New Dietary Ingredient (NDI) Notification Requirements

Any dietary ingredient that was not sold in the United States as, or in, a dietary supplement before October 15, 1994, triggers the New Dietary Ingredient (NDI) notification requirements: the manufacturer or distributor must file a premarket safety notification with the FDA at least 75 days before shipping the product in interstate commerce. The statutory framework sits at 21 U.S.C. 350b, and the procedural rules live at 21 CFR 190.6. Skipping the filing turns the product into adulterated food under federal law, with criminal penalties attached.

What Counts as a New Dietary Ingredient

The statute defines a new dietary ingredient as any dietary ingredient that was not marketed in the United States before October 15, 1994.¹ “Dietary ingredient” itself is broad. It includes vitamins, minerals, herbs and other botanicals, amino acids, any dietary substance used to supplement the diet by increasing total dietary intake, and any concentrate, metabolite, constituent, extract, or combination of those.² A newly isolated plant metabolite or a novel amino acid derivative falls under the framework just as squarely as an unfamiliar herb.

Establishing that an ingredient is “old” — and therefore outside the notification requirement — takes documentary evidence that the exact substance was sold as or in a dietary supplement domestically before the cutoff. Manufacturers usually rely on catalogs, invoices, purchase orders, and shipping records from that period. Traditional use in other countries does not qualify; the marketing history must be in a U.S. dietary supplement context.

When a Notification Is Required

A supplement containing an NDI is deemed adulterated unless one of two conditions is met. The first: the supplement contains only dietary ingredients that have been present in the food supply as articles used for food in a form that has not been chemically altered. Where the new ingredient already exists in the food supply in its unaltered form, no notification is required.¹ The second: the manufacturer submits safety evidence to the FDA at least 75 days before the ingredient enters commerce. Most NDIs travel the second path.

The notification attaches to the individual ingredient, not the finished product. If every ingredient in a multi-component supplement was marketed before October 15, 1994, no filing is required. If even one component is new, that component needs its own safety submission.³ And each manufacturer or distributor files separately. Another company’s notification on the same ingredient does not clear your product; you need your own submission backed by your own evidence.

Chemical Alteration Can Create a New Ingredient

Even where the source material predates 1994, processing changes can produce a legally new ingredient. The FDA’s position is that a process chemically alters a food ingredient if it makes or breaks chemical bonds, unless those bonds reverse when the substance is ingested or dissolved in water.⁴

Solvent choice matters. The agency generally treats extraction with solvents other than water or aqueous ethanol as chemical alteration, because different solvents pull different constituents and change the extract’s composition. Filtration, chromatography, and distillation fall on the same side of the line. Certain physical modifications do not count as alteration: dehydration, freeze-drying, milling, making a tincture or solution in water, minor loss of volatile components, and forming a slurry, powder, or solid in suspension. Those exclusions trace back to the Congressional Statement of Agreement from October 1994.⁴ Switching from a water-based extraction to a hexane extraction can create a new dietary ingredient even where the source plant has been used for centuries.

What the Notification Must Contain

21 CFR 190.6 sets the minimum contents of the filing. Every notification needs:

Name and description of the NDI. For botanicals, this includes the Latin binomial with the taxonomic author.
Description of the dietary supplement that will contain the ingredient, including the proposed serving size, dosage in milligrams or micrograms, and recommended frequency of use.
Conditions of use, such as daily supplementation, short-term use, or use limited to a specific population.
Safety evidence establishing that the ingredient is reasonably expected to be safe under the labeled conditions of use. Published clinical studies, toxicology reports, and peer-reviewed articles all qualify, but the regulation requires full reprints or copies of any cited references, not just bibliographic listings.
Signature of the person designated by the manufacturer or distributor as responsible for the accuracy of the information.

⁵

Any foreign-language supporting material must be accompanied by a complete and accurate English translation.⁵ Paper submissions require an original and two copies of the full notification.

Safety Studies That Support a Strong Filing

The statute does not prescribe a fixed list of required toxicology studies, and reviewers evaluate submissions case by case. In practice, a well-supported package commonly includes:

A 90-day repeated-dose oral toxicity study (sometimes described as a 13-week subchronic study). This is typically the backbone of the safety package and establishes the no-observed-adverse-effect level (NOAEL) that reviewers use to judge whether the proposed serving size leaves an adequate margin.
A genotoxicity battery, generally a bacterial reverse mutation test, a micronucleus test, and a chromosomal aberration test.
A single-dose acute toxicity study covering short-term exposures at higher-than-normal doses.

Human clinical data, epidemiological evidence, and a documented history of traditional food use can also support a filing, particularly for ingredients with long usage histories abroad. A thin toxicology package invites questions, and the 75-day clock keeps running while you assemble answers.

How to Submit and When to Send It

The FDA accepts NDI notifications through two channels. The preferred route is the Centralized Online Submission Module (COSM), a secure electronic filing portal operated by the Center for Food Safety and Applied Nutrition.⁶ Electronic filing produces an immediate receipt confirmation, which is useful for pinning down the start of the 75-day period.

