FDA Releases Updated NDI Guidance: Focus on Ingredient Identification & Detailed Submission Requirements

On October 19, 2026, the FDA simultaneously issued two NDI guidance documents to further refine the requirements for submitting New Dietary Ingredients (NDI) for dietary supplements. CIRS Group provides an in-depth analysis of the key changes in the guidance to assist companies in conducting NDI compliance assessments and filing submissions for the U.S. market.

Summary of Content

On October 19, 2026, the U.S. FDA released two NDI guidelines: one is the Final Guidance: “NDI Notification and Related Issues: NDI Identification and Safety Information”, which formally finalizes the “Identification Information, Historical Use, and Safety Evidence” section from the 2016 draft; the other is the updated and revised draft guidance, “Dietary Supplements: NDI Notification and Related Issues”, which replaces the August 2016 draft and the two revisions from 2024. The public comment period is 60 days following publication in the Federal Register.

Both guidance documents largely retain the main content of the previous 2016 draft, primarily refining the requirements for NDI submission materials and providing more detailed explanations regarding NDI identity determination and whether chemical changes have occurred.

Key Points and Major Changes

1. Regarding microbial and fermentation-derived ingredients

• Clarification of identity determination (Draft): The use of fermentation media different from those used in conventional food production (e.g., using a specific commercial medium to produce a strain traditionally fermented in milk) constitutes a “chemical change” and requires NDI notification. Similarly, altering agricultural or fermentation conditions to modify the composition (e.g., preparing selenium-enriched yeast using a sodium selenite medium) also constitutes a chemical change.
• Refined submission requirements (Final): Live microorganisms must be identified through whole-genome sequencing, among other methods. Reference strains must also be preserved. The FDA clarifies that each strain within the same species is considered a separate ingredient. Submissions must include information on the production strain; for strains modified through random mutagenesis or biotechnology, the modification process and characterization of the new strain must be described in detail. For the production process, the complete medium formulation and process parameters, harvest methods, and measures to prevent contamination by foreign microorganisms and genetic drift must be submitted. If the production strain is not inactivated or removed from the finished product, limit specifications must be established.
• One-size-fits-all regulation for pathogenic bacterial species (Final): For any species containing human pathogenic bacteria (such as Escherichia coli, Enterococcus faecalis, Enterococcus faecium, etc.), all strains are considered potentially hazardous and unsuitable for use as dietary ingredients.

Regarding Plant Extract Ingredients

• Clarification of identity determination (Draft): Extraction using solvents other than water and aqueous ethanol; the use of filtration, chromatography, or distillation steps; or the use of supercritical extraction; and the use of plant parts or growth stages different from those in conventional foods (e.g., immature vs. mature fruits, mycelium vs. fruiting bodies) are all considered “chemical alterations” and trigger an NDI submission. Furthermore, chemically synthesized plant ingredients do not meet the definition of a plant extract dietary ingredient.
• More detailed submission requirements (Final): Plant-derived ingredients must include the Latin binomial name and the specific medicinal part; extracts must specify the type and amount of solvent used, the concentration ratio (based on fresh weight/dry weight), the method for standardizing marker content across batches, and controls for residual solvents.

Other Key Points

Stricter requirements for historical dietary ingredient evidence (Draft): Evidence is limited to products marketed as dietary ingredients within the United States prior to October 15, 1994. Products marketed outside the United States or listed by industry associations cannot be considered as grounds for exemption from filing; written commercial records from the same period must be provided as proof.

More flexible safety evidence strategy (Final): A single notification may cover multiple products; however, a new submission is required if the maximum daily intake exceeds the previously assessed level, if blended ingredients are replaced, or if the target population is changed. The greater the discrepancy between historical usage data and the intended use, the more supplementary safety studies are required. Criteria for EDI/ADI ≤ 1 and methods for calculating the coefficient of uncertainty have been introduced. The submission of non-animal data, such as scientifically validated alternative methods, is encouraged.

Guidance for Companies

Using the two newly released NDI guidelines as a benchmark, companies are advised to review the compliance status of their existing ingredients. Particular attention should be paid to microbial and fermentation-derived ingredients (probiotics, proteins, enzyme preparations, and other fermentation products), as well as plant extracts obtained through new extraction processes, as these generally fall under the scope of NDI notification. Companies are advised to complete safety data as soon as possible and develop a strategic plan for notification.

What Can CIRS Do for You

Established in 2007, the CIRS Group is a leading product safety and regulatory consulting firm. CIRS has branch offices in the Republic of Ireland, South Korea, the United States, the United Kingdom, Japan, and China. CIRS Group utilizes its technical expertise, various resources, and international network to provide one-stop compliance services, from regulatory compliance, laboratory testing, and R&D to data services across multiple industries. This includes chemicals, cosmetics, food and food beverages, medical devices, agrochemical products, disinfectants, and consumer goods. It helps clients gain a competitive advantage by reducing business risks associated with regulatory affairs.

The vast majority of members in CIRS Food Business Division have over 10 years of professional experience in food compliance, with more than 80% holding Master’s or Doctoral degrees in food-related disciplines. The CIRS toxicology expert team consists of 24 Chinese Certified Toxicologists (DCST), 2 American Board Certified Toxicologists (DABT), and 1 European Registered Toxicologist (ERT). CIRS has provided one-stop food compliance services to over 1,000 domestic and international food and related enterprises. Leveraging its technical expertise, diverse resources, and global network, the CIRS Food Business Division offers global food compliance services, including but not limited to:

• Application for “Three New Foods (new food additives, new food raw materials and new food-related products” in China;
• U.S. GRAS, NDI, and CAP;
• EU Novel Food, food additives, and food enzymes applications; and
• Application for new feed ingredients and feed additives in China, the U.S., and the EU.

If you need any assistance or have any questions, please get in touch with us via service@cirs-group.com.

References:

1. NDI Notifications and Related Issues; Identity and Safety Information About the NDI (Final Guidance)

2. Draft Guidance: NDI Notifications and Related Issues (Draft Guidance)