Cosmeceuticals: myths and misconceptions

Clinics in Dermatology (2009) 27, 446–452 Department of Dermatology, St. Luke's Roosevelt Hospital Center, 1090 Amsterdam Avenue, Suite 11D, New York, NY 10025, USA Abstract Cosmeceuticals, or physiologically active cosmetics, are subject to many misconceptions.
Most consumers mistakenly believe that cosmeceuticals are regulated and tested as drugs. They alsobelieve that the ingredients and final products have been tested for safety and that the claims made inadvertisements are valid. Although cosmeceuticals and pharmaceutical ingredients have never beencloser together, their regulatory environments are vastly different due to the distinct Congressionalmandates given the Food and Drug Administration. Physicians are in a good position to help patientsand potential cosmeceutical users understand the benefits and realistic limitations of these products.
2009 Elsevier Inc. All rights reserved.
No market regulated by the United States (U.S.) Food and beyond the time of application. These definitions imply a Drug Administration (FDA) is more affected by fashion and physiologic or pharmacologic action.
whim than the cosmetic industry. The cosmetic market is big With the exception of tretinoin and tazarotene the products business, responsible for billions of dollars of consumer in this class are sold over-the-counter (OTC) and are spending in the United States aloneIt is subject to myths and regulated as cosmetics, not pharmaceuticals. The government misconceptions, in part because of aggressive and competitive does not recognize a separate “cosmeceutical” category. This marketing tactics. Implied claims of potency and effectiveness fact affects the type of product testing done, the format and can easily mislead the consumer and professional, alike.
substantiation of claims, and the language used in promotion The term “cosmeceutical” was coined in 1961 by of the products. Lack of awareness of this important issue Raymond Reed, founding member of the U.S. Society of among physicians, skin care professionals, and consumers Cosmetic Chemists.He originally conceived the word to has led to many misunderstandings about cosmeceuticals.
describe “active” and science-based cosmetics. The word and Some of the most common myths and misconceptions, all concept were further popularized by Dr Albert Kligman in the late 1970s, with the development of prescription-strengthtretinoin for the enhanced appearance of ultraviolet (UV) • Cosmeceuticals and cosmetics are regulated as drugs.
damaged and wrinkled skin. Common usage has expanded • Cosmeceutical claims in labeling and advertising are the definition to include “a cosmetic that has or is purported substantiated and approved before market.
to have medicinal properties.” The cosmetic industry uses the • Cosmetic ingredients undergo premarket testing and term to indicate those products that affect the health of skin or that have a sustained effect on the skin's appearance • Cosmetic ingredients undergo premarket testing and • “Natural” products are safer than synthetic.
⁎ Dermatology Consultants of Westchester, 2 Overhill Road, Scarsdale, • “Cruelty-free cosmetics” have had no animal testing, 0738-081X/$ – see front matter 2009 Elsevier Inc. All rights reserved.
doi: • Hypoallergenic means that the product has been tested were used to clean or change the appearance of the skin by to remove all allergenic materials and the product will be tolerated by the allergic or sensitive individual.
Congress specifically put more stringent controls on the manufacture and preparation of foods and drugs than on The following review of the history cosmetic regulation cosmetics because of the potential greater hazard from and the current regulatory framework will help to clarify ingestion of substances than from the application of products used for personal grooming or beautification. Through theFDCA and its amendments, the FDA was authorized toregulate aspects of cosmetic safety, manufacture, ingredients,labeling, and advertising. An overview of the current state of affairs of regulation of cosmetics follows.
