Manufacturers may need to reformulate or re-label more than 2,000 OTC antibacterial soaps unless they can prove by December 2014 that the products are safe for long-term, frequent use and that they more effectively prevent illness than plain soap and water, FDA says.

The agency hopes to finalize a proposed rule by September 2016 to amend the tentative final monograph for OTC antiseptic drug products, establishing conditions under which OTC antimicrobial products used by consumers with water are generally recognized as safe and effective, said Sandra Kweder, Office of New Drugs deputy director in the Center for Drug Evaluation and Research, during a Dec. 16 media briefing.

To meet the deadline and determine “one way or another” if antibacterial soaps used by consumers with water are generally recognized as safe and effective (GRASE), the agency needs data and studies by December 2014 demonstrating ingredients’ safety and efficacy, Kweder said.

The proposed rule, if finalized, “would require manufacturers who want to continue marketing their products to provide the required data on the safety and effectiveness of these products to support an antibacterial claim, or reformulate their products by removing the antibacterial active ingredients and relabeling them by removing the antibacterial claim from the product’s labeling,” CDER Director Janet Woodcock said in a staff memo.

Even though the proposed rule, published Dec. 17 in the Federal Register, appears to impose a tight review timeline, rulemaking can take years, and until a rule is finalized, antibacterial products can stay on the market, FDA said.

“It is important to point out that these products are not being taken off the market,” and “consumers are encouraged to continue to wash their hands thoroughly – with or without these particular products – to prevent the spread of germs,” the Consumer Healthcare Products Association notes in a Dec. 18 email.

The proposed rule was mandated by a Nov. 21 consent decree as part of an FDA settlement with the Natural Resources Defense Council, which orders the agency to finalize its OTC topical antimicrobial drug products monograph Also see "Consent Decree Orders FDA Action On Triclosan OTC Monographs" - HBW Insight, 9 December, 2013..

Studies Needed To Confirm Claims

Kweder said FDA wants to raise the bar for establishing the safety and efficacy of OTC antiseptics because millions of U.S. consumers use the products daily and many believe they will help prevent the spread of disease. However, FDA does not have data demonstrating these products are any more effective at preventing illness than washing with plain soap and water, she said.

The American Cleaning Institute and the Personal Care Products Council said in a Dec. 16 release they “are perplexed that the agency would suggest there is no evidence that antibacterial soaps are beneficial, as industry has long provided data and information about the safety and efficacy of these products,” including a review of two dozen relevant published studies.

In addition, the trade groups say they previously submitted “in-depth data showing that antibacterial soaps are more effective at killing germs when compared to non-antibacterial soap.”

The organizations will submit comments to FDA reaffirming that use of antibiotic wash products in the home does not contribute to antibiotic or antibacterial resistance. They have referred previously to a study published in the International Journal of Microbiology Research that showed no statistically significant difference in antibiotic resistance to Staphylococcus isolates from skin washed with antibacterial products verses non-antibacterial products Also see "Triclosan Does Not Contribute To Antibacterial Resistance, New Study Says" - HBW Insight, 10 October, 2011..

New Efficacy Studies To Replace Outdated Tests

As industry scrambles to compile data, FDA says tests demonstrating that antibacterial soaps kill germs more effectively than non-antibacterial soap are not enough. According to the agency, data from clinical outcome studies demonstrating a reduction in infections are necessary to support efficacy for consumer antiseptic-wash active ingredients, according to the proposed rule.

This is a more rigorous standard than stated in the 1994 tentative final monograph, which proposed a clinical simulation standard that measured reduction in the number of bacteria removed from the skin after use. FDA says in the proposed rule that the amount of bacteria removed from the skin is a non-valid surrogate endpoint, and that a clinical outcome, such as reducing the number of infections, is needed.

“Data from these clinical outcome studies will help assure that any potential risk of consumer antiseptic washing products is balanced by a demonstrated clinical benefit,” according to the proposed rule.

This change would be consistent with recommendations a Nonprescription Drugs Advisory Committee made in 2005. The committee also said generalizing the effectiveness of products in a health-care setting to the consumer setting is not possible because of unaccounted-for risk factors and differences in the populations.

