Is a US Sunscreen Public Health Crisis Brewing?

The viewpoints expressed in this article are those of the authors and do not necessarily reflect those of any Competent Authority or their respective companies. The purpose of this article is to guide and inform the reader. The reader is encouraged to verify any opinions and facts the authors present.

Excerpts of this article were presented by C. D'Ruiz at the Society of Cosmetic Chemist (SCC) 77^TH Annual Scientific Meeting & Showcase, December 13, 2023, New York, NY. 


In the November 2022 issue of Happi, we reported on how “Sunscreens in The US are Under Attack from Two Fronts.”¹

Sunscreen actives, classified as drugs and not cosmetics in the US, must undergo FDA approval to ensure their safety for human use.² Additionally, they may be subject to an evaluation of their potential environmental impacts.³ These challenges could potentially have significant implications for both the sunscreen industry and public health. If they materialize, they could lead to unintended consequences for public health. Insufficient access to effective sunscreens could contribute to an increase in skin cancer cases, which is already a significant public health issue in the United States, especially considering that skin cancer is the most common cancer in the US.^3,4,5 The health and economic burden of skin cancer treatment in the US is substantial and increasing. Incredibly, more than 9,500 people are diagnosed with skin cancer every day, and more than two people die from the disease every hour.⁶ Putting this into further perspective, approximately 6 million adults in the US were treated for skin cancer from 2016 to 2018, at cost of almost $9 billion.^7,8,9

Considering that the incidence of skin cancer has been extensively reported to be increasing,^{10,11,12,13,14,15,16}  and given the substantial cost of skin cancer treatment, ongoing public health efforts to implement evidence-based sun-safety interventions may play a crucial role in reducing the risk of skin cancer and associated treatment costs. It is widely acknowledged that regular sunscreen use helps prevent sunburn and lowers the risk of developing skin cancer.^{17,18,19,20,21,22,23,23,24}  Despite this information, recent surveys shockingly indicate that most Americans don't know that sunscreens are drugs, don’t apply sunscreens correctly, and either don’t like how sunscreens feel or use them regularly, with 11% to 34% reporting that they rarely or never use sunscreen.^25,26,27,28 

Hence, the FDA, sunscreen industry and special interest groups should concentrate their efforts to get more people to use sun protection products. What we don’t need is further discouragement of their use. However, the FDA's request for additional safety information (Generally Recognized as Safe and Effective – GRASE) on existing sunscreen monograph active ingredients,²⁹  many of which have been used for nearly 50 years without any significant or notable safety issues,³⁰  might unintentionally create consumer confusion and erode trust and confidence in the US sunscreens that have been previously reviewed and determined to be GRASE by the FDA.³¹

Moreover, consumers are becoming increasingly frustrated and lack optimism that any new filters will be available soon given FDA calls for further testing on existing sunscreen active and the long timelines for approval of new actives. The last UV filter to be added on the sunscreen monograph was ensulizole 24 years ago in 1999.^32,33 This situation has prompted many US consumers to purchase, either online or on vacation, those internationally approved and more modern sunscreen products, even if these are not approved by the FDA.³⁴ This scenario heightens the urgency to review the FDA’s current sunscreen policy and devise more efficient and effective ways to incorporate new safe and effective active ingredients into the FDA's OTC Sunscreen Monograph without compromising safety or efficacy.

Since our last article (November 2022), the overall sunscreen situation in the US has not changed much. Following FDA’s 2021 Proposed Sunscreen order, only zinc oxide and titanium dioxide are classified as GRASE Category I (safe and effective).^1,35  The other 12 sunscreen actives that have been used for decades now require additional safety data for FDA to move them into GRASE Category I.¹  Of these, the sun care industry has indicated to FDA that it was prepared to support seven of these 12 actives ingredients. As detailed in our previous article, the seven active ingredients currently under consideration for testing by the sunscreen industry are octocrylene, avobenzone, octisalate, homosalate, octinoxate, oxybenzone and ensulizole. These were selected as they are widely used by the industry for formulating various consumer broad-spectrum sunscreen products. The aim was, and still is, to ensure that adequate UV filters remain available to protect the US population from the dangers of UV exposure.¹ 

