Holoclar
autologous corneal epithelial cells containing limbal stem cells
Sources:EMA assessment report ↗
Species
no relevant
Longest study
none
Genotox
Not conducted Not conducted
Carcinogenicity
Not conducted Not conducted
Repro
Not conducted Not conducted
First dose
Not conducted Not stated publicly
Speciesopen answer page →
Species
No animal species; abridged programme of in vitro tumorigenicity assays and literature
“Conventional non-clinical studies were generally not considered appropriate for Holoclar as a cell-based medicinal product (CBMP).”
Why that species
Lack of relevant animal models due to differences in ocular structure; xenograft and primate concerns
“the lack of relevant animal models due to differences in the ocular structure of most other mammals.”
Surrogate molecule
No surrogate; published rat/rabbit literature considered supportive only
“published non-clinical data were only considered supportive.”
Study lengthopen answer page →
Longest pivotal study
0 (no in vivo tox study)
“in vivo studies in a homologous animal model were considered by the CAT not to be necessary”
Pivotal GLP studies
No in vivo tox; in vitro karyotype, growth factor dependence and soft agar assays
“in order to investigate the proliferative capacity of the 3T3-J2 feeder cells, the applicant performed in vitro karyotype analysis and soft agar assays.”
Route in tox
Topical ocular (no animal dosing); in vitro only
“the product is intended for administration to the eye where it remains locally at the site of application”
Skipped studiesopen answer page →
Genotoxicity
Not conducted (classical); in vitro karyotype analysis of cells
“The analysis demonstrated a consistent karyotypic profile throughout the tested cell cultures.”
Carcinogenicity
Not conducted (conventional); in vitro tumorigenicity assays instead
“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.”
Reproductive & developmental
Not conducted; no systemic exposure and autologous product
“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”
Safety pharmacology
Not conducted; local ocular administration
“conventional pharmacodynamic safety and drug interactions studies were not conducted.”
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
NOAEL / key findings
No NOAEL; no animal tox. In vitro: no chromosomal aberrations, soft agar negative
“No evidence of chromosomal aberrations or minor chromosomal damage was detected”
Risksopen answer page →
Immune & cytokine safety
No immunogenicity studies; no significant adaptive immune response in clinical setting
“no significant adaptive immune response was observed after repeated transplantation in the clinical setting”
Biodistribution & persistence
No biodistribution studies; cells remain on ocular surface, supported by clinical histology
“classical absorption, distribution, metabolism and excretion studies were not considered relevant for a human CBMP”
Modality-specific risk
Tumorigenicity of proliferative cells; murine 3T3-J2 feeder cell microchimerism
“One of the main concerns with the use of any cell therapy, in particular those comprising a heterogeneous population of cells including cells with proliferative potential, is the formation of tumours.”