Holoclar: genotox, carcinogenicity and repro: done or skipped?

“The analysis demonstrated a consistent karyotypic profile throughout the tested cell cultures.”

“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.”

“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”

“conventional pharmacodynamic safety and drug interactions studies were not conducted.”

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

“The karyotype analysis included chromosomal counts and the frequency of hyperploidy, hypoploidy, polyploidy, breaks and structural abnormalities in 50 metaphasic cells in six batches cultured from the drug product.”

“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.”

“tumourigenicity of Holoclar drug substance and product was investigated in three different in vitro approaches, all of which pointed towards a low risk of tumour formation.”

“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.”

“conventional pharmacodynamic safety and drug interactions studies were not conducted.”