The newest regulations and comments on sunscreens from the US Food and Drug Administration (FDA) were officially published in the Federal Register on June 17, 2011, and will go into effect June 17, 2012. The final rule titled Labeling and Effectiveness Testing; Sunscreen Drug Products for Over-the-Counter Human Use amends the Final Monograph that went into effect in May 1999 but has been stayed until now. Parts are still stayed until the FDA issues further rules. The recently published regulations are a small part of the overall regulations; therefore, this column will clarify the overall regulations by reviewing the full picture—sunscreen drugs, labeling, registrations and unanswered questions.
US Sunscreen Requirements
In the United States, sunscreen drugs are listed in 21CFR352. This listing (see Permitted Filters) provides the allowed active ingredients and permitted combinations of these actives in addition to the required tests and labeling. Labeling and registrations will be covered later. Note that these are the drug names (not INCI) and the maximum permitted level. They must be United States Pharmacopoeia (USP) grade. A sufficient level of a UV filter must be used to give an SPF of at least 2.
Active combinations: All actives can be combined with each other up to the maximum stated with the exception of avobenzone. Avobenzone can only be used with cinoxate, dioxybenzone, homosalate, octinoxate, octisalate, octocrylene, oxybenzone, sulisobenzone and trolamine salicylate.
When using combinations, each UV filter must add a minimum of SPF 2 to the final product. In other words, two filters must have an SPF 4; three filters must have an SPF 6, etc. This becomes difficult if the UV filter absorbs in the UVA range, as SPF measures UVB protection. A methodology was presented at the 2004 International Federation of the Societies of Cosmetic Chemists (IFSCC) Congress in Orlando, Florida, presented by John Staton and this author, to take this into account.
Testing requirements: All sunscreens must be tested for efficacy by running the FDA’s SPF method. This is one of the major changes to the regulations as of June 17, 2011. The first change is the standard sunscreen to validate the laboratory SPF tests. The new standard is based on 7% padimate O (the FDA left out the “O”) and 3% oxybenzone. This gives an SPF > 15. The adoption of COLIPA’s 2006 Emission spectrum specifications is another change. The critical major change is the number of subjects—starting with 10–13 and requiring at least 10 or more valid results. This is in line with the European Union (EU) and is down from the 20–25 subjects previously required.
The most important and critical changes besides labeling concerns the FDA’s regulations for UVA testing. In the 2007 proposed rules, the FDA required both an in vivo test (PPD) and an in vitro test (modified Diffey/Robson) and labeling with the lower of the two results for UVA protection. In the new rules, the critical wavelength (λc), an in vitro test, is required. The FDA refers to this as the broad-spectrum test. There are several changes in the procedures and equipment. The new regulations use PMMA plates (roughness between 2 and 7 µm) instead of quartz, and application of 0.75 mg/cm2 instead of 2.0 mg/cm2 of sunscreen. To pass the test and be able to claim broad-spectrum, a λc of at least 370 nm is required.
The test has been slightly modified by reducing the drying time from 20 to 15 minutes. Like all drugs, stability testing is required. This is critical to assure the API remains stable in the formulation, not the stability of the formulation. Accelerated testing is permitted but should always be verified, when possible, by real time. The FDA does not currently require expiration dates on sunscreens. One common question is the tolerance of change in the active. This is based on the range for the API in the USP. If the USP says ± 5%, that is the range. Some API are ± 2.5%, the lowest range used. The major failures are almost always due to the inorganic API. Companies forget to subtract out the coatings, stabilizers, etc. After accelerated stability, the actual level is measured and compared to the starting material.
Labeling: The new regulations lift the stay on Drug Facts labeling for sunscreens. Effective June 18, 2012, all sunscreens must have full Drug Facts labels. They eliminated the reduced requirements for labeling small packages, which only required active ingredients and minimal warning, for small areas of the face such as the eyes and lips. This will cause manufacturers of lipsticks and possibly liquid makeup, who have been claiming SPF (mainly because the products contain titanium dioxide for coloring), to address this labeling. Requiring the full Drug Facts label and in correct size would entail either attachment to a card (blister packs) or using an expansive type label. Both of these options are not particularly aesthetically pleasing and are expensive. Further, having the required directions: Apply liberally 15 minutes before sun exposure; use a water-resistant sunscreen if swimming or sweating; and reapply at least every two hours, would not make sense for these types of cosmetics. See the section in this column on directions. The critical question on this will be: Does claiming SPF for these types of cosmetics increase sales sufficiently to cover the significant increase in costs and attractiveness of the packaging and testing?
