Kathrin Möllenhoff

Assessing the Similarity of Drug Dissolution Profiles

Equivalence analyses are a frequently addressed problem during drug development. One of the main issues is the comparison of drug dissolutions profiles in order to investigate bioequvialence of two formulations. According to current guidelines this problem is usually assessed using the similarity factor f2. This quantity measures the mean difference over time between test and reference formulation and their dissolution profiles are declared similar if the f2 is larger or equal than 50, which corresponds to allowing for an average difference of at most 10% between the profiles.

However, the usage of this factor is limited through several conditions which have to be fulfilled, for instance, a restricted variability of the data. This talk presents a (parametric) bootstrap procedure, applicable irrespectively of these validity criteria, based on the maximum distance between the profiles, which is obtained by fitting pharmacokinetic curves to the data. We showed that this test procedure controls its level properly and we demonstrated a reasonable high power by means of a simulation study motivated from real case-studies provided by the European Medicines Agency.

The talk is based on joint work with Holger Dette (Ruhr-Universität Bochum, Germany), Stanislav Volgushev (University of Toronto, Canada), Olivier Collignon and Evangelos Kotzagiorgis (European Medicines Agency).

Recorded Presentation