New Dietary Ingredients (NDI) and Innovation in Dietary Supplements: A Call for New Compliance and Enforcement Strategies
By Megan Olsen and Andrew Shao, Council for Responsible Nutrition
Edited by Suzie Trigg, Haynes and Boone LLP
On May 16, 2019, dietary supplement industry spokespersons, Food and Drug Administration (FDA) leaders, and other interested parties gathered together for a public meeting at the FDA’s Center for Food Safety and Applied Nutrition (CFSAN) College Park, MD headquarters to discuss dietary supplement innovation. The meeting—entitled “Responsible Innovation in Dietary Supplements”—predominantly focused on FDA’s approach to New Dietary Ingredient (NDI) provisions of the Food, Drug and Cosmetic Act (FDCA), but also addressed many other areas in which participants felt that FDA was affecting innovation and impacting consumer safety. This was a well-attended event, with a full auditorium of speakers and attendees.
The FDA announced the Public Meeting on April 11, 2019 via a Federal Register notice in which FDA sought comments from interested parties to help the agency facilitate “responsible innovation in the dietary supplement industry while preserving and strengthening FDA’s ability to efficiently and effectively protect the public from unsafe and unlawful products.” To help achieve this balance, FDA is seeking comments on a number of topics from the scope of substances that are considered dietary ingredients, to ways to incentivize responsible innovation, to how FDA can promote overall compliance with regulatory requirements. Though the Public Meeting has concluded, those interested in contributing comments to this process may submit written comments to the Docket until July 15, 2019.
Who’s Who of the May 16th Meeting and Their Roles
Notable attendees included Steven Tave, Director of the FDA Office of Dietary Supplement Programs (ODSP) and Dr. Cara Welch, Special Assistant to the Deputy Commissioner of Policy, Legislation, and International Affairs at FDA. Leadership from major trade organizations representing the dietary supplement industry also attended and provided presentations during the Public Meeting, including representatives from the Council for Responsible Nutrition (CRN), Consumer Healthcare Products Association (CHPA), American Herbal Products Association (AHPA), United Natural Products Alliance (UNPA), and the Natural Products Association (NPA). Representatives from consumer protection groups, including the Center for Science in the Public Interest (CSPI) and Truth in Advertising (TINA), also attended and provided comment. Attendees were also fortunate to hear from the FDA’s Acting Commissioner, Dr. Ned Sharpless, who reiterated FDA’s commitment to modernize supplement regulations—a goal first articulated by his predecessor, Dr. Scott Gottlieb, in February 2019.
The meeting consisted of four panels, on which industry and consumer representatives were invited to speak. Participants also heard from representatives from Health Canada to help assess whether Canada’s regulation of health products could serve as a model to improve regulation in the U.S. The other panels explored (1) the scope of what ingredients are permissible under section 201(ff) of the FDCA; (2) issues related to when a company is not required to file a notice with FDA that they are using an NDI; and (3) how FDA can better enforce NDI notification requirements and incentivize companies to file these notifications. General attendees to the meeting also were given an opportunity to provide comments and questions following each panel and at an open public comment session at the end of the meeting.
Why All the Fuss About NDIs?
Under Section 413(a)(2) of the FDCA, the manufacturer or distributor of a dietary supplement must notify FDA 75 days before introducing a new product containing an NDI into interstate commerce. An NDI is an ingredient that was not marketed in the U.S. in a dietary supplement before October 15, 1994. As part of this notification process, companies must provide evidence establishing that “the dietary ingredient when used under the conditions recommended or suggested in the labeling of the dietary supplement will reasonably be expected to be safe” (emphasis added). There are exemptions to NDI notification requirements, such as whether the NDI has previously been used in the food supply, but, overall, NDI notifications are intended to be an important part of FDA’s process for ensuring the safety of dietary supplements.
Responsible industry participants and trade associations have often communicated to the FDA that there is a need for greater enforcement of NDI requirements since the NDI process is an important safety process. To this end, Steven Tave with FDA’s ODSP acknowledged that the number of NDI submissions has been far less than what the agency would expect given the number of dietary supplements in the marketplace.
Commenters provided potential reasons for the disconnect between the number of products on the market and NDI notifications filed. For example, the manner in which FDA treats NDI notification data was highlighted during the public meeting as problematic. While some information that a submitter provides to FDA in connection with an NDI notification is subject to limited protection under exemptions from disclosure provided by the Freedom of Information Act (FOIA) and other federal laws, data filed with an NDI notification will, for the most part, be made publicly available because FDA is required to make NDI notifications public.
Second, companies marketing what may be perceived as similar ingredients to those that were the subject of an earlier and successful notification often piggyback on the first company’s NDI notification, neglecting to file their own notification. Such a system, many commentators noted, disincentivizes companies to generate the necessary safety data specific to their NDI and to file NDI notifications. On one hand, the NDI notification process requires ingredient manufacturers to invest significant resources to establish the safety of new ingredients, when instead such manufacturers could more easily rely on an already successful notification on a similar ingredient. On the other hand, a competitor marketing a similar ingredient could potentially rely on the same notification for their own use, with no repercussions. Several commentators offered up for FDA’s consideration possible solutions to help protect a company’s valuable investment in NDI safety research and incentivize companies, not only to innovate, but also to comply with the NDI notification process.
