This article discusses the US Food and Drug Administration's (FDA's) revised draft guidance, Dietary Supplements: New Dietary Ingredient Notifications and Related Issues, and its potential impact on the regulatory status of probiotic ingredients. It outlines the opportunities for probiotics as medical foods, as well as the potential regulatory challenges associated with this category. The author encourages probiotics manufacturing companies to engage in 'self-regulatory initiatives.'
"Probiotics," defined as live microorganisms which, when administered in adequate amounts, confer a health benefit on the host,1 are one of the fastest growing segments of the dietary supplement industry. With the rise in popularity of probiotics comes an influx of products to the dietary supplement marketplace and a concomitant exploration of categories outside of the supplement space. Consequently, given the unique characteristics of probiotics, there are many regulatory considerations that both new and existing manufacturers and marketers of probiotics should keep in mind.
Implications of the Revised Draft New Dietary Ingredient Guidance
In August 2016, the US FDA issued the revised draft New Dietary Ingredient (NDI) guidance taking into consideration stakeholder comments on the original draft guidance from 2011.2 The revised draft guidance offers FDA's views on "live microbial organisms" used in dietary supplements. Specifically, the agency indicated that, "Bacteria that have never been consumed as food are unlikely to be dietary ingredients," raising questions regarding the regulatory status of innovative probiotic strains not isolated from food.
FDA's interpretation of "chemical alteration" in the revised draft guidance also could impact probiotics. Under the Dietary Supplement Health and Education Act (DSHEA), an NDI is exempt from notification requirements if the ingredient is present in the food supply in a form that has not been chemically altered.3 In the revised draft guidance FDA said changes in the fermentation media used to make conventional foods are a process that results in chemical alteration, triggering the requirement for an NDI notification. Applying this interpretation of chemical alteration would have a large impact on the probiotics industry because changing media components is a common practice undertaken to improve yield and increase stability, among other things, without impacting the genetic identity of the organism.
Probiotic manufacturers should pay close attention to how these issues are addressed in the final NDI guidance. To date, there has been no indication of when the agency plans to finalize the document.
Probiotics as Medical Foods
In addition to dietary supplements, there may be opportunities for probiotics as medical foods. Although both categories, unlike drugs, are prohibited from being marketed for treating, diagnosing, preventing, or curing diseases, the medical food category allows for the benefits of food products intended for the 'dietary management of a disease or medical condition' to be communicated, hence providing opportunities not available to dietary supplements. Conditions related to the digestive system, such as inflammatory bowel disease, are potential targets for probiotic medical foods.
However, FDA has already indicated in a previous warning letter on a product marketed as a medical food for patients with inflammatory bowel conditions and/or inflammatory bowel disease that it "is not aware of any distinctive nutritional requirement for patients with inflammatory bowel conditions or inflammatory bowel disease."4 FDA concluded, "Because these products are intended to support diseases or conditions that do not have distinct requirements for certain nutrients, these products do not meet the statutory definition or regulatory criterion for medical foods."5 Based on FDA's narrow interpretation of what qualifies as a medical food,6 this route to market may pose regulatory challenges for the probiotics industry.
Self-regulatory initiatives, such as industry-developed guidelines, play an important role in complementing the existing regulatory framework. They also help industry operate responsibly in areas lacking regulatory clarity and demonstrate industry's commitment to responsible, consumer-focused behavior. In January 2017, the Council for Responsible Nutrition (CRN) and the International Probiotics Association (IPA) announced the development of scientifically-based best practices guidelines for the labeling, storing, and stability testing of dietary supplements and functional foods containing probiotics.7 These guidelines were designed to facilitate transparency and consistency in the probiotic sector.
