In 2015 the U.S. Food and Drug Administration (FDA) proposed an amendment to 1994’s Tentative Final Monograph (TFM) which regulated healthcare antiseptics and topical antimicrobial drug products for over-the-counter human use. The proposed amendment considers the safety and effectiveness of healthcare antiseptics separately from topical antimicrobial drug products for over-the-counter human use. The reason for this distinction is that health care workers are systemically exposed to antiseptics more frequently than the average consumer. Furthermore, the risks of infections with serious outcomes are different in a healthcare setting rather than a consumer setting. As per this new guidance document health care personnel hand wash and rubs, surgical hand scrubs and rubs, and patient preoperative skin preparations are categorized as healthcare antiseptics.

Like the 1994 TFM, the 2015 proposed amendment to the TFM uses the concepts of generally recognized as effective and safe (GRAE/GRAS) to determine if antiseptics are to be placed on the market. The folloring criteria are used by the FDA to determine if an active ingredient meets the criteria to be categorized as GRAE/GRAS.


Like the 1994 TFM, log10 reductions in microorganisms at the test site remain the industry standard for determining if an active ingredient is GRAE. In the tentative final monogrpah the FDA acknowledges that clinical outcome trials would be a preferred method to measure product efficacy, however the number of confounding factors and the ethical concerns of clinical outcome trials make this a nearly impossible feat. In the proposed amendment to the TFM, the FDA has changed its success criteria to be more stringent for log reductions to determine if an active ingredient is GRAE. This FDA guidance also points out the following study design elements, which they consider critical to the scientific interigty of topical antiseptic testing:

  • A vehicle control
  • An active control
  • A large enough sample size
  • 70% success rate (i.e. 70% responder rate)
  • Neutralization verification
  • Two- sided test for superiority and 95% confidence intervals


New scientific developments have allowed us to more accurately measure how active ingredients in antiseptic drug products affect the human body. One major concern that motivated the amendment of the Tentative Final Monograph was that pre-existing data on the effects of long term or systemic exposure may no longer be accurate. Another concern that the FDA has is that wide spread use of antiseptics in healthcare settings could lead to antimicrobial resistance in microorganisms. Now, the FDA is proposing the following four types of tests be performed to classify antiseptic active ingredients as generally recognized as safe (GRAS):

  • Human safety studies (e.g. maximal use trials, or MUsT trials)
  • Nonclinical safety studies (e.g. developmental and reproductive toxicity and carcinogenicity studies)
  • Data to characterize potential hormonal effects
  • Data to evaluate potential antimicrobial resistance

Benefit-to-Risk Ratio

To determine that an active ingredient in an antiseptic product is GRAE and GRAS, the FDA considers its benefit-to-risk ratio. For example, the FDA has evidence that despite claims, antimicrobial soap may not be significantly more effective at removing bacteria from hands than non-antimicrobial soap and water alone. However, it has also been shown that disinfecting hands and tools in a healthcare setting lowers infections rates, and is an important component to hospital safety. This is one reason why more efficacy data is needed to show that antiseptic active ingredients are GRAE/GRAS. Additionally, the risk that widespread use of antiseptics in healthcare settings could lead to antimicrobial resistance in microorganisms must be examined closely and weighed against the benefit that using antiseptic products brings. 

This proposed amendment currently remains tentative and is expected to become final in the fourth quarter 2017 or first quarter 2018.

Vivo Clinical Testing Is:

An FDA GLP and GCP-compliant testing organization staffed by skilled, experienced microbiologists and subject recruiters.  Vivo can help speed your project to completion.

Quick Contact