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 final 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-due either to irritation or sensitization-may preclude
development of a transdermal product despite efficacious plasma levels. For
viable projects with acceptable toxicologic profiles, a strategy is implemented
to manage risk of irritation and sensitization. In addition to the usual drug-
specific 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 FDA’s categoriza-
tion of new transdermal systems as new chemical entities (NCEs) subject to
standard nonclinical testing procedures.
