Stringent New Regulations are on the Horizon
George A. Burdock, PhD
President, Burdock Group
A total reformation of cosmetics regulation is on the way! Not since the 1958 Amendment (requiring food ingredient pre-market approval) has there been such a fundamental change in the core mission of the FD&C act! Buried in the 1,653 pages of the Consolidated Appropriations Act (of) 2023 and signed into law on January 3, 2023, are 14 pages reforming how cosmetics will be regulated. The following article highlights four important mandates of which our readership should be aware of and for which preparations should be made.
A change in the safety standard.
Basic to all the changes mandated, is a change in the safety standard of cosmetics. The standard has changed from an undefined “adequate substantiation of safety” (21CFR§740.10) by an unnamed entity, which is now defined as meaning “a reasonable certainty of no harm” as determined by “tests or studies, research, analyses or other evidence” [considered by] “experts qualified by scientific training and experience” – there is now no daylight between the safety standard for food ingredients and cosmetic ingredients and, no provision for the equivalent of a food additive petition, nor is there a provision for demonstration of safety on the basis of prior safe use as there is in the law for GRAS (i.e., for use prior to January 1, 1958). Although the change in standard to a "reasonable certainty of no harm" is encouraging, the lack of detail on exactly what evidence is needed puts this provision square in the crosshairs of the FDA under Chevron Deference (which gives FDA considerable flexibility to interpret what Congress meant when proposing a regulation).
A new emphasis on exposure – “the dose makes the poison”.
The safety requirements for cosmetics could conceivably go beyond that for a food ingredient. Why? Traditionally, consumers are not exposed to the same food ingredients daily, except for perhaps salt, sugar, hot sauce, or other condiments and, although picas (an unhealthy craving for a non-nutritive substance) are relatively rare for food ingredients, the adverse health consequences of the pathologic consumption of ingredients such as salt or licorice, are well known. [1]
However, unlike foods, daily application of some cosmetic products can persist for weeks, even years, and for some, almost a lifetime of use of a specific brand (and formulation) of deodorant, antiperspirant, eye and facial makeup, lipstick, depilatories, makeup remover, breath mints and a plethora of other products, some of which are applied to very sensitive and often highly absorptive areas including, but not limited to the external genitalia. It is known that some cosmetic ingredients may be absorbed percutaneously, such as parabens [2] or triclosan. [3]
Therefore, to prove safety determined by “tests or studies, research, analyses,” it may require an assessment of the consequences of purposeful absorption of cosmetic ingredients (such as moisturizers) or the unintended absorption of cosmetic ingredients (such as preservatives). These determinations may require data from benchtop in vitro testing and possibly in vivo testing using live animals. Either method will require the use of sensitive and validated, detection methodology to determine the amount of chemical having successfully crossed the skin barrier. These data can be compared to the presumptive absorption of the same chemical from oral administration, to gain insight into what amount of circulating chemical causes toxicity. Ultimately, if toxic effects cannot be extrapolated from oral studies to the in vitro data, an animal study involving repeated (daily) dermal administration to animals might be required, but this process is labor-intensive and very costly.
Irritations and a list of allergens.
The law specifically indicates that the term “safe” means “…that [FDA][4] shall not consider a cosmetic ingredient or cosmetic product injurious to users solely because it can cause minor and transient reactions or minor and transient skin irritations in some users”. Irritants can be sorted out easily enough through a history of use and humane in vitro irritation tests.
Because fragrances are one of the major causes of allergic contact dermatitis from the use of cosmetics, the law takes a page from the Food Allergy Labeling and Consumer Protection Act of 2004 by requiring FDA to publish a list of fragrance allergens and further, the presence of a fragrance allergen in a product must be clearly identified as such on the cosmetic product label. The European Union Cosmetics Directive includes a list of 26 fragrance ingredient allergens that includes several cinnamyl derivatives, isoeugenol, oak moss, and tree moss extracts. It is likely the FDA allergen list will include photosensitizers as well.
[1] Campbell and Train (2017). Nutrients 9:648; McHugh et al (2021) BMC Endocrine Disorders 21:158.
[2] Dal Pozzo and Pastori (1996) International Journal of Cosmetic Science 18:57-66; Pedersen et al. (2007) International Journal of Cosmetic Science 29:361
[3] Allmyr et al (2006). Science of the Total Environment 372:87-93.
[4] The notation of FDA in brackets ([FDA]) is substituted for the word “Secretary” (of HHS) in the law.
Serious adverse event reporting and the “responsible person”
Taking a page out of the Dietary Supplement and Nonprescription Drug Consumer Protection Act of 2006, MoCRA requires serious adverse event reporting and defines what it means by a serious adverse event (see table); adverse events not described in the table are not required to be reported to FDA. Allergic responses are reportable, even though they may not reach the threshold effects described in the table.
MoCRA: Serious Adverse Event – is an adverse event that:
(A) results in:
death;
a life-threatening experience;
inpatient hospitalization;
a persistent or significant disability or incapacity;
a congenital anomaly or birth defect;
an infection; or
significant disfigurement (including serious and persistent rashes, second- or third-degree burns, significant hair loss, or persistent or significant alteration of appearance), other than as intended, under conditions of use that are customary or usual; or
(B) requires, based on reasonable medical judgment, medical or surgical intervention to prevent an outcome described in subparagraph (A).
MoCRA indicates the “responsible person” must submit a serious adverse event report to the FDA along with a label of the cosmetic product no later than 15 business days after the report is received by the responsible person. Further, as described in “New Medical Information”, if, within one year, there is any material medical information related to the original serious adverse event report, this must also be reported within 15 business days to FDA. Interestingly, the law dictates that all adverse event reports (not just serious adverse events) are maintained for a period of 6 years (for a small company this may only be 3 years).
