Your Monthly Regulations Radar: Sunscreen - November 2024

The First Sunscreen UV Filter Submitted to the FDA in Nearly 25 Years!

In October 2024, under the Coronavirus Aid, Relief, and Economic Security (CARES) Act of 2020, DSM-Firmenich announced it had submitted the first Over-the-Counter Monograph Order Request (OMOR) Tier 1 application to the U.S. FDA for its sunscreen active ingredient Bemotrizinol, branded as PARSOL® Shield. You would be surprised to know that “PARSOL® Shield” has been safely used worldwide for over 20 years, but has yet to be approved in the U.S.. This marks a significant milestone, as it officially starts the FDA’s 17.5-months, or by March 2026, review process to determine whether Bemotrizinol will be classified as Generally Recognized as Safe and Effective (GRASE) for inclusion in the OTC sunscreen monograph M020.

How are Sunscreens Regulated by the U.S. FDA?

Many are surprised to learn that sunscreen containing UV filters, which protect you against the sun’s harmful UV rays, are actually regulated as drugs by the U.S. FDA. The FDA defines a drug as “intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease” or “intended to affect the structure of the body” (Section 201(g) of the Federal Food Drug and Cosmetic Act (FFDCA)). Because sunscreen UV filters are intended to prevent skin cancer, they are classified as drugs and sold Over-The-Counter (OTC). It should be mentioned that the FDA also recognizes that a product can be both a drug and a cosmetic or so-called “cosmeceutical”. In 1972, the FDA established the OTC drug monograph process through rule making. If an OTC drug product complies with a monograph, it does not need FDA approval prior to marketing. A monograph is like a “recipe" book in that it provides instructions on active ingredients, dosage level, combination of active ingredients, labeled indication, claims, warning and adequate directions of use. Not following the monograph may result in a product being misbranded or adulterated (Section 301(a) (b)), and subject to recall under Section 505G(b) of the FFDCA. On the other hand, if a drug is not listed in the monograph, a new drug application (NDA) must be submitted to the FDA.

Why Did It Take So Long to Submit the First UV Filter for FDA Approval?

To better understand why it took so long for the first UV Filter to be submitted for FDA approval, we must review the history of OTC in the U.S. Historically, monographs have been established and amended through rule making which was inefficient and time consuming with “limited speed and flexibility in responding to urgent safety issues”¹. As a result, some monographs remained unfinalized for decades, resulting in OTC drugs being on the market without final safety and effectiveness determination. Another challenge was the industry’s ability to propose innovations to marketed OTC drugs, without submitting an NDA, essentially hindering innovation. Therefore, there was no regulatory path through which a company could request an amendment to the OTC monograph until the CARES Act.

On March 27, 2020, the CARES Act was enacted which included important statutory provisions that reform and modernize the way OTC monograph drugs are regulated by the U.S.. The Act created a new process for issuing monographs through administrative orders rather than rule making. Specifically, FFDCA Section 505G, as added by the CARES Act, provides a process through which the FDA, on its own initiative or upon request from a requestor(s) (OMOR), may issue an administrative order determining whether there are conditions under which a drug, or class or combination of drugs, is GRASE or not GRASE. FFDCA Section 505G also specifies which OTC monograph drugs may continue to be marketed without an approved application prior to the monograph finalization and which drugs may not be marketed. Specifically, FFDCA Section 505G - deems as GRASE drugs that are classified in Category I. Category II considered not GRASE and Category III applies to drug for which safety and effectiveness cannot be determined.

What Does CARES Act Mean for Sunscreens?

In order to determine the GRASE status of UV filter active ingredient, The FDA tasked sunscreen manufacturers with the job of testing, ranging from human clinical safety studies (including the conduct of a Maximal Usage Trial (MuST)^2,3), human effectiveness studies, and nonclinical animal studies such as, but not limited to, reproductive and carcinogenicity studies⁴. It became evident that to classify an active ingredient as GRASE would require a few years of testing at a cost of several millions of dollars.

In 2019, the FDA issued a proposed rule stating that only two of the 16 ingredients used in sunscreens — zinc oxide and titanium dioxide — are GRASE (Category I). These make up the active ingredients in mineral sunscreens and they can be marketed without finalizing the monograph. Two other ingredients — aminobenzoic acid (PABA) and trolamine salicylate — which were used in chemical sunscreens, are now considered not GRASE (Category II) due to risks for toxicity, allergic reactions, sensitization to other drugs and bleeding.

