FDA announces enforcement discretion, amnesty window on missing NDI filings

The US Food and Drug Administration said that it is aware that there are many new ingredients on the market whose safety has never been officially assessed via a New Dietary Ingredient notification. 

Thousands of missing notifications

“Although not every dietary supplement requires an NDI notification, we estimate that more than 4,600 notifications should have been submitted and were not. Despite the expanded marketplace, however, we have received only about 1,200 NDI notifications since DSHEA’s enactment,”​ the guidance states.

 Under DSHEA a manufacturer of a New Dietary Ingredient—i.e. one that was not marketed as a dietary ingredient prior to Oct. 15, 1994—is required to filed a notification with FDA 75 days before putting the ingredient on the market.  The dossier is supposed to provide scientific backing to prove that the ingredient can be ‘reasonably expected to be safe’ under the conditions of use.

Within that time frame FDA is supposed to respond with a letter either concurring with the assertion of safety or raising objections.  (FDA never puts itself in the position of ‘approving’ ingredients.)

In the past companies filing NDI notifications have experienced a high rate of failure.  Some of this can be attributed to ignorance about the process that saw notifications come in with ingredients that were poorly characterized or that had poorly assembled scientific citations. On the other hand, some companies have alleged that the Agency moved the scientific goalposts over the years, making the proof required resemble a drug application.

Alternative GRAS route

Many companies have either ignored the NDIN requirement altogether, or have filed GRAS notices on their ingredients.  Those have usually been of the self affirmed type, though some firms have filed GRAS notices directly to the Agency.  (It’s unclear if some of the more than 3,000 ingredients FDA alluded to are claiming GRAS status.)

In the six-page guidance released today, FDA said it is granting an amnesty period of sorts so that the missing notifications can be filed without fear of having products that are technically adulterated pulled from the market.

“To increase the amount of safety information we have about NDI-containing dietary supplements in the marketplace and to promote risk-based regulation, we are informing manufacturers, distributors, and other interested persons of our intent to exercise enforcement discretion, for a limited time and in limited circumstances, to encourage firms to correct past failures to submit an NDI notification,”​ the draft guidance states.

The enforcement discretion applies to any ingredient marketed on or before May 20, 2022.  It also assumes that such ingredients are not being marketed with impermissible disease treatment claims. The marketers of such new ingredients will have 180 days to file notices from the day that the draft guidance is made final, which would happen sometime later this year.  Starting today there is a 60-day window for comments on the guidance and then the process of crafting a final draft would begin.  As the guidance is of limited scope it could be expected that would take place fairly quickly.  

The guidance also sets out an intention to develop a special portal to speed the submission of the missing notifications. The guidance does say, though, that FDA does not expect to be able to respond with the 75-day window required by law except to acknowledge receipt of the notification.  If a large percentage of the missing notifications were to be filed under the program it’s anyone’s guess how long it would take for FDA to work through that backlog.

Stakeholders: With little enforcement now, ‘discretion’ doesn’t mean much

Attorney Marc Ullman, of counsel with the firm Rivkin Radler, said without any teeth to the enforcement that FDA says it is putting on hold, today’s announcement has less impact than it might at first glance.  

“When that window closes, what are they going to do?  Send another letter?” ​Ullman said.

“We have brought specific cases to them, of astaxanthin with residual formaldehyde, of PQQ on the market with unknown peaks and failed NDI notifications, and beta alanine with residual e coli and the Agency did nothing about any of that,”​ he said.

Daniel Fabricant, PhD, president and executive director of the Natural Products Association, concurred with Ullman’s view (NPA had worked with Ullman on some of letters that were sent to FDA on behalf of clients).

“Until there is real enforcement, nothing is going to change.  If folks haven’t submitted an NDI that product is adulterated and they can enforce on that. We have given them examples of beta alanine without NDIs and they reaction was they’re not interested,”​ he said.

Ullman said he also suspects this is more of the ‘enforcement theater’ he alleges FDA has been engaging in to support the  Mandatory Product Listing requirement that has recently been proposed under a bill sponsored by Sen. Dick Durbin, D-IL.

“I know I sound like a broken record, but it’s because I hear this nonsense of FDA saying they don’t know what’s on the market.  Here they are saying they know exactly what’s on the market, and yet they did nothing. The trade needs real enforcement,”​ he said.

CRN: FDA bears some blame for present situation

Steve Mister, president and CEO of the Council for Responsible Nutrition, said CRN applauds any move that could bring more companies into compliance and make the marketplace safer for consumers.  But he said FDA bears some blame for the situation as it exists. It has been more than a decade since the first draft NDI guidance was issued and another draft version has been issued since, and hundreds of comments were submitted to FDA as part of that process.  But still a number of fundamental questions remain unresolved.

The Agency's reluctance to take action against companies that ignored the requirement didn't provide a big incentive for other firms to spend the money and take the risk of filing, Mister said.  And  the lack of a Master File system such as that proposed by CRN means companies are unsure of how much of their confidential trade information must be exposed to put together a successful filing. A Master File system would allow companies to sequester some of the information in the filing and choose how, when and to whom it would subsequently be divulged.

"Unfortunately, the concerns the Agency expressed are partially of its own making by failing to provide a clear direction for when an NDI notification is required and failing to enforce the existing requirements. FDA has refused to develop an authoritative list of grandfathered ingredients—or to accept as authoritative—the well-documented lists developed by the industry. Eleven years after FDA first proposed a draft guidance to clarify when an ingredient qualifies as ‘new,’ consumers and industry alike are still waiting for the agency to finalize that guidance," ​Mister said.

The full text of the guidance can be found here​​.