Holoclar: which tox species, and why?

“Conventional non-clinical studies were generally not considered appropriate for Holoclar as a cell-based medicinal product (CBMP).”

“the lack of relevant animal models due to differences in the ocular structure of most other mammals.”

“published non-clinical data were only considered supportive.”

“Overall, the omission of classical toxicology animal studies, including single and repeat dose studies as well as immunogenicity studies, was considered by the CAT to be justified due to the lack of suitable animal models and in light of the available clinical safety data.”

“As no systemic exposure was to be expected and since the product was autologous in nature, the risk for product-related toxicity to the reproductive system was considered to be negligible and therefore omission of reproductive toxicity testing was deemed acceptable.”

“While conventional carcinogenicity studies have not been performed, the potential for transformation and formation of tumours by the human corneal epithelial cells in Holoclar was investigated in in vitro assays.”

“in vivo studies in a homologous animal model were considered by the CAT not to be necessary and the absence of non-clinical PD data was accepted.”