By: Ashley Dao, PharmD Candidate c/o 2024

Melanoma is the fifth most common cause of cancer in the United States (US). Unprotected exposure to ultraviolet (UV) radiation from the sun is the primary risk factor for developing melanoma.¹ In order to reduce damage from UV exposure, the American Cancer Society (ACS) recommends practices such as avoiding the sun during peak hours, wearing appropriate clothing, and using broad-spectrum sunscreen with a sun protection factor (SPF) of 30 or higher.² Sunscreen use has been shown to effectively protect against skin cancer in the general population.³ Despite the crucial role sunscreens play in melanoma prevention, the US Food and Drug Administration (FDA) has been stagnant in approving new UV filters, with the most recent update in 1999. The FDA sunscreen monograph currently contains 16 approved UV filters (Table 1).⁴

In the US, sunscreens are regulated strictly by the FDA as over-the-counter (OTC) drugs. On the other hand, the European Union (EU) considers sunscreen to be cosmetic, therefore approving products more liberally, but not without a similar rigor of testing.⁵ In order to understand why the FDA is lagging behind its international counterparts in terms of sunscreen quality and quantity, the OTC drug approval process must be evaluated.

FDA Sunscreen Approval Process

There are two ways that OTC drugs can be approved by the FDA. One way is through either a New Drug Application (NDA) or an Abbreviated New Drug Application (ANDA). The other option is to go through the OTC Drug Review process, also referred to as the OTC monograph. Drugs that meet the OTC monograph’s requirements do not need an NDA/ANDA, nor do they require FDA premarket approval. Despite the benefits of this process, the FDA previously faced challenges when updating older monographs because any changes required lengthy notice-and-comment rulemaking. This resulted in OTC monographs, including the sunscreen monograph, to be outdated.⁶ In 2020, the Coronavirus Aid, Relief, and Economic Security Act (CARES Act) was enacted. This act has since transformed the way in which the FDA regulates OTC monographs. It replaced rulemaking with a much quicker administrative order process and allowed the FDA to collect valuable fees from manufacturers. The CARES Act has provided the FDA with the resources needed in order to efficiently revise OTC monographs based on new data and/or safety concerns.⁶

The OTC Monograph M020: Sunscreen Drug Products for OTC Human Use (M020) is a “rulebook” that establishes guidelines, including those regarding active ingredients, labeling, and test procedures, that all OTC sunscreen products must follow. If a product meets the conditions stated in M020, it is deemed “generally recognized as safe and effective” (GRASE) and can be marketed without an NDA/ANDA or FDA premarket approval.⁶ The passing of the CARES Act required the FDA to post M020 as a Deemed Final Order (DFO); a proposal of significant changes to the DFO was made in September 2021 for the first time since 1999 after the passage of the CARES Act.⁷ On September 24, 2021, the FDA proposed an order that would cut down the list of approved safe and effective UV filters from the 16 to 2; under this proposal, aminobenzoic acid (PABA) and trolamine salicylate would lose their status as GRASE ingredients due to safety concerns.⁸ The other 12 active ingredients would also be categorized as not GRASE due to insufficient data.⁸ The implementation of the CARES Act has clearly been promising for those hoping for advancements in the safety and effectiveness of American sunscreen. Hopefully, with this act in place, the time required for the FDA to implement a new OTC monograph will be shortened, and the quicker approval of novel GRASE UV filters will be soon to come as well.

Choosing the Right Sunscreen

Sunscreen has been demonstrated to reduce the risk for skin cancer, prevent photoaging, and reduce sunburns. However, less than 40% of Americans report practicing sun protection including regular sunscreen wear.³ The lack of sunscreen use is a multifactorial problem. Sunscreen formulations, UV coverage, allergic reactions, and cost are all factors that patients consider when looking for a product. As a consequence of the lack of new sunscreen filters approved by the FDA, some patients have resorted to traveling abroad or using third-party retailers to purchase non-FDA approved products in order to fulfill their desires for what they want in a sunscreen.^5,9

A study conducted by Xu et al. analyzed the top 1 percentile of sunscreen products being sold on Amazon.com, Inc. as of December 2015. The study found that the most cited positive features of sunscreens were aspects of cosmetic elegance (61% of 325 comments), described with words such as “rub in well,” “positive tactile skin feel,” and “not greasy.” The most notable negative features were concerns with cosmetic elegance (22%), as well as product performance (11%), product ingredients (10%), and expense (9%). Consumers preferred sunscreens with physical UV filters such as zinc oxide and titanium oxide – the two ingredients deemed as GRASE in the FDA’s proposed order.¹⁰ However, despite the popularity of these 2 ingredients, many US consumers are left looking for more in a sunscreen than what these filters can offer. Many titanium dioxide sunscreen formulations can leave a white cast, especially in patients with darker skin tones.⁹ Additionally, results from this study showed that physical sunscreens (i.e., those containing zinc and titanium dioxide) are more expensive than chemical ones.¹⁰

