FDA Finalizes Additional Sections of New Dietary Ingredient Notification Guidance, Yet Significant Questions Remain

On October 19, 2026, the U.S. Food and Drug Administration (FDA) issued final guidance for industry, New Dietary Ingredient (NDI) Notifications and Related Issues; Identity and Safety Information About the NDI (Final Identity Guidance), which finalizes certain portions of its August 2016 revised draft guidance, Dietary Supplements: New Dietary Ingredient Notifications and Related Issues (2016 Draft Guidance).¹ FDA also updated the 2016 Draft Guidance to reflect which segments are in final form and which remain — since 2011 — in draft form. This piecemeal approach to finalizing a guidance is highly unusual and leaves stakeholders in a wait-and-see posture with regard to the most contentious issues in the 2016 Draft Guidance.

While the Final Identity Guidance provides useful, updated recommendations concerning FDA expectations regarding identity and safety information in a New Dietary Ingredient Notification (NDINs), critical questions remain.

What the October 2026 Final Identity Guidance Addresses

While not establishing new requirements, the Final Identity Guidance provides more detailed recommendations concerning the identity and safety information that the agency expects in an NDIN and offers some indication that FDA is preparing to address the remaining issues. In particular, FDA provides the following input regarding identity, manufacturing, and analytical documentation:

• Identity verification: The Final Identity Guidance offers recommendations for analytical methods, data, and calculations to verify NDI identity, along with examples of supporting data to demonstrate conformance with identity specifications.
• Manufacturing and ingredient characterization: Notably, the Final Identity Guidance provides additional examples of manufacturing information relevant to identity and safety — in a manner that would position FDA to make determinations about whether a substance is chemically altered. Thus, FDA requests information including extraction methods and solvents, process parameters, concentration and drying steps, the physical form of the final NDI, standardization procedures to ensure consistent potency and composition across batches, and filtration or purification steps to remove undesirable components. FDA also provides detail concerning in-process manufacturing controls, quality measurements, and analytical methods as well as examples of supporting documentation suggested for certain ingredients, including salts, covalently modified derivatives, and live microbial ingredients.
• Safety narratives: The Final Identity Guidance replaces the 2016 Draft Guidance’s recommendation for two separate safety profiles with a single comprehensive safety narrative explaining how the available evidence supports a reasonable expectation of safety, while largely retaining the underlying safety information recommendations, including where safety evidence concerns related but nonidentical ingredients or combinations of NDIs.

The Final Identity Guidance also provides additional detail and some flexibility about the evidence that could support a history of safe use, including qualifying FDA’s longstanding recommendation of 25 years of widespread use and recommending additional evidence to address gaps between traditional medicinal and proposed uses, revised from the 2016 Draft Guidance recommendation that such evidence is “almost always needed.” FDA also expands its discussion of new approach methodologies (NAMs), along with in vitro assays and in silico modeling, which may support safety determinations and reduce, refine, or replace animal testing, while stating that such methods generally may not be sufficient on their own. In this context, the Final Identity Guidance updates safety recommendations for nonviable microbial ingredients and ingredients involving nanotechnology. It also provides further clarification concerning safety calculations, including the selection of no-observed-adverse-effect levels (NOAELs) and calculations of margins of safety.

The net takeaway for stakeholders preparing NDIN submissions is that the Final Identity Guidance provides some clarity regarding FDA’s expectations for identity and recognizes advances in scientific methodologies and safety assessment approaches that have emerged over the past decade; however, it leaves uncertainty regarding the type and extent of safety evidence FDA will consider sufficient to establish a reasonable expectation of safety.

Remaining Issues in FDA’s Draft NDI Guidance

Critical sections of the 2016 Draft Guidance have not yet been addressed by FDA. These include:

• FDA’s recommendations concerning what qualifies as a dietary ingredient or NDI under Section 201(ff)(1)(E);
• FDA’s position on recognition of dietary ingredients marketed before October 15, 1994, and documentation of their historical marketing;
• further explanation of when an NDIN is required and applicable exceptions, including for NDIs with a history of use in conventional food, and what constitutes chemical alteration such that an NDIN may not be needed;
• clarity on who must submit an NDIN and when separate notifications are required for dietary supplements containing the same NDI; and
• dietary ingredient eligibility and related restrictions, including synthetically produced substances, chemically modified ingredients, and ingredients approved or investigated as drugs or licensed as biologics.

As noted in the Final Identity Guidance, FDA has indicated it intends to prioritize finalizing the remaining portions as it completes its review and analysis. However, 10 years on, the timing of such finalization remains unclear.

Background and History of FDA’s NDI Guidance

The NDIN requirement was added to the Federal Food, Drug, and Cosmetic Act by the Dietary Supplement Health and Education Act of 1994 (DSHEA) and requires a safety notification for dietary ingredients that are new to the market. Pursuant to the statute, dietary ingredients marketed in the United States before October 15, 1994, are not “new” dietary ingredients and are exempt from the notification requirement. DSHEA also provides an exemption for dietary ingredients present in the food supply as articles used for food in a form that has not been chemically altered. See 21 U.S.C. § 350b.

On July 5, 2011, FDA issued its first draft guidance, Dietary Supplements: New Dietary Ingredient Notifications and Related Issues. The 2011 draft set out FDA’s views on what qualifies as an NDI, when an NDIN is required, the procedures for submission, and the data and information relevant to evaluating safety. FDA received significant comments from industry and other stakeholders objecting to the agency’s take on dietary ingredient eligibility, recognition of pre-DSHEA ingredients, chemical alteration, and notification requirements.

Following extensive meetings with industry and stakeholders on these issues, on August 12, 2016, FDA issued the 2016 Draft Guidance revising the 2011 guidance and explaining its thinking on certain critical issues. FDA received significant feedback on the 2016 Draft Guidance as well, including a range of industry concerns around exemptions from the NDI notification, along with expectations around grandfathered products and other critical issues. FDA promised to consider these and issue a revised version of the guidance.

FDA’s Approach to Finalizing the Guidance

Instead of addressing this feedback comprehensively, as is typical in FDA practice, the agency has issued revised draft and final portions its 2016 NDI Guidance in an incremental fashion. These publications include the following:

• May 20, 2022 — Enforcement Discretion (draft). FDA issued Draft Guidance for industry: Policy Regarding Certain New Dietary Ingredients and Dietary Supplements Subject to the Requirement for Pre-Market Notification, describing its intent to exercise enforcement discretion for a limited time and in limited circumstances regarding past failures to submit required NDINs.
• March 5, 2024 — Procedures and Timeframes (final). FDA issued Guidance for Industry: Dietary Supplements: New Dietary Ingredient Notification Procedures and Timeframes, addressing frequently asked questions about the submission and review process, primarily procedural and administrative matters.
• April 4, 2024 — Master Files (draft). FDA issued Draft Guidance for Industry: New Dietary Ingredient Notification Master Files for Dietary Supplements, addressing submission and use of Master Files containing identity, manufacturing, or safety data that may support an NDIN. This guidance expanded on and replaced the 2016 draft’s Master File recommendations.
• October 19, 2026 — Identity and Safety Information (final). FDA finalized Sections VI.A, VI.B, and VI.C of the 2016 Draft Guidance, addressing identity information, history of use or other evidence of safety, and the basis for a conclusion of safety.

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FDA’s announcement notes that interested stakeholders may submit comments on the Final Identity Guidance at any time and that the agency will consider such comments in determining whether further revisions are warranted.

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1 FDA, Draft Guidance for Industry: New Dietary Ingredient Notifications and Related Issues (Oct. 2026).