On October 18, 2018 the EMA published the Draft Guideline on Quality and Equivalence of Topical Products. On June 30, 2019, the period of Consultation will end and it is expected to be in force by the end of the year. The guideline clearly states that regulatory applications based in literature to demonstrate safety and efficacy should be supported by equivalence data of the formulation. At the same time, provides details of in vivo and in vitro models that may substitute clinical data and when biowaivers are applicable. The guideline specifically covers: in vitro release test (IVRT), in vitro skin permeation studies (IVPT), stratum corneum sampling through tape stripping, and vasoconstriction assay for corticosteroids.
IVRT is not a model of in vivo performance of the formulation but may be used as a quality attribute for batch release and shelf life specification. IVRT is intended to evaluate the rate and the extend of release of an active substance in the formulation through a membrane and the parameters to test are the drug release rate, the cumulative amount and the lag time.
IVPT uses human skin in discriminative studies to demonstrate equivalence between a test formulation and a well-known comparator and may avoid clinical trials with efficacy endpoint. Pilot and pivotal studies should be conducted in line with ICH E8 in terms of randomization and blinding.
IVPT may also be used to assess the lack of absorption in drug substances, cosmetics or biocides with local activity that should not be absorbed for safety reasons.
IVRT and IVPT are usually conducted using vertical diffusion cells, being the most commonly used the so-called Franz cells. The use of automated instruments reduces the variability, especially when using donors’ skin, and with the appropriated software, provides reliable results 21 CFR part 11 compliance.
From the quality point of view, the use of in vitro testing for topical products is an important tool to develop consistent formulations during their life cycle and will become an attribute to certify the quality and the homogeneity of manufacturing batches. From the equivalence perspective, it is an opened door for registration of generic products at affordable costs and will have a big impact in the following years for the market access of these products.