FDA issues sunscreen safety and effectiveness guidances

The FDA issued two final guidance documents dealing with safety and effectiveness data submissions related to nonprescription sunscreen drug products. The guidances detail the data requirements that will allow the FDA to determine whether an over-the-counter (OTC) sunscreen active ingredient or combination of ingredients is generally recognized as safe and effective (GRASE) as evaluated under the Sunscreen Innovation Act (SIA) (21 U.S.C. Ch. 9, Sub. 5, Part I), and requirements governing the content and format of submissions. The final guidances replace draft guidances issued in 2015 (see FDA puts sunscreen safety on thick with four new guidance documents, November 23, 2015).

When the FDA determines that an active ingredient is GRASE and not misbranded for use in nonprescription sunscreens, it issues a final sunscreen order listing the requirements that sunscreen products containing the active ingredient must meet to be marketed without an approved new drug application (NDA). Active ingredients determined to be GRASE may be included in different formulations marketed without product-specific review and approval.

Safety and effectiveness

In “Nonprescription Sunscreen Drug Products: Safety and Effectiveness Data,” the FDA describes its approach to nonclinical safety testing in its evaluation of nonprescription sunscreen active ingredients as focusing on potential long-term adverse effects or effects not otherwise readily detected from human use. The agency generally expects sponsors to submit data from human irritation studies, human skin sensitization studies, and human photosafety studies. It recommends that sponsors provide data from a maximal usage trial (MUsT) “designed to capture the effect of maximal use on absorption into the blood with standard pharmacokinetic assessments.” The FDA will take pediatric differences into consideration. It also recommends that sponsors conduct carcinogenicity studies for any pharmaceutical either with an expected continuous clinical use of at least six months or with an expected clinical use of a minimum of six months in an intermittent manner, and developmental and reproductive toxicity (DART) studies. Sponsors should also collect animal toxicokinetic data. The FDA requests that sponsors include specific postmarketing safety information, including, among other items, summaries of potentially associated serious and nonserious adverse drug experiences and expected or frequently reported side effects.

It also requests that sponsors provide evidence from at least two SPF studies demonstrating that the active ingredient effectively prevents sunburn. The FDA currently requires final formulation testing to ensure the effectiveness of OTC sunscreen products, but anticipates that final sunscreen orders will also include conditions requiring final formulation testing to ensure the safety of permitted sunscreen formulations.

Format and content

Nonprescription Sunscreen Drug Products: Format and Content of Data Submissions,” detailed format and content guidelines for sponsor requests for GRASE recommendations for active OTC sunscreen ingredients submitted under section 586A (586A request) of the federal Food, Drug, and Cosmetic Act (FDC Act) (21 U.S.C. §360fff-1), as amended by the SIA, or in support of a pending request. The guidance outlined specific timeline requirements for submissions and FDA responses once the FDA determines that an application is sufficiently complete to allow the agency to perform a GRASE review. If the agency determines that an application is insufficient, it may refuse to begin the GRASE review.

The guidance lists the characteristics of a complete submission, which include, among other qualities, a single submission for an active ingredient including all data on which a sponsor chooses to rely and specific references and copies of or links to referenced documents. The FDA encourages electronic submissions. The guidance provides a specific structure that it would like sponsors to follow in their submissions. It also includes a detailed list of submissions characteristics that could cause the FDA to refuse to file a data submission, such as disorganization and electronic submissions that cannot be easily opened or navigated.

FDA: No lab-developed test final guidance in the near future

The FDA will not finalize its 2014 draft guidance on “FDA Notification and Medical Device Reporting of Laboratory Developed Tests” any time soon due to the changing political administration, according to a statement the agency provided to GenomeWeb. Intended to balance “patient protection with continued access and innovation,” the draft guidance is unpopular in the laboratory and pathologist communities, which view lab-developed tests (LDTs) as services that should be regulated under the Clinical Laboratory Improvement Amendments (CLIA) of 1988, rather than medical devices within the FDA’s regulatory purview. The FDA’s hesitation stems, in part, from the uncertainty of the new political landscape, including the views of the as-of-yet unnamed incoming HHS Secretary.

The FDA has taken the position that LDTs are subject to its enforcement discretion pursuant to the Medical Device Amendments because they are intended for clinical use and designed, manufactured, and used within one laboratory (see FDA seeks notification of lab developed tests, October 3, 2014). According to GenomeWeb, the FDA believes that gaps in the CLIA-authorized system present a public health risk. However, some senators from the Republican party—which will control Congress—believe the agency is “too plodding to keep up with innovation in the molecular diagnostics space.”

The agency continues to emphasize the importance of its role in regulating LDTs and is considering issuing best practices, rather than a final guidance. Senator Lamar Alexander (R-Tenn) and Representative Fred Upton (R-Mich) applauded the FDA’s decision not to finalize the guidance in the near future, while the American Clinical Laboratory Association (ACLA) called it “a victory for diagnostic innovation and most importantly, patients.”