Use of Small Animals in IND Enabling Studies — Posterior Segment of the Eye Indications

Afshin Shafiee, PhD

Large animal models such as rabbits, dogs, pigs/minipigs, and nonhuman primates are associated with ophthalmic drug development for the posterior segment of the eye indications. Similarities in anatomy and size to human eye and availability of noninvasive methodologies to monitor the progression of the disease or drug-related adverse effects have made these models invaluable in investigating the safety and efficacy of various drug entities.

For new drug entities, small animal species including mice and rats have an important role in toxicological evaluations such as safety pharmacology, initial systemic toxicity, genotoxicity, and reproductive toxicology studies and they can be a cost-effective way to follow and implement the US FDA guidelines. 

Safety pharmacology specifically looks at respiratory, cardiovascular, and central nervous systems. Systemic toxicology dose escalation in rodent models would allow toxicologists to more accurately extrapolate the systemic doses (1-2 doses) to larger more expensive animal models. A complete battery of tests for genotoxicity (pharmaceuticals) that include in vitro and in vivo rodent models (micronuclei or chromosomal aberration assays or assay for micronuclei using rodent hematopoietic cells plus a DNA strand breakage assay in liver) should be completed prior to the initiation of Phase 2 trials.

Preferred animal models for the development of therapeutics for the posterior segment of the eye indications

*Significant differences in retinal structure, thickness of sclera and cornea to human that needs to be taken into account when selecting the most appropriate species