Questions and Answers: FDA requests label changes and single-use packaging for some over-the-counter topical antiseptic products to decrease risk of infection

Q1. What are these over-the-counter (OTC) topical antiseptic skin preparation products used for?

A: OTC topical antiseptic skin preparation products are used across the United States every day to reduce the number of bacteria on the skin prior to surgery or injections. Health care professionals use them in hospitals. Consumers and caregivers also use these products, for example, to clean skin for insulin injections in diabetic patients and when they are preparing for outpatient surgery.

These products are marketed as solutions, swabs, pads saturated with a solution, and applicators containing a solution. Commonly used products contain isopropyl or ethyl alcohol, povidone iodine, poloxamer-iodine, benzalkonium chloride, benzethonium chloride, or chlorhexidine gluconate as a single agent or in combination with alcohol.

Some OTC topical antiseptic products are intended for one-time use only (single-use); others are intended for repeated use from the same container (multiple-use).

Q2. Why is FDA requesting these label changes for over-the-counter (OTC) topical antiseptics for preinjection or preoperative skin preparation products? 

A: FDA has been and continues to be vigilant about monitoring the safety of all the products it regulates. The request for labeling and package changes is the result of our ongoing evaluation of infrequent reports of infections resulting from use of these products. As part of our evaluation, FDA held a public meeting on December 12, 2012, to gather comments on how to address microbial contamination of antiseptic drug products indicated for preoperative or preinjection skin preparation. FDA also wrote an article to raise awareness of the issue, which was published in the New England Journal of Medicine.¹

Sporadic reports of patient infections associated with contaminated products are the reason FDA is moving forward to address this issue. Infections have occurred with the use of all of the commonly used antiseptic ingredients.

One goal of this action it to improve recognition that topical antiseptic products are not all sterile (meaning they have been treated with a process during manufacturing to eliminate all potential microorganisms) and that such a product could be the source of a bacterial infection. FDA hopes that health care professionals and consumers consider this possibility, and report patient infections that may be linked to contaminated preoperative and preinjection antiseptic skin preparation products.  

Q3. How does contamination of over-the-counter (OTC) topical antiseptics for preinjection or preoperative skin preparation products occur? 

A: Contamination of OTC topical antiseptics for preinjection or preoperative skin preparation may occur through two mechanisms:

• Intrinsic contamination occurs when microorganisms are introduced into a product during the manufacturing process. Cases of intrinsic contamination have been identified in which microorganisms have been isolated from pharmaceutical water supplies and nonsterile manufacturing environments. Once introduced into the product during manufacturing, these microorganisms may remain viable and multiply.
• Extrinsic contamination occurs when microorganisms are introduced in association with product use. For example products can become contaminated when diluted with nonsterile water, or transferred for storage into nonsterile containers.

Q4. How did FDA identify the sterility issue associated with over-the-counter (OTC) topical antiseptics for preinjection or preoperative skin preparation products?  

A: In recent years, there have been published reports linking outbreaks of infection to OTC topical antiseptics for preinjection or preoperative skin preparation that were contaminated with microorganisms and have led to product recalls (see specific data in the Drug Safety Communication on reports). FDA held a public hearing on this issue on December 12, 2012.

Q5. What does sterile mean? Sterile vs. nonsterile? 

A: Sterile means free of microorganisms (any microscopic organism such as bacteria). Sterile products are treated with a process during manufacturing to eliminate potential microorganisms. Over-the-counter (OTC) topical antiseptics for preinjection or preoperative skin preparation products are not required to be manufactured as sterile. If a product does not state “sterile” on the label, health care professionals should be aware that they are using a nonsterile product.

A product labeled as nonsterile does not mean the product is contaminated with microorganisms, but rather that its contents have not been sterilized, or treated with a process during manufacturing to eliminate potential microorganisms.

Q6. Should health care professionals and consumers stop using nonsterile over-the-counter (OTC) topical antiseptics for preinjection or preoperative skin preparation? 

A: No. However, FDA recommends  that practitioners and patients do not dilute the products; do not use the products after their expiration dates; and do not use products that have been sitting exposed in open containers.

Q7. Should nonsterile and/or non-single-use products be removed from the market or destroyed?  

A: FDA is encouraging companies to voluntarily adopt single-use packaging and to label their products as sterile or non-sterile.  FDA also wants health care professionals to be aware that OTC topical antiseptic products, if contaminated, pose a risk of infection and that particular microorganisms isolated from clinical specimens have been traced to the contamination of such products. FDA advises that the products be used as recommended on their labels.

Q8. Will these products be required to be manufactured as sterile?

A: FDA is currently not proposing a requirement that these products be manufactured as sterile, but will continue to monitor and evaluate risks associated with microbial contamination.

Q9. What advice does FDA have for health care professionals and consumers who use these products so frequently now? 

A: FDA considers OTC topical antiseptics for preinjection or preoperative skin preparation as safe and effective to reduce the number of bacteria on the skin prior to surgery or injections. To reduce the risk of infection, health care professionals and consumers should ensure the products are used properly according to the directions on the label.

FDA also recommends that OTC topical antiseptics used for preoperative and preinjection skin preparation be packaged in single-use containers. These single-use containers should only be used once and then thrown away. These products also should not be diluted after opening. Report side effects from topical antiseptics to the FDA MedWatch program at http://www.fda.gov/Safety/MedWatch/HowToReport/default.htm.

Footnote:

1. Chang CY, Furlong L-A. Microbial stowaways in topical antiseptic products. N Engl J Med 2012;367:2170-3.