However, if anything, the sunscreen industry is now more discouraged. While the FDA is agreeable to the industry's proposed clinical (human) testing approach to support ingredient safety, it remains adamant about its nonclinical study requirements, which involve animal testing. Currently, the FDA is unwilling to embrace more modern and alternative toxicological safety and risk assessment methods that minimize or eliminate the need for animal testing. This reluctance is attributed to concerns about the time required to develop such approaches, coupled with the pressing need to finalize the sunscreen monograph. This is particularly discouraging, given that finished product manufacturers have made long-standing commitments not to test on animals.

Moreover, while approximately 30 sunscreen active ingredients are available for use globally, subject to local regulations, there is a relatively small number of about 12 actives that are most frequently used in effective sunscreen products.⁹ In comparison to Europe and Asia, the US market has the fewest approved sunscreen actives. Currently, only nine ingredients are commonly used for formulating marketable US sunscreen products. It should be apparent, therefore, that the loss of even one active from this subset represents a significant and disproportionate loss in formulation agility, flexibility and corresponding consumer protection. Hence, a further decrease or elimination in the number of approved UV filters would substantially restrict the options for providing American consumers with a diverse range of innovative, broad-spectrum and effective sun protection products that guard against skin cancer. This situation raises the question: Is a US sunscreen public health crisis brewing?

How Did We Get Here? The Long, Winding Road of Regulation

In 1972, the FDA established the OTC monograph process, which organized the thousands of different over-the-counter drugs marketed at the time into 26 OTC monograph therapeutic categories. One of these was the sunburn prevention/treatment products category which evolved into the sunscreen monograph in 1978.³⁶ The sunscreen monograph is basically a “rule book” for marketing safe and effective OTC sunscreen drugs.³⁷  For more than 40 years, the FDA has modified and revised the draft monograph several times but has yet to finalize it. Critically, during this time, the number of active ingredients available for sunscreen use has decreased from 21 to 14 in 2021.³⁸  Moreover, no new sunscreen actives have been added to the monograph in nearly a quarter of a century. The last two UV filters to be added to the OTC monograph were avobenzone (1996) and ensulizole (1999). Key milestones associated with the sunscreen monograph 50-year history are shown below.



The FDA's most recent revision to the sunscreen monograph comes in the form of a proposed order (PO) titled “Amending Over the Counter (OTC) Monograph M020: Sunscreen Drug Products for OTC Human Use.” This announcement was made on November 12, 2021, following the FDA's issuance of the February 2019 “Tentative Final Sunscreen Monograph” and the enactment of the 2020 Coronavirus Aid, Relief and Economic Security Act (CARES Act), which aimed to reform the FDA’s OTC monograph process.³⁹  Alongside the 2021 PO, the FDA issued a deemed final order temporarily making sunscreens containing 16 specified sunscreen active ingredients Generally Recognized as Safe and Effective (GRASE). This inclusion involved incorporating the ingredients from the 1999 sunscreen monograph, which is not currently in effect.⁴⁰

Furthermore, the FDA indicated that all other active ingredients for sunscreen, not deemed to be GRASE (i.e., cinoxate, dioxybenzone, ensulizole, homosalate, meradimate, octinoxate, octisalate, octocrylene, padimate O, sulisobenzone, oxybenzone, and avobenzone), were categorized as Category III. After decades of safe use, these ingredients per FDA, now required additional data before they could be considered GRASE.⁴¹

