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