Sites and Duration of Application

The BE study should include measurements of drug uptake into the stratum corneum and drug elimination from skin. Each of these elements is important to establish BA and/or BE of two products, and each may be affected by the excipients present in the product. A minimum of eight sites should be employed to assess uptake/elimination from each product. The time to reach steady state in the stratum corneum should be used to determine timing of samples. For example, if the drug reaches steady state in three hours, 0.25, 0.5, 1, and 3 hours post-treatment may be selected to determine uptake and 4, 6, 8, and 24 hours may be used to assess elimination. A zero time point (control site away from test sites) on each subject should be selected to provide baseline data. If the test/reference drug products are studied on both forearms, randomly selected sites on one arm may be designated to measure drug uptake/ steady state. Sites on the contralateral arm may then be designated to measure drug elimination. During drug uptake, both the excess drug removal and stratum corneum stripping times are the same so that the stratum corneum stripping immediately follows the removal of the excess drug. In the elimination phase, the excess drug is removed from the sites at the steady-state time point, and the stratum corneum is harvested at succeeding times over 24 hours to provide an estimate of an elimination phase

Left arm drug update

Test

15 min

30 min

Reference min

^Control)

Right arm drug elimination

Test

Reference

Test

Reference

FIGURE 2 Schematic for drug uptake and drug elimination for bioequivalence study.

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