US New Dietary Ingredient (NDI) Notification - USA - Food & Food Contact Materials

Updated on March 14, 2025

Introduction

An ingredient intended for use in or as a dietary supplement in the United States is called a dietary ingredient (DI). The term was introduced into U.S. law by the Dietary Supplement Health and Education Act of 1994 (DSHEA). DIs are regulated separately from ingredients intended for use in conventional foods.

A new dietary ingredient (NDI) is defined as a DI that was not marketed in the United States before October 15, 1994.

A DI that was marketed in the United States before October 15, 1994, is referred to by the FDA as a “pre-DSHEA DI”; however, such DIs are commonly referred to as old DIs (ODI). While several trade organizations maintain ODI lists, none are officially recognized by the FDA.

Dietary Ingredient, DI & Dietary Supplement

The DSHEA defines any one of the following as a “dietary ingredient”:

A vitamin;
A mineral;
An herb or other botanical;
An amino acid;
A dietary substance for use by man to supplement the diet by increasing the total dietary intake; or
A concentrate,* metabolite, constituent,* extract,* or combination of any of the above-listed ingredients.

*FDA does not consider synthetic copies of botanical constituents to meet the definition of a DI.

The DSHEA defines a dietary supplement as a product (other than tobacco) intended to supplement the diet that contains one or more DIs and that is intended for ingestion in the form of a tablet, capsule, powder, soft gel, or liquid measured in drops or similar small units. Furthermore, any of the listed forms or other forms of ingestion must not be represented as conventional foods (e.g., a liquid beverage cannot be represented as a dietary supplement) or as a sole item of a meal or diet. The term ingestion means “orally swallowed” (i.e., products intended for administration via sublingual, topical, inhalation, rectal suppository, or injection routes are excluded from the definition of a dietary supplement).

New Dietary Ingredient Notification (NDIN)

There must be a history of use or other evidence of safety that establishes an NDI will reasonably be expected to be safe when used under the conditions recommended or suggested in the labeling of a dietary supplement containing the NDI.

As such, unless the NDI has been legally present in the food supply as an article used for food in a form in which the food has not been chemically altered, the manufacturer or distributor of an NDI, or of a dietary supplement that contains an NDI, must submit a New Dietary Ingredient Notification (NDIN) to the FDA at least 75 days before marketing a dietary supplement containing the NDI for interstate commerce in the United States.

The purpose of the NDIN is to provide the FDA with the information that is the basis of the manufacturer or distributor’s conclusion that the dietary supplement containing the NDI will reasonably be expected to be safe.

The FDA provided the following table to assist in determining:

1) whether a DI is a pre-DSHEA DI or an NDI;

2) whether an NDI requires an NDIN; and

3) whether the NDI adulteration standard applies.

	Is this an NDI?	Is NDIN Required?	*Does the NDI adulteration standard apply?**
A DI that was marketed in the US before October 15, 1994	No	No	No
A DI that was NOT marketed in the US before October 15, 1994, AND was [legally] present in the food supply as an article used for food that has	Yes	See a) or b)	Yes
a) not been chemically altered	Yes	No	Yes
b) been chemically altered	Yes	Yes	Yes
A dietary ingredient that was NOT marketed in the US before October 15, 1994, AND was NOT present in the food supply as an article used for food.	Yes	Yes	Yes

*The NDI adulteration standard provides that a dietary supplement containing an NDI is adulterated unless there is adequate information to provide reasonable assurance that the NDI does not present a significant or unreasonable risk of illness or injury.

Voluntary Submission of an NDIN

Even though an NDI that is legally present in the food supply as an article used for food in a form in which the food has not been chemically altered is exempt from the requirement to submit a 75-day premarket NDIN, because the NDI adulteration standard still applies, there must still be evidence that establishes the reasonable expectation of safety of the use of the NDI. For example, if the NDI is legally present in the food supply because it is a GRAS substance, approved food additive, or approved color additive if the recommended, suggested, or ordinary intake level of the NDI in a dietary supplement is higher than the intake level resulting from use in conventional food (e.g., 200 mg/day versus 60 µg/day), it is necessary to perform a safety assessment to establish the reasonable expectation of safety of the higher intake level. Such an assessment could be put in the form of an NDIN and voluntarily submitted to the FDA even though there is no requirement to do so.