Social media has introduced consumers to well-rated, but non-FDA approved, sunscreens from other countries. Notably, Korean beauty brands have gained popularity lately through reviews posted on YouTube and TikTok. Once sunscreen in particular,  Isntree’s Hyaluronic Acid Watery Sun Gel SPF 50, has repeatedly been claimed to be one of the best sunscreens on the market. The sunscreen contains 7 active UV filters: octisalate, homosalate, polysilicone-15, etc. Only 2 of these UV filters are approved by the FDA, while 5 of them are approved by the EU.¹¹ Another popular Korean sunscreen is Beauty of Joseon Rice Probiotics Sunscreen SPF 50, which contains 2 UV filters: diethylamino hydroxybenzoyl hexyl benzoate and bis-ethylhexyloxyphenol methoxyphenyl triazine.¹² Both UV filters are approved in the EU, but not in the US.^4,5 The FDA should take note of the popularity of these sunscreens’ ingredients among consumers and professionals to expand approved UV filters.

Limitations of US Sunscreen

Furthermore, one key difference between US and EU sunscreen filters is UVA coverage. The EU requires that UVA protection be at least one-third the SPF of the product. On the other hand, the FDA currently does not require sunscreens to provide adequate protection against UVA (the proposed order should revise the DFO to include adequate protection against UVA).⁵ Only 7 of the 16 FDA-approved filters provide UVA and UVB protection, including titanium dioxide and zinc oxide.⁵ To achieve both UVA and UVB coverage as seen in many EU sunscreens, US manufacturers must combine UV filters. For example, Supergoop! Unseen Sunscreen SPF 40 is a mix of 1 UVA and 3 UVB coverage filters.^4,5,13

Research by Matta et al. demonstrated that sunscreens containing popular ingredients such as oxybenzone, homosalate, and octisalate surpassed the FDA safety threshold of 0.5 ng/mL in plasma after single application, hence their categorization as not GRASE in the FDA’s proposed order until further safety studies are conducted.^5,8,14 Oxybenzone is a common ingredient found in US and EU sunscreens; it is also, unfortunately, the most frequent allergen in these products. Research demonstrates that oxybenzone has the potential to induce contact allergy, photo contact allergy, and contact urticaria.⁵ Despite the concerns surrounding this ingredient, it may be difficult to replace due to the limited number of other GRASE and FDA approved UV filters available in the US.

Although it may be a while before the FDA approves any radical changes to the DFO, pharmacists can still play an important role in providing sunscreen recommendations for everyday use. When pharmacists help patients select a sunscreen, they should factor in cosmetic elegance, effectiveness, patient allergies, and cost. Patients should be asked about their preference between physical or chemical UV filters, if they have had previous sensitivity to sunscreens, and how much they are willing to spend. Sunscreens sold in Europe and Asia offer benefits that are not observed in many US formulations. Broad-spectrum coverage from both UVB and UVA radiation and the cosmetic elegance of novel UV filters are some advantages these products have over many US sunscreens. However, pharmacists should caution patients to be mindful when purchasing sunscreens online or abroad, as they may not be approved by the FDA. The power of the CARES Act, along with concerns about current US UV filters and the popularity of EU-approved ingredients among consumers, should hopefully spur the modernization of US sunscreens in the upcoming years.

Table 1. List of UV filter approved in the United States^4,5

UV Filter	GRASE Status	OTC examples	Mechanism	UV Coverage
Aminobenzoic acid (PABA)	Not GRASE*	N/A	Organic	UVA2
Avobenzone	Not GRASE**	Supergoop! Unseen Sunscreen SPF 40	Organic	UVA1/2
		La Roche-Posay Anthelios Cooling Water Sunscreen Lotion SPF 30
		Banana Boat Ultra Sport Sunscreen Lotion SPF 100
		Coppertone Sport Sunscreen Continuous Spray SPF 30
Cinoxate	Not GRASE**	N/A	Organic	UVB
Dioxybenzone	Not GRASE**	N/A	Organic	UVA2, UVB
Ensulizole	Not GRASE**	N/A	Organic	UVB
Homosalate	Not GRASE**	Supergoop! Unseen Sunscreen SPF 40	Organic	UVB
		La Roche-Posay Anthelios Cooling Water Sunscreen Lotion SPF 30
		Sun Bum SPF 50 Spray Sunscreen
		Neutrogena Ultra Dry-Touch Sunscreen SPF70
Meradimate	Not GRASE**	N/A	Organic	UVA2
Octinoxate	Not GRASE**	EltaMD UV Clear Broad-Spectrum SPF 46	Organic	UVB
Octisalate	Not GRASE**	Supergoop! Unseen Sunscreen SPF 40	Organic	UVB
		Neutrogena Ultra Dry-Touch Sunscreen SPF70
		Sun Bum SPF 50 Spray Sunscreen
		La Roche-Posay Anthelios Cooling Water Sunscreen Lotion SPF 30
		Coppertone Sport Sunscreen Continuous Spray SPF 30
Octocrylene	Not GRASE**	Supergoop! Unseen Sunscreen SPF 40	Organic	UVB
		La Roche-Posay Anthelios Cooling Water Sunscreen Lotion SPF 30
		Banana Boat Ultra Sport Sunscreen Lotion SPF 100
		Coppertone Sport Sunscreen Continuous Spray SPF 30
Oxybenzone	Not GRASE**	La Roche-Posay Anthelios Cooling Water Sunscreen Lotion SPF 30	Organic	UVA2, UVB
		Banana Boat Ultra Sport Sunscreen Lotion SPF 100
		Coppertone Sport Sunscreen Continuous Spray SPF 30
Padimate O	Not GRASE**	N/A	Organic	UVB
Sulisobenzone	Not GRASE**	N/A	Organic	UVA2, UVB
Titanium Dioxide	GRASE	La Roche-Posay Anthelios Sunscreen	Inorganic	UVA1/2, UVB
		EltaMD UV Physical Broad-Spectrum SPF 41 Sunscreen
Trolamine Salicylate	Not GRASE*	N/A	Organic	UVA1/2, UVB
Zinc Oxide	GRASE	La Roche-Posay Anthelios	Inorganic	UVA1/2, UVB
		Sunscreen
		EltaMD UV Clear Broad-Spectrum SPF 46
		EltaMD UV Physical Broad-Spectrum SPF 41 Sunscreen