All sunscreens must have the word “sunscreen” on the front label. If the sunscreen product passes the broad-spectrum test, then the product must be labeled: “Broad-spectrum SPF (insert the number).” If it does not pass the test or if it is not tested, then it must be labeled “SPF (insert the number).” There are no restrictions on the number except it must be 2 or above, with a proposed maximum of 50+. If the sunscreen passes the water-resistant test, it can now state: “Water Resistant (40 minutes) or (80 minutes),” depending on the test results.
The regulations of this are complex. The panel must be in sharply contrasting colors with no design within the panel being permitted. The words “Drug Facts” must be bold italics and minimum 9-point font. All headers must be bold italics and 8-point font, while text must be 6-point font without bold or italics unless specified under the warnings section. These 9 to 8 to 6 differences are required for larger type such as 12-11-9.
Here are the headings with required and optional verbiage:
a. Active ingredients: Active ingredients (lower case “i”) are listed alphabetically using United States Adopted Names (USAN) names followed by the use percentage (%). Be careful when using coated filters where only the actual active is listed, not the active plus the coatings, etc. This is followed by the word “sunscreen” under purpose.
b. Uses: The usage of the sunscreen must read, “Helps prevent sunburn.” If optional uses are added, these must have bullets that do not run on. Broad-spectrum products that have an SPF of 15 or higher may claim, “If used as directed with other sun protection measures (see Directions), decreases the risk of skin cancer and early skin aging caused by the sun.”
c. Warnings: Warnings appear in bold on the Drug Facts panel. All other text is not in bold. The warning will read, “For external use only—followed by a fine line that does not touch the outline. For products that are not broad-spectrum or that pass the broad-spectrum test but have an SPF less than 15 the warning will read, “—Skin cancer/Skin Aging Alert: Spending time in the sun increases your risk of skin cancer and early skin aging. This product has been shown only to prevent sunburn, not skin cancer or early skin aging,” followed by a fine line that does not touch the outline. Additional warnings for sunscreens include: “Do not use on damaged or broken skin,” followed by a fine line that does not touch the outline; “Stop use and ask a doctor if rash occurs,” followed by a fine line that does not touch the outline; “When using this product keep out of eyes. Rinse with water to remove,” followed by a fine line that does not touch the outline; and “Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away.”
d. Directions: Non-water resistant products must include the following directions exactly as they appear:
• apply liberally 15 minutes before sun exposure
• use a water-resistant sunscreen if swimming or sweating
• reapply at least every 2 hours,
• children under 6 months: Ask a doctor.
Water-resistant products must include the following directions exactly as they appear:
• apply liberally 15 minutes before sun exposure,
• after 40 [or 80] minutes of swimming or sweating
• immediately after towel drying,
• at least every 2 hours.
• children under 6 months: Ask a doctor
Water-resistant or nonwater-resistant products that are broad-spectrum and an SPF of 15 or higher must include the following directions exactly as they appear:
• Sun Protection Measures. Spending time in the sun increases your risk of skin cancer and early skin aging. To decrease this risk, regularly use a sunscreen with a broad-spectrum SPF value of 15 or higher and other sun protection measures including:
• limit time in the sun, especially from 10 am–2 pm
• wear long-sleeved shirts, pants, hats and sunglasses.
e. Other information (lower case “i”): This section must feature the following bullet exactly as it appears:
• protect this product from excessive heat and direct sun.
