Probiotics in FDA's NDI Draft Guidance: Where Do We Stand?

Probiotics are a controversial point in FDA's NDI Draft Guidance. The new dietary ingredient (NDI) draft guidance document, when introduced by FDA in July 2011, became a cause of significant consternation in the dietary supplements industry. While the guidance is meant to clarify when an ingredient would require a NDI notification, under the Dietary Supplement Health and Education Act of 1994 (DSHEA), many industry members say that the guidance is vague in certain areas while being too specific in others. Concerns are especially high in the probiotics sector, for reasons discussed ahead, leaving manufacturers and marketers of probiotics worried that the guidance creates confusion and potentially serves to significantly hinder innovation and new developments in the field.

In the probiotics industry, the main reason for concern is this: While probiotics historically have been categorized under the umbrella of dietary supplements, the draft guidance emphasizes-albeit without mentioning probiotics by name-that “microbial ingredients in dietary supplements” which have never been consumed for food are unlikely to be considered dietary ingredients and would therefore require a NDI filing. And with those words, the guidance evoked industry concerns about potential confusion with respect to which microbial species and/or strains would qualify as dietary ingredients.

Other areas of concern revolve around the status of probiotics grown on innovative and uniquely selective culture media and whether these would require NDI notifications. Some state that FDA’s draft guidance indicates these would require separate NDI notifications. Leaders in the industry say that this would be unusually burdensome and not in keeping with the spirit of DSHEA or realities associated with the safe history of use of probiotics in general.

Tony Blanch, director of quality for Nutraceutix Inc. (Redmond, WA), a probiotics manufacturer, feels that under the current regulatory framework “generally available probiotic cultures that have been in the food supply should not be subject to the new dietary ingredient notification requirement.” Based on the guidelines in DSHEA for dietary ingredients, this makes sense. However, based on language in the draft guidance document and in subsequent conferences and webinars attended by FDA representatives, Blanch says that FDA is intent on finding reasons to negate this reasoning-either by suggesting that there are questions regarding the activity, identity, or safety of these organisms, or by suggesting that concentrations of these organisms in dietary supplements are much higher than the amounts present in foods.

He also questions what he feels is FDA’s position that bacterial identity and safety must be documented to the strain level, and that NDI notifications would be required down to the strain level. As Blanch continues, “This goes beyond the European Food Safety Authority’s (EFSA) recommendations, where a ‘qualified presumption of safety’ list is established and maintained for cultures properly identified to [be] genus and species used in foods.”

Industry concerns regarding the restriction of innovation and development if the draft guidance were to be implemented are echoed by Dr. Anurag Pande, vice president of scientific affairs at Sabinsa Corp. (East Windsor, NJ): “From a research and industry point of view, Sabinsa views the draft guidance as having a negative impact on future development of probiotics.” Dr. Pande emphasizes that it is important for FDA to recognize that probiotics are unique dietary supplements and should be treated as such. As an example of innovation that could be hindered as a result of the draft guidance, he says that the draft guidance in its present form would “negatively impact the research and development of new strains of bacteria, including those that are heat or acid resistant, which could severely limit food applications.”

Given these potential adverse impacts to innovation and research in the field, the decision by FDA to reconsider the draft guidance has been welcomed by industry players. The hope is that FDA takes these issues into consideration with any potential rewrite of the draft guidance, realizing the potential impact on innovation and new development within the industry.

Blanch from Nutraceutix would advocate that FDA take a risk-based approach to safety considerations. “The minimal risk associated with probiotics supplementation, and the good safety history of the entire industry segment, should be evidence that these products can be classed as a group and evaluated based on genus and species level identity for product marketing purposes.” He also says that the EFSA model of evaluation may be a good example: “Consideration of adopting the EFSA ‘qualified presumption of safety’ list or a similar evaluation process should be given to characterize probiotic food cultures as a general class rather than as new individual entities.”