Key Insights For Safety Assessments Of Ophthalmic Products

Preclinical trial design for ocular drugs depends on the specifics of the drug being developed, such as whether it is a new chemical entity (NCE) or a reformulation of a previously approved drug. When preparing for First-in-Human (FIH) studies, two non-rodent species are generally preferred. Large species like dogs and rabbits are suitable for drugs administered via all routes, including topical, subconjunctival, intracameral, subretinal, and intravitreal (IVT). Pigs are more appropriate for subretinal and IVT injections, while nonhuman primates (NHPs) are better suited for subconjunctival, intracameral, subretinal, and IVT routes. Small species such as rats and mice with retinal mutations, such as those seen in retinitis pigmentosa, are ideal for subretinal gene therapy injections. In certain cases, a single species may be sufficient, provided there is strong justification, such as a lack of biological homology in other species or existing nonclinical or clinical data from previous ocular drug administrations.

Ocular pharmacokinetic (PK) studies, which assess the absorption, distribution, metabolism, and excretion (ADME) in various ocular compartments, are typically conducted in a single species and do not require target pharmacological relevance. Before conducting pivotal repeat-dose ocular studies, an ocular tolerability study is recommended, often using a single-dose approach in rabbits. These studies typically involve a 20 to 30 µl drop size, with hourly observations and scoring, using modified Draize criteria. The study also includes increases in concentration or dose frequency over several days, with complete ophthalmological evaluations, including slit-lamp biomicroscopy and indirect ophthalmoscopy.