The New New Dietary Ingredient Notices
March 8, 2024
Written By: Jim Lassiter
The fact remains that ALL New Dietary Ingredients require NDI Dossier assembled and on file (formerly known generically as an NDI “Master File”), and these were generally to be filed by the supplier of the NDI without intention to sell a Dietary Supplement finished product themselves. The press announcement from the FDA back in May 2022 from the FDA was a shot across the bow alerting industry of impending actions based on a broad review of NDI’s requiring notification, but so far, the Agency has remained inactive in this regard. The most recent Final Guidance issued on March 5, 2024, clarifies and finalizes only one section of the 2016 Draft Guidance as described by FDA in its announcement. How we arrived here is of some importance in recognition of the effects of the beginning of finalization.
The creation of any legislation involves a series of documented compromises from all parties and sides involved. These results are compromises on differing positions attained in order to move the legislative ball forward. One of these compromises, devised at the time of passage of the Law that is known as DSHEA was the basic approach to the handling of Dietary Ingredients. According to Section 2 of DSHEA, Congress found that “although the Federal Government should take swift action against products that are unsafe or adulterated, the Federal Government should not take any actions to impose unreasonable regulatory barriers limiting or slowing the flow of safe products and accurate information to consumers”. Congress also found that “dietary supplements are safe within a broad range of intake” and that “a legislative action that protects the right of access of consumers to safe dietary supplements is necessary to promote wellness”[1].
In these findings Congress said the products in the market at the time were safe and thus not comprised of materials that needed to undergo further evaluation for allowance of sale to the consumer. Congress, in recognition of this critical finding regarding safety, excluded Dietary Ingredients from food additive regulations. The compromise came in with the criteria for any future (New) Dietary Ingredient intended for sale AFTER the passage of DSHEA and the need for notification. We may debate the language of the Law regarding such notifications needing to be of any Dietary Supplement that uses a New Dietary Ingredient or whether it is only the Dietary Ingredient that was intended to be the subject of the notification requirements. The present system is based on the still current Draft Guidance for such notifications from 2016. The latest Final Guidance takes on one of the sections of this Draft Guidance and moves it to Final. Closer inspection of the Final Guidance reveals that there are a number of now finalized items of importance. What industry does with this finalization should include input directly to FDA regarding issues that even this finalization misses. At the same time, questions are raised within this Final Guidance that require clarity.
Some initial questions out of the Final Guidance involve missing clarity. We recognize that FDA’s initial identification of a “Master File” to be completed by a supplier of a New Dietary Ingredient was an unfortunate turn of phrase. The phrase did and does continue to make sense from the standpoint of understanding the concept. This Final Guidance does nothing to clarify the situation. The naming of the relationship to other NDI notification required is not germane to the issue. How these are supposed to be used and what is their intended purpose? What does a manufacturer of a Dietary Supplement finished product do when filing (as FDA has determined necessary, which we don’t agree with) to appropriately include this external documentation? How should the NDIN be filed for the Dietary Ingredient itself be referenced? How then does COSM handle the cross-reference? The incompleteness of thought on the topic is glaring and needs to stop for all our sakes.
The solutions to this include a mix of the practical and the coverage of concept. Solutions for the challenges presented lie in the clear application of the structures and requirements for both the filing of the Dietary Ingredient but also the Dietary Supplement. The structures for linkage of the notification of the Dietary Ingredient need not be complex at all, especially if everything is electronic. Assuming that an NDIN has been filed on a Dietary Ingredient for use up to a certain level in Dietary Supplements finished products, the inclusion of said material in a Dietary Supplement up to that notified level should be a standard consistent automatic acceptance without further need of such notification. This, however, moves into the notification argument at its core. The simple identification of the successfully notified NDI should suffice without further need for reference. In the case of electronic filing, the NDIN number can be placed in an uploaded link section so that the entirety of the NDIN for the Dietary Ingredient is visible for review. The suggestion is one that improves efficiency, allows for streamlining of the review process and clarity for the industry required to use the system, not to mention would help alleviate the resource burden and budget requirement of the Agency.
Addressing additional issues within the “need to include” information that has emerged since the issuance of the 2016 Draft Guidance is another area where clarity and consideration of the actual need for data should be reviewed. The evolving requirements across multiple submissions and reviews demonstrate that further clarity as to the specific needs for data inclusion is required. Is there, as an example, a need to present stability data on the NDIN at the component stage? If yes, this should be universally described as such in guidance. The opposite of this is when submitting the NDIN for a Dietary Ingredient, what purpose does it serve to present a hypothetical Dietary Supplement that “contains” the NDI? This further goes to the establishment of a specification for the same fictitious product and the inconsistent request for stability data on the imaginary product. Each of these considerations would solve the preparation time constraints that contribute to the cost along with the review time removed from having to evaluate completely superfluous information.
In other portions of the Final Guidance, the clarity of the words used in the Final Guidance belie what interpretations will arise. A couple of examples follow:
In Section III B, FDA describes the requirement for and how to notify a Dietary Ingredient being used across multiple Dietary Supplements, but there is no clarity on the inclusion of multiple NDIs in a single Dietary Supplement. Referencing the different NDI notifications is presumed to be sufficient.
In Section III O, FDA appears to be willing to accept unpublished scientific data in support of the notification. Statement of information needed for inclusion is likely not a complete path to achieving No Objection.
In Section III Q, FDA is excluding any correspondence regarding the submission from confidentiality regardless of the topic of such correspondence. This would strangle such inquires as useful both in completion of the task but in attempting to work with FDA in such matters.
The issues with the NDI notification process include more than the matters touched on here. The issues of previously notified GRAS self-determinations and their applicability (even though a resolution has been promised); how does one make use of the NDI notification of the NDI used in a specific Dietary Supplement? What comes next in the safety evaluation of complex formulas with multiple Dietary Ingredients, both Old and New, and where can we find a current inventory list? The finalization of one section of the 2016 Draft Guidance is the first alert to address any remaining issues in the Draft Guidance in very short order, though not likely during this election cycle. This first finalization indicates that there is work remaining before this system gains the efficiency and effectiveness that it deserves.
[1] Dietary Supplement Health and Education Act of 1994. Public Law 103-417 103rd Congress. October, 1994.