US FDA New Dietary Ingredient Notification Submissions in Recent 4 Years

NDI, or New Dietary Ingredient is defined in 21 CFR as dietary ingredients, ingredients used a supplements, introduced to the US market after October 15, 1994. As required by the FDA, manufactures must notify the FDA as least 75 days prior to the marketing of a product containing NDI. Almost all NDI notifications (NDIN) and their corresponding FDA response letters are available to the public on the FDA website. The acceptance of the information provided in each NDIN is a procedural matter that does not preclude the FDA from taking action against the NDI if it is found unsafe in the future. NDIN submission statistics are summarized below.

NDIN submissions since 2021

Since 2021, a total of 136 NDIN’s submitted (Figure 1) among which 79 are accepted and 42 are not accepted (The reasons for not acception are stated in the FDA’s responding letter), and 12 with no response as the FDA were not able to identify the notified substances as dietary ingredients (Figure 2 and Figure 3).

Figure 1. The number of NDIN’s submitted to the FDA per year since 2021

Data is updated as of October 2024

Figure 2. Statistics of the FDA responses to each submission since 2021

Data is updated as of October 2024

Figure 3. Reasons for non-accepted submission

Data is updated as of October 2024

Resubmissions

Approximately a fifth among those that have been accepted after they have been resubmitted (See Figure 4). Generally, most resubmissions could be accepted in the second time. But NDIN #1306 is an exception. It was only accepted after the fourth submission.

Figure 4. Number of accepted NDIN’s that are from a single submission or of a resubmission of a previously not accepted submission.

Data is updated as of October 2024

Nicotinamide mononucleotide (NMN): A Special case

Among those with no response from the FDA as they could not be identified as dietary ingredients with the information provided in the notification, several were Nicotinamide mononucleotide (NMN). Previously, the FDA has approved β-NMN submitted by Syncozyme (Shanghai) after the second submission (NDID #1247) on May 16, 2022. However, this was withdrawn on November 4, 2022 in a supplemental response letter.

Then on March 6, 2023, the National Products Association (NPA) filed a citizen petition to the FDA asking to the FDA to reconsider their view on NMN as an NDI. The FDA replied in an Notification that their response to the notification will depend on their decision on this petition. On August 30, 2023, the FDA replied to this citizen petition saying that “due to competing agency priorities”, they have not come to an decision regarding the status NMN.

A year later on August 28, 2024, NPA filed a lawsuit against the FDA “requesting that the agency cease its unlawful retroactive application of the Food, Drug, and Cosmetic Act against Nicotinamide Mononucleotide (NMN)”. Then on October 24, 2024, the FDA requested a stay of the legal proceedings to the U.S. District Court for the District of Columbia in regards to this lawsuit while they evaluate the concerns of the NPA’s petition. The FDA stated that they will provide a conclusion to the approval of NMN by July 31, 2025. As they assess the citizen petition, the FDA presented to the NPA that they will not prioritize enforcement actions against the marketing of NMN as an ingredient in dietary supplements, provided that they would be lawful if NMN is not excluded from the definition of being a “dietary supplement”.

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