A key element of the guidelines is the recommendation to label probiotic products in Colony Forming Units (CFUs), the scientifically accepted unit of measure for probiotics and used to report probiotic quantity in many studies conducted to assess the safety or benefits of probiotics. Consistent with scientific literature, CFUs are commonly used on probiotic product labels in many jurisdictions around the world to help consumers and healthcare professionals identify products providing probiotics in amounts shown to have benefit. However, US regulations require dietary ingredients (with the exception of some vitamins) be labeled by weight. Labeling probiotic quantity by weight is not meaningful because weight does not indicate the viability of the microorganisms in the product throughout shelf life. To the contrary, CFUs are more representative of the quantity of viable microorganisms and gives consumers and healthcare professionals accurate information.
In addition to the recommendations for labeling quantity in CFUs in the best practices guidelines, IPA recently submitted a citizen's petition to FDA requesting the dietary supplement labeling regulations (21 CFR 101.36) be amended to require the quantitative amount of probiotic ingredients in a dietary supplement to be presented in CFUs instead of by weight.8 CRN voiced support for this petition in comments to the agency, requesting FDA exercise immediate enforcement discretion on dietary supplements containing probiotics that declare probiotic quantity in CFUs instead of weight on the product label.9
Best practices guidelines address additional labeling considerations and provide stability testing and storage recommendations encouraging manufacturers to consider individual formulations, packaging, and storage environments. These recommended practices in the guidelines promote transparency and help ensure that probiotic products contain the labeled amount through the end of the stated shelf life.
As the probiotics sector continues to grow, manufacturers and marketers should pay close attention to regulatory developments affecting existing products as well as products in the pipeline. Companies also should be engaged in self-regulatory initiatives to demonstrate industry's dedication to transparency and consistency, thus increasing the trust and confidence consumers have in probiotic products.
- Joint FAO/WHO Expert Consultation on Evaluation of Health and Nutritional Properties of Probiotics in Food including Powder Milk with Live Lactic Acid Bacteria. (2001). Health and Nutritional Properties of Probiotics in Food Including Powder Milk With Live Lactic Acid Bacteria. ftp://ftp.fao.org/docrep/fao/009/a0512e/a0512e00.pdf. Accessed 10 October 2017.
- Dietary Supplements: New Dietary Ingredient Notifications and Related Issues: Guidance for Industry, August 2016. FDA website. http://www.fda.gov/downloads/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/UCM515733.pdf. Accessed 10 October 2017.
- Dietary Supplement Health and Education Act of 1994 (Public Law 103-417, 103rd Congress).
- Warning letter to Metagenics, Inc. 13 August 2013. https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm367142.htm. Accessed 10 October 2017.
- CRN-IPA Best Practices Guidelines for Probiotics. https://www.crnusa.org/sites/default/files/pdfs/CRN-IPA-Best-Practices-Guidelines-for-Probiotics.pdf. Accessed 10 October 2017.
- Giordano-Schaefer, J., Ruthsatz, M. and Schneider H. "Distinctive regulatory barriers for the development of medical foods." Regulatory Focus. October 2017. Regulatory Affairs Professionals Society.
- Citizen Petition from International Probiotics Association. Docket ID: FDA-2016-P-3968-0001. https://www.regulations.gov/document?D=FDA-2016-P-3968-0001. Accessed 10 October 2017.
- Comment from Council for Responsible Nutrition. Docket ID: FDA-2016-P-3968-0028. https://www.regulations.gov/document?D=FDA-2016-P-3968-0028. Accessed 10 October 2017.
About the Author
Andrea Wong, PhD, is vice president, scientific and regulatory affairs for the Council for Responsible Nutrition (CRN). Wong is an integral part of CRN's science and regulatory affairs department, responding to emerging regulatory issues as well as advocating for science-based nutrition. Wong provides scientific expertise in evaluating research relevant to the benefits and safety of ingredients and dietary supplements, and in support of CRN's nutrition policy activities. She also leads proactive self-regulatory initiatives, including the development of best practices guidelines for industry on product labeling and formulation. Wong earned her PhD in toxicology from the University of Toronto. She may be contacted at firstname.lastname@example.org.
Cite as: Wong, A. "The US Regulatory Environment for Probiotics in Food." Regulatory Focus. October 2017. Regulatory Affairs Professionals Society.