A Tough Stain to Beat: Decades After Taking Enforcement Action Alleging “Drug” Status, FDA Says Most Peroxide Tooth Whiteners are “Cosmetics” (for Now)

April 24, 2014

By Kurt R. Karst –      

FDA’s recent denial of a November 2009 Citizen Petition (Docket No. FDA-2009-P-0566) submitted by the American Dental Association (“ADA”) requesting that the Agency “review and establish an appropriate regulatory classification” for the safe use of peroxide-containing tooth whiteners that lighten tooth color by chemical means caught our attention.  After all, the classification of tooth whiteners, such as the Rembrandt brand of bleaching tooth whiteners, as “drugs” or “cosmetics” has been an open issue for decades.  According to FDA’s petition response, however, the Agency has settled on a classification (at least for now): most peroxide-containing tooth whiteners are only “cosmetics” under the FDC Act until evidence points FDA into the “drug” direction as well.

Before we delve into FDA’s recent petition response, some legal and historical context is useful. . . . 

Under the FDC Act, a “drug” is defined (FDC Act § 201(g)(1)) to mean:

(A) articles recognized in the official United States Pharmacopoeia, official Homoeopathic Pharmacopoeia of the United States, or official National Formulary, or any supplement to any of them; and (B) articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals; and (C) articles (other than food) intended to affect the structure or any function of the body of man or other animals; and (D) articles intended for use as a component of any article specified in clause (A), (B), or (C).

A “new drug,” the marketing of which requires FDA approal of an application, is defined at FDC Act § 201(p) to mean:

(1) Any drug (except a new animal drug or an animal feed bearing or containing a new animal drug) the composition of which is such that such drug is not generally recognized, among experts qualified by scientific training and experience to evaluate the safety and effectiveness of drugs, as safe and effective for use under the conditions prescribed, recommended, or suggested in the labeling thereof, except that such a drug not so recognized shall not be deemed to be a “new drug” if at any time prior to June 25, 1938, it was subject to the Food and Drugs Act of June 30, 1906, as amended, and if at such time its labeling contained the same representations concerning the conditions of its use; or

(2) Any drug (except a new animal drug or an animal feed bearing or containing a new animal drug) the composition of which is such that such drug, as a result of investigations to determine its safety and effectiveness for use under such conditions, has become so recognized, but which has not, otherwise than in such investigations, been used to a material extent or for a material time under such conditions.

To fully determine “new drug” status, FDA initiated the OTC Drug Review, under which a product is not a “new drug” because it is generally recognized as safe, effective, and not misbranded when marketed in accordance with the conditions of an applicable monograph.  Several dental and oral hygiene categories of products were established under the OTC Drug Review.  Hydrogen peroxide is permitted as an active ingredient in certain amounts in OTC drug products under tentative monographs for oral antiseptics and antigingivitis/antiplaque agents.  

Finally, a “cosmetic,” the marketing of which does not require FDA’s preapproval but is subject to FDA regulation under 21 C.F.R. Part 700, is defined at FDC Act § 201(i) to mean:

(1) articles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body or any part thereof for cleansing, beautifying, promoting attractiveness, or altering the appearance, and (2) articles intended for use as a component of any such articles; except that such term shall not include soap.

Importantly, the definitions of “drug” (and, by extension, “new drug”) and “cosmetic” are not mutually exclusive.  A product can be either a “drug” or a “cosmetic,” or both.  A dual status product must meet all of the applicable requirements of both categories.  (As an aside, as we recently reported, the U.S. Court of Appeals for the Federal Circuit recently waded into the drug/cosmetic waters.)

Peroxide-containing tooth-whitening products made their debut in the 1980s.  By the early 1990s, FDA had begun to take interest in the products, and initiated enforcement action against one company, Den-Mat Corp., which marketed the Rembrandt brand of bleaching tooth whiteners.  In September 1991, FDA sent a Warning Letter to Den-Mat, saying that the company was marketing an unapproved new drug.  The Warning Letter, signed by former FDA Office of Compliance Director Daniel L. Michels, does not appear to be available on FDA’s website, so here are the relevant portions of the correspondence:

The agency is aware of several products that have been introduced onto the market bearing claims for the bleaching of teeth.  None of these products have been approved by the agency through the new drug (NDA) procedures nor have they been sanctioned by the agency under any other provisions of the Act.  The agency has completed an evaluation of these products that claim to whiten teeth through a bleaching process and concludes that, based on claims such as those cited above, “Rembrandt Lighten Bleaching Gel” is a drug under section 201(g) of the Federal Food, Drug, and Cosmetic Act.