This is also the section where the optional statement can be placed (the other option is outside the Drug Facts box) concerning reporting serious adverse reactions to this product. For more information see www.reportreaction.com.
f. Inactive ingredients: In the Inactive ingredients listing (lower case “i”), if the manufacturer makes no cosmetic claims, they are to be listed in alphabetical order using their USAN names only. If they make any cosmetic claim, they are to be listed in descending order of predominance down to 1% and then any order; using only INCI names. Sunscreens in the United States typically make some cosmetic claim, so this requirement can be questioned.
g. Questions: The “Questions?” labeling is optional with no required statements. If a telephone number is listed, and it should be answered by a person 24/7 unless the hours, such as 9 am–5 pm Monday through Friday, EST, are stated.
The FDA has prohibited the following claims anywhere on the product, packaging, label or advertising: “sunblock, waterproof or sweatproof”; and “instant protection, all day or extended wear protection.” This are found to be false and misleading. The use of any of these terms makes the product automatically misbranded and subject to FDA action such as warning letters, seizures or even criminal charges.
As of June 2009, all OTC drug listings must be submitted electronically in Structural Product Labeling XML format using the FDA’s Electronic Submissions Gateway (ESG) portal. Before beginning, a company needs to obtain a Data Universal Numbering System (DUNS) number. This is available for free from Dun & Bradstreet. Once a DUNS number is obtained, apply for an National Drug Code (NDC) Labeler Code. All marketers (private label distributors, the name on the label), manufacturers and bulk sellers of API need a labeler code. Once obtained, this is no longer needed to be re-registered. You only need one labeler code. Companies that are both the marketer and manufacturer and go by the same name need only one labeler code. There is only one label code assigned to a company for different manufacturing sites.
After a labeler code has been assigned, an Establishment Registration for the manufacturing site must be obtained. This must be renewed at least annually. Foreign locations are required to have a US liaison person and address included in their submission.
Finally, the drug listing must be filed and updated whenever changes occur. An image of the drug’s label (PDP) must be attached with the submission.
The complex question is who files the drug listing? It is always the private label distributor’s responsibility to drug list the product it is distributing. The manufacturer is also required to file the drug listing if it is under contract to make the product for a private label distributor. A contract manufacturer may file the drug listing on behalf of the private label distributor. If it is a bulk API (100% strength) and the manufacturer is distributing the product under its brand name, it is also responsible for drug listing the API products.
If a formulation contains titanium dioxide or any other ingredient on California’s cosmetic list, an additional filing must be made under the California Safe Cosmetic Act.
Unanswered Questions or Work in Progress
When the FDA issued its final requirements on effectiveness, it stated that there were other issues that still needed to be addressed.
GRASE determination for sunscreen ingredients: Included in this are: approving the safety of current UV filters, increasing the maximum level of avobenzone from 3% to 5%, approving the filters listed in the 2007 Federal Register notice on sunscreens, allowing the combinations of avobezone and/or zinc oxide or ensulizole, allowing the combination of avobenzone and titanium dioxide, and allowing either USP-grade of zinc oxide/zinc oxide neutral, to be allowed as active UV filters.
Issues affecting multiple OTC drug monographs: These include expiration dates, country of origin and finally, the use of the word “Final” in final monograph.
Draft Guidance for Sunscreen Enforcement Policy: This draft guidance, which is not official, proposes that the FDA will not enforce the regulation to retest for SPF using the new method, for sunscreens on the market as of June 17, 2011, until June 17, 2013. This allows an extra year for testing. However, this does not exempt companies from compliance with the new broad-spectrum testing and labeling. It also does not exempt compliance with Drug Facts, adverse reaction reporting and banned claims. It will allow SPFs higher than 50+ provided the number is obtained using the new method, and the FDA has not issued a final ruling on this subject. It also will continue to allow sprays until they have a final rule.
Request for data for sprays: In Sunscreen Drug Products for Over-the-Counter Human Use; Request for Data and Information Regarding Dosage Forms, the FDA requests appropriate testing (both safety and effectiveness) and labeling for spray sunscreens or it may prohibit this form in future rules.
Proposed rules on maximum SPF: In Revised Effectiveness Determination; Sunscreen Drug Products for Over-the-Counter Human Use, the FDA proposes a cap SPF at 50+ for lack of sufficient data to indicate that there is additional clinical benefit above SPF 50.