As for the remaining 12 ingredients, the FDA decided that more safety information was needed after determining that there was insufficient data providing their safety (Category III). For example, recent data showed that oxybenzone, one of the 12 ingredients, is absorbed through the skin more than previously thought and was present in human breast milk, amniotic fluid, urine, and blood plasma. However, a developmental and reproductive toxicity study published in 2022 by the National Toxicology Program (NTP) did not show evidences of reproductive toxicity or endocrine effects (estrogenic, androgenic or antiandrogenic action) in rats⁵. To make matters worse, oxybenzone use has decreased due to harmful impact on coral reefs (ban in Hawaii, Key West as well as Palau, Bonaire and Aruba). 

What is Next?

The CARES Act basically outlined the specific conditions for marketing OTC drugs like sunscreen without an approved application. The FDA released records last year from a meeting with the OTC Industry Working Group (IWG), the Personal Care Products Council, or PCPC, showing that Federal Officials were frustrated with a lack of progress with respect to the testing requirements (including reproductive and carcinogenicity animal studies) made by the IWG tasked with demonstrating the GRASE status for avobenzone, ensulizole, homosalate, octinoxate, octisalate, octocrylene, and oxybenzone. In February 2023, PCPC formerly withdrew from the IWG which is now lead by Integral Consulting. We are still waiting on Integral Consulting to provide updates to the FDA with regards to the progress made for the OTC monograph for the remaining active ingredients.

Despite congressional efforts to facilitate marketing of new OTC sunscreens via the monograph process, such efforts may not have had the intended effect, which is delaying the ability of the industry to submit new application to the OTC sunscreen monograph. The CARES Act generally provided sunscreen companies with the option of either continuing marketing without an approved application according to the OTC monograph M020 (until a certain date) or switching to the administrative order process proposed in the OTC bills.

💡 Christine's Takeaways: As per the latest update of OTC Monograph M020, I would recommend continuing applying the "rule book" until the FDA provides new updates with regards to the use of sunscreens in OTC. Alternatively, if you have a new ingredient that you would like to market in the U.S., your option is to submit an Over-the-Counter Monograph Order Request (OMOR) application to the FDA (see Figure 1). 

Figure 1⁶. Administrative Order Process under the CARES Act

Notes:

1. Final orders are subject to dispute resolution, administrative hearings, and judicial review.
2. FDA may initiate the administrative order process through expedited procedures made possible under the CARES Act.

👉 If you want to know more about sunscreen and your regulatory and safety obligations as a manufacturer don't hesitate to reach out to Christine Thiffault, PhD DABT ERT at cthiffault@toxessential.com, Toxicology Expert at ToxEssential, or click here to visit the website. 

🔎 To search for ingredients and alternatives for your personal care formulations, register to Covalo for free.

References:

1. Congressional Research Service. (2021) FDA Regulation of Over-the-Counter (OTC) drugs: Overview and issues for Congress. CSR Report R46985. Available online.
2. Matta MK, Zusterzeel R, Pilli NR, et al. (2019) Effects of sunscreen application under maximal use conditions on plasma concentration of sunscreen active ingredients a randomized clinical trial. JAMA 321 (21): 2082-2091 doi:10.1001/jama.2019.5586
3. Matta MK, Florian J, Zusterzeel R, et al. (2020) Effects of sunscreen application on plasma concentration of sunscreen active ingredients a randomized clinical trial. JAMA 323 (3): 256-267 doi:10.1001/jama.2019.20747
4. ibid
5. National Toxicology Program (NTP). (2022) 2-Hydroxy-4-methoxybenzopheneon (CASRN 131-57-7) administered in feed to Sprague Dawley (HSD:Sprague Dawley® SD®) rats with prenatal and reproductive performance assessments in F 1 offspring. NTP Dart 05.

6.  Source FDA, “Monograph Reform is Here!” presentation by Theresa M. Michele, MD, Director Office of Nonprescription Drugs CDER, FDA, May 29, 2020 as cited by Congressional Research Service, 2021. Available online.