The New Dietary Ingredient notification requirement under 21 U.S.C. 350b and 21 CFR 190.6 is one of the most frequently overlooked pre-market obligations for supplement brands. It applies whenever a product contains an ingredient that was not marketed as a dietary supplement in the United States before October 15, 1994 — the date DSHEA was enacted.
What Is a New Dietary Ingredient
An NDI is any dietary ingredient that was not marketed in the US as a dietary supplement or as part of a dietary supplement prior to October 15, 1994. The key date is the date of first marketing as a dietary supplement — not the date the substance was discovered or first studied.
Examples of categories that frequently raise NDI questions:
Novel botanical extracts and concentrates introduced after 1994
Synthetic forms of naturally occurring compounds (e.g., synthetic versions of amino acids or metabolites)
Isolated constituents of botanicals not previously marketed in that form
Fermentation-derived compounds
Ingredients at levels or in forms not previously marketed
The 75-Day Pre-Market Notification
Under 21 U.S.C. 350b(a)(2), a manufacturer or distributor must submit an NDI notification to FDA at least 75 days before introducing a product containing an NDI into interstate commerce. The notification must include:
The name and complete address of the manufacturer or distributor
The name of the NDI
The proposed conditions of use of the supplement containing the NDI (dosage, population)
The history of use or other evidence establishing that the ingredient is reasonably expected to be safe under those conditions of use
FDA does not "approve" NDI notifications — it reviews them and may object if the safety information is inadequate. An objection letter from FDA means the product may not be marketed until the safety question is resolved.
When an NDI Notification Is Not Required
21 U.S.C. 350b(a)(1) provides an exemption from the NDI notification requirement when the dietary ingredient has been "present in the food supply as an article used for food in a form in which the food has not been chemically altered." This exemption is narrow and frequently misapplied.
FDA has also published a list of ingredients with pre-DSHEA marketing history, but the list is not exhaustive and brands cannot assume that absence from an NDI notification database means an ingredient is pre-DSHEA.
FDA's NDI Draft Guidance
FDA published updated draft guidance on NDI notifications in 2016 and has issued additional Q&A guidance since. Key positions FDA has taken:
A chemically synthesized copy of an NDI is itself an NDI requiring notification
A change in the form of delivery (e.g., from whole herb to extract) may create a new NDI
Higher doses of a pre-DSHEA ingredient may constitute a new NDI if the higher dose was not marketed before 1994
The burden is on the manufacturer to demonstrate pre-DSHEA marketing history, not on FDA to disprove it
Consequences of Failing to File
A dietary supplement containing an NDI without a filed notification is deemed adulterated under 21 U.S.C. 342(f)(1)(B). FDA has cited NDI violations in warning letters — often in combination with disease claim violations — and has used NDI status as a basis for import alerts and product seizures.
How Truli Helps with NDI Compliance
NDI screening: Truli flags ingredients in your formulation that may require an NDI notification based on their first-marketed date and form
Pre-market review: Truli identifies NDI obligations before you finalize a formula, not after FDA sends a warning letter
Regulatory history research: Truli surfaces relevant FDA guidance and prior NDI notifications for similar ingredients to help build your safety substantiation
Related Regulations
DSHEA — The foundational law establishing the NDI requirement
21 CFR Part 111 — cGMP requirements for dietary supplements
FDA Warning Letter Patterns — How NDI violations appear in FDA enforcement actions
Frequently Asked Questions
How do I know if my ingredient is an NDI?
Start by researching whether the ingredient — in the specific form and at the specific dosage you're using — was marketed as a dietary supplement in the US before October 15, 1994. If you cannot document pre-DSHEA marketing, treat it as an NDI and consult with a regulatory advisor.
Is there a list of pre-DSHEA ingredients?
There is no definitive FDA-published list of all pre-DSHEA ingredients. FDA's NDI notification database shows submitted notifications but does not indicate which ingredients are pre-DSHEA. Industry groups maintain some reference lists, but none are authoritative.
Can I market my product while FDA reviews my NDI notification?
No. You must wait until 75 days after FDA receives your notification before marketing the product containing the NDI. If FDA objects within that 75-day window, you cannot market the product until the objection is resolved.
A note from Truli: Truli is not a law firm, and this article does not constitute or contain legal advice or create an attorney-client relationship. When determining your obligations and compliance with respect to relevant laws and regulations, you should consult a licensed attorney.
Last updated: April 2026. NDI guidance continues to evolve — Truli monitors FDA updates to NDI requirements. Book a demo to see how.