Master Files Proposed as a Solution for FDA’s NDI Notification Woes
A number of participants at the meeting emphasized that FDA should work to provide intellectual property protection for safety data that an industry participant submits to the FDA in connection with an NDI notification. Commenters, including one of this article’s coauthor’s—Dr. Andrew Shao—noted that companies are disincentivized to participate in the process because other companies can rely on the safety data of the first notifier and come to the market without having to make the same safety investment or even file a notification.
Thus, many commenters, such as Dr. Jay Sirois with CHPA, supported the idea of a “Master File”—a system that would allow FDA to establish a means to collect and protect data investments made by ingredient manufactures that are specific to their products. Under this system, an ingredient manufacturer would submit proprietary data (including detailed specifications, manufacturing processes, safety studies, etc.) on its ingredient to FDA, which would create a Master File maintained by the agency. Other companies wishing to leverage this information for their own NDI notification, with the permission of the company that submitted the original NDI Master File, would be required to cite the Master File.
Many commenters pointed out that FDA already uses a similar system for drug products, and thus the agency already has a precedent on which to base a similar system for dietary supplements. This system would provide confidence that ingredient manufacturers could file the requisite NDI notifications without the concern of competitors pirating their information and would require competitors to either perform their own due diligence on their ingredients or seek permission for relying on others’ Master File information.
Further, commenters noted that for any system to be successful, FDA must pursue enforcement actions targeted toward failures to comply with the NDI process. The FDA’s recent issuance of eleven warning letters to dietary supplement marketers that, among other alleged violations of law, failed to submit NDI notifications for a variety of ingredients found in sports and weight loss products indicate that the agency is already working toward this goal.
It is the authors’ belief that if companies do not believe there are consequences for failing to comply with NDI requirements, nefarious companies will take advantage of the opportunity to distribute products without following regulatory requirements, while responsible companies will be burdened with following the requirements that others ignore. This simultaneously creates a culture of noncompliance and fosters an unlevel playing field. Examples of the host of authorities that FDA may be able to use to enforce these regulatory provisions include using its mandatory recall authority, seizing violative product, using administrative detentions, imposing fines, debarments and injunctions, and issuing import alerts. Commenters, such as Dr. Shao with CRN and Dr. Fabricant with NPA, urged FDA to examine its existing enforcement framework to develop enforcement schemes that provide the best “return on investment” by deterring wrongdoers while using limited FDA resources efficiently.
Certain comments during the Public Meeting also highlighted the extensive responsibilities that FDA’s ODSP must accomplish with relatively limited resources. Manon Bombardier, Health Canada’s Director General for Natural and Non-Prescription Health Products (NHPD), noted that NHPD employs approximately 150 staff and has a budget of about $10.4 million (U.S. dollars) for premarket review of products. In contrast, FDA’s ODSP has 24 employees and an annual budget of approximately $7 million to oversee a wide array of both pre-market and post-market surveillance activities.
A Variety of Other Concerns May Be Affecting Industry Innovation
In addition to discussing NDIs, a number of presenters raised the subject of a mandatory premarket product listing. Former FDA Commissioner, Dr. Gottlieb, along with other FDA staff, have repeatedly brought this issue to the forefront of industry attention in recent months. Dr. Gottlieb first highlighted whether mandatory listing was necessary to effectively regulate the dietary supplement industry in comments in February 2019, and FDA has requested this authority as part of its fiscal year 2020 budget. FDA is seeking authority to require dietary supplement companies to provide FDA a list of products they have on or are bringing to the market.
There are still a variety of opinions in the industry as to whether mandatory product listing is necessary, or even helpful, for effective enforcement; however, several speakers at the Public Meeting supported the concept, including dietary supplement trade associations and long-time industry attorneys. Supporters have cited the prospect that such a registry would assist FDA in more easily identifying violative products and noncompliant companies.
The topic of synthetic botanicals was another significant issue discussed during the meeting. Dr. Welch, with FDA, noted that “[t]here is no such thing as a synthetic herb or botanical,” but left the door open as to whether the use of synthetic copies of botanical constituents or nutritional compounds is permissible. Synthetic vitamins are permitted, as well as synthetic food substances, drugs, and cosmetics—raising questions from panelists as to why FDA has made distinctions on the legality of synthetic compounds as dietary ingredients in dietary supplements based on their source. Industry trade groups generally support that synthetic copies of botanical constituents should be legal dietary ingredients, and panelists raised two important issues: (1) should companies developing synthetic copies of botanical constituents (even if bioidentical to the botanical constituent) file an NDI notification to help FDA better assess their safety (issue identified by Scott Bass, attorney with Sidley Austin); and (2) should synthetic constituents be disclosed on the label to distinguish from the naturally occurring versions and for consumer transparency (raised by Larisa Pavlick with UNPA).
FDA Should Seize on Current Strong FDA-Industry Relationship to Move Dietary Supplements into the Future
The Public Meeting showed a collaborative relationship between FDA and responsible industry. Both FDA and industry appear to be communicating more frequently and working together more collegially than has historically been the case. It is clear now more than ever, that both groups share key areas of common ground, including the desire to provide consumers with safe, well-made, properly labeled dietary supplements, along with the proper information to make informed decisions. This strong relationship and collaborative spirit presents FDA an opportunity to achieve its goals to modernize dietary supplement regulation and oversight, but FDA should be careful to continue to do so in a transparent manner that involves responsible industry.