Moreover, the FDA stated that it would initially defer issuing a revised final order on the Generally Recognized as Safe and Effective (GRASE) status of Category III ingredients requiring further data if it received a satisfactory indication from the industry of timely and diligent progress on the necessary studies for a specific ingredient. These deferrals would be granted annually, with a possibility of extension depending on further satisfactory progress with the studies. The FDA also indicated that if the studies for any active ingredient did not appear to be proceeding in a timely manner or otherwise did not seem productive, it would proceed to issue a revised final order for sunscreens containing the ingredient after the initial deferral. The FDA would then determine whether the sum of the data, if timely submitted, is adequate to provide all the necessary information for a determination of general recognition of safety and effectiveness.⁴⁰ As mentioned earlier, the sun care industry has informed the FDA that it is prepared to support seven of these 12 Category III active ingredients. However, due to time pressures associated with finalizing the monograph, the FDA continues to require that the industry conduct animal tests to support the long-term safety of these sunscreen active ingredients. They are not new drug substances per se and have already been marketed and used by US consumers for over 50 years. Additionally, FDA is unwilling to accept the industry’s proposal to conduct the required in-vitro and clinical testing and, in parallel, also develop and validate alternate non-animal testing approaches (commonly referred to as new approach methodologies – NAMs). These approaches are like those used globally by other regulatory agencies including the US Environmental Protection Agency (EPA) for assessing the safety of chemicals and sunscreen ingredients without the need for animal testing. This is problematic, given that US consumers generally do not support sacrificing animals in safety studies. Consumer product manufacturers have made long-standing commitments not to test on animals and may be supportive of such an approach when other alternatives are available.

The OTC Monograph Order Requests (OMOR) Process

So, what about new sunscreen actives? In response to the dismal failure of the FDA’s Time and Extent Application (TEA) process and the Sunscreen Innovation Act’s (SIA) inability to introduce new active ingredients and innovation under the OTC sunscreen monograph, the OTC reform provisions of the 2020 Cares Act sunset the SIA and established two new, fee-based OTC innovation pathways called Tier 1 and Tier 2 “OTC Monograph Order Requests” (OMORs). Tier 1 OMORs allow industry requests for Generally Recognized as Safe and Effective (GRASE) determinations for new active ingredients, indications, combination test methods, routes of administration, doses or concentrations. Tier 2 requests allow for changes in drug fact labeling, conditions of use and the standardization of doses. A summary of how the industry-initiated OMOR process works is shown below. It is the FDA’s hope that this new process will spur innovation and add new sunscreen ingredients to the OTC sunscreen monograph.


Currently, DSM-Firmenich's personal care division is seeking a Generally Recognized as Safe and Effective (GRASE) determination for the inclusion of a broad-spectrum UV sunscreen active ingredient, through the FDA’s new OMOR Tier 1 regulatory pathway.⁴³  This DSM-Firmenich sunscreen active (Bemotrizinol) was originally subject to a TEA that was submitted in 2005 and has been under FDA review for over 17 years. It required studies like those currently requested for existing sunscreen actives. The studies were recently completed and are currently under review by the FDA. It is anticipated that an FDA OMOR Tier 1 GRASE eligibility determination will be made later this year. If successful, DSM-Firmenich’s ingredient would become the first (and only) new US sunscreen active ingredient (“new molecular entity”) sponsored and evaluated under the FDA’s new OMOR Tier I process, even though it has been globally approved for almost 20 years in other countries. The FDA timeframe associated with the approval of new active ingredients seems excessive. Surely, we can do better.

Studies Required to Support Sunscreen GRASE I

Based on the OMOR process, FDA sunscreen safety and efficacy guidances^2,44  and personal knowledge with FDA data submissions for a new chemical sunscreen ingredient; i.e., new molecular entity that has not been previously approved in the US, the following three categories of safety studies are normally required. It is important to note that these are the exact same studies that FDA is requesting for the current active ingredients that have been used by American consumers for nearly 50 years without notable health issues.