Cosmetics were unregulated in the United States 80 years ago; however, the 16 cases of blindness associated with the use of Lash Lure Eyelash aniline dye in the 1930s impelledCongress to take action to protect the American public. Theresulting passage of the (Copeland-Lea) Federal Food, Drug, Product safety is difficult to ensure because the FDCA did and Cosmetic Act of 1938 (FDCA),set the regulatory not mandate premarket approval of cosmetics, which is in infrastructure for cosmetics, based on the prevailing knowl- sharp contrast to the tightly controlled marketing of drugs.
edge. It was modified in 1960 by the Color Additives Congress did not discuss how the FDA should ascertain and again in 1966 by the Fed. Fair Packaging cosmetic product safety; there are no defined measures for and Labeling Act,which set forth further FDA mandates.
safety testing. The FDA requires that if the product At the time that the Food, Drug, and Cosmetic Act was incorporates untested ingredients or if the final product is passed, not much was known about the normal physiology of untested, a safety warning must be placed on the products the skin, and far less was known about the effect of topically that states: “Warning—the safety of this product has not been applied hygienic or decorative products on the skin. Most of determined.”The actual types of testing, and the adequacy the study of the structure and function of skin was oriented and rigor of testing, are left to the discretion of the towards disease processes. Normal skin was viewed as having an almost “Saran Wrap” like function.
Today, we know much more about the function of healthy skin, partly because of the plethora of research conducted in cosmetic industry laboratories as well as from industrysupport of basic science investigations in university and The FDA is empowered to prevent adulteration and other institutional settings. We also now know that many misbranding of the product. To facilitate safe product cosmetics, formulated of ingredients “generally recognized manufacturing practice, because it has not been mandated as safe” (GRAS), certainly do affect the structure and to issue definitive regulations, the FDA has issued good function of skin and that there are many well-studied actives manufacturing practice (GMP) guidelines, which are pat- that offer more than just adornment or cleansing of the skin.
terned after the food GMP regulations. These guidelines state These factors, however, were not a consideration in 1938 that products must be prepared in a clean environment under when Congress defined the words, “drug” and “cosmetic” sanitary conditions and must not contain any poisonous, with a clear-cut distinction. According to the statutory filthy, putrid, decomposing, or otherwise deleterious sub- definition, drugs are “articles intended for use in the stances in order to avoid adulteration.
diagnosis, cure, mitigation, treatment or prevention of The FDA refers to both the Bacteriologic Analytical disease in man… and articles intended for use as a component Manual, published by the Association of Official Analytical of any such articles.” a Another part of the statutory drug Chemists, and the Cosmetic, Toiletry, and Fragrance definition states that any substance that is intended to alter Association (CTFA) guidelines for its guidance documents.
the structure or any function of the body of man (including Misbranding refers to misleading or incomplete information physiologic processes thereof) is also considered to fall on package labeling, improper labeling of ingredients, or Cosmetics are “articles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwiseapplied to the human body or any part thereof for cleansing, beautifying, promoting attractiveness, or altering the appear-ance and articles intended for use as a component of any such According to FDA guidelines, any component ingredient article, except that such term shall not include soap.” c Thus, may be used as long as it is “safe.” A precise review of drugs were used to treat and prevent disease, and cosmetics selected ingredients is done by the Cosmetic Ingredient Review (CIR) Expert Panel. The CIR was established by print and electronic advertising; the FDA regulates the the CTFA and the Consumer Federation of America in package labeling, which includes the product package, any 1976. The panel meets frequently to assess cosmetic insert and instructions, and the Web site, under certain ingredients in an unbiased, open, and expert manner, after circumstances, so there is considerable overlap. The FDA which the results are published. The review list is is mandated to prohibit “misbranding.” This means that prioritized by the extent to which the public is exposed the label must not be misleading or false, must contain the to the ingredient and its potential biologic activity.
accurate product identity and all the other labeling Thousands of ingredients are used in modern cosmetic information, and must not contain any nonapproved manufacturing that are GRAS substances, based on industry testing many years ago and historical Thus far, theCIR has only been able to definitively review hundreds ofthem. Ingredient safety remains an issue both in the United Some companies that promote their products as “cruelty-free” or “not tested on animals” do not display Today, cosmetics are regulated by the FDA's Center for the warning label that the safety of the product has not Food Safety and Applied Nutrition (CFSAN). OTC drugs been established. They either rely on the suppliers of that may also have a cosmetic function are regulated jointly ingredients or contract with outside laboratories to do the through the Center for Drug Evaluation and Research and animal testing. Others may use historical studies of similar CFSAN. CFSAN fulfills its broad responsibilities by issuing products, or may use the literature, raw material safety guidelines and performing field inspections, surveillance, testing, or perform clinical human safety testing to satisfy and registration of manufacturers through the Voluntary the safety Most raw materials used by these Cosmetic Registration Program, which registers the sites of companies were tested in animals years ago, which has manufacture as well as the formulation and raw material been recognized as the gold standard.
