoviral vectors in clinical trials

Vectors derived from adenoviruses (adenoviral (AdV) vectors) are the most commonly used vectors in clinical gene therapy trials. A distinction is made between vectors that can replicate (replication-competent) and vectors that cannot replicate (replication-deficient).
On a number of occasions in the past COGEM has issued advice on clinical studies in which AdV vectors were used. Further to a request for advice on a broad licence application for clinical vaccine trials with replication-deficient AdV vectors, COGEM has prepared a generic environmental risk assessment for clinical applications that use these vectors. This generic environmental risk assessment is limited to replication-deficient AdV vectors in which at least the E1 region of the viral genome has been removed.
Replication-deficient AdV vectors are attenuated and biologically contained, and because they are replication-deficient they cannot spread in the environment. COGEM is of the opinion that, given the properties of replication-deficient adenoviral (AdV) vectors, the risks to human health and the environment of clinical trials with these vectors are negligible, provided a number of conditions are met. This generic environmental risk assessment can simplify and streamline the authorisation process for clinical trials, because it can provide the basis for drawing up a set of standard licence conditions (vergunning onder vaste voorwaarden – VoV) for these applications.