ABSTRACT
Predicting potential toxicologic responses to transdermal delivery is a complex procedure, involving both traditional toxicology protocols for evaluating results of systemic exposure and topical studies assessing skin-drug interactions and reactions. Evaluation of individual drug and system components is followed by fi nal system testing to assess possible interactions. Risk is estimated by analyzing toxicologic data quantitatively, with estimation of human exposure based on dose-response extrapolations. Formulation or system changes designed to minimize risk are evaluated. In some instances, local intolerance to a compound-either due to irritation or sensitization-may preclude development of a transdermal product despite effi cacious plasma levels. For viable projects with acceptable toxicologic profi les, a strategy is implemented to manage the risk of irritation and sensitization. In addition to the usual drug-specifi c systemic toxicology and regulatory issues, a toxicology evaluation plan for transdermal dosage forms must include primary and cumulative irritation and sensitization testing. The plan must also take into account the U.S. Food and Drug Administration’s (FDA) categorization of new transdermal systems and novel excipients as new chemical entities (NCEs), subject to standard nonclinical testing procedures.
