US NDI Notification: A Step-by-Step Guide to Understanding FDA Letters

To sell dietary supplements containing new dietary ingredients (NDI) in the U.S. market, you must submit an NDI notification (NDIN) to the FDA at least 75 days in advance. However, the FDA’s response to an NDIN does not have a clear conclusion like a GRAS notice, such as “FDA has no questions”. As a result, many companies often find it difficult to determine whether their notification has been “notified” when faced with a response filled with regulatory clauses and template terminology. CIRS Group combines FDA official guidelines and real cases to break down the types of NDIN responses and interpret the notification results for your reference.

1. What does a “notified” letter look like?

Core Indicators

Typically, an NDIN “notified” response includes the following standard procedural paragraph:

“In accordance with 21 CFR 190.6 (c), FDA must acknowledge its receipt of a notification for a new dietary ingredient. For 75 days after the filing date, you must not introduce or deliver for introduction into interstate commerce any dietary supplement that contains the new dietary ingredient that is the subject of this notification. Please note that acceptance of this notification for filing is a procedural matter, and thus, does not constitute a finding by FDA that the new dietary ingredient or supplement that contains the new dietary ingredient is safe or is not adulterated under 21 U.S.C. § 342. FDA is not precluded from taking action in the future against any dietary supplement containing your new dietary ingredient if it is found to be unsafe, adulterated, or misbranded.”

And it does not contain the following negative statements:

• “does not comply with the requirements”
• “do not provide a sufficient basis/not a dietary ingredient”
• “has significant concerns about”

Case Analysis

NDIN 1411

The FDA confirmed in its response that the NDIN was received and clearly informed the company that it cannot be marketed within 75 days from the date of filing. The FDA emphasized that the filing of this NDIN is a “procedural matter” and does not represent the FDA’s final endorsement of safety. This letter used standard procedural language and is a typical “notified” response.

2. Four Types of “Non-notified” Letters

Based on real cases, CIRS Group has summarized the typical characteristics of four types of “non-notified” responses.

Type 1: Incomplete documents

Key Phrase

“…… Your notification concerning your new dietary ingredient … does not comply with the requirements of 21 CFR 190.6 and is incomplete for the following reasons: …”

Case Analysis

NDI N1393

The FDA pointed out that the NDIN did not submit a complete copy of the supporting documents.

Type 2: Does not meet the definition of dietary ingredients

Key Phrase

“After careful review, FDA has determined that … do not provide a sufficient basis for us to conclude that …, the subject of your notification, is a “dietary ingredient” within the meaning of 21 U.S.C. § 321(ff)(l) that may be lawfully used in dietary supplements.”

Case Analysis

NDIN 1379

The FDA pointed out that the NDIN did not demonstrate that the declared substance meets the definition of dietary ingredients.

Type 3: Insufficient identity data

Key Phrase

“FDA has carefully considered the information in your submission, and the Agency has significant concerns about the evidence on which you rely to support your conclusion that … FDA was unable to establish the identity of your new dietary ingredient … did not provide adequate scientific data to support the identity, starting materials, manufacturing process, or specifications.”

Case Analysis

NDI N 1412

The FDA pointed out that the NDIN did not provide sufficient scientific data to demonstrate identity information, production materials, production processes, and specifications.

Type 4: Insufficient evidence of safety

Key Phrase

“FDA has carefully considered the information in your submission, and the Agency has significant concerns about the evidence on which you rely to support your conclusion that … FDA was unable to establish the safety of your new dietary ingredient … did not provide adequate history of use data, or other evidence of safety, that would demonstrate a reasonable expectation of safety of the NDI for the proposed conditions of use.”

Case Analysis

NDI N 1417

The FDA pointed out that the toxicological experiments or historical consumption records provided in the NDI notification could not cover the proposed high dosage or long-term use situations, and the safety conclusion is not valid.

3. Special Reminder: Two Common Misinterpretations

1) We have filed your notification” ≠ Notified

Almost all response letters will say “FDA received and filed the notification”

— This is merely a procedural acceptance and is unrelated to the final result. It is necessary to read the subsequent content for specific judgment.

2) Disclaimer in the notified reply ≠ Non-notified

Even in the reply, the FDA will certainly emphasize that “does not constitute a finding by FDA that the new dietary ingredient… is safe or is not adulterated… FDA is not precluded from taking action in the future.”

— This is not a signal of “non-notified”, but a statutory disclaimer intended to remind companies even if the NDIN is notified, the FDA still reserves the right to enforce in the future.

4. Summary

Interpreting the FDA reply, the key is to find the right landmark paragraphs. If the reply you received contains discussions on ingredient definitions, identity, or safety deficiencies, you need to reassess compliance strategies or supplement gap data. When preparing the NDIN, you should strictly adhere to the identity and safety requirements in the FDA guidelines, and prepare a complete and scientific dossier.

About CIRS Food Division

Established in 2012, the Food Business Division of CIRS Group has helped over 1,000 food companies globally in achieving one-stop compliance solutions. CIRS offers a full range of regulatory services, including but not limited to China novel food applications, synthetic biology-derived foods, U.S. GRAS notices, EU novel food applications, health food registration, and food for special medical purposes (FSMP).

If you need any assistance or have any questions, please get in touch with us via service@cirs-group.com.