Richard H Guy - Comment

Subject: Methods development for the assessment of bioequivalence between topical topical drug products The FDA currently has an RFA published (RFA-FD-13-016: "In vitro release tests for topical dermatological products (U01") that seeks to identify in vitro release test conditions that are best correlated with in vivo performance. This is a laudable objective in which the regulatory agency has had a long-standing interest. The evolution of technologies, such dermatopharmacokinetics and microdialysis, as well as an enormous step-change in the sensitivity of analytical techniques based on mass spectrometry, means that there are real opportunities for advancement, such that new approaches can be rigorously tested and validated. It seems likely, therefore, that the current reliance on clinical studies to establish the equivalence of generic topical formulations to the reference listed drug product will soon be a thing of the past and this, of course, is to be welcomed. However, the development of better tools with which to assess and compare topical BA/BE also affords an opportunity to incorporate new technology into the formulation development process, not only to make it more efficient and discerning, but also (and perhaps even more importantly) to guide the development of significantly better products. Specifically, it should not be forgotten that, in general, the performance of typical topical dosage forms, in terms of the 'payload' actually delivered into the skin, is rather poor (often just a few percent of the 'applied dose', in fact). Thus, the ultimate goal of innovating better tools for BA/BE assessment is not to have a more accurate way of distinguishing (or not) between poor formulations! The long-term objective must be to apply these new approaches, and the science underpinning them, to the evolution of new drug delivery systems that work much better than the ones at our disposal right now.