Paper submissions go to the Office of Dietary Supplement Programs, 5001 Campus Drive, College Park, MD 20740. When mailing a paper filing, the FDA recommends following up by email to NDITeam@fda.hhs.gov with the subject line “NDIN Written Submission,” and warns that failure to do so may delay processing.⁶ There is no user fee.

The 75-day waiting period is fixed by statute. It cannot be shortened, waived, or expedited.¹ The clock starts when the FDA officially logs the submission. An incomplete filing, or one routed to the wrong office, delays that logging and can push back a planned launch. Shipping the product before the waiting period ends renders the ingredient adulterated under 21 U.S.C. 342.⁷

What the FDA Does During Review

During the 75-day window, the FDA reviews the safety data and technical description. The agency usually issues an acknowledgment letter confirming the filing date and assigning a tracking number. That letter is not an approval. The FDA does not approve dietary ingredients the way it approves drugs; the NDI process is a premarket safety review, and the absence of an objection means only that the agency did not identify grounds to object based on what was submitted.

Review closes in one of three ways:

Acknowledgment without objection. The FDA has no further questions at this time, and you can proceed to market. The agency retains authority to act later if new safety concerns emerge.
Response identifying deficiencies. The FDA flags problems with the safety evidence, ingredient description, or proposed conditions of use, which you can address in a resubmission.
Objection letter. The FDA concludes the ingredient is unsafe or the notification is fundamentally incomplete. You cannot legally market the ingredient until you resolve the issues in a new filing.

There is no formal appeals process for an objection letter. The path forward is to correct the deficiencies and file again. Throughout the review, FDA staff may contact you to clarify scientific points or request additional data.

Confidentiality and Public Disclosure

The FDA keeps the existence and contents of a notification confidential for 90 days after the filing date.⁸ After that window closes, the notification and its safety data go on public display, except for information the FDA agrees qualifies as a trade secret or confidential commercial information.¹ To protect anything, you must identify it clearly in the submission and explain why it qualifies. The agency publishes a running list of submitted 75-day notifications, which competitors regularly monitor.

Consequences of Skipping the Notification

Selling a supplement that contains an un-notified NDI is not a paperwork lapse. A dietary supplement is adulterated if it contains a new dietary ingredient for which there is inadequate safety information.⁷ Introducing an adulterated product into interstate commerce is a prohibited act under 21 U.S.C. 331.⁹

Penalties escalate. A first offense carries up to one year in prison and a fine of up to $1,000. A second offense, or a first offense committed with intent to defraud, carries up to three years in prison and a fine of up to $10,000.¹⁰ These penalties can reach individuals, including corporate officers responsible for the violation. The FDA can also seek product seizures, court injunctions, and import alerts. Where the agency determines a reasonable probability of serious adverse health consequences or death, it can order a mandatory recall after first giving the company an opportunity to act voluntarily.¹¹

Protecting Supplier Data With Master Files

Ingredient suppliers who invest in safety research face a real problem: filing an NDI notification makes most of that data public after 90 days. The FDA’s Dietary Supplement Master File system offers a workaround. A Master File is a separate, confidential submission containing identity, manufacturing, and safety data for an NDI. The supplier retains ownership and control of its contents.¹²

When a supplement manufacturer needs to file for a product using that supplier’s ingredient, the supplier can grant a written “right of reference” to the Master File. The manufacturer then incorporates the Master File data into its own notification without seeing the file’s contents. The FDA reviews the Master File alongside the notification, and if questions arise about the file itself, the agency contacts the supplier directly.¹²

The supplier can limit authorization to specific sections or specific business partners. There is no automatic presumption that everything in a Master File qualifies as a trade secret. To protect specific data, you have to identify it and explain to the FDA why it qualifies as confidential commercial information.¹² For suppliers serving multiple downstream customers, the setup effort is usually worth it.

1
Office of the Law Revision Counsel. United States Code Title 21 – 350b New Dietary Ingredients
2
Office of the Law Revision Counsel. United States Code Title 21 – 321 Definitions
3
U.S. Food and Drug Administration. New Dietary Ingredients in Dietary Supplements – Background for Industry
4
U.S. Food and Drug Administration. Speaker Presentation – American Herbal Products Association
5
eCFR. 21 CFR 190.6 – Requirement for Premarket Notification
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U.S. Food and Drug Administration. How to Submit Notifications for a New Dietary Ingredient
7
Office of the Law Revision Counsel. United States Code Title 21 – 342 Adulterated Food
8
U.S. Food and Drug Administration. Dietary Supplements – New Dietary Ingredient Notification Procedures and Timeframes
9
Office of the Law Revision Counsel. United States Code Title 21 – 331 Prohibited Acts
10
Office of the Law Revision Counsel. United States Code Title 21 – 333 Penalties
11
U.S. Food and Drug Administration. Guidance for Industry and FDA Staff – Questions and Answers Regarding Mandatory Food Recalls
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U.S. Food and Drug Administration. New Dietary Ingredient Notification Master Files for Dietary Supplements – Guidance for Industry