A silver lining to potentially requiring more stringent clinical outcome studies under the proposed amendment is that FDA officials “no longer believe that a demonstration of in vitro antiseptic activity against an extensive list of organisms is necessary,” the agency says in the proposal.

Rather, a “modified time-kill assay designed to provide an adequate assessment of how rapidly an anti-septic active ingredient produces a bactericidal effect and to estimate the antibacterial spectrum of an antiseptic active ingredient would be sufficient to characterize the in vitro antimicrobial activity,” FDA says. It lists nine reference strains for which this assay should test.

Additional Safety Data Needed

Additional safety data also are necessary to address emerging scientific information that suggests some antibacterial ingredients, such as triclosan, could pose health risks, including hormonal effects, and could contribute to increasing antibacterial resistance, Kweder noted. Triclosan is in about 93% of OTC antibacterial products.

In one example, the proposed rule notes triclosan is absorbed through the skin and has been found in human breast milk and urine at consistent levels in the U.S. population since sampling began in 2003, the consequences of which need to be assessed.

While triclosan is a common ingredient in popular products, it is not the only ingredient the proposed amendment would impact.

Because OTC antiseptic drug products are used by all populations throughout life, studies would need to look at the effects on sensitive populations, such as pregnant women and children, according to the proposed amendment. The proposal suggests the inclusion of animal studies on the pharmacokinetic, absorption, distribution, metabolism and excretion of the ingredient applied orally and dermally. Human pharmacokinetic studies should look at dermal administration under different conditions, and investigations into carcinogenicity, developmental toxicity and reproductive toxicity should be conducted.

New Bacterial Resistance Tests

Finally, the agency proposes adding bacterial-resistance tests to the list needed to establish safety. It suggests laboratory studies evaluating the impact of antiseptic active ingredients on human bacterial pathogens; the resident microflora of human skin, gut and oral cavity; food-related bacteria; and nonpathogenic organisms and opportunistic pathogens in the environment, like soil. If these show increased resistance, additional studies will be necessary, FDA says.

Ultimately, the agency’s objective in requiring such tests “is the same goal we have for most products,” Kweder asserted.

“If a company is making a claim that something is antibacterial, and in this case promoting the concept that consumers who use these products can prevent the spread of germs, then there ought to be appropriate data behind that.”

Rule Restricted To OTC Washes

The proposed rule only addresses use of the ingredients in consumer soaps regulated as drugs, FDA said Dec. 18 during a Twitter chat. It does not apply to antibacterial products used in health-care settings or antibacterial products that are used without water, such as wipes and hand sanitizing gels.

Nor does it apply to consumer soaps not regulated as drugs, FDA said during the Twitter chat. As a result, if firms opted to drop the antibacterial claim they could continue to use the ingredient in the product as long as it was no longer an OTC drug.

This apparent loophole that would allow the ingredient to remain in non-OTC consumer products has some clamoring for an outright ban of certain antibacterial ingredients.

In a Dec. 17 comment, the advocacy group Beyond Pesticides urges FDA to ban triclosan “given the availability of safer alternatives,” such as plain soap and water. The group made the same request in a 2010 petition to FDA and the Environmental Protection Agency.

Firms Already Reformulating

FDA’s Dec. 16 announcement sparked significant discussion about triclosan among consumers, who noted in comments on media stories, in blogs and via Twitter that they either plan on resorting to, or already seek, products without the antibacterial ingredient triclosan.

Several consumer product firms already are distancing themselves from the controversial ingredient. In August 2013, Procter & Gamble Co. announced it would remove triclosan from its products by 2014 even though it “is known to be safe,” because of the ongoing efficacy discussions around the ingredient compared with regular soap ([A#02130930001]).

Likewise, Johnson & Johnson said it would remove triclosan from personal-care products by the end of 2015 in response to consumer demand Also see "J&J To Remove Formaldehyde, Other Concerns From Personal-Care Items" - HBW Insight, 20 August, 2012..

FDA Says Antiseptics Need Testing Or Face Reformulation, Relabeling

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