A Penetration and Safety Assay for Generic Ophthalmic Drugs

Abstract

Generic topical ophthalmic medications are poorly regulated by the Food and Drug Administration, resulting in an uncertainty of generics' efficacy and safety and unnecessarily placing patients at risk. In 1999, more than 200 documented cases of corneal damage as severe as corneal melting were linked to the use of a generic formulation of diclofenac, which was consequently pulled from the market. These devastating iatrogenic effects demonstrate the need for stricter testing of generic ophthalmic drugs prior to reaching the public. This report addresses this urgent need by proposing an in vitro model for simultaneously predicting corneal penetration and epithelial toxicity of topical ophthalmic formulations. Penetration and safety of ophthalmic medications have been studied separately, but until now, the development of an assay to accurately predict both penetration and safety in parallel has been overlooked. In this report, recent and ongoing research will be reviewed to (1) elucidate the complexities of corneal penetration and the effects of topical ophthalmic formulations on corneal penetration, and (2) identify important characteristics of existing models to incorporate in the proposed in vitro penetration and safety assay. Critical features of the model proposed here include a trephinated porcine cornea from tissue discards affixed in a Franz diffusion cell, permitting concurrent drug penetration and epithelial health monitoring. A robust, cost-effective penetration and safety assay such as this would provide drug companies with a valuable tool to eliminate chances of future iatrogenic effects due to topical ophthalmic drugs.