New dietary ingredient notification: what counts as an NDI, when FDA needs 75 days' notice and what its replies mean

A new dietary ingredient notification tells FDA why a new dietary ingredient (NDI), one not marketed in the US before October 15, 1994, is reasonably expected to be safe. It must reach FDA at least 75 days before a supplement containing it enters interstate commerce, unless every dietary ingredient in the supplement has been in the food supply as an article used for food, in a form not chemically altered.

Before the details, run your formula through the three questions the law turns on. It's a first screen, not a legal opinion: this post describes US rules as of October 2026 and isn't legal advice.

Does your supplement need an NDI notification?

A first screen based on section 413 of the FD&C Act

1Can you show, with dated records, that every dietary ingredient in the product was marketed in the US before October 15, 1994?

Yes, for every ingredientNo, or not sure

FDA's draft guidance recommends business records, promotional materials or press reports dated before that day. Recollection alone is generally not enough.

2Has every dietary ingredient in the product been in the food supply as an article used for food, in a form not chemically altered?

Yes, every oneNo, or not sure

3Do you have a history of use or other evidence that the new ingredient will reasonably be expected to be safe at your dose and labeled directions?

YesNo

Best fit

No NDI, so no notification

Every dietary ingredient was marketed in the US before October 15, 1994, and you hold dated records that show it. None is a new dietary ingredient, so no notification is needed. Keep those records in the formula file: FDA puts the job of documenting pre-1994 marketing on the manufacturer or distributor.

Best fit

The food-supply exception may apply

At least one ingredient may be new, but every dietary ingredient in the product has been in the food supply as an article used for food, in a form not chemically altered. In that case the law asks for no notification. The test is narrow, so have the basis reviewed and keep it in writing.

Best fit

File a notification at least 75 days before launch

An ingredient may be new, the food-supply exception isn't established for the product, and you have a history of use or other safety evidence for your dose and directions. Send FDA that evidence at least 75 days before the supplement enters interstate commerce, and count the days from the filing date FDA gives you.

Best fit

Not ready to sell

An ingredient may be new, the food-supply exception isn't established for the product, and there is no history of use or other safety evidence for your dose. Without both the evidence and a notification, a supplement with an NDI is deemed adulterated. Change the formula or build the evidence first.

What counts as a new dietary ingredient?

The definition is in section 413(d) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 350b(d)): a new dietary ingredient is "a dietary ingredient that was not marketed in the United States before October 15, 1994." Anything marketed before that date isn't one. Older articles that cite section 413(c) use the old numbering: a 2011 amendment inserted a new subsection and moved the definition to (d).

FDA's background page for industry puts the test as marketed "in a dietary supplement" before that date, and the wording matters for ingredients with a food history. On FDA's phrasing, being eaten as food before 1994 is not the same as being marketed in a dietary supplement. A food history counts under a different test, the food-supply route described below.

Two consequences follow, and both put the work on the company selling the product.

Proving an ingredient is old is your job. FDA says manufacturers and distributors are responsible for determining whether an ingredient is an NDI and, if they conclude it isn't, for documenting that it was marketed before the cutoff. Its revised draft guidance (August 2016, updated in 2024) recommends written business records, promotional materials or press reports with a contemporaneous date before October 15, 1994. Affidavits based on recollection alone are generally not enough.

There's no official list to check. FDA's background page is blunt: "There is no authoritative list" of dietary ingredients marketed in dietary supplements before October 15, 1994. Asked in its revised draft whether such a list exists, FDA answers "Not currently" and says it is prepared to develop an authoritative list of "pre-DSHEA" ingredients (DSHEA is the Dietary Supplement Health and Education Act of 1994). It held a public meeting on that list on October 3, 2017. You may come across industry-compiled lists of "old" ingredients. Treat them as leads to dated records; they don't replace them.

So when a supplier tells you an ingredient is old, this is what separates proof from reassurance:

Proving an ingredient is "old"

What FDA's revised draft guidance points to, and what falls short

Dated before October 15, 1994Evidence FDA points to

• Written business records
• Promotional materials
• Press reports
• Each with a contemporaneous date before the cutoff

Ask which ingredient, in which form, each record shows being marketed in the US.

