Methods
For the analysis of the non-clinical data packages for cell-based products, we collected scientific advice reports on ATMPs, written between January 2013 and July 2018, from the EMA database. We selected products containing cells (including genetically modified cells) for which the information on the non-clinical development program was available in the advice reports and, if available, from the accompanying briefing books. For all products, it was recorded whether dedicated or combined studies addressing pharmacology, safety, biodistribution and/or tumourigenicity had been performed. In case no studies were performed to address biodistribution and tumourigenicity, it was recorded for what reason: not necessary, planned or whether they were requested by the regulator.
Regarding the biodistribution studies, it was scored per product whether distribution to target and non-target tissues was assessed, whether persistence of the cells was analysed and if quantitative techniques were used. When available, it was noted whether the sponsor regarded the study of value for proof-of-concept and/or safety.
Regarding the tumourigenicity studies, the number and type of studies were recorded. For the in vitro studies, the method was scored. For the in vivo studies the following aspects on the design of the studies were noted as well: species, cell dose, administration route and duration.
Analyses of the scored information were performed for all products and for classes of cell-based products when categorisation was applied based on the cell source (autologous versus allogenic) and the presence or absence of genetic modification.
More detail on which data were acquired and how these were analysed is provided in the Appendix.
Results