Human Clinical Studies
• Dermal irritation and sensitization
• Dermal phototoxicity and photoallergenicity
• Human PK/absorption studies/maximum usage trials (MUsT)

Nonclinical (Animal) Studies
• Dermal carcinogenicity
• Systemic oral carcinogenicity – dependent on Pivotal MUsT/ADME
• Developmental and reproductive toxicity (DART)
• Toxicokinetics (ADME)
• Hormonal Effects

Other
• In vitro permeation tests (IVPT)
• Clinically relevant metabolites
• Pediatric data (case-by-case basis–depending on MOS)
• Postmarketing Safety Data -Adverse Event (AE) Profile
• Efficacy (SPF)
• Chemistry (CMC)/USP

For new UV filters, the GRASE and MUsT⁴⁴ safety data must be generated prior to FDA review. As per current estimates, the total cost for the required tests can be around $18 million and may take more than 10 years to complete, with an addition 2-3 years for FDA review once all the studies are completed. There is also an upfront FDA OMOR fee of $537,471 to open a review that is not guaranteed to lead to an approval. But if it does, an 18-month exclusivity may be obtained.

Hence, based on current FDA requirements, new sunscreen actives will need to undergo extensive human and environmental safety testing prior to being approved. Moreover, to be readily formulated into sunscreen products and taken up by the industry, they will also need to be affordable (i.e., acceptable cost/kg for the manufacturer and as low as possible a total delivered cost to the consumer), photostable and compatible with other UV filters.⁹ This is already a high bar for existing UV filters. Furthermore, for manufacturers, financial incentive may be missing and compared to other countries that utilize more efficient and modern toxicological, safety and risk assessment methods for reviewing and approving new sunscreen actives, this approval process seems to be extremely inefficient and burdensome.⁴⁵ Furthermore, the 18-month exclusivity provision is too short to encourage such a large-scale investment for products that will ultimately be sold as USP active pharmaceutical ingredients (APIs).

Despite these hurdles, we understand that at least one new chemical UV absorber is nearing FDA review completion and may be available in the next couple of years.

Conclusion

Skin cancer rates in the US are on the rise, and sunscreen use is not the cause. There is a pressing need for simpler, cost-effective, and efficient regulatory and risk assessment approaches that do not require animal testing to incorporate modern, effective and sustainable sunscreen UV filters into the FDA's OTC Sunscreen Monograph.⁴⁵  This is crucial to provide consumers with a wider array of sunscreen options that are not only more efficient and sustainable, but also deliver improved UV protection, enhanced cosmetic characteristics and increased compatibility with different skin types.

The lack of optimism regarding the availability of new filters in the US has led many consumers to purchase internationally approved sunscreen products through the internet, bypassing FDA regulations. Even US Representative Alexandria Ocasio-Cortez (D-NY) has called for better sunscreens and opts for products manufactured outside the US.⁴⁶ Meanwhile, Rep. Dave Joyce (R-OH), a skin cancer survivor, organized an event on Capitol Hill to encourage actions to permit more sunscreen filters in the US.⁴⁷ In summary, consumer and industry frustration, trust and confidence in US sunscreens are being eroded by the FDA's call for further animal testing of ingredients that have been used worldwide and in the US for nearly 50 years with minimal safety issues.

Lastly, individuals with darker skin tones may find sunscreens containing titanium dioxide and zinc oxide, which may leave a chalky residue, cosmetically unacceptable. Consumers tend to choose products they like, and, for the most part, opt for sunscreens with chemical UV absorbers due to their versatility in creating aesthetically-pleasing products. Clearly new and existing chemical UV absorbers play a critical role in promoting sunscreen use and compliance among consumers with diverse skin types and aesthetic preferences. • 

References

1 Lambros Kromidas and Carl D'Ruiz. December 2022. Sunscreens in the US are Under Attack on Two Fronts. HAPPI, 59(12): 44-47 (https://happi.texterity.com/happi/december_2022/MobilePagedArticle.action?articleId=1840346&app=false#articleId1840346).

