In Vitro Skin Permeation Methodology

Final international acceptance of the Organisation for Economic Cooperation and Development (OECD) 428 “Guideline for the Testing of Chemicals: Skin AbsorptionIn Vitro Method” and the associated Guidance 28 in 2004 marked an important point in the regulatory acceptance of in vitro methods for examination of skin permeation and distribution. These set out a detailed framework of the numerous issues that should be addressed in study design if meaningful data are to be obtained. However, they allow significant variations in protocol design that, although to some extent are desirable in terms of ensuring that a particular study uses conditions that are relevant and appropriate to the use of the data, some experts believe that this results in a guideline and guidance that are actually too imprecise to ensure that study data are consistent and reproducible. The latter view can be effectively countered by the argument that a “one size fits all” protocol cannot be appropriate for all test substances and exposure scenarios. It is important to appreciate that the OECD has provided guidelines and not a specific protocol that can be instantly applied without extensive preexperimental consideration of the nature of the test material, exposure scenario, and the objectives of the study. It is also important to appreciate that in the “ reporting ” section, OECD 428 includes an extensive list of required experimental detail, together with the requirement to justify the test system . Comprehensive justification of the test system includes a wide range of parameters, including species, membrane type, receptor fluid, integrity testing, test vehicle, dose applied, time points and experimental duration, terminal washing procedures, extraction methods, and assay validation. Only prestudy performance of such a justification procedure in the design of a specific experimental protocol can ensure that production of relevant data is possible.