Two dozen active ingredients are not generally recognized as safe and effective and may no longer be included in health care antiseptic products that are intended for use by health care professionals in hospital settings and other health care situations outside the hospital, the U.S. Food and Drug Administration announced in a final rule.
The affected products include health care personnel hand washes and hand rubs, surgical hand scrubs and hand rubs, and patient antiseptic skin preparations. The final rule was published Dec. 20 in the Federal Register and becomes effective in December 2018.
The agency determined that a deferral is warranted for six health care antiseptic active ingredients – benzalkonium chloride, benzethonium chloride, chloroxylenol, alcohol, isopropyl alcohol, and povidone-iodine – to allow more time for interested parties to complete the studies necessary to fill the safety and effectiveness data gaps identified for these ingredients.
“The FDA expects that this information may help better inform us on antiseptic resistance and antibiotic cross-resistance in the health care setting,” FDA Commissioner Scott Gottlieb, MD, said in a statement. “Importantly, this doesn’t mean that products containing these six ingredients are ineffective or unsafe. These antiseptic products remain an important resource in health care settings. Personnel should continue to use these products consistent with infection control guidelines while the additional data are gathered.”
No additional data was provided for another 24 products, which were deemed not generally recognized as safe and effective. The minimum data needed to demonstrate safety for all health care antiseptic active ingredients fall into four broad categories: human safety studies, nonclinical safety studies (developmental and reproductive toxicity studies and carcinogenicity studies), data to characterize potential hormonal effects, and data to evaluate the development of antimicrobial resistance, the final rule states.
The FDA noted that manufacturers started to remove nearly all of these 24 active ingredients from their products following a 2015 proposed rule. Triclosan is currently being used in available products.
The active ingredients affected are chlorhexidine gluconate; cloflucarban; fluorosalan; hexachlorophene; hexylresorcinol; iodophors (iodine-containing ingredients including iodine complex [ammonium ether sulfate and polyoxyethylene sorbitan monolaurate], iodine complex [phosphate ester of alkylaryloxy polyethylene glycol], iodine tincture USP, iodine topical solution USP, nonylphenoxypoly [ethyleneoxy] ethanoliodine, poloxamer–iodine complex, undecoylium chloride iodine complex); mercufenol chloride; methylbenzethonium chloride; phenol; secondary amyltricresols; sodium oxychlorosene; tribromsalan; triclocarban; triclosan; triple dye; combination of calomel, oxyquinoline benzoate, triethanolamine, and phenol derivative; and combination of mercufenol chloride and secondary amyltricresols in 50% alcohol.
If manufacturers want to use one or more of these 24 active ingredients in future OTC health care antiseptic drug products, those products will be considered new drugs for which a new drug application approval will be required, the agency said.
The rule does not affect health care antiseptics that are currently marketed under new drug applications and abbreviated new drug applications.
FDA’s action follows a similar final rule published Sept. 6, 2016, which removed triclosan and 18 other active ingredients from consumer antiseptic products.