2 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/nonprescription-sunscreen-drug-products-safety-and-effectiveness-data

3 https://www.aad.org/media/stats-skin-cancer

4 https://www.cdc.gov/cancer/skin/statistics/index.htm

5 Kao SZ, Ekwueme DU, Holman DM, Rim SH, Thomas CC, Saraiya M. Economic burden of skin cancer treatment in the USA: an analysis of the Medical Expenditure Panel Survey Data, 2012-2018. Cancer Causes Control. 2023 Mar;34(3):205-212. doi: 10.1007/s10552-022-01644-0. Epub 2022 Nov 30. PMID: 36449145. (https://pubmed.ncbi.nlm.nih.gov/36449145/)

6 Cancer Facts and Figures 2023. American Cancer Society. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2023/2023-cancer-facts-and-figures.pdf

7 https://www.skincancer.org/skin-cancer-information/skin-cancer-facts/

8 Guy GP Jr, Machlin SR, Ekwueme DU, Yabroff KR. Prevalence and costs of skin cancer treatment in the U.S., 2002-2006 and 2007-2011. Am J Prev Med. 2015 Feb;48(2):183-187. doi: 10.1016/j.amepre.2014.08.036. Epub 2014 Nov 10. PMID: 25442229; PMCID: PMC4603424. (https://pubmed.ncbi.nlm.nih.gov/25442229/)

9 Matts PJ, Nash JF. Sunscreens – another endangered species? Int J Cosmet Sci. 2023 Oct;45 Suppl 1:20-32. doi: 10.1111/ics.12902. PMID: 37799079.

10 Apalla Z, Lallas A, Sotiriou E, Lazaridou E, Ioannides D. Epidemiological trends in skin cancer. Dermatol Pract Concept. 2017 Apr 30;7(2):1-6. doi: 10.5826/dpc.0702a01. PMID: 28515985; PMCID: PMC5424654. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5424654/

11 Khayyati Kohnehshahri, M., Sarkesh, A., Mohamed Khosroshahi, L. et al. Current status of skin cancers with a focus on immunology and immunotherapy. Cancer Cell Int 23, 174 (2023). https://doi.org/10.1186/s12935-023-03012-7

12 https://www.cancer.org/cancer/types/basal-and-squamous-cell-skin-cancer/about/key-statistics.html#:~:text=The%20number%20of%20these%20cancers,from%20these%20cancers%20are%20not

13 https://www.who.int/news-room/questions-and-answers/item/radiation-ultraviolet-(uv)-radiation-and-skin-cancer

14 https://www.medscape.com/viewarticle/984407?form=fpf

15 https://www.skincancer.org/skin-cancer-information/skin-cancer-facts/

16 https://www.aad.org/media/stats-skin-cancer

17 https://www.hhs.gov/surgeongeneral/reports-and-publications/skin-cancer/consumer-booklet/index.html

18 Sander M, Sander M, Burbidge T, Beecker J. The efficacy and safety of sunscreen use for the prevention of skin cancer. CMAJ. 2020 Dec 14;192(50):E1802-E1808. doi: 10.1503/cmaj.201085. PMID: 33318091; PMCID: PMC7759112. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759112/)

19 https://www.cdc.gov/chronicdisease/programs-impact/pop/skin-cancer.htm

20 https://www.skincancer.org/skin-cancer-prevention/sun-protection/sunscreen/#:~:text=When%20used%20as%20directed%2C%20sunscreen,melanoma%20risk%20by%2050%20percent

21 https://www.fda.gov/drugs/understanding-over-counter-medicines/sunscreen-how-help-protect-your-skin-sun

22 https://www.who.int/news-room/questions-and-answers/item/radiation-sun-protection

23 https://www.cdc.gov/cancer/skin/basic_info/sun-safety.htm

24 https://www.aad.org/media/stats-sunscreen#:~:text=Sunscreen%20use%20can%20help%20prevent,skin%20cancer%20in%20their%20lifetime.

25 Patlola M, Shah AA, Stead T, Mangal R, Ganti L. Sunscreen use amongst US adults: a national survey. Arch Dermatol Res. 2023 Sep;315(7):2137-2138. doi: 10.1007/s00403-023-02603-8. Epub 2023 Mar 17. PMID: 36930290.