Generally not enoughWhat falls short

• An affidavit based on recollection alone
• An industry-compiled list: FDA says no authoritative list exists
• A supplier's "it's pre-1994" with no documents behind it

With no official list to check, the records have to carry the claim.

When does a new dietary ingredient need a notification?

Under 21 U.S.C. 350b(a), a supplement that contains an NDI is deemed adulterated unless it meets one of two conditions:

1. The food-supply route. The supplement contains only dietary ingredients that have been present in the food supply as an article used for food, in a form in which the food has not been chemically altered.
2. The notification route. There is a history of use or other evidence of safety establishing that the NDI will reasonably be expected to be safe under the conditions in the supplement's labeling, and the manufacturer or distributor gives FDA the information behind that conclusion at least 75 days before the product is introduced, or delivered for introduction, into interstate commerce.

A fictional formula shows how one ingredient decides it. It has three dietary ingredients: A and B, which the supplier documents with catalogs dated 1991 and 1993, and C, an extract first sold in 2019 that has never been used as food. A and B are not new. C is, and since it was never part of the food supply, the first route is closed. The supplement needs a notification for C, reaching FDA at least 75 days before launch, or a formula without C.

Read the first route word by word, because it's narrower than it sounds. It covers the product only if every dietary ingredient in it qualifies. It asks whether the ingredient itself, in its form, has been in the food supply as an article used for food, not whether its source plant can be bought in a grocery store. And it isn't a "GRAS exception": the test is presence in the food supply, not a safety status. If your ingredient is a concentrated extract of something people eat, the question is whether that extract, as made, has been in the food supply without chemical alteration. That's a call for a regulatory specialist, documented in writing.

The second route is the notification, and two details in it are easy to miss. Safety is judged under the conditions in your labeling, so your dose and directions are part of the case. And the law puts the duty on the manufacturer or distributor, which is why a brand can't treat a supplier's "it's been notified" as the end of the conversation. Ask for the notification number and FDA's response letter, and compare the conditions of use in it with your label. With a stock or private label formula, the manufacturer picked the ingredients, so these questions go to them before you sign.

What goes into a new dietary ingredient notification, and how the 75 days run

FDA's rule at 21 CFR 190.6 lists what a notification must contain:

• the name and complete address of the manufacturer or distributor;
• the name of the NDI, and for an herb or other botanical, its Latin binomial name, including the author;
• a description of each supplement that will contain it: the level of the NDI and the conditions of use recommended or suggested in the labeling, or the ordinary conditions of use if the labeling gives none;
• the history of use or other evidence of safety, with copies of the references and English translations of anything in another language;
• the signature of the person the manufacturer or distributor designates.

Here is the whole sequence, from naming the ingredient to FDA's reply, with what goes wrong at each stage:

Preparing and filing an NDI notification

From 21 CFR 190.6 and FDA's March 2024 final guidance

1. 1Identify
2. 2Define
3. 3Evidence
4. 4Submit
5. 5Wait
6. 6Reply

1Pin down the ingredient

What happens: Name the NDI exactly; for an herb or other botanical, give its Latin binomial name, including the author. Match the description to the material your supplier actually ships.

Why it matters: FDA's objection letters can turn on the adequacy of the identity information.

What goes wrong:

• A trade name instead of what the ingredient is
• A description that fits a different grade or form than the one you buy

2Describe the supplement

What happens: For each supplement that will contain the NDI, state the level of the NDI and the conditions of use your labeling recommends or suggests.

Why it matters: Safety is judged under the labeled conditions of use, so the dose and directions are part of the notification.

What goes wrong:

• Changing the dose or directions after filing, which can mean a substantive amendment and a new 75 days
• A label draft that no longer matches what was notified

3Build the safety case

What happens: Assemble the history of use or other evidence of safety, with copies of every reference and English translations of anything in another language.

Why it matters: It is the basis the law asks for: evidence that the NDI will reasonably be expected to be safe under the labeled conditions.

What goes wrong:

• Evidence on a different form or dose than yours
• Foreign-language sources without translations

Read more: Supplement Clinical Studies: Find, Read and Cite Them

4Sign and submit

What happens: Send it to FDA's Office of Dietary Supplement Programs, signed by the person your company designates. The regulation describes an original and two copies on paper; FDA's 2024 guidance prefers electronic submission.