Materials required for an NDIN

Businesses are required to provide documentation for both the NDI and the dietary supplement containing the NDI as outlined in the following table (note, the table lists general, rather than detailed, requirements and may not be comprehensive for all cases):

Required Information	NDI	Dietary Supplement
Name and description	Yes	Yes
Examples of information to describe various NDIs:	Yes	NA
Herbs and other botanicals (or substances derived from them): Latin binomial name (including the author citations), common or usual name, plant part (e.g., leaf, bark, root), unusual forms (e.g., immature apples or malted barley), curated voucher of botanical source material, conditions of propagation, geographic origin, conditions of cultivation, period of cultivation and harvest, extraction ratio, standardization, solvents
Singular molecular entity: common or usual name of the molecular entity, synonyms, chemical identity and properties, structural formula, Chemical Abstracts Service (CAS) registry number, International Chemical Identifier (InChI) Key (InChIKey)
Microorganisms: Latin binomial name and strain designation, genetic identification, phenotypic identification, source and repository, unusual constituents (e.g., selenium yeast), and how they are obtained
Level of NDI and recommended conditions of use	NA	Yes
Characteristics and levels of other DIs	NA	Yes
Characteristics and levels of non-dietary ingredients	Yes	Yes
Manufacturing processes	Yes	Yes
List of all raw materials	Yes	Yes
Product specifications and COAs	Yes	Yes
Full copies of specification analytical methods	Yes	Yes
Specifications and/or COAs for each raw material and other ingredient	Yes	Yes
Data supporting expiration dates (e.g., stability studies) if stated	Yes	Yes
Safety Information	Yes	Yes
Supporting Information (e.g., full copies of cited studies)	Yes	Maybe

Note: If any part of the submitted material is in a language other than English, it must be accompanied by an accurate and complete English translation.

Procedures for an NDIN

Client	Collect substance information (see above section)
CIRS provides services	Gap analysis: CIRS assesses ingredient, and safety information.
	Seek the most suitable solution(s) for filling data gaps
	FDA pre-notification meeting (optional): Provide information, raise questions, and receive preliminary feedback from the FDA. This is only useful when there are specific questions to which FDA feedback is necessary to fill data gaps.
	Compile the NDIN dossier
	Submit the completed NDIN to the FDA
US FDA	FDA files the NDIN upon receipt of a complete submission, and an NDIN number is assigned, starting the 75-day premarket review period (an acknowledgment of filing is sent to the notifier or their agent (i.e., CIRS)). If a submitted NDIN is incomplete, the FDA will allow the notifier 14 days to provide the missing information. After 14 days, the FDA will issue an “incomplete NDIN” response letter (see below).
	During the review period, the FDA may raise questions and request the notifier submit additional information or materials. Upon receipt of questions or other requests from the FDA, CIRS will respond as necessary.
	Upon receipt of additional information, if the FDA determines that the submitted information is a substantive amendment, the FDA will reset the filing date and start a new 75-day review period.
	Within 75-days of the final filing date, the FDA may send a response letter of one of the following types: Letter of acknowledgment without objection; Letter listing deficiencies that make the NDIN incomplete; Objection letter raising concerns with the adequacy of the identity information or safety information (e.g., identifying gaps in the history of use or that the safety information on the NDI does not support the conditions of use); or A letter raising other regulatory issues with the ingredient or product (e.g., the ingredient is not a dietary ingredient, or the product does not satisfy all parts of the dietary supplement definition). Failure of FDA to send a response letter does not constitute a finding by the agency.
	No less than 90-days after filing, the NDIN, except for information that is trade secret or confidential commercial information, will be placed on public display at www.regulations.gov.

Estimated timeframe

Steps	Estimated timeframe
Data gap analysis	1-3 month
Compose NDIN dossier	3-6 months
NDI submitted and filed	1 day
FDA review	75-days (may be extended if substantive amendments are made during the review period)
Total	6.5–11.5 months (if no data gaps identified)

Our services

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Further Information

FDA new dietary ingredient notification submissions in recent 4 years

Name	Domain	Description
_ga	cirs-group.com
_gat	cirs-group.com
_gid	cirs-group.com