26 https://www.advdermatology.com/

27 https://www.sciencedaily.com/releases/2015/05/150519091129.htm

28 Kimberly G. Norman, Linda Loretz, Alexandra Kowcz, Lewis E. Kaufman, Eduardo Ruvolo, Michael Traudt, Idalina Santos, Rachel Rose Mansfield, J Frank Nash, Application habits practices of regular sunscreen users in the United States: Results of an online survey, Food and Chemical Toxicology, Volume 181, 2023,114093, ISSN 0278-6915, https://doi.org/10.1016/j.fct.2023.114093

29 https://www.fda.gov/drugs/news-events-human-drugs/update-sunscreen-requirements-deemed-final-order-and-proposed-order

30 Pantelic MN, Wong N, Kwa M, Lim HW. Ultraviolet filters in the United States and European Union: A review of safety and implications for the future of US sunscreens, Volume 88, Issue 3, P632-646, March 2023, JAAD, Published: November 25, 2022 DOI: https://doi.org/10.1016/j.jaad.2022.11.039. https://www.jaad.org/article/S0190-9622(22)03141-3/fulltext

31 https://www.govinfo.gov/content/pkg/FR-1999-05-21/pdf/99-12853.pdf

32 https://www.pbs.org/newshour/show/why-sunscreen-in-the-united-states-is-behind-the-rest-of-the-world

33 https://www.forbes.com/sites/anafaguy/2023/08/14/why-the-us-has-limited-access-to-sunscreens—and-why-some-including-aoc-are-pushing-to-change-that/?sh=29a2f4b52547

34 Why Other Countries Have Better Sunscreen – The Atlantic, July 2022 (https://www.theatlantic.com/technology/archive/2022/07/us-sunscreen-ingredients-outdated-technology-better-eu-asia/661433/)

35 https://www.fda.gov/media/153964/download

36 https://www.gao.gov/assets/gao-20-572.pdf

37 https://sgp.fas.org/crs/misc/R46985.pdf

38 https://www.fda.gov/drugs/historical-status-otc-rulemakings/rulemaking-history-otc-sunscreen-drug-products#Original

39 https://dps-admin.fda.gov/omuf/omuf/sites/omuf/files/primary-documents/2022-09/Proposed%20Administrative%20Order%20OTC000008_Amending%20M020_Sunscreen_Signed24Sept2021.pdf

40 Final Administrative Order OTC000006_M020-Sunscreen Drug Products for OTC Human Use.pdf (fda.gov)

41 Questions and Answers: FDA posts deemed final order and proposed order for over-the-counter sunscreen | FDA

42 https://www.fda.gov/drugs/cder-small-business-industry-assistance-sbia/small-business-assistance-frequently-asked-questions-regulatory-process-over-counter-otc-drugs#:~:text=As%20described%20in%20section%20744L%20%288%29%20of%20the,ingredients%20that%20have%20been%20found%20to%20be%20GRASE.

43 D'Ruiz CD, Plautz JR, Schuetz R, Sanabria C, Hammonds J, Erato C, Klock J, Vollhardt J, Mesaros S, Preliminary clinical pharmacokinetic evaluation of bemotrizinol – A new sunscreen active ingredient being considered for inclusion under FDA's over the counter (OTC) sunscreen monograph, Regulatory Toxicology and Pharmacology, Volume 139, 2023, 105344, ISSN 0273-2300, https://doi.org/10.1016/j.yrtph.2023.105344

44 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/maximal-usage-trials-topically-applied-active-ingredients-being-considered-inclusion-over-counter

45 https://digitalcommons.law.seattleu.edu/cgi/viewcontent.cgi?article=2811&context=sulr

46 Happi. Breaking News. August 13, 2023. US Rep. Alexandria Ocasio-Cortez Calls for Better Sunscreens (https://ajay.happi.rodmanadmin.com/contents/view_breaking-news/2023-08-13/us-rep-alexandria-ocasio-cortez-calls-for-better-sunscreens/?widget=listSection).

47 Gardner, L. and K.E. Foley. December 8, 2023. Watchdog weighs in on FDA cosmetics plans. POLITICO (https://www.politico.com/newsletters/prescription-pulse/2023/12/08/watchdog-weighs-in-on-fda-cosmetics-plans-00130760).