FDA Staff Gets Support for New Antiseptic Standards, but...

Larry Hand

September 04, 2014

A US Food and Drug Administration (FDA) advisory committee strongly supported FDA staff members' proposed new minimum safety data standards for antiseptics used by healthcare providers but stopped short of going along with recategorizing 3 highly common topical antiseptics.

Such an action would remove alcohol (ethanol), isopropyl alcohol, and iodine from the category of generally recognized as safe (GRAS; category 1) and put them in category 3 (insufficient data to classify).

Committee members, however, questioned why such a move is necessary, considering that the antiseptic ingredients have been used for decades and the FDA staff did not present evidence that chronic, repetitive use by healthcare providers was unsafe.

Such a reclassifying could be interpreted as a warning and leave the public at greater risk for potential infection by reducing handwashing compliance at healthcare centers, committee members said.

No such warnings are necessary, "until we know what they are and how they're going to be communicated," said committee chair Ruth M. Parker, MD, professor of medicine at Emory University Medical School in Atlanta, Georgia.

Meeting September 3, the FDA's Nonprescription Drugs Advisory Committee voted unanimously (12 to 0) to recommend that the staff members go ahead and propose new safety standards for 11 common over-the-counter healthcare antiseptic ingredients.

Five ingredients — alcohol, isopropyl alcohol, povidone-iodine, iodine tincture, and iodine aqueous solution — are classified as GRAS. (The committee generalized iodine for 3 of the 5 ingredients to arrive at the 3 common antiseptics mentioned earlier.)

Six ingredients — benzalkonium chloride, benzethonium chloride, chloroxylenol, hexylresorcinol, triclocarban, and triclosan — are category 3.

The substances are regulated according to the FDA's monograph process rather than under the agency's drug approval process. Under that process, over-the-counter drug products are subject to a "rule book," overseen by FDA staff and approved by the FDA commissioner, and are not subject to review and approval by the FDA overall.

Active Ingredients Only

In addition, regulation covers only how active ingredients are used and not subsequent marketed formulations. Active ingredients, once included in a monograph, can be combined with other ingredients to make a product.

At the committee meeting, FDA staff members said that since the products were initially classified as safe, new data have emerged, as well as more sophisticated scientific methods to test products. The 5 GRAS products mentioned earlier were included in a 1994 monograph. New proposed safety data standards, they said, are warranted even for commonly used products.

"Because these products are so ubiquitous, we tend to take them for granted," Theresa Michele, MD, director of the FDA's Division of Nonprescription Clinical Evaluation, told panel members. In addition, she said, the benefit/risk profile is different for these products because the benefit is provided to a different person (a patient) than the person taking the risk (a healthcare provider).

Staff members were asking committee members for advice only on safety, not efficacy, which proved to be another issue later in the day.

Staff members provided the panel with some of the data that have developed in more recent years, including:

  • indications that exposure to topical antiseptic ingredients may be greater than "previously thought";

  • studies showing blood alcohol levels after use of alcohol-based hand rubs or surgical hand rubs;

  • studies showing that triclosan gets absorbed through the skin and has been found in human breast milk and urine;

  • information suggesting that some healthcare antiseptics may have hormonal effects; and

  • new information pointing to possible concerns regarding how widespread use of these antiseptics may affect development of antimicrobial resistance mechanisms in common with antibiotics.

Staffers emphasized, however, that many other healthcare antiseptic ingredients have not been studied at all in a safety context and that large data gaps exist. In addition, most studies have only looked at short time frames, not long-term use as it applies to healthcare workers.

The staff proposed 4 broad categories of studies as "the minimum data FDA believes necessary to establish the safety of long-term, daily, repeated exposure to healthcare antiseptic active ingredients." The categories are human safety studies, nonclinical animal studies including toxicokinetics, studies to characterize hormonal effects, and studies to assess any effect on antimicrobial resistance.

Going Too Far?

Industry representatives voiced strong concerns at the meeting about the proposed new standards.

"Category 1 products could be called into question with no evidence to suggest a real risk," said Paul C. DeLeo, PhD, associate vice president of the American Cleaning Institute, Washington, DC. "Alcohol-based hand rubs have been used safely for decades on a global basis."

He said that healthcare antiseptics have a long history of safe use with no evidence of adverse effects, and that "a robust body of research supports their use."

Dr. DeLeo added that the FDA staff document presented to panel members "falls well short of the totality" of available evidence.

In addition to reducing the rate of hospital-acquired infections and mortality from those infections, hand rubs improve healthcare efficiency by saving nurses' time spent cleaning their hands, said William R. Jarvis, MD, a consultant in infection control. He cited a study that found that in a typical nurse's 8-hour day, soap and water handwashing could take up 56 minutes compared with 18 minutes of cleaning with hand rubs.

Industry representatives emphasized that patient safety could be highly jeopardized, particularly if any healthcare antiseptic products ended up being taken off the market.

FDA officials countered about the marketing, saying that the intent was to leave all products on the market as future testing took place. "We're not trying to take ingredients off the market," Dr. Michele said. "We're trying to set standards on what data are needed."

End of the Day

Although the panel members voted unanimously to recommend the new standards, they backed off quickly about the reclassifying of category 1 antiseptics, saying generally that enough information is available on those products to keep them classified as GRAS.

Panel member David J. Margolis, MD, PhD, professor of dermatology and epidemiology at the University of Pennsylvania Perelman School of Medicine, Philadelphia, said he "didn't hear any data today that there's a real safety issue.... It doesn't make sense to move them out of that category."

Dr. Parker, the committee chair, said she had difficulty only considering the safety aspect of the antiseptics and not considering safety and efficacy together. "I can't just care about the [safety], I care about the [efficacy] also. At the end of the day, the last thing I want to see is unintended consequences."

The committee members have disclosed no relevant financial relationships.

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