Pre-clinical/ non-clinical testing refers to the in vitro and in vivo animal testing conducted to evaluate the safety and efficacy of a therapy. Under the FDA requirements, you as a Sponsor are to submit data showing the toxicity and pharmacologic effects of your therapy.
The BGTC’s goal for pre-clinical testing is to streamline the process of going from proof-of-concept studies to a first-in-human trial. To that end, the BGTC Pre-clinical Sub-team has been developing a minimum set of animal toxicology studies that meet the threshold of adequate safety data for IND submissions while reducing the use of non-human primates (NHPs) as much as possible. These toxicology minimum packages will be based on route of administration – e.g., systemic AAV gene therapies administered intravenously (IV) will have different considerations compared to ocular (subretinal/intracorneal) or central nervous system via cerebrospinal fluid (intrathecal/intracerebroventricular/intracisterna magna). These minimum set of animal toxicology studies will be made available in future iterations of the BGTC Regulatory Playbook.
These minimum pre-clinical testing requirements are limited to toxicology at the moment and address animal species, dose, and length without including details such as number of animals to be used in each study. We intend to add more content in the next version and any updates to content can be found on the landing page (recently created, recently updated articles). From here, the BGTC intends to integrate pharmacology and toxicology plans into an overall broader strategy to define a standard clinical dosing strategy that can be applied for AAV gene therapies. It is important to note that in addition to the pharmacology and toxicology parameters listed above, there are other important considerations equally important, such as the delivery device, age and disease severity of the target population, prospect of direct benefit for pediatric target populations, etc.