As Memorial Day approaches, FDA has shed light on several important facets of sunscreen regulation this week, issuing two draft guidances and four Warning Letters. One guidance is sunscreen specific: Enforcement Policy — OTC Sunscreen Drug Products Marketed Without an Approved Application (the “Draft Enforcement Policy”). The second is relevant for topical OTC drugs to be marketed under a monograph: Maximal Usage Trials for Topical Active Ingredients Being Considered for Inclusion in an Over-The-Counter Monograph: Study Elements and Considerations (the “MUST Draft Guidance”).
Draft Enforcement Policy
The OTC sunscreen monograph has had a convoluted history even by monograph standards and although a final monograph appeared on the books some years ago, a stay plus the Sunscreen Innovation Act of 2013 have left the waters murky. You can see the history of this monograph in the four page summary of previous FDA Federal Register notices that can be found in the Draft Enforcement Policy. It may be the first time such a thorough (and helpful) description of this long and winding road has been published.
More importantly, this draft guidance clarifies FDA’s current thinking on several issues that remain open while the sunscreen monograph remains in a state of flux. Among these issues are products labeled with a sun protection factor (SPF) higher than 50, specific dosage forms, ingredients being considered under a pending request under the SIA, and insect-repellent-sunscreen combination products.
Among the particularly interesting issues covered are sunscreen spray dosage forms which have become extremely popular in the past decade. FDA clarifies that it will exercise enforcement discretion for sunscreen spray stating that “pending further rulemaking action on [sunscreen sprays],” it does not intend to object if manufactures include the warnings and directions discussed in the 2011 ANPR, including variations on the labeling regulation at 21 CFR § 201.327(e)(1)(ii). The specific warnings and directions are laid out in the Draft Enforcement Policy.
Draft MUsT Guidance
A recurring issue for both the sunscreen and antiseptic monographs over the past four or so years has been FDA’s insistence that information about the extent to which an ingredient may be absorbed through the skin must be available in order to evaluate whether an ingredient intended to be applied topically is generally recognized as safe and effective (GRASE). Because an ingredient determined to be GRASE may be formulated with an essentially infinite array of excipients or inactive ingredients, FDA has also taken the position that the absorption information for a topical dosage form monograph ingredient must include data from testing several formulations that contain the highest concentration of the active ingredient, as well as at least some inactive ingredients typically used in the category of drug being tested that are known to increase absorption. FDA names alcohol as such an ingredient in the draft guidance.
FDA’s position that the safety information from sunscreens and antiseptics must include information from MUsTs has been criticized by members of industry who, in some cases, have claimed that in addition to being unnecessary, the MUsT is ill-defined and FDA has not provided information on how to do them. Further, industry has been reluctant to seek specific feedback from the agency because meetings with FDA on monograph issues are required to be public, and companies did not want to discuss the specifics of their formulations or proposed MUsT protocols in that setting. FDA would argue that sufficient information was already available about how to conduct a study and that it was willing to provide feedback, but that point may now be moot.
In addition to providing specific considerations for designing a MUsT, the draft guidance states that FDA recognizes that industry has concerns about sharing certain information publicly prematurely while still considering how and whether to conduct testing, and that the agency may hold private meetings with sponsors upon request. FDA clarifies that it will make public meeting minutes that provide a summary of “general concepts” discussed while excluding confidential commercial information, trade secrets, and “other types of information at this stage of testing that study sponsors generally do not publicly disclose.” FDA notes that, of course, if the data from such studies will be relied upon for a GRASE determination, that data and the information necessary to evaluate the data will need to be made publicly available.
FDA issued four Warning Letters this week to companies marketing oral products for which claims were made for, among other things, preventing sunburn for people who are at risk for skin cancer and to “protect from the harms of radiation,” “strengthen your skin’s defenses against ultraviolet radiation,” and other claims sun protection claims. FDA stated that the products were not GRASE and these claims rendered the products new drugs requiring prior approval.
- For several of the topics covered in the Draft Enforcement Policy, FDA hints that further rulemaking action may be forthcoming. The SIA requires FDA to issue a final rule on sunscreens in 2019. FDA has not yet issued a proposed rule, but has included it on the Unified Agenda with the target of publication in Spring 2018. It is probably safe to say that anything that FDA has said it will not exercise enforcement discretion about in this Draft Enforcement Policy will be proposed as nonmonograph in the pending rulemaking.
- It’s possible FDA has issued this Draft Enforcement Policy so close in time to when a proposed rule may be issued to forestall questions about how it will enforce during the time after the proposed rule that includes limitations on some of these issues is published, but before a final rule becomes effective.
- FDA has told companies individually for some time that it would follow the procedures outlined in the Draft MUsT Guidance for private meetings, but at least some companies have hesitated to take advantage of the opportunity to speak with FDA absent a formal policy on how information from those meetings will be handled. As outlined, the process still leaves some details a bit murky (what does “general concepts” mean, e.g.), but having a written draft guidance that describes the meeting process is much more than we had before.
- No one should be surprised that FDA takes the position that oral sunscreen products are not GRASE and the proposed sunscreen monograph rule will likely say it again.