composition of the CFSAN also keeps product Unlike other ingredients, the FDA exerts strict regulatory experience reports, which are reported to the CFSAN control over coloring agents used in cosmetics as well as a Adverse Experience Reporting System. Much of its regula- small number of banned or restricted ingredients.Of all the tion of cosmetics involves postmarket enforcement because, ingredients in use, colors are the only ones that must be as has been emphasized, it does not have the premarket preapproved. All batches of petroleum-derived color addi- statutory authority to approve cosmetic products, cosmetic tives (except for hair dyes) must be tested and certified in the FDA Color Certification Branch Laboratories before being Time is allocated each year by the field staff for routine sold. Particular colors are approved for specific end uses, for inspections and investigations of the regulated products. The example, for coloring the final formulation vs making a resources devoted to its enforcement efforts are somewhat colored decorative cosmetic.Of particular note is that none limited, however, because of higher-priority obligations, including concerns about drugs, devices, biologics, fooddefense, and safety, Thus, the field offices are directed to inspect the cosmetic firms with the greatest potential forhealth hazard, such as producers of eye area products or Labeling laws were established to help the consumer those that have had past violations. Inspections may be make value and function comparisons. They were also triggered for other reasons, such as notification to the FDA of created to enable the consumer to avoid potential allergens.
a complaint or adverse event from a consumer, health Accurate labeling includes clear placement on the product professional, or industry. In addition, a voluntary recall of a label of its identity, the name and address of the product, ongoing compliance situations, and follow-up to manufacturer, the distributor, the quantity of the product product promotion or scientific studies, may all lead to an contained therein, and the ingredients listed in rank order, using specific nomenclature, to 1%. Trade secrets and Violators of the adulteration and misbranding provisions specific flavorings or fragrances are exempt from this and of the FDA may be subject to a variety of enforcement may be listed as “other ingredients” or may be listed in any tools, including formal correspondence such as warning order at concentrations of less than 1%. All safety warnings letters, which may be on the FDA Web site, and related to the use of the product must also be placed publication in the press, product recalls and seizures, targeted establishment inspections, and sampling pro-If a product has been misbranded or adulterated, the FDA may request a “voluntary recall.” The productmay be seized if there is a serious violation, and an Truthful advertising is coregulated by the Federal Trade injunction may be issued against further commercial Commission and the FDA. The FTC regulates operations. Rarely, criminal prosecution ensues.
Recent examples of warning letters on the FDA Web site The primary reason companies try to avoid a drug claim is include products that have been found to have bacterial economic. There are multiple regulatory interfaces within the contamination and incorrect ingredient listings. A well-known drug approval process and, in contrast, few hurdles in example of a seizure is case from the 1990s of Rio Hair Relaxer, imported from Brazil. It was removed from the U.S.
An example is the time and expense required to bring market because its use resulted in hair loss, severe dermatitis, Renova to the market. Its active ingredient, tretinoin, was and hair discoloration for more than 3000 peopl already legally marketed for decades as a treatment for acne Another, more complex case and recent seizure is that vulgaris (as Retin-A), with a well-established safety profile.
