Last month, FDA’s Center for Food Safety and Applied Nutrition (CFSAN) and Office of Food Policy and Response (OFPR) released an updated list of draft and final guidance topics that are a priority for the Agency’s Foods Program to complete during 2023. At the top of the list was dietary supplement Master Files.
A Master File is an elective submission to FDA that contains data deemed proprietary by a company, such as an ingredient manufacturer. The Master File submission procedure is already used extensively in the drug industry. In general, Master Files would allow a party other than the holder of the Master File to reference material without seeing proprietary contents of the file.
FDA views Master Files as a tool to promote better compliance with New Dietary Ingredient (NDI) notification requirements. Ingredient manufacturers see the concept as a way to protect investments in technology and innovation.
CRN: “NDI master files can only succeed when FDA commits to rigorous enforcement of its use”
In its new letter to Cara Welch, PhD, Director of the FDA’s Office of Dietary Supplement Programs, CRN states: “NDI master files can only succeed when FDA commits to rigorous enforcement of its use. This means FDA must be willing to allocate resources to identifying and prosecuting bad actors who ignore their obligation under the law to submit their own NDI notification and instead claim that their ingredient is identical to the innovator company’s ingredient. Effective deterrence requires FDA to prosecute some of these offenders to establish that a negative consequence may result from flouting the requirements.
“Proper enforcement of a master file program is essential to protect public health as well as to provide assurances to the innovating firms that there is sufficient economic incentive to invest the funds and time necessary to properly submit the NDI notification,” continues the letter, which is signed by Steve Mister, CRN’s President & CEO.
“The assurance of protection of the ingredient innovator’s intellectual property goes hand-in-hand with consumer safety. Unfortunately, three years ago, ODSP indicated to CRN that the agency could not commit resources to enforcement in this area.
“Indeed, FDA’s enforcement of the NDI program thus far has been negligible, with only occasional warning letters issued to firms that have not filed the requisite NDI notifications for their new ingredients.
“We were disappointed when FDA informed CRN that it did not intend to devote resources for enforcement of a master file program for dietary supplements three years ago and surprised last month when the agency announced it is moving forward with a guidance on master files. Unless resources are allocated to the regulation of dietary supplements, including enforcement of NDI notification requirements, FDA should rethink prioritizing a master files guidance,” added Mister.
NDI draft guidance
Under DSHEA (Dietary Supplement Health & Education Act), a manufacturer of an NDI —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.
FDA is supposed to respond with a letter either concurring with the assertion of safety or raising objections within that 75-day window. (FDA never puts itself in the position of ‘approving’ ingredients.)
The Agency issued its first draft guidance for New Dietary Ingredients in 2011, 17 years after the passage of DSHEA. Such was the backlash from the industry over this first attempt that the Agency agreed to go back to the drawing board, subsequently issuing a revised draft guidance in 2016. Seven years on from that and the industry is still awaiting a complete final guidance.
FDA officials admitted last year that the Agency intended to release multiple NDI draft guidance documents to the industry as smaller, discreet topics.
In the new letter to FDA CRN’s Mister stated: “Other pressing dietary supplement issues are awaiting the agency's action, including issuing other parts of the NDI guidance to address major concerns related to the agency's revised NDI draft guidance issued in August 2016, as well as a response to industry's citizen petition on the application of section 201(ff)(3)(B) of the federal Food, Drug and Cosmetic Act--the drug preclusion provision. FDA's attentions would be better spent on these endeavors.”
FDA has long maintained that there are potentially thousands of new ingredients on the market whose safety has never been officially assessed via an NDI notification.
In a six-page guidance released in May 2022, 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.