The applications for probiotics are increasingly expanding, causing the market for probiotics to grow significantly. New beneficial applications of probiotic microorganisms include effects on nutrient absorption, intestinal tract integrity, liver function and support of the immune system (Hemarajata and Versalovic, 2013). Although probiotic use originated from the consumption of fermented dairy products (e.g., yogurt), vegetables and other foods, recently probiotics are being found in dietary supplements, toothpastes and chewing gum. With such diverse beneficial applications for probiotics, and so many different options for product delivery, market possibilities for probiotics and probiotic-containing foods seem endless. However, in the United States, the World Health Organization’s seemingly simple definition of probiotics has resulted in a regulatory dilemma for probiotic products marketed with claims that fit this definition of a “probiotic." FDA has not yet established a formal definition for a “probiotic." The preclinical and clinical studies conducted to substantiate the “confer a health benefit on the host" statement, and the claims based on the findings of those studies, may classify the specified probiotic as either a dietary supplement, food or beverage, or even a drug, according to FDA and FTC, which together evaluate claims made on food and drugs.

Regulation Challenges

In the United States, there are numerous regulatory challenges and limitations for probiotics when marketed as a supplement, functional food or beverage, or drug. How the probiotic is regulated is influenced mainly by how the described benefit impacts the health of the person consuming the probiotic product. There are three main product categories where a probiotic is found, with different levels of regulatory compliance: (1) when added to food, a probiotic is considered a part of “food," with the corollary that a probiotic added to animal feed is considered a feed ingredient and therefore “food"; (2) a probiotic may be a dietary supplement ingredient; and (3) when administered to treat, prevent, cure or mitigate disease, or to competitively inhibit the growth of a pathogenic organism, the probiotic would be considered a drug (this applies to addition of the probiotic to either human or animal food) (Matulka, 2015).

Dietary supplements, by definition, are meant to “supplement the diet" in order to maintain a healthy body and mind, while foods are consumed “primarily for taste, aroma or nutritive value" (Nutrilab Inc. v. Schweiker, 713 F.2d 335, 338 [7th Cir. 1983]). “Functional food" is a term not recognized by FDA, but it suggests that certain foods provide benefits greater than those that fall under taste, aroma or nutritive value, such as fiber. Probiotics are one of those food ingredients that may be able to confer an extensive diversity of different health benefits, which may fall outside of the “maintenance" of the body or solely nutritive value. Does this automatically make probiotics drugs in the eyes of FDA and FTC? To state this question another way, do probiotics delivered in supplement or food form technically “fit" within the confines of the dietary supplement definition? To address this question, one must keep in mind that there are different types of claims that may be made for probiotics, which could promote the probiotic as either a dietary supplement or as a drug. The type of claim made on a supplement or drug product depends on the regulatory category of the delivery system for the probiotic; for example, claim statements on how a substance affects the normal structure or function of the body (i.e., a structure/function claim) may be made for probiotics as food ingredients or dietary supplement ingredients.

On the other hand, a probiotic stated to treat, prevent, cure or mitigate disease would be considered a new drug. The delineation between a structure/function claim and a drug claim may be minor in terms of verbiage used to express it, but substantial in terms of regulatory domain. As an example, the statement “helps maintain a healthy intestinal lining" may be considered an appropriate structure/function claim, while the claim “helps maintain a healthy intestinal lining for those with irritable bowel syndrome (IBS)" would be considered a drug claim, as IBS is a recognized disease in the ICD-10 codes.

The Importance of Substantiation

Not only must the claim for a dietary supplement or food meet the regulatory confines for a structure/function claim, but FTC (which has jurisdiction over the advertising of food, drugs and medical devices) states that the claim must also be truthful, not misleading, and substantiated with “competent and reliable scientific evidence." In recent months, the amount of evidence needed to substantiate claims for probiotic dietary supplements has been called into question through litigation between the U.S. Justice Department, on behalf of FTC and Bayer Corp. The agency stated that Bayer did not provide adequate scientific evidence to substantiate the claim for its probiotic product (i.e., when all probiotic bacteria were consumed in the same product) to help “defend against occasional constipation, diarrhea, and gas and bloating." FTC further stated that at least one randomized, well-controlled, double blind clinical trial (RCT) conducted with the actual product at the same level of proposed use was necessary to substantiate the claim, which is a significant deviation from current standards utilized to prepare a dossier that explains the scientific evidence substantiating a structure/function claim.

Will this specific request for an RCT for Bayer’s product become the new standard? Is an RCT on a probiotic product necessary to show efficacy and a reasonable expectation of safety (the regulatory requirement for dietary supplement ingredients)? Or, is there a better process to evaluate the safety and efficacy of probiotics, which would include the ability to make stronger claims for probiotics in food and dietary supplements without applying for drug status? Possible options have been suggested, but these would require a substantial shift in how probiotics are evaluated and approved, blending aspects of both the food ingredient approval and the drug approval processes, with FDA oversight.

Ray A. Matulka, Ph.D. is the director of toxicology at Burdock Group, bringing more than a decade of experience in the analysis of toxicity data and conducting safety and risk assessments. He earned a doctorate in toxicology from the Medical College of Virginia, and has post-doctoral experience at both Boston University School of Medicine and the University of North Carolina. He has industry experience at the Nebraska Dept. of Environmental Control and as a senior genetic toxicologist at Genesys Research in North Carolina. He is co-author of two book chapters and has authored 20 publications since obtaining his doctoral degree. Matulka has experience presenting information to FDA, USDA and EPA. Among other responsibilities, Matulka is accountable for the development of consumption analysis and reporting, and offers guidance in strategic scientific business planning and critical decision making to Burdock Group clients in the food ingredient, health and nutrition industries.

Looking for more information on Regulatory Issues around Probiotics?

Ray Matulka, Ph.D., will speak on “Defining Probiotics: The Regulatory Challenges of Classification" as part of the Probiotics Workshop at SupplySide West. The three-hour workshop will take place on Friday, Oct. 9, at Mandalay Bay in Las Vegas. Visit http://west.supplysideshow.com/workshops.aspx for the complete agenda and to get registered.