Elaboração de guia para a equivalência terapêutica de produtos com liberação lipossomal

Abstract

Therapeutic Equivalence is the terminology applied for proving the efficacy and safety of generic and brand generic medicines, developed for having the same therapeutic purpose of the reference listed medicines. Whilst the latter ones go through the complete development program (pre-clinical assays, phase I, II, III and IV clinical trials) the first ones can be registered by performing comparability assays. The therapeutic equivalence proof generally is based on pharmaceutical equivalence and relative bioavailability / bioequivalence studies and these studies are guided by specific legislation. However, for more complex pharmaceutical dosage forms, among those the liposomes, additional requirements should be verified for ensuring the efficacy and safety of the medicines that use this form of release. In order to supress the regulatory gaps that are in place for the comparability of liposomal medicines a comparability guidance has been written and establishes the in vitro and in vivo assays that should be performed for proving the therapeutic equivalence of these products. For doing so the guidance from the American (FDA) and European (EMA) agencies were studied. Additionally the characterization assays that could indicate the product stability in vivo were also studied, in order to minimize the risks that arise from the medication dosing, when administered to the trial´s subjects that will be included in the comparability studies defined in the guidance Among the characterization assays included in the guidance there are the particle size distribution, the determination of the superficial charge and the temperature of the transition phase. For the determination of the bioequivalence the confidence interval should be built for the free portion of the active ingredient, the encapsulated portion and also the total amount of the pharmaceutical active ingredient (free + encapsulated portion). We conclude that this guide will assist Anvisa in the elaboration of regulatory norms for the comparability of liposomal drugs.