Under the agency’s general regulatory policy governing OTC products during the pendency of the OTC Drug Review, OTC products may be permitted to be marketed without the risk of regulatory action provided:

1. The product or similarly formulated products were marketed as OTC drugs at the inception of the OTC Review (May 11, 1972), a date that was then extended to December 4, 1975 (21 CFR 330.13).

2. Such product does not constitute a hazard to health.

3. The product formulation is not regarded to be a prescription drug within the meaning of 503(b).

4. It is an OTC drug and does not bear claims for serious disease conditions that require the attention and supervision of a licensed practitioner.

The agency is not aware of any evidence that “Rembrandt Lighten Bleaching Gel,” or any similarly formulated and labeled product, has been commercially marketed within this country under the parameters of item #1 listed above.  Further, the agency is unaware of substantial evidence that “Rembrandt Lighten Bleaching Gel”  is generally recognized as safe and effective for use under the conditions prescribed, recommended or suggested in its labeling.  We, therefore, consider “Rembrandt Lighten Bleaching Gel” to be a new drug within the meaning of [FDC Act § 201(p)] which may not be legally introduced into interstate commerce under section 505(A) of the Act since no approval of an application filed pursuant to section 505(b) is effective for such drug.  The article of drug is misbranded within the meaning of section 502(a) in that it labeling is false and misleading by representing and suggesting that there is substantial scientific evidence to establish that bleaching agent.  The article of drug is further misbranded within the meaning of section 502(f)(1) of the Act in that its labeling fails to bear adequate directions for use for the conditions for which it is being offered; and, it is not exempt from this requirement under regulation 21 CFR 201.115 since it is an unapproved new drug.

Den-Mat ultimately sued FDA challenging the Agency’s classification of Rembrandt Lighten Bleaching Gel as a “drug” instead of as a “cosmetic.”  In April 1992, the U.S. District Court for the District of Maryland denied without prejudice FDA’s Motion to Dismiss the case, pending a further hearing to determine whether “the extent of the direct impact the FDA’s actions are having on Den-Mat constitutes enforcement of an agency determination.”  Den-Mat later withdrew its case after FDA agreed to review new information from the company and issue a determination as to whether that information would affect the Agency’s assessment that Rembrandt Lighten Bleaching Gel is a “new drug.”  Fast-forward 22 years and FDA still has not issued that determination.  But FDA’s April 2014 response to the ADA does address the lingering drug/cosmetic dispute.

According to FDA, “most peroxide-containing tooth whiteners would meet the definition of a cosmetic in the FD&C Act because they generally ‘are intended to be . . . applied to the human body or any part thereof for cleansing, beautifying, promoting attractiveness, or altering the appearance.’”  But their status as a “drug” (either prescription or OTC) is not fully known, says FDA, because “there is insufficient data to determine whether, as a group, peroxide-containing tooth whitening preparations that act by chemical means to lighten tooth color meet the definition of a drug.”

The Agency notes that there are different types of tooth stains – intrinsic (i.e., stains that occur within the enamel or dentin) and extrinsic (i.e., staining on the tooth surface) – and different causes of tooth stains – e.g., the presence of foreigh material within the enamel or dentin (intrinsic stains), and deposits from solid and liquid food substances, and tobacco (extrinsic stains).  As a result of these differences and others (e.g., different ingredient concentrations), says FDA, it’s difficult to characterize peroxide-containing tooth whitening preparations as a group.  “A better understanding of the mechanisms of action, conditions of use, safety, and formulation of specific peroxide-containing tooth whitener products is necessary to determine whether such products also meet the definition of a drug under the FD&C Act.” (Emphasis added)

In its Citizen Petition, the ADA makes a a lot of hay about potential safety concerns with peroxide-containing tooth whiteners, saying that such concerns create the need for heightened scrutiny and regulation of such products.  Among other things, the ADA alleges that there are risks of damage to mouth tissue, tooth structure and dental restorations, as well as risks related to the potential carcinogenicity of hydrogen peroxide.  But according to FDA, the available data are insufficient to raise safety concerns about the entire class of peroxide-containing tooth whiteners.  In light of that dearth and insufficiency of data to substantiate any safety concerns, FDA does not – at this time – find any basis to regulate peroxide-containing tooth whiteners as drugs under the FDC Act.  Of course, that could change if FDA, at a later date, gathers evidence on a particular product or the entire class of peroxide-containing tooth whiteners.

Probably the most important takeaway from FDA’s petition decision is the Agency’s proper recognition that the intended use of a product controls the regulatory status of that product under the FDC Act.