Planning Bioequivalence Studies of Drugs with Narrow Therapeutic Indices

Abstract

The principles for assessing therapeutic equivalence based on bioequivalence studies as accepted in Russia are significantly different from those adopted abroad, in particular with respect to drugs with narrow therapeutic indices (NTI). Certification of these drugs based on bioequivalence studies with commonly recognized limits is unacceptable in practice because drugs in this concentration range can cause serious adverse side effects and be more dangerous than the reference drug. The situation becomes especially critical when the reference drug is replaced by a generic. This circumstance creates the need to develop stricter regulations for NTI drugs. This article analyzes possible approaches to planning bioequivalence investigations for NTI drugs as adopted by leading world regulatory institutions in order to harmonize them with bioequivalence studies of NTI drugs in the Russian Federation. General recommendations for planning bioequivalence studies of NTI drugs were formulated based on the analysis.