FDA issues draft guidance on NDIN Master Files

Published this morning, this new draft guidance responds to requests from the dietary supplement industry for specific guidance on recommendations about Master Files for new dietary ingredient notifications (NDINs), according to a Constituent Update from the Agency​.

A Master File is an elective submission to FDA that contains data deemed proprietary by a company. 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.

In other words, as explained in today’s draft guidance, Master Files can be used to facilitate the submission of NDI-related identity, manufacturing and/or safety information to the FDA for use in evaluating a potential future NDIN.

According to the Agency, the recommendations in the new draft guidance expand upon and replace the recommendations related to Master Files in the FDA’s revised draft guidance “Dietary Supplements: New Dietary Ingredient Notifications and Related Issues​".

Commenting on the new draft guidance, Robert Durkin, partner and co-chair of the Food & Drug practice and Dietary Supplements industry team at Arnall Golden Gregory LLP, told us: "I’m surprised to see a second guidance document follow so closely to the first [“NDI Notification Procedures and Timeframes”​, which was issued at the start of March].

"I’m also curious why this guidance, on a far less controversial topic, is in draft, while the first, which covered a more significant topic, went immediately to final. What could be FDA’s basis for making this decision?" asked Durkin, who is a former acting Director and Deputy Director of FDA's Office of Dietary Supplement Programs (ODSP). "I suppose master file has its place in the NDIN space, but I don’t think is solves any problems. I think you can accomplish the same end with stand-alone agreements with an NDIN holder."

To read the Draft Guidance, please click HERE​​.

Questions​

Daniel Fabricant, president and CEO of the Natural Products Association (NPA), called the draft guidance, "progress, or something that resembles progress. The key thing is that the master file concept is great but without enforcement what does it really mean? There's no new resource burn here."

Loren Israelsen, founder and President of the United Natural Products Alliance (UNPA), told us that Master Files (MF) were an industry idea which FDA agreed to consider, “so let's see if almost 10 years later there is more or less interest in the MF concept than in 2015/16”.

Israelsen added that that the draft guidance raises two questions for UNPA and its membership:

First, how will the confidential information process work? “FDA assumes nothing is confidential unless you specifically say it is, and then FDA may disagree  / how to deal with that,” said Israelsen.

Second, what is the regulatory status of same or near same non-MF-authorized dietary ingredients? “Are they an unnotified NDI's and thus unlawful, or is the burden on the MF holder to go after the copycat (rather than FDA non enforcement for lack of resources). This will make the whole MF idea a long road to a small house, and therefore a less effective mechanism.”

Michael McGuffin, President of the AMerican Herbal Products Association (AHPA), said his organization is again pleased to see the Agency issue a standalone guidance to industry on new dietary ingredient notification (NDIN) issues. "As we have previously noted, this action is consistent with a suggestion AHPA made at an in-person meeting at FDA’s office in 2012, specifically that FDA address the issue of NDIN guidance with a section-by-section based approach," he said. 

"A well-functioning process for FDA to receive master files for NDINs may be of significant value to new dietary ingredient manufacturers that wish to ensure the distribution of their ingredients to only compliant customers. We look forward to FDA’s continued attention to a section-by-section approach to issuance of guidance for NDINs."

"A good start"

Striking a similar tone, Steve Mister, president and CEO of the Council for Responsible Nutrition (CRN), stated: "It's a positive development to see the FDA moving ahead with this draft guidance. In 2020, CRN developed an NDI master file framework for dietary supplements to protect our members' investments and intellectual property, and this is clearly a step in the right direction, incorporating many of the elements we put forward.​

"But as we have previously stated, meaningful enforcement alongside guidance is crucial in supporting responsible companies desiring to innovate, to protect investment while doing so, and to fairly compete. FDA must deter bad actors who circumvent the law thereby posing risk to public safety.​

"So, while we welcome this draft guidance, we, at the same time, strongly urge FDA to publicly announce its resolve to enforce the proper use of master files." ​

George Paraskevakos, Executive Director, International Probiotics Association (IPA), said his organization applauds the draft guidance as IPA has been a long-term proponent of Master Files. For an earlier article on the same topic​, Paraskevakos told NutraIngredients-USA that Master Files for probiotic strains have been successful in Canada, and the concept of Master Files and a pre-application approach of going to market has been proposed to many other governments around the world. The model was adopted into legislating probiotics in several cases, he said.

Paraskevakos added that the opportunity to comment on the draft guidance is a good start, and the ideal scenario would be to enter into discussions with the FDA on the topic through meetings and a workshop.

Duffy MacKay, Sr VP of Dietary Supplements at the Consumer Healthcare Products Association, said CHPA is pleased to see FDA move forward on its commitment to release a separate draft guidance document this year on master files.

“We have been a longtime supporter of a master file system for NDINs that will establish a framework to safeguard scientific data supporting an NDIN on a specific ingredient, preventing its unauthorized use by firms marketing similar, but not identical, ingredients. A well implemented master file system has the potential to benefit both industry and FDA by increasing submissions, enhancing public safety, and spurring product innovation and investments in science. Overall, this system should encourage companies to increase investments in research that demonstrate the safety of new ingredients and finished products," said Dr MacKay. 

“CHPA is currently reviewing the draft guidance in detail, but is generally pleased with the concept, while also recognizing FDA enforcement of the NDI regulation is critical for the master file system to realize its full potential. We appreciate FDA's ongoing efforts to advance this guidance, which will foster innovation and scientific development.”

Stakeholders can submit comments on the draft guidance within 60 days after publication in the Federal Register, and the Agency will take these into consideration before it begins work on the final version of the guidance. Submit electronic comments to www.regulations.gov​ to docket number FDA-2024-D-0706.

NDI notifications​

Under DSHEA (Dietary Supplement Health and Education Act of 1994), 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 file 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.)

First issued in 2011​, the initial NDI draft guidance was met with significant industry backlash​, which led to the Agency to admit that it was going back to the drawing board with the document. Five years later, a revised draft guidance was released​. At the time, Steve Mister, president and CEO of the Council for Responsible Nutrition, described the revised version as “more positive than negative”​, but some stakeholders still voiced concerns that the Agency’s approach would dampen innovation​.

Since then, the Agency has adopted more of a piecemeal approach to the NDIN guidance, stating that it is working “expeditiously”​ to finalize sections as and where it can.

Last month, it announced that it had finalized Section V (“NDI Notification Procedures and Timeframes”​), in addition to several related questions from other sections of the draft guidance.

When asked by NutraIngredients-USA if FDA has an anticipated timeline for release of other parts of the guidance, an Agency spokesperson told us that FDA is "prioritizing finalization of additional sections as the Agency completes its review and analysis in light of competing priorities". One industry source told us recently that he thought the industry would not have to wait too long for additional sections to be finalized over the course of 2024. 

Rend Al-Mondhiry, Partner at Amin Talati Wasserman, LLC, told NutraIngredients-USA: "It’s a positive sign to see FDA moving forward with this concept, especially so soon after it released the finalized version of Section V of the 2016 Revised Draft Guidance. While this draft guidance on master files certainly has the potential to make the process more efficient for NDIN submitters and might encourage more submissions, the major concerns with the 2016 Guidance still need to be addressed. Until industry and FDA can agree on what is an NDI that requires submission, issues like Master File just don’t seem as pressing."