In vitro release tests for transdermal drug delivery systems (U01)

Background Many transdermal delivery systems (TDDS) are labeled to warn against applying heat to the TDDS as it may increase the rate of drug release. When the reference product contains these warnings, the generic product must also have the same labeling. As part of its review FDA does require evidence that the formulation of a generic product is not less safe than the RLD. It is possible that different transdermal formulations of the same drug may have different responses to heat. To ensure that the RLD labeling with respect to heat is applicable to the ANDA product, the ANDA applicant should provide information about the formulation performance to ensure that the sensitivity to heat of the generic product is not more pronounced than that of the RLD. Because the identified concern is specifically related to differences in product formulation, in vitro data provides a direct measure of the formulation properties and thus is more appropriate than in vivo studies for this evaluation. Objectives This project will investigate in vitro - in vivo correlations of transdermal systems. The goal is to identity in vitro release test conditions that best identify heat effects on transdermal system release. These in vitro tests would be used in the review process to ensure that the performance of the proposed generic products does not introduce any additional safety risk. Detailed Description This project will investigate in vitro - in vivo correlations of transdermal systems. The project has several phases 1) Identification or generation of an in vivo data set of heat effects on transdermal products. The in vivo data set may be obtained from the literature or generated as a part of this grant. It may include identification of approved transdermal systems with in vivo heat effects on systemic exposure mentioned in the approved labeling. 2) Evaluation of these transdermal systems in a range of different in vitro test conditions to identify the in vitro conditions and study design that best identify the effect of heat on transdermal systems. These studies should be in-vitro skin flux permeation studies and include comparative in vitro release data at normal and elevated temperatures. 3) Evaluation of approved generic products with no in vivo heat effect data using the optimal in vitro conditions from phase 2.