of Age Intervention Eyelash, manufactured by Jan Marini It took almost a decade and millions of dollars before the Skin Research, San Jose, California. The product, which approval was granted this drug for cosmetic use in wrinkle was promoted as a cosmetic that increased eyelash growth, smoothing and for treatment of tactile roughness, mottled contained bimatoprost, a prostaglandin analog drug that is hyperpigmentation, and correction of photodamage indica- FDA-approved to treat glaucoma. Bimatoprost has well tions. The important distinction is that although the product known side effects of darkening and lengthening lashes, was marketed for cosmetic “indications,” it was never the iris, and periocular skin. Potential side effects could also include compromised vision in those already receivingthe drug for medical purposes. It was seized by the FDAfor the unapproved use of a drug active ingredient (ie, asan adulterated cosmetic) as well as for misbranding because it was promoted to alter the structure of a tissuein the body.Subsequently, a bimatoprost solution product To legally market a drug, a manufacturer must submit to has received FDA approval for this same purpose, but as a the FDA a premarket application (PMA). The PMA includes drug, not a cosmetic. Studies were submitted to the FDA defined clinical studies documenting safety and efficacy for a with the rigor required for drug approval.
specific indication, with statistical significance (P b .025).
The efficacy is determined by a specified end point (eg,microbiologic cure, cancer remission), depending on theclass of drug.In contrast, no preapproval is necessary to market a cosmetic,and no predetermined end point isnecessary for efficacy or product claims.
Data now show that many cosmetic products, previously For a pharmaceutical drug, safety studies are required to thought to be inert, have an effect on the structure or function generally include animal, toxicology, pharmacokinetics, of skin. The classification of a product has tremendous pharmacology, drug-drug interaction, and other relevant ramifications on its production and marketing. In general, the data. In comparison, a cosmetic must be safe for intended FDA reviews the types of product claims made to determine use, but there is no definition of safety and there is great The FDA is guided by the intended use, which is inferred Another important aspect of marketing a product is its from promotional materials such as the labeling, advertise- label. A drug has extremely complex labeling requirements, ments, oral and written statements, and testimonials.These with an extensive package insert that includes a description can be used as evidence of drug intent, even if the of the chemical structure of the active ingredient, formula- manufacturer issues a disclaimer. In many cases, however, tion, strength, additives, clinical pharmacology, mechanism no clear line of differentiation exists between cosmetic and of action, indications for use, contraindications, precautions, drug claims. The cases are reviewed individually based on all warnings, adverse reactions, dosage, and forms. The of the involved facts, not on a simple phrase taken out of requirements for labeling of a cosmetic are well defined by context, but instead on how the product in total is labeled and regulation, but are far less complex, as previously noted.
promoted. This is similar to Supreme Court Justice Potter Pharmaceutical manufacturing facilities have a mandatory Stewart's statement regarding pornography, “I shall not registration and inspection requirement that may be repeated today attempt further to define the kinds of material I every 2 years. GMP regulations apply. The cosmetic facility understand to be embraced… but I know it when I see it.” should follow the GMP guidelines and should comply with Manufacturers have some latitude to engage in hyperbole the Voluntary Cosmetic Registration Program, but can expect and “creative” marketing about the benefits of the product, but they cannot engage in misrepresentation or impute All drug ingredients must be preapproved, including active physiologic or therapeutic properties to a product. If they ingredients and fillers, which are often from the GRAS list.
make physiologic (eg, disease prevention) or pharmacologic Any change in formulation must be reviewed by the FDA. This claims, they must then comply with the drug or device is clearly distinct from the cosmetic ingredient regulations, provisions of the FDCA. Most manufacturers would like to where a change in formulation is a matter of course—a prevent their products from being labeled “drugs.” business decision—and not reviewed with the FDA.
