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Focus on Regulation

Certain Antiseptic Ingredients No Longer GRAS/GRAE, Says FDA

FDA announced a final rule today determining that certain common ingredients, most notably triclosan and triclocarban, in over-the-counter consumer antiseptic washes are not generally recognized as safe and effective (GRAS/GRAE), and thus, can no longer be provisionally marketed under the OTC Drug Review. The final rule affects the status of antibacterial soaps, hand washes, and body washes containing these ingredients, which now must be the subject of an approved New Drug Application (NDA) or Abbreviated New Drug Application (ANDA) in order to be lawfully marketed in the United States.

Back in December 2013, FDA announced that it was revisiting the status of a number of ingredients commonly used in consumer antiseptic wash products. These products include hand washes and body washes that are intended for use with water and are rinsed off after use, such as antibacterial hand washes.  At that time, FDA stated that it was reconsidering the status of 22 ingredients commonly included in these products.  Today, FDA announces that 19 of these ingredients are not considered GRAS/GRAE when used in consumer antiseptic hand and body washes:

  • Cloflucarban
  • Fluorosalan
  • Hexachlorophene
  • Hexylresorcinol
  • Iodophors (Iodine-containing ingredients):
    • Iodine complex (ammonium ether sulfate and polyoxyethylene sorbitan monolaurate)
    • Iodine complex (phosphate ester of alkylaryloxy polyethylene glycol)
    • Nonylphenoxypoly (ethyleneoxy) ethanoliodine
    • Poloxamer—iodine complex
    • Providone-iodine 5 to 10 percent
    • Undecoylium chloride iodine complex
  • Methylbenzethonium chloride
  • Phenol (greater than 1.5 percent)
  • Phenol (less than 1.5 percent)
  • Secondary amyltricresols
  • Sodium oxychlorosene
  • Tribromsalan
  • Triclocarban
  • Triclosan
  • Triple dye

The remaining three ingredients are benzalkonimum chloride, benzethonium chloride, and chloroxylenol. FDA has deferred further rulemaking on these three active ingredients in response to several comments submitted to the public docket, and the promise from industry to conduct additional safety and efficacy data.  FDA intends to analyze the currently ongoing studies of these ingredients designed to address safety and efficacy data gaps before making a final determination concerning their status.

By its terms, the requirement for pre-approval before lawful marketing under the federal Food, Drug, & Cosmetic Act, which governs drug products in the United States, only applies to “new drugs.” New drugs are defined as drugs that were not marketed prior to 1938 and are not generally recognized as safe and effective among scientific experts. See 21 USC 321(p).  Thus, new drugs must be the subject of an NDA or an ANDA approved by FDA before they can be shipped in interstate commerce or marketed for sale. See 21 USC 355(a).  In 1972, FDA established the OTC Drug Review under which FDA publishes monographs that describe certain ingredients as GRAS/GRAE and establish the conditions under which the drug products can be sold in the US without preapproval.  While the agency is considering whether an ingredient is GRAS/GRAE for a specific use under the OTC Drug Review, the agency most often publishes a tentative final monograph which contains uses that may be GRAS/GRAE but about which it has not made a final determination.  FDA generally does not take enforcement action against products that are marketed without an approved application in conformity with a tentative final monograph.

The antiseptic hand and body washes that are the subject of today’s rule were being marketed under a tentative final monograph. FDA had issued this tentative final monograph in 1994 for OTC antiseptic drug products that included the ingredients listed above.  Thus, companies were permitted to manufacture and market consumer antiseptics with these ingredients in accord with the conditions set forth in the 1994 tentative final monograph.  Then, in December 2013, FDA announced that it was proposing to change the tentative GRAS/GRAE designation based on new data received and concerns raised related to systemic exposure to the ingredients and the long-term impact on the development of bacterial resistance. See 78 FR 76444, 76445 (Dec. 17, 2013).  At that time, FDA called for the submission of any additional safety or efficacy data for these ingredients to a public docket to determine whether long-term, daily, repeated exposure to these ingredients could be supported.  FDA considered approximately 40 comments from drug manufacturers, trade associations, academia, testing laboratories, consumer groups, and health professionals, and over 1,800 comments from individuals.  After evaluating the data and these comments, FDA determined that there was not sufficient data to determine that use of these ingredients provides additional benefit compared to washing with nonantibacterial soap and water.  It also did not find sufficient data to show that these ingredients are GRAS for this use, considering ongoing concerns with systemic exposure and an effect on the development of antibacterial-resistant bacteria.  As a result, FDA determined that these ingredients are not GRAS/GRAE for this use.

The result of this rule is that certain antibacterial hand soaps, hand washes, and body washes cannot continue to be lawfully marketed under the OTC drug review. To lawfully market drug products with the ingredients now determined to be non-monograph as an antiseptic wash, a company would need to obtain approval of an application demonstrating their safety and efficacy through clinical studies.  Notably, this rule covers only the use of these ingredients in OTC consumer antiseptic washes that are intended for use as either a hand wash or a body wash.  It does not cover other uses of the ingredients, including as health care antiseptics, consumer antiseptic rubs, first aid antiseptics, or antiseptics used by the food industry.  FDA has given marketers 1 year to come into compliance with today’s rule.  It remains to be seen whether marketers will reformulate their products, remove them from marketing, or try to develop sufficient data for FDA approval.  FDA approval is an expensive and time-consuming proposition, and companies may not find it in their interest to pursue an application.  The rule does not address whether these ingredients are appropriate for marketing in cosmetic products.

Hogan Lovells regularly counsels clients with issues in drug development, drug approval, drug labeling, and cosmetics marketing. We are available to assist our clients with the impact of this new rule.