Current FDA guidance requires specific monitoring for replication-competent viruses and insertional oncogenesis in gene therapy products to mitigate the risks of clonal expansion and malignancy.
Integrating vectors are associated with alterations in cellular function related to disruption of normal gene function. This has been associated with clonal expansion of cells and, in some instances, cancer. These events have been associated with replication-defective vectors and suggest that the inadvertent exposure to a replication-competent virus arising during vector manufacture would significantly increase the risk of treatment-related adverse events. These risks have led regulatory agencies to require specific monitoring for replication-competent viruses, both prior to and after treatment of patients with gene therapy products. Monitoring the risk of cell expansion and malignancy is also required. In this review, we discuss the rational potential approaches and challenges to meeting the US FDA expectations listed in current guidance documents.
Cornetta et al. (Fri,) conducted a review in Gene therapy-related adverse events (replication-competent virus and insertional oncogenesis). Replication-competent virus and insertional oncogenesis testing was evaluated. Current FDA guidance requires specific monitoring for replication-competent viruses and insertional oncogenesis in gene therapy products to mitigate the risks of clonal expansion and malignancy.