Why it matters: Nothing starts until FDA acknowledges receipt: the date it received the notification becomes the filing date.

What goes wrong:

• A missing signature or an incomplete address
• Counting the 75 days from the day you sent it instead of the filing date

5Wait out the 75 days

What happens: The supplement may not enter interstate commerce for 75 days after the filing date. A substantive amendment gets a new filing date and a new 75 days.

Why it matters: Selling early leaves a supplement with an NDI adulterated, and so does marketing it on an incomplete notification.

What goes wrong:

• Ads and inventory booked before the clock has run
• Reading silence as approval: no response is not a finding of safety

6Reply and public display

What happens: FDA answers with one of four kinds of letter. Ninety days after the filing date, the notification goes on public display, minus trade secrets and confidential commercial information.

Why it matters: Competitors can read what you filed, and you can read what they filed.

What goes wrong:

• Assuming the whole file stays private

The notification goes to FDA's Office of Dietary Supplement Programs. The regulation still describes an original and two copies on paper; FDA's 2024 guidance prefers electronic submission through what it calls the CFSAN Online Submission Module.

The clock is where launch plans go wrong. FDA acknowledges receipt, and the date it received the notification becomes the filing date. The supplement may not enter interstate commerce for 75 days after that date. If FDA decides that information you send later is a substantive amendment, it assigns a new filing date, the day it received that amendment, and the 75 days start again. FDA keeps the notification confidential for 90 days after the filing date, then places it on public display, minus trade secrets and confidential commercial information. And if FDA never responds, the rule says that silence is not a finding that the ingredient is safe or that the product isn't adulterated.

Say FDA's acknowledgment gives a filing date of March 1, 2027. With no amendment, the 75 days run to May 15, and FDA keeps the file confidential through May 30: the waiting period ends about two weeks before the public can read what you filed. Now say you send information that FDA treats as a substantive amendment, and it reaches FDA on April 20. April 20 becomes the new filing date, and the 75 days now run to July 4, seven weeks later than planned. Book the launch, the first production run and the ad budget against the later date.

Four kinds of reply, and none is an approval

A notification isn't an application for approval, and no reply from FDA is one: FDA doesn't approve new dietary ingredients or supplements. Its March 2024 final guidance sorts its replies into four kinds of letter:

FDA's four kinds of reply

From the March 2024 final guidance, section IV.D

No objectionIncompleteObjectionOther issues

An acknowledgment without objection

FDA acknowledges the notification and raises no objection to it.

• Not an approval, and not an independent FDA finding that the ingredient is safe
• Keep the letter and the NDIN number in the formula file

What to do: launch after the 75 days, within the dose and conditions you notified.

A letter listing deficiencies

FDA lists what makes the notification incomplete under 21 CFR 190.6.

• A product marketed relying on an incomplete notification is deemed adulterated
• Completing it takes a further submission; if that is a substantive amendment, the 75 days start again

What to do: hold the launch and fill the gaps.

An objection letter

FDA raises concerns about the adequacy of the identity information or the safety information.

• Treat it as a reason not to launch the product as notified
• Better identity or safety evidence is the way back, not a reworded label

What to do: take the letter to a regulatory specialist before you spend more.

A letter raising other regulatory issues

FDA questions something more basic: for example, that the substance is not a dietary ingredient, or that the product is not a dietary supplement.

• The notification route may not be open to the product at all
• The formula, not the paperwork, may have to change

What to do: get a regulatory opinion before you go further.

Two rules follow. Never describe an ingredient as "FDA approved" on the strength of a letter: an acknowledgment without objection is not an independent FDA finding of safety. And a product marketed on the strength of an incomplete notification is deemed adulterated, so a deficiency letter means the launch waits.

Every reviewed notification that can be made public ends up on FDA's list of submitted 75-day premarket notifications, with links to the files on Regulations.gov. You can download it as a spreadsheet covering 1995 to the present and sort it by NDIN number, ingredient, firm, submission date and FDA's response date. Search it for your ingredient before you commit to a supplier, by its common name and, for a botanical, by its Latin name too. Then open the response letter itself rather than stopping at the row, and note which firm notified which form of the ingredient, at what level and for what conditions of use.