* Not GRASE for use in sunscreens because of safety concerns

** Not GRASE for use in sunscreens because additional data needed

References

1. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17-48. doi:10.3322/caac.21763
2. The American Cancer Society medical and editorial content team. How do I protect myself from ultraviolet (UV) rays? American Cancer Society. Last Revised July 23, 2019. Accessed September 3, 2023. https://www.cancer.org/cancer/risk-prevention/sun-and-uv/uv-protection.html
3. Saginala K, Barsouk A, Aluru JS, Rawla P, Barsouk A. Epidemiology of Melanoma. Med Sci (Basel). 2021;9(4):63. doi:10.3390/medsci9040063
4. Over-the-Counter Monograph M020: Sunscreen Drug Products for Over-the-Counter Human Use. U.S. Food and Drug Administration. September 24, 2021. Accessed March 30, 2023. https://dps-admin.fda.gov/omuf/omuf/sites/omuf/files/primary-documents/2022-09/Final%20Administrative%20Order%20OTC000006_M020-Sunscreen%20Drug%20Products%20for%20OTC%20Human%20Use.pdf
5. 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. J Am Acad Dermatol. 2023;88(3):632-646. doi:10.1016/j.jaad.2022.11.039
6. Michele TM. An Exciting New Chapter in OTC Drug History: OTC Monograph Reform in the CARES Act. FDA. 2020. Accessed April 1, 2023. https://www.fda.gov/news-events/fda-voices/exciting-new-chapter-otc-drug-history-otc-monograph-reform-cares-act
7. Questions and answers: FDA posts deemed final order and proposed order for over-the-counter sunscreen. U.S. Food and Drug Administration. Last Revised December 16, 2022. Accessed September 3, 2023. https://www.fda.gov/drugs/understanding-over-counter-medicines/questions-and-answers-fda-posts-deemed-final-order-and-proposed-order-over-counter-sunscreen
8. FDA proposed order: sunscreen drug products for over-the-counter-human use; proposal to amend and revise the deemed final order established by the Cares Act. U.S. Food and Drug Administration. 2022. Accessed April 2, 2023. https://www.fda.gov/media/153964/download
9. Printz C. Sunscreen slow down: The US FDA’s sluggish approval of new sunscreens frustrates physicians, manufacturers, and consumers. Cancer. 2015;121(17):2861-2862. doi:10.1002/cncr.29001
10. Xu S, Kwa M, Agarwal A, Rademaker A, Kundu RV. Sunscreen Product Performance and Other Determinants of Consumer Preferences. JAMA Dermatol. 2016;152(8):920-927. doi:10.1001/jamadermatol.2016.2344
11. Isntree Hyaluronic Acid Watery Sun Gel. Insntree. Accessed October 1, 2023. https://en.isntree.com/Mobile/Product/Detail/view/pid/216.
12. Rice Probiotics Sunscreen spf50+ pa++++. INCI Decoder. Accessed August 28, 2023. https://incidecoder.com/products/beauty-of-joseon-rice-probiotics-sunscreen
13. Unseen sunscreen SPF 40. Supergoop! Accessed September 9, 2023. https://supergoop.com/products/unseen-sunscreen
14. Matta MK, Florian J, Zusterzeel R, et al. Effect of Sunscreen Application on Plasma Concentration of Sunscreen Active Ingredients: A Randomized Clinical Trial. JAMA. 2020;323(3):256–267. doi:10.1001/jama.2019.20747

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