On September 6, 2016, the Food and Drug Administration (FDA) published a final rule on the use of certain active ingredients which were proposed for inclusion in the Over-The-Counter (OTC) Consumer antiseptic washes portion of the OTC Monograph. The products subject to this rule are hand and body washes that make antibacterial claims, and now according to the FDA, those that contain one of 19 active ingredients are making drug claims.
Under this final rule, the agency determined that the ingredients listed below are not considered safe and effective under the hand wash section of the OTC Antibacterial Monograph. Unless a manufacturer has an approved New Drug Application, the manufacturer can no longer make antibacterial claims based on the presence in the product of these ingredients. In order to provide the industry with a reasonable period for compliance, the FDA has provided a one-year grace period for manufacturers to comply. After this time, manufacturers using these 19 ingredients will have to discontinue their antibacterial claims or reformulate their products. Product shipped after September 5, 2017 will have to comply with this final rule.
The ingredients that have now been found to be non-Monograph compliant and can no longer be used in antibacterial wash products are the following:
- 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
- Povidone-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
- Triple dye
Notably, however, the FDA is in the process of evaluating additional data submitted by the manufacturers of three other ingredients, all of which are still under consideration for inclusion in the final Monograph for antiseptic hand washes:
- Benzalkonium chloride
- Benzethonium chloride
We will have to wait and see whether the data submitted by the manufacturers of these three remaining ingredients will prove sufficient. Until the agency makes a final determination, manufacturers of products containing these three ingredients can continue to market products under the Monograph.
This final rule on antibacterial hand washes is not a surprise. In 2013 as a result of litigation brought by an Activist group, the FDA announced in a notice of proposed rule-making that it would begin to require additional data to support all the ingredients proposed for inclusion in the Monograph. The request for data made at that time reflected a change in the FDA’s position regarding the nature of the data required to prove efficacy. The agency changed its standard from a bacterial kill standard to a requirement to prove clinical significance, through a showing of reduced infections. This required the submission of robust clinical data which was not submitted by the manufacturers of the 19 ingredients that have now been excluded from the Monograph. The FDA changed its position on the type of data required to support efficacy for these products because it found that the ingredients presented additional safety risks. Accordingly, the agency found that it was necessary to provide more definitive evidence of safety to address the potential hormonal effects and bacteria resistivity as well as demonstrate more definitive efficacy. The minimum data needed to demonstrate safety for all consumer antiseptic wash active ingredients falls into three broad categories: (1) safety data studies described in current FDA guidance (e.g., nonclinical and human pharmacokinetic studies, developmental and reproductive toxicity studies, and carcinogenicity studies); (2) data to characterize potential hormonal effects; and (3) data to evaluate the development of bacterial resistance. For efficacy, manufacturers must present studies that demonstrate a direct clinical benefit (i.e., a reduction of infection)—that the product is superior to washing with non-antibacterial soap and water in reducing infection (78 FR 76444 at 76450).
Although it is possible that the finality of this action could be challenged, such a challenge is unlikely given the current regulatory environment.
Another pending issue in the consumer antibacterial area is the Monograph’s finalization of alcohol rubs. We expect, however, that there will be no significant change in the actives or indications made for these products.