A “gift” from MoCRA is a clear statement made in the law indicating that the serious adverse event report is not an admission of fault.
Ingredient listing
Each year, the “responsible person” must submit a list of ingredients used; these include the ingredients in fragrances, flavors (both of which were exempt from ingredient disclosure in the current regulation, 21CFR§701.3,) and colors, as well as the finished products in which these ingredients are used. The expectation is the ability to detect a “repeat offender” ingredient causing an adverse or allergic reaction whether in one or several products. However, this list of ingredients could also lead to ferreting out non-federally compliant flavor ingredients, or fragrance ingredients having been banned (e.g., musk ambrette), or improperly used colors (e.g., guaiazulene, henna, D&C Blue No. 4, or D&C Orange No. 10 used in the eye area or in lipstick). Because cosmetics include breath fresheners, a breath freshener containing the prohibited (synthetically derived) flavor ingredients benzophenone, ethyl acrylate, methyl eugenol myrcene, or pulegone, would likely receive an order to recall the product or, at the very least, a warning letter. While these synthetically derived flavor ingredients were banned because of the Delaney Amendment banning the addition of carcinogenic substances to foods, it is assumed that carcinogenic substances would be banned from applied cosmetics as well.
While the law is directed toward medium to large manufacturers, intuitively, the most likely to be affected by these bans or preclusions would be small manufacturers (i.e., those with less than an average of $1 MM over the last three years of business), as the result of inadequate regulatory support; however, these small manufacturers are exempt from ingredient listing unless the company manufacturers cosmetic products that (1) come into contact with the mucus membrane of the eye, (2) are injected, (3) are intended for internal use, and (4) are intended to alter the appearance for more than 24 hours and removal by the customer is not customary.
A low threshold for action by the FDA
The law provides the FDA with a low threshold (i.e., reasonable) for taking an action against an offending cosmetic in certain instances:
If the [FDA] has reasonable grounds to believe that an ingredient or combination of ingredients in a fragrance or flavor has caused or contributed to a serious adverse event required to be reported … the [FDA] may request in writing a list of such ingredients…
The [FDA] may suspend the registration of a facility if [FDA] determines that a cosmetic product manufactured or processed by a registered facility and distributed in the United States has a reasonable probability of causing serious adverse health consequences or death to humans and the [FDA] has a reasonable belief that other products manufactured or processed by the facility may be similarly affected…
If the [FDA] determines that there is a reasonable probability that a cosmetic is adulterated … or misbranded…and the use of or exposure to…and the use of or exposure to such cosmetic will cause serious adverse health consequences or death…and the [FDA] has a reasonable belief that other products…may be similarly affected…
In the third instance (above), the [FDA] is granted the power of mandatory recall authority, after first consulting with the responsible person, who is given the opportunity to voluntarily cease distribution and recall the offending product. The recall is much like the Class I recall of a food ingredient or product, with a public notification (including a press release) with an image of the product and ensuring this press release (with the product image) is also on the FDA website. Failing to voluntarily cease distribution and recall by the responsible person, within a time limit set by the [FDA], will result in the agency taking the action to recall the product and, in all probability, some enforcement action to prevent the distribution of the product.
Other mandates in MoCRA
Other mandates include Good Manufacturing Practices, registration of facilities, small business exemptions, and others.
Conclusion
The Modernization of Cosmetics Regulation Act (MoCRA) of 2022 is the most profound reformation of FDA cosmetics oversight since the 1938 Amendment of the 1906 Food and Drug Act, which was then appropriately re-named the “Food, Drug and Cosmetics Act”.
The mandates included in MoCRA are scheduled to take effect January 3, 2024, and the labeling changes shall take effect January 3, 2025 – what are you doing to prepare? Do you have access to safety data on your product constituents? Do you know where to look for information? Do you know how to determine what information is valid and what is trash? How do you present information in a persuasive manner – a data dump at FDA is not acceptable nor very convincing that you have confidence that you have shown “adequate substantiation of safety” to the new standard of “a reasonable certainty of no harm”.
Burdock Group has been preparing dossiers supporting the safe use of substances for over 30 years for a variety of clients.
Burdock Group has the experience, expertise, and infrastructure to get you ready for these sweeping reforms. We have five full-time and on-site Ph.D. toxicologists and two Research Associates to take on your projects. As evidence of our capabilities, we are proud to say that as a demonstration of our expertise, we are the most published safety and regulatory consultants in the US, if not the world. In fact, Dr. Burdock has published several editions of Fenaroli’s Handbook of Flavor Ingredients and the only edition of The Encyclopedia of Food and Color Additives both of which are often cited in cosmetics journals. We can help you get prepared to meet these new mandates – contact us now before we get flooded with requests from your competitors.
The Author
Dr. George Burdock is President of the safety and regulatory consulting company Burdock Group, in Orlando, FL. He holds a Ph.D. degree in toxicology, he is a Diplomate of the American Board of Toxicology, a Fellow of the Academy of Toxicological Sciences, and a Fellow of the American College of Nutrition. He was once the Manager of Biological Services for the Shulton Research Division of the American Cyanamide Corporation where he managed efficacy testing and the safety of an extensive catalog of personal products and was the Director of Scientific Affairs for the Flavor and Extract Manufacturers Association (FEMA) for five years.
This article on MoCRA constitutes our opinions or beliefs as we have determined them, based on facts obtained, as well as various suggested courses of action and the results that might be anticipated. Any statements are intended to be an expression of opinion only, based on information available to us at the time, and should not be construed as a promise, guarantee, or legal advice.