In vitro permeability studies as substitute for in vivo studies - which requirements have to be met?

In order to reduce costs and shorten time-to-market, the permeability of dr ug substances can be characterized by in vitro techniques including the sue of cell and tissue models. It is required to apply appropriate quality sta ndards similar to those used in animal or clinical studies. The Caco-2 cell model is a well-established and recognized in vitro technique in research, industry and in the drug discovery sector. However, the lack of standardiz ed operating is reflected in the heterogeneity of the data acquired using t his model. Using the Caco-2 cell model as an example, this paper demonstrat es how to test the suitability of a cell culture model for conducting drug permeability studies. The procedures involve not only the characterization of cell morphology but also functional assessment of the model and the peri odic testing of monolayer permeability. Both the useful comparison of perme ability data and the reliable prediction of in vivo permeability require pr ior classification of the in vitro permeability in accordance with the FDA' s Biopharmaceutics Classification System (BCS).