The FDA closely monitors the language of drug market- and in vitro systems is the inability to accurately ing claims to ensure that approved indications are correctly assess percutaneous penetration in humans. The promoted in advertisements and labeling. The adept drug claims obtained from these studies focus on manufacturer consults with the FDA before issuing labels and launching advertising because it understands the level of 3. Subjective assessment is generally a sensory regulatory scrutiny is high and the consequences are costly.
evaluation. It is valuable, because the consumer In contrast, cosmetics claims are seldom monitored and are may perceive changes before they are clinically only investigated if brought to the attention of the evident to the observer. Types of claims from this appropriate agency. There is no statutory mandate allowing testing include statements like “feels softer, the FDA to monitor performance advertisements and no smoother, looks more radiant” and also includes “appears to reduce the appearance of…” or “helps The time and cost for drug development are in sharp contrast to those of cosmetics. The average time for drug 4. Product formulation claims, such as “contains development is from 7 to 15 years from the laboratory to the X, contains 5% of aloe vera, more concentrated,” pharmacy shelf. The time for cosmetic development of a relate to the constituents of the product. Of breakthrough technology is 3 to 5 years. The average cost of course, the active ingredient must be stable in the research and development for a new drug is $800 million.
final formulation, able to penetrate the corneum, In contrast, the cost of creating and developing a break- and be biologically active at the target site for through cosmetic technology is between $2 and $3 million clinical benefits to ensue. The consumer may be (personal communication: Maria Corbiscello, January 22, unaware of the effectiveness of the ingredient in 2007 Studio MC2). The costs, time, and effort expenditures are why the drug classification is avoided by the cosmetic 5. Performance characteristics may be assessed with industry and why it actively works to prevent the imposition use tests such as the 28-day repeat insult patch test of further regulation of their products.
or open patch testing. These may generate claimssuch as “gentler,” “milder,” and “noncomedogenic.” “Unscented” is a straightforward performanceclaim. “Hypoallergenic” has no federal definition or standard and can mean whatever the manufac-turer wants it to Product claims are the cornerstone of effective marketing 6. Endorsement claims include testimonials by citi- in the cosmetic industry. To support their product perfor- zens and celebrities, “tested by dermatologists,” and mance claims, cosmetic companies rely on a variety of “developed by dermatologists.” Increasing numbers of physician named or associated brands arepromoted for the marketplace. Many of these 1. Clinical evaluation is meaningful when it is physicians are actually paid “spokesdoctors.” Pro- blinded, controlled, and when clinical grading is ducts are also labeled with various institutional “seal done by an expert, unbiased evaluator. “Antiwrin- kle,” “shinier hair,” and “smoother skin” are 7. Cultural claims include “100% natural ingredients” examples of the claims that may be made from 8. Superiority claims include “milder than…,” “more 2. Instrumental assessment can provide insights into soothing than.,” “more hydrating.” etc. The the mechanism of action of the product and can manufacturer must be prepared to substantiate the objectively measure its physiologic effects. Instru- mentation found in the industrial laboratory 9. Emotive claims such as “Because I'm worth it commonly includes techniques to determine trans- (L'Oreal)” or “you'll look like a million dollars” do epidermal water loss, barrier function, surface irregularities, wrinkle depth, skin firmness, elasti- 10. Preference claims should be documented with a city, and epidermal turnover. These tests are often performed in volunteers, but may include animal 11. Mind claims are a new area relating to how the and in vitro studies. The latter are interesting but product makes one feel. Some may consider them a have less real-world application. A limitation of subclass of subjective assessment claims, but they both in vivo and in vitro studies is that one cannot are based on innovative assessment tools, including do a placebo control. Because even bland sub- detailed questionnaires and instrumentation such as stances have an effect on the structure and function of skin, controls are generally obtained from the 12. “Puffery” claims are those which make fanciful or vehicle. A major limitation of both animal models outrageous claims.Puffery is a legal term that refers to promotional statements and claims that 2. Reed R. The definition of “cosmeceutical”. J Soc Cosmet Chem express subjective rather than objective views, such 3. Riordan T. Inventing beauty. New York: Broadway Books; 2004.
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also believe that “natural,” “cruelty-free,” and “hypoaller- genic” claims are truthful and substantiated. The reality is that 19. Federal Trade Commission Act, 15 U.S.C. §§45 and 55.
active cosmeceutical and pharmaceutical ingredients have 20. Federal Food, Drug, and Cosmetic Act (FDCA), 21 U.S.C. §362(a-(f)).
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