Pilot Equivalence Study Comparing Different Batches of Topical 0.025% Capsaicin Emulsion: Product Microstructure, Release, and Permeation Evaluation.

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.