Here's The 'Rub' On Antiseptic Washes: FDA Wants Additional Safety, Efficacy Data
This article was originally published in The Tan Sheet & The Rose Sheet
Executive Summary
FDA says in a proposed rule that it currently does not intend to remove any products containing alcohol or benzalkonium from the market, but asks firms that want to continue marketing the products to submit additional GRAS/GRAE data on the ingredients.
The future of some OTC consumer antiseptic washes hangs in the balance as FDA requests data on ethyl alcohol, isopropyl alcohol and benzalkonium chloride used in products the agency calls "rubs."
In a proposed rule prepared for publication in the June 30 Federal Register, FDA says it currently does not intend to remove any products containing the ingredients from the market, but advises firms marketing the products under a section of the OTC antimicrobial monograph to submit additional data, including information on evaluating absorption, needed to confirm the ingredients' safety and effectiveness in light of emerging concerns.
FDA said it may consider removing the three ingredients from the OTC consumer topical antiseptic final monograph if it does not receive sufficient data to support findings of generally recognized as safe and generally recognized as effective (see additional coverage in this issue, (Also see "OTC Antiseptic Wash Industry Disputes FDA Cost Estimate For Proposed 'Rub' Monograph" - Pink Sheet, 5 Jul, 2016.).
The proposed rule for the first time differentiates consumer antiseptic products intended for use without water – called consumer antiseptic rubs or consumer rubs by FDA – from other OTC antiseptic washes not identified as "first aid antiseptics" in the OTC monograph and would establish an additional monograph for the products, which include "hand sanitizers" and wipes.
The rule also would establish new conditions under which active ingredients used in consumer antiseptic rubs are GRAS/GRAE based on FDA’s re-evaluation of the safety and effectiveness data requirements proposed in a 1994 tentative final monograph for OTC topical antiseptics.
FDA also points out in a June 27 statement it is particularly interested in additional data on the long-term safety of daily, repeated exposure to the ingredients by pregnant women and children (see chart at end of story).
Active ingredients were proposed for the 1994 TFM based on safety data FDA evaluated in its ongoing review of OTC antiseptic drug products, according to the proposed rule.
It's Complicated
However, the process since then has become more complicated by factors including a deadline for completing the monograph for consumer antiseptic rubs and certain other monographs for the active ingredient triclosan imposed in a consent decree settling a suit brought in 2010 by the National Resources Defense Council environmental advocacy group (Also see "Consent Decree Orders FDA Action On Triclosan OTC Monographs" - Pink Sheet, 5 Dec, 2013.).
For one, the 1994 TFM did not distinguish between rubs and products currently known as "antiseptic washes." Washes are rinsed off with water and include consumer hand and body washes, and health care personnel hand washes and surgical hand scrubs; rubs are intended to be used when soap and water are not available, sometimes are referred to as "leave-on products" and are not rinsed off after use.
"In light of more recent scientific developments and changes in the use patterns of these products, we are now proposing that additional safety data are necessary to support the safety of antiseptic active ingredients for this use," according to the proposed rule.
Additional information on the use of consumer antiseptic rubs also has complicated the process, FDA points out. Research the agency seeks includes in vitro data characterizing all consumer antiseptic rub active ingredients' antimicrobial properties and in vivo clinical simulation studies showing specified reductions in the amount of certain bacteria are achieved using the ingredients.
The proposal explains that ethanol or ethyl alcohol at 60% to 95% in the 1994 TFM was listed as "category I," meaning it was found to be safe and effective, but isopropyl alcohol at 70% to 91.3% was categorized as "IIIE" – additional data needed for efficacy, and the category for benzalkonium chloride was IIISE – additional data needed for safety and efficacy. However, each of the three is category IIISE in the proposal.
FDA also asks for parameters on product formulation and use which impact efficacy, including the number of times a day a product is used; the volume of product applied; and skin coverage achieved by the applied volume.
“We also need to understand the extent to which variability in product-related parameters must be reduced to ensure that products achieve the results expected based on their use of GRAE ingredients,” FDA says, noting the data it will receive will inform final formulation testing and labeling requirements.
The re-evaluation also follows input from four meetings of the Nonprescription Drugs Advisory Committee from 1997 through 2014 and comments from a public meeting in 2008 (Also see "Industry Groups Need FDA Input On Antibacterial Ingredient Studies" - Pink Sheet, 26 Jan, 2015.).
In the 1994 TFM, certain antiseptic active ingredients were proposed as GRAS for antiseptic rub use by consumers based on safety data evaluated by FDA as part of its ongoing review of OTC antiseptic drug products.
The latest proposal is part of a larger, ongoing review of OTC antiseptic active ingredients to ensure the substances under the monograph are safe and effective. The agency issued proposed rulemakings on consumer antiseptic washes in December 2013 and in health care antiseptics in April 2015, when it required additional safety and effectiveness data to demonstrate active ingredients are GRAS (Also see "Industry Roundup: Colgate, GNC, Sanofi, Pfizer Earnings" - Pink Sheet, 4 May, 2015.).
The agency also notes that due to "the complexity of this proposed rule," it is providing a 180-day comment period and will accept new data or information submitted to the docket within 12 months of publication; for another 60 days after that it will accept additional information.
"In addition, FDA will also consider requests to defer further rulemaking with respect to a specific active ingredient for use as a consumer antiseptic rub to allow the submission of new safety or effectiveness data to the record if these requests are submitted to the docket within the initial 180-day comment period," according to the proposed rule.
