The US Food and Drug Administration (FDA) on Tuesday issued draft guidance for drugmakers on the design and conduct of maximal usage trials for the purpose of adding a topical active ingredient to an over-the-counter (OTC) drug monograph.
Maximal usage trials are conducted to determine the in vivo
bioavailability of topical drugs and can help the agency understand the potential for systemic exposure to a topically applied active ingredient.
“Such information can help inform an FDA determination of whether additional safety data are needed to support a finding that an OTC drug containing that active ingredient is generally recognized as safe and effective (GRASE) for its intended use,” FDA writes.
FDA also recommends maximal usage trials, often referred to as maximal-use pharmacokinetic (PK) trials, for sponsors developing topical drugs under a new drug application (NDA). However, FDA says that maximal usage trials conducted to support an ingredient’s inclusion in an OTC monograph warrant additional considerations, as such ingredients may be used in multiple drug products and in varying formulations.
“Before including an active ingredient in an OTC monograph, it is important to evaluate the absorption of a representative range of formulations,” FDA writes.
FDA says it developed the guidance in response to comments it received from industry on its guidance on demonstrating safety and effectiveness for non-prescription sunscreen products. While that guidance recommends sponsors conduct maximal usage trials for sunscreen ingredients, comments in the public docket called on FDA to provide more detailed guidance on maximal usage trials.
However, the newly issued draft guidance goes beyond just sunscreen ingredients and provides recommendations for other topically applied drugs.
Based on the results of the trials, FDA says it may establish specific conditions for an active ingredient to be marketed under an OTC monograph.
For example, FDA says it “may consider establishing monograph conditions for final product formulations containing [an] active ingredient, such as in vitro
permeation testing for final formulations using the formulation that resulted in the greatest absorption … as a benchmark,” FDA writes.
The guidance also lays out FDA’s thoughts on critical study elements for conducting such studies, data analysis and special considerations for specific populations, such as pediatric or elderly patients.
, Federal Register Notice