The FDA’s best decisions in the recent final rule was to change the front of the packaging and use a simple in vitro UVA test with a pass/fail result. The complexity of the 2007 proposed testing and labeling would be costly and the label would be confusing. The new SPF tests are much closer to the EU’s method, which is a large step to global harmonization of SPF.
In 2007, the FDA completely rejected suggestions of using the critical wavelength test.1 It would have been better if the FDA adopted the current critical wavelength test used in most of the world, as referenced by a recent article in the October issue of Cosmetics & Toiletries magazine by Lutz et al., which compared the two methods.2
The labeling change for water resistance to include the minutes was a wise decision. This has been used in Australia for years, and consumers are better informed with this information.
Finally, the FDA moved the parabens in the sunscreen standard to the water phase, where they function. Also, by insisting on Drug Facts labels for all sunscreens, it will probably eliminate secondary makeup sunscreens from the market.
The cancer warning allowed by the FDA in 2007 was, “UV exposure from the sun increases the risk of skin cancer, premature skin aging, and other skin damage. It is important to decrease UV exposure by limiting time in the sun, wearing protective clothing and using a sunscreen.”3 Conversely, products that are broad-spectrum and have an SPF of 15 or higher, according to the 2011 final rule may have the cancer warning, “If used as directed with other sun protection measures (see Directions), decreases the risk of skin cancer and early skin aging caused by the sun.” For sunscreens that are not broad-spectrum and SPF 15 or higher, the following cancer warning must be included, “Skin cancer/Skin Aging Alert: Spending time in the sun increases your risk of skin cancer and early skin aging. This product has been shown only to prevent sunburn, not skin cancer or early skin aging.”4 Previous cancer warnings can be found in the Federal Register.5–7
The FDA admits that all consumers do not apply 2 mg/cm2. Therefore, all SPF numbers are not a reflection of what consumers should expect. Directions should be amended to read, “For best results apply 15 minutes before sun exposure.” Further, it can be assumed that when applying every two hours, the consumer does not go indoors and wait 15 minutes before re-emerging into the sun.
The major problem with the new regulation is the FDA’s failure to approve the combinations of avobenzone with ensulizole and zinc oxide. The FDA should have approved the combination of avobenzone and titanium dioxide as well. There were no objections to the FDA’s proposed approval of avobenzone with ensulizole and zinc oxide. Two separate and complete applications where submitted to show the safety and efficacy of avobenzone and titanium dioxide.
The FDA’s new reference standard is a good idea in theory, but padimate O is nearly obsolete due to concern over the safety of para-aminobenzoic acid. Obtaining commercial materials to manufacture the standard could be difficult in the future. It would make more sense to base the standard on octinoxate, which is the most popular UV filter in the United States. Since it is only a standard, this is not an important issue. The lack of any progress in approving the Time and Extent Applications for new UV filters is important. The industry has waited more than eight years for the first UV filters to be approved by this process.
In its Request for Data and Information Regarding Dosage Forms,8 the FDA focused only on sprays. No comments for sprays were submitted to the FDA request in 2007, but sprays where given another chance. Rinse-off sunscreens submitted the requested data and did not even get a comment. At a webinar,9 the FDA noted that spray sunscreens were on the market before 1972, which is hard to believe since there were no sprays listed as being submitted, FR Page 38207. The FDA needs more than speculation that sprays were a pre-existing drug form.
As this is called a work in progress, more regulations will slowly come out from the FDA. Just remember, there is nothing final about a final monograph.
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1. Federal Register 72, No 165, 49104 (Aug 27,2007)
2. Lutz et al, FDA Rule for Broad-spectrum Labeling: Key Stubstrate Findings, October 2011
3. Federal Register 72, No 165, 49113 (Aug 27, 2007)
4. Federal Register 76, No 117, 35660–35661 (Jun 17, 2011)
5. Federal Register 43, No 164, 38267 (Aug 23, 1978)
6. Federal Register 58, No 90, 28298 (May 12, 1993)
7. Federal Register 64, No 98, 27689 (May 21,1999)
8. Federal Register 76, No 117, 35669–35672 (Jun 17, 2011)
9. What is the latest word on sunscreens? webinar, presented by Happi (Aug 8, 2011)