Over-the-counter (OTC) drugs are defined by the FDA as drugs that are safe and effective for use by the general public without seeking treatment by a health professional. Currently, there are more than 300,000 OTC products on the market. Instead of reviewing each individual drug product, the FDA reviews the active ingredients and labeling of more than 80 classes of drugs.
Active ingredients are classified into three categories:
- Category I is for active ingredients that are generally recognized as safe (GRAS) and effective for the claimed therapeutic indication.
- Category II is for active ingredients that are not GRAS and effective or for unacceptable indications.
- Category III is for active ingredients where insufficient data is available to permit final classification.
For each drug class, the FDA develops a monograph that is then published in the Federal Register. OTC drug monographs are essentially a recipe book of conditions for each therapeutic area that covers the acceptable ingredients, doses, formulations, labeling, and testing of OTC drugs.
OTC monographs specify the following:
- Active ingredients
- Dosage strength, form, and route of administration
- Patient population demographics and indications for use
- Required labeling that includes usage, warnings, and directions
- Final formulation testing, if required for a specific product
The current OTC monograph rulemaking process requires the following three-step public notice and comment period be followed: (1) Advance Notice of Proposed Rulemaking (ANPR) followed by a period for public comment; (2)Issuance of a Tentative Final Monograph followed by a period for public comment; and (3) publishing of the final monograph in the Federal Register.
After it has been published, a final monograph may be amended, either on the FDA Commissioner’s own initiative or upon the petition of any interested person. OTC drug monographs are continually updated to add, change, or remove ingredients, labeling, or other pertinent information, as needed.
Once a final monograph is implemented, companies can make and market an OTC drug without the need for pre-approval from the Agency as long as the drug completely conforms to the monograph. If the drug doesn’t conform to the monograph, it must be reviewed by the FDA using the new drug application (NDA) process.
Products introduced to the market under an OTC monograph are bound to the same standards of safety and efficacy as an NDA-approved drug, and compliance with GMPs is still required. However, unlike products marketed under an approved NDA, OTC products are only required to report serious adverse events.
FDA has developed format and content requirements that manufacturers must follow when labeling their OTC drugs. The standardized format is called the “Drug Facts,” and the content requirements are outlined in 21 CFR 201.66.
The current monograph state for sunscreen products
The regulation of sunscreen products provides an excellent look at the monograph process. The FDA issued a proposed rule on February 26, 2019 to put into effect a final monograph for nonprescription, OTC sunscreen products. The proposed rule describes the conditions under which the FDA proposes that OTC sunscreen monograph products are GRAS and effective and not misbranded. Final comments on the proposed rule were due on May 28, 2019.
The reasoning behind the proposed rule is that the FDA is considering certain active ingredient safety issues further. As such, in forthcoming rulemaking, the FDA intends to request additional data regarding the safety of the individual sunscreen active ingredients in light of changing conditions, including substantially increased sunscreen usage and exposure and evolving information about the potential risks associated with these products since they were initially evaluated. This further review will have the impact of updating the original sunscreen final rule that was published in 1999.
The proposed rule is in line with the FDA’s current understanding regarding the evaluation of safety of topical drug products for chronic use, including topical safety studies (irritation, sensitization, and photosafety), and bioavailability (absorption). Given the long history of marketing the active ingredients in sunscreen products, unlike the nonclinical data required to meet the standard for approval of chronic-use topical NDA products, the approach to nonclinical safety testing is largely focused on potential long-term adverse events or effects not otherwise readily detected from human use (i.e., carcinogenicity and reproductive toxicity).
Proposed safe and effective categorizations were as follows:
- Sufficient safety data on both zinc oxide and titanium dioxide support a proposal that sunscreen products containing those ingredients would be GRAS and effective. These ingredients are Category I.
- Safety data for aminobenzoic acid (PABA) and trolamine salicylate caused the FDA to conclude that risks associated with the use of these active ingredients in sunscreen products outweigh the benefits. Accordingly, the FDA proposed that these two ingredients are Category II.
- For other ingredients, such as cinoxate, dioxybenzone, ensulizole, homosalate, meradimate, octinoxate, octisalate, octocrylene, padimate O, sulisobenzone, oxybenzone, and avobenzone, there is not sufficient data available in the public domain to support positive generally recognized as safe and effective determinations and therefore the FDA proposed that these ingredients are Category III.
