BOX 6-1FDA Draft Guidance on New Dietary Ingredients: Implications for Probiotics

FDA published draft guidance in July 2011 to help industry and other stakeholders understand when new dietary ingredients require pre-market notification and what those notifications should include. With respect to live microbial ingredients, here is what the guidance recommends for identity and safety. The italicized text is text that Levy highlighted during his presentation.

On identity, the guidance reads: “FDA considers each strain of a bacterial or yeast species to be a separate ingredient. You should explain how your strain was obtained and how it varies from other members of the same species. If your strain was genetically modified using either random mutagenesis or bioengineering, you should describe the process used and how you characterized the properties of the new strain.… You should include a complete description of the organism, including: the strain, methods used to establish the identity of the strain, such as identification by internationally recognized third-party repositories (e.g., the American Type Culture Collection), and the relationship of the strain to the strain(s) of the same species used to establish the history of use or other evidence of safety for the dietary ingredient.… For organisms that come from species or genera with pathogenic strains: Is there a consensus that there are valid scientific ways to distinguish between pathogenic and non-pathogenic members or to prevent horizontal transfer of genes for pathogenic traits?”

On safety, the guidance reads: “You should identify any human pathogens that are phylogenetically related to the microbial NDI at the species or genus level. You should identify any toxins, classes of toxins, or other deleterious substances known to be present in the same species or in a phylogenetically related family or genus. You should also document the absence (or the amount, if present) of such toxins or other deleterious substances in the NDI. You should document resistance to any clinically relevant antibiotics, and if applicable, the genetic nature of the resistance. If the microbial NDI is resistant to any clinically relevant antibiotics, it is also recommended that you perform an assessment of the ability of the antibiotic resistance genes to mobilize and transfer to human pathogens under the conditions of use of the dietary supplement.… If your notification cites the history of use of a live microorganism as evidence of safety, FDA recommends a careful assessment of the relative level of historical exposure compared to the proposed conditions of use of the NDI, including a discussion of how the form of the dietary supplement and any excipients used in it affect delivery of the NDI to various points in the human gastrointestinal tract.… If history of use data are inadequate to support the safety of the microbial NDI, you should include safety studies in humans or appropriate animal models in your notification. FDA considers pigs to be the most appropriate animal model for the human digestive tract. Human or animal safety studies should include measurements of the persistence of the organism in the body after administration, the ability of the organism to translocate outside of the gastrointestinal tract, and tolerance of the ingredient using the proposed serving form. Because this is a rapidly evolving scientific discipline, FDA recommends that notifiers be familiar with the state of the recent scientific literature at the time the notification is submitted.

SOURCE: FDA, 2011b.

From: 6, Societal and Policy Implications

Cover of The Human Microbiome, Diet, and Health
The Human Microbiome, Diet, and Health: Workshop Summary.
Institute of Medicine (US) Food Forum.
Washington (DC): National Academies Press (US); 2013.
Copyright © 2013, National Academy of Sciences.

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