Abstract
The European Medical Agency (EMA) has issued a draft guideline on the quality and equivalence of topical products. The equivalence for complex semisolid formulations involves several steps: the same quantitative content, the same microstructure, the same release, and permeation profile. In this paper, several batches of a low strength topical product, which we used as a reference/comparator product, were evaluated according to the recommendations of the EMA draft guideline. The batches were 0.025% capsaicin emulsions from the same manufacturer that were evaluated in terms of droplet size, X-ray diffraction patterns, rheology, release, and permeation profile. The generated data revealed a large batch-to-batch variability, and if the EMA guideline was applied, these batches would not be considered equivalent, although they were produced by the same manufacturer. The result of this work illustrates the difficulties in obtaining equivalence according to the current draft guidelines. It also highlights that the equivalence guidelines should consider the variability of the comparator product, and in our opinion, the guidelines should allow for claiming equivalence by comparing the limits in the variability of the data generated for the comparator product with the limits in the variability of the data generated for the intended equivalence product.
Highlights
Published: 4 December 2021The European Medical Agency (EMA) recently issued a new draft guideline to study the equivalence of topical products [1]
The quantitative composition is usually obtained by reverse engineering [2], and the maximum difference between both products must be ± 5%, except for excipients not related to the performance, which could increase to a maximum of ±10%
The non-commercial 0.05% emulsion was manufactured as follows: oil phase components were melted at 65–70 ◦ C; the CAP was suspended in a small portion of isopropyl myristate before being added and mixed to the melted oil phase; sorbitol was dissolved in purified water and heated to 65–70 ◦ C; the water phase was transferred to the oil phase and homogenized at approximately 1500 rpm for 8 min; the emulsion was cooled during slow stirring to
Summary
The European Medical Agency (EMA) recently issued a new draft guideline to study the equivalence of topical products [1]. The equivalence of a test product involved, on the one hand, the extended pharmaceutical equivalence, where the quality attributes of the new formulation, should have the same qualitative (Q1), quantitative (Q2) composition, and microstructure (Q3) as the reference product. The performance of the test product should be the same as of the reference (using an in vitro release test), and for complex topical formulations, equivalence with respect to efficiency should be shown (using permeation kinetics studies, i.e., an in vitro permeation test). Two in vitro additional equivalence tests are required: the characterization of the drug release (IVRT) and permeation profile (IVPT). For the in vitro release test (IVRT) parameters, release constant at a Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
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