Proposed requirements related to dosage forms were as follows:
- After considering comments and other available data, the FDA proposed the following dosage forms as Category I: oils, lotions, creams, gels, butters, pastes, ointments, sticks, and sprays (subject to testing necessary to minimize potential risks for unintended inhalation and flammability, together with related labeling requirements). The FDA also proposed to add sunscreen powders to the list of dosage forms eligible for inclusion in the final monograph as Category III.
- For sunscreens in all other dosage forms – including wipes, towelettes, body washes, and shampoos – these would be considered new drugs as there is no data showing that they were marketed prior to 1972, as required for inclusion in this monograph.
Proposed maximum sun protection factor and broad spectrum requirements were as follows:
- Regarding the sun protection factor, in the Stayed 1999 Final Monograph, the FDA established SPF 30+ as the maximum labeled SPF value for sunscreen monograph products. Subsequently, in 2001, this was raised to SPF 50+. Because of evidence showing additional meaningful clinical benefit associated with broad spectrum sunscreen products with an SPF of 60, the FDA is proposing to raise the maximum labeled SPF value to SPF 60+. Given the lack of data showing that sunscreens with SPF values above 60 provide additional meaningful clinical benefit, the FDA proposed to not allow labeled SPF values higher than 60+. While the proposed limit for SPF labeling is SPF 60+, the FDA has proposed to permit the marketing of sunscreen products formulated with SPF values up to 80.
- Regarding broad spectrum requirements, the body of scientific evidence linking UVA exposure to skin cancers and other harms has grown significantly which raises concerns about the potential for inadequate UVA protection in marketed sunscreen products – particularly in high SPF products that either do not pass the current broad spectrum test or have inadequate uniformity in their UVA protection. Consumers using these products may, while successfully preventing sunburn, accumulate excessively large doses of UVA radiation – thereby exposing themselves to additional risks related to skin cancer and early skin aging. Because sunscreens with SPF 2-14 have not been demonstrated to reduce the risk of skin cancer and early skin aging caused by the sun, whether or not they provide protection against UVA and UVB radiation, the FDA is not requiring those products to pass the revised broad spectrum test. However, the FDA has sought comment on whether these low SPF products should remain on the market. And, the FDA has proposed that sunscreen products with SPF values of 15 or above are labeled with an SPF number corresponding to the lowest number in a range of tested SPF results. For example, sunscreens testing at SPF 15-19 would be labeled with “SPF 15”; those testing at 40-49 would be labeled “SPF 40”. This is because new evidence has caused the FDA to reexamine the variability inherent in the SPF test.
- Regarding principle display panel labeling requirements, the FDA proposed that the statement of identity (SOI) consists of an alphabetical listing of the sunscreen active ingredients in the product, followed by “sunscreen” and the product’s dosage form (such as lotion or spray). This is due to the fact that the PDP is the part of a product label that is most likely to be viewed or examined when the product is displayed for retail sale and having the SOI laid out in a way that provides a succinct summary of the product’s key characteristics on the front of the package or container, permitting consumers to more readily compare products and either select or avoid a given product accordingly.
- Regarding requirements related to final formulation testing processes and record-keeping, the FDA proposed to require records of required final formulation testing of sunscreen products to be maintained for one year after the product expiration date, or, if the product is exempt from expiration testing (as most sunscreens are), for three years after distribution of the last lot labeled in reliance on that testing. The FDA has also proposed a number of revisions to the labeling and testing regulations designed to clarify FDA expectations about clinical final formulation testing processes and to ensure that the testing of marketed sunscreen products is conducted in a manner that both protects human subjects and produces reliable results.
- Regarding the status of sunscreen-insect repellent combination products, these products are jointly regulated by the FDA as sunscreen drugs and by the EPA as pesticides. The FDA proposed to classify those products as Category II because incompatibilities between FDA and EPA labeling requirements prevent these products from being labeled in a manner that sufficiently ensures safe and effective use of the sunscreen component and provides adequate directions for use.
It’s clear that the regulation of sunscreen products is going through a substantial overhaul. However, when the final monograph is published, drug makers in the sunscreen industry will have a clear mandate regarding whether and how they can market their products.
Do you manufacture a sunscreen or other OTC product? We can help ensure that you are in compliance with all of FDA’s monograph requirements. To learn more about our OTC services, contact us and how we can help you, today.