Why an unnotified NDI can't be fixed with marketing

A supplement with an NDI that meets neither route is deemed adulterated under the statute. That's a problem with the product, not the marketing: no disclaimer, rewritten claim or new landing page changes it. A VSL can be paused in an afternoon; a production run of the wrong formula can't be rewritten.

VSL brands should check sooner than most. When a script's mechanism story turns on a "little-known compound", that compound is exactly the kind of ingredient whose NDI status needs checking before anyone writes a word. Our guide to the unique mechanism covers building that story; this post covers whether the ingredient behind it can legally be in the bottle.

A notified ingredient doesn't settle what you may say about it, either. The notification is about safety under the labeled conditions of use. What the product does, and how you may describe it, follows its own rules, covered in our post on structure/function claims. And the safety evidence behind a notification is not evidence that the product works; for that, see how to read supplement clinical studies.

FDA's NDI guidance, from 2011 to now

FDA's views on NDIs sit in a stack of guidance documents, two of them final and the rest drafts:

New dietary ingredients: the cutoff and FDA's guidance

1. Oct 15, 1994The cutoff dateA dietary ingredient not marketed in the US before this date is a new dietary ingredient.
2. July 2011First draft guidance"Dietary Supplements: New Dietary Ingredient Notifications and Related Issues."
3. August 2016Revised draftIts sections on what counts as an NDI are still a draft; its identity and safety sections became final guidance in October 2026.
4. Oct 3, 2017Public meeting on a pre-DSHEA listFDA discussed developing a list of ingredients marketed before the cutoff. Its background page still says no authoritative list exists.
5. May 2022Draft on certain NDIsA draft policy on certain NDIs and dietary supplements subject to premarket notification.
6. March 2024Final guidance on procedures and timeframesThe first final piece. FDA revised the 2016 draft in March and April 2024 and marked its procedures section reserved.
7. April 2024Draft guidance on master filesA master file holds identity, manufacturing and/or safety information on an NDI. This draft replaces the 2016 draft's master-file recommendations.
8. Oct 19, 2026Final guidance on identity and safety informationFinalizes sections VI.A to VI.C of the 2016 revised draft, in question-and-answer form (docket FDA-2025-D-6501).

Two pieces are now final. The March 2024 guidance covers procedures and timeframes. On October 19, 2026, FDA finalized the identity and safety sections of the 2016 revised draft, sections VI.A to VI.C (identity information about the NDI and the supplement, the history of use or other evidence of safety, and the summary of the basis for your conclusion of safety), as question-and-answer guidance under docket FDA-2025-D-6501 (FDA). FDA's Human Foods Program had listed final guidance on "the safety and identity information required" for NDI notifications among its deliverables for 2026. What counts as an NDI is still covered by the revised draft: FDA says it will update that draft to show which sections are final, and it is still working to finalize the rest. So when an article tells you what FDA "requires" on identity or safety data, check which document it's quoting, and whether a final version has replaced it.

A brand's NDI checklist

The output of all this is one page per ingredient: what it is and in what form, who supplies it, the basis for selling it (dated pre-1994 records, the food-supply route, or an NDIN number with FDA's reply), when it was confirmed and by whom. Run the checks below for every ingredient before you commit to a formula, and again whenever a supplier, a source or a form changes:

NDI checks before you commit to a formula

• List every dietary ingredient by what it is, not by its trade name
• Ask each supplier in writing: is it an NDI, and on what basis?
• For a "marketed before 1994" answer, ask for business records, promotional materials or press reports dated before October 15, 1994
• For a notified ingredient, get the NDIN number and FDA's response letter
• Search FDA's list of submitted notifications and read the response letter, not just the row
• Compare your dose and directions with the conditions of use in that notification
• If you rely on the food-supply route, write down the basis and have it reviewed
• If you must notify, plan the launch at least 75 days after the filing date, plus time for amendments
• Never call an ingredient "FDA approved" because of a letter
• Keep every answer in the formula file, dated, with the name of whoever gave it

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If you're earlier in the process, how to start a supplement company puts the ingredient check in order with the manufacturer, the label and the launch.