The US Food and Drug Administration (FDA) on Thursday finalized guidance on conducting maximal usage trials (MUsT) to support the inclusion of an active ingredient in an over-the-counter (OTC) monograph.
MUsTs are conducted to determine the in vivo
bioavailability of topical drugs and can help FDA understand the potential for systemic exposure to a topically applied active ingredient.
The guidance finalizes a draft version
released for comment in May 2018 and comes just days after an FDA study
published in JAMA
found that all four sunscreen active ingredients tested were systemically absorbed under maximal usage conditions, demonstrating the need for more testing of topically applied OTC drug products.
According to FDA, the MUsT guidance was developed in response to comments it received from industry on its draft and final guidances on demonstrating safety and effectiveness for nonprescription sunscreens that called on the agency to provide more detailed guidance on MUsTs.
“The MUsT paradigm is now widely used to assess topical drug products developed under an NDA,” FDA writes. However, FDA notes that drugs developed under an NDA typically represent a single formulation and strength, while ingredients included in an OTC monograph may be used in multiple formulations.
“The review to establish an OTC monograph necessitates determining the conditions under which any of multiple drug products would be generally recognized as safe and effective. The resulting monograph authorizes marketing of every formulation that meets each of its conditions and complies with other applicable regulatory requirements,” FDA writes.
While the final guidance is largely the same as the draft version, FDA has made some clarifications regarding its approach in the citations, including an explanation of why references to MUsT were removed from a final guidance on developing drugs to treat acne vulgaris.
FDA also explains that despite interest from industry in alternative methods for assessing absorption, it is limiting its recommendations in the guidance to MUsTs “because, in light of the myriad of possible formulations for OTC products, there is currently insufficient information available to validate alternative absorption models.”
Aside from those differences, the recommendations FDA makes regarding design considerations for MUsTs are unchanged from the draft version of the guidance.
, Federal Register Notice