On February 26, FDA published the proposed rule, “Sunscreen Drug Products for Over-the-Counter Human Use,” which describes the conditions under which Over-the-Counter (OTC) sunscreen monograph products are generally recognized as safe and effective (GRASE) and not misbranded. Primarily, the proposed rule seeks additional information on sunscreen ingredients so that FDA can evaluate their GRASE status in light of changed conditions, including substantially increased sunscreen usage and exposure, and evolving information about the potential risks associated with these products. The proposal is for a final monograph on sunscreens, which would substantially amend the 1999 final rule on sunscreens that was stayed before its effective date.
Challenging Timeframe for FDA
Under the Sunscreen Innovation Act (SIA), 21 USC 360-fff-5, FDA is required by law to finalize and make effective the sunscreens final monograph by November 26, 2019. FDA is aware that time is running out on this deadline, and the agency is vulnerable to litigation if FDA fails to meet the statutory deadline. See Ctr. for Food Safety v. Hamburg, 954 F. Supp.2d 965 (N.D. Cal. 2013) (providing declaratory relief regarding statutory deadlines for rulemaking).
Having the rule become effective by November 26, 2019, will be very challenging for FDA. Under the Administrative Procedure Act, 5 USC 553(d), a rule generally cannot become effective until at least 30 days after publication, which means that FDA should publish the final rule by October 25. But the comment period on the proposed rule does not close until May 28, which gives FDA less than five months to prepare and publish the final rule. This timeframe will be very difficult for FDA for several reasons. First, this is a lengthy and complex rule that has been under development for many years. The proposed rule covers 71 (three-column) pages in the Federal Register, including multiple scientific, legal, and policy issues. FDA will need to address multiple comments and deferral requests. Second, OTC drug monograph work requires specialized knowledge, and FDA has a relatively small team dedicated to this work. Third, ordinarily, a final rule would be expected to be submitted to OMB for interagency review at least 90 days before publication, unless OMB waives review. See Executive Order 12866, Sec. 6(b)(2)(B). Adding time for the review processes at FDA and, possibly, the Department of Health and Human Services (HHS), further adds to the challenge facing the OTC drug team at FDA.
Sunscreen Ingredients and Enforcement Policy
The proposed rule states that there is still not enough evidence to determine the GRASE status of most of the ingredients from the stayed 1999 final sunscreens rule. The proposal does not address the sunscreen active ingredients that were originally submitted under FDA’s Time and Extent Application regulations, which are being addressed through the process established under the SIA. However, FDA proposes that two sunscreen ingredients are GRASE (Category I) and two are not GRASE (Category II). The ingredients proposed for Category I are zinc oxide and titanium dioxide. The ingredients proposed for Category II, based on safety concerns, are para-aminobenzoic acid (PABA) and trolamine salicylate. FDA states that neither of these ingredients is currently marketed in a sunscreen product in the U.S.
For the remaining twelve ingredients from the stayed 1999 sunscreens rule, FDA is seeking more information (Category III), based in part on concerns about the lack of data characterizing their absorption or, in the case of oxybenzone, concerns about the effect of absorption. The twelve ingredients are: cinoxate, dioxybenzone, esulizone, homosalate, meradimate, octinoxate, octisalate, octocrylene, padimate O, sulisobenzone, oxybenzone, and avobenzone. Many of these ingredients are in sunscreens that are currently marketed in the U.S. The data gaps that FDA has identified for these products are significant and are not likely to be resolved before FDA finalizes this rule as required by the statutory deadline. When FDA publishes the final sunscreen rule the agency will have two choices for each of these Category III ingredients: FDA can either (1) determine that the ingredients are not GRASE, which will require an NDA for continued marketing, or (2) defer rulemaking for these ingredients to allow the necessary research to be conducted, submitted, and evaluated.
The proposed rule states that any requests for the deferral of rulemaking must be submitted within the 90-day comment period (by May 28, 2019). Data submitted in such “timely and complete” deferral requests will be reviewed along with data and information already in the docket. “FDA will determine whether the sum of the data, if timely submitted, is likely to be adequate to provide all the data that are necessary to make a determination of general recognition of safety and effectiveness.” 84 FR 6204, 6249 (Feb. 26, 2019). This language in the proposed rule implies that even if a deferral request is submitted within the deadline, FDA may decide not to grant a deferral for certain ingredients for which FDA believes the data are unlikely to be adequate. Products containing these ingredients would need to be reformulated or come off the market.
However, FDA would extend the compliance period for one year after the effective date of the final rule, allowing products to be sold that are already delivered for introduction into interstate commerce before May 28, 2020. This would be a substantial shift from the enforcement policy that has been in place for sunscreen ingredients for more than 20 years and was revised less than a year ago for all of the ingredients in the stayed 1999 sunscreens rule. However, the May 2018 enforcement policy was clear that it “only applies until a final sunscreen monograph becomes effective.” Nonetheless, after many years of little change in the active ingredients in sunscreen products marketed in the U.S., significant change is clearly on the horizon.
What to Make of All of This?
Clearly FDA has the authority to seek additional safety data to assess the GRASE status of these sunscreen ingredients. However, companies may argue in their comments on the proposed rule that these products have a long history of use in the U.S. by millions of consumers without any significant harm, and thus have a favorable risk benefit profile. Further, they will likely assert that when weighing the dangers of skin cancers associated with sun exposure versus the absorption concerns FDA has, that the products should be considered GRASE.
Next, the twelve Category III sunscreen ingredients are used in numerous sunscreen products in the U.S. Ninety days is not a long time for companies to decide, perhaps by banding together, to evaluate available data on absorption for each of the ingredients and to seek deferrals. If deferrals are not sought and/or if FDA determines that the data are unlikely to be adequate and denies deferral requests, some or all of these ingredients may be determined to be not GRASE (Category II) in the final rule. If FDA decides not to grant deferrals for all twelve of these ingredients, the U.S. market would be cleared of chemical sunscreens, and only result in two mineral-based options. An unintended effect of this scenario may be that less consumers use sun protection products, thereby increasing unprotected sun exposure—definitely not a desirable public health outcome.
It is worth noting that the U.S. has been criticized for years as lagging behind the rest of the world in our sunscreen technology. Numerous other countries allow ingredients not considered GRASE in the U.S. on their retail shelves. The SIA was enacted, in part, to catch us up by allowing additional sunscreen active ingredients in to the drug review. FDA has evaluated several time and extent applications for additional ingredients using the process set forth in the SIA, but has found them all to have significant data gaps. Now with the looming deadline to finalize the sunscreen monograph, and the potential to find fourteen additional ingredients as non-monograph, the U.S. sunscreen market may significantly depart from the variety of skin protection availability elsewhere around the globe, which could have potentially adverse net consequences for public health.
If you have any questions about the proposed rule or may be interested in submitting a comment or deferral request, please contact any of the authors of this blog or the Hogan Lovells lawyer with whom you regularly work.