FDA finalizes recommendations for studying absorption of active ingredients in topically-applied OTC monograph drugs
For Immediate Release: May 9, 2019
Media Inquiries: Sandy Walsh, 301-796-4669, sandy.walsh@fda.hhs.gov
Topical over-the-counter drug products applied to the skin, such as topical antiseptic or sunscreen, are often meant to be used repeatedly over time. People may wonder if these product are absorbed, and if so, what happens: for example, how much gets into the body or bloodstream, whether they’re safe to use, and whether there are any considerations for using these products in children or older individuals. While research indicates that some topical drugs can be absorbed into the body through the skin, this does not mean these drugs are unsafe, but this finding does call for further testing to determine the safety of repeated use and that once in the body the ingredient or product does not cause harm. The FDA has been working to better understand the level of this absorption and the resulting safety profiles for topical drugs,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research. “Over the past several decades, collecting human absorption data to study potential risks of using a product according to the maximum levels of its directions for use has become a routine part of the application for new drugs before approval, and is also an important type of study for topical drug products marketed under the OTC drug monograph system. Today, in response to requests from industry for direction on the best way to collect these data for active ingredients seeking inclusion in an OTC monograph, we are issuing final guidance that provides recommendations on how to design and conduct these studies, known as Maximal Usage Trials, or MUsT trials. This information will help identify the need for further testing to assess potential safety concerns and help determine whether an adequate safety margin exists for an active ingredient to be included in a relevant OTC monograph.
This guidance, Maximal Usage Trials for Topically-Applied Active Ingredients Being Considered for Inclusion in an Over-the-Counter Monograph: Study Elements and Considerations, finalizes a draft guidance on this topic that was issued in May 2018. MUsT is a standardized approach to assess the absorption of topical drugs into the body. Understanding systemic absorption of topical drugs consistent with maximal use of the product as specified by its labeling is a standard step in assuring their safety. The resulting absorption data can then be used with other safety testing to inform the overall benefit-risk evaluation of the drug or active ingredient. The guidance includes advice on, for example, how to choose the study population, noting that the study population should be representative of the population expected to use the product. It also provides recommendations for sample size, amount of the product to be applied, frequency of dosing and other important considerations, as well as recommendations about studying the active ingredient’s effects on specific subgroups of patients, such as children and the elderly.
Recent rulemakings and guidances on OTC antiseptics and sunscreens included MUsT studies among the list of studies being requested from industry in order to show whether an ingredient is generally recognized as safe and effective for use for the labeled indication.
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