BACKGROUNDER
FDA Draft Guidance on New Dietary Ingredient Notifications for the Dietary Supplement Industry
Background
In the early 1990s, FDA attempted to regulate dietary ingredients as unapproved new food additives, thereby imposing on particular dietary ingredients the same requirements for premarket approval as it applied to chemicals that were added to food for non-nutritive reasons. Courts struck down that effort, accusing FDA of trying to make an end-run around the statutory scheme.1
Congress enacted the Dietary Supplement Health and Education Act (DSHEA) in 1994, declaring that dietary supplements shall not be regulated as food additives or as drugs. DSHEA defined the types of ingredients that would be permitted in dietary supplements and authorized statements of nutritional support describing how a product affects the structure and function of the body. Since its passage, DSHEA has succeeded in providing consumers with a broad range of safe and beneficial products. However, in 2011, FDA issued a draft guidance on New Dietary Ingredient (NDI) notifications that appeared to revive the “food additive” approach to regulating dietary supplements. After receiving more than 7,000 comments, in addition to many letters of concern from Members of Congress, including the authors of DSHEA, FDA committed to issue a revised draft guidance to address misinterpretations and align with the original intent of the law. In August 2016, FDA issued a revised—and improved—draft guidance on NDIs.
What is a New Dietary Ingredient?
DSHEA created two kinds of dietary ingredients for use in supplements: old (“grandfathered”) dietary ingredients (ODIs) that were already being sold prior to the enactment of DSHEA, and new dietary ingredients (NDIs) that were not marketed as dietary supplements in the United States before October 15, 1994. Dietary supplements containing ODIs were considered by Congress to be safe unless FDA demonstrated they were not. FDA has the burden to show that a “grandfathered” ingredient presents “a significant or unreasonable risk of injury or illness.”2 Since the passage of DSHEA, FDA has rarely invoked that part of the law for old ingredients (e.g., ephedra). For new dietary ingredients, however, DSHEA requires a pre-market notification to FDA at least 75 days before the NDI is placed into commerce. The 75-day pre-market notification must provide evidence that a dietary supplement containing the NDI is “reasonably expected to be safe.” 3
Overview of NDIs and DSHEA:
Over the past 22 years, the industry and FDA have developed different views of when an NDI notification is required and what data should be presented to FDA to satisfy the “reasonably expected to be safe” standard. In 1997, FDA issued a regulation4 on the NDI notification process that reiterated the statutory requirements but offered little clarity on FDA’s interpretation of the law. For 17 years, FDA provided no additional guidance to manufacturers on what should be included in an NDI notification; and companies could only glean from the experiences of other manufacturers. By 2011, FDA objected to more than 450 notices, while acknowledging (i.e., not objecting to) only 162 notifications. Despite the Agency’s criticism that the industry was filing far too few NDI notifications, FDA had only issued one warning letter to a firm for failing to file the required paperwork. Clearly, there was confusion as to when an NDI notification should be submitted and what should be included in the notification.
Against this backdrop, the dietary supplement industry began pressing for a guidance to clarify the NDI notification requirements. Finally, at the insistence of Congress in the Food Safety Modernization Act,5 FDA issued a draft Guidance for Industry: New Dietary Ingredient Notifications and Related Issues in July 2011. At the time, industry believed that FDA’s interpretation had disregarded Congress’ original intent for NDIs and raised fundamental questions for the implementation of DSHEA.
2016 Revised Draft NDI Guidance Still Raises Concerns for Implementation of DSHEA
CRN filed thoughtful and extensive comments that elaborated how the 2011 draft guidance misread the statute, misinterpreted the legislative history of DSHEA, and ignored the precedent of 17 years of FDA’s implementation of the NDI requirements. After reviewing over 7,000 comments from stakeholders, FDA responded with a revised draft guidance in August 2016 in which the agency affirmed many of its previous positions while providing further clarification in areas that were subjects of consternation.
In the revised draft guidance, FDA addressed a few of the major issues raised by the original draft guidance. Notably, FDA offered to establish an authoritative list of old dietary ingredients that are not subject to NDI notification requirements. This list would create a safe harbor for newer companies that do not have physical evidence that an ingredient was on the market over 20 years ago. The revised draft guidance introduced the option to create a confidential “umbrella notification” and master file and allows a supplement manufacturer to reference safety data contained in a NDI master file created by its supplier instead of submitting redundant safety data. The NDI master file enables supplement manufacturers to purchase and use NDIs that have safety data on file, while protecting the intellectual property of the ingredient supplier that originally submitted the notification. Finally, the revised draft guidance clarified how ingredients that are generally recognized as safe (GRAS) for use in conventional foods can also be used in dietary supplements.
However, the following areas of the revised draft guidance continue to contravene the intent of DSHEA and create unnecessary barriers to market for new dietary ingredients:
- FDA continues to apply a narrow reading of the definition of a dietary ingredient and erroneously excludes synthetic versions of botanical ingredients from all categories of dietary ingredients. Even if the ingredient is chemically identical to its botanical counterpart, FDA states that it was “never part of the botanical” so it cannot be characterized as a constituent. FDA’s narrow interpretation does not consider the safety of the ingredient. Manufacturers use chemically identical synthetics because they are as safe as their botanical counterparts while being more uniform, more environmentally sustainable and more commercially viable.
- An authoritative list of old dietary ingredients that are not subject to NDI notification requirements creates an opportunity for a safe harbor; however, CRN still has concerns that FDA continues to place undue burden to prove an ingredient is “old” onto the marketer. FDA rejects industry-prepared lists of pre-1994 ingredients and affidavits of manufacturers as evidence of pre-1994 sales, saying marketers must prove to FDA with documentary evidence that the ingredient was marketed prior to 1994. Any list to which FDA agrees is likely to contain few ingredients and omit a number of ingredients included in the trade association lists, which industry has relied on for over 20 years.
- While the law is clear that a food or food constituent that is “chemically altered” becomes a new dietary ingredient if it is marketed in or as a dietary supplement, FDA broadly defines what is “chemically altered” so that even slight changes that do not affect safety may make a food or food constituent—long presumed to be safe—into new dietary ingredients subject to additional, burdensome scientific assessment.
- FDA applies a similar burden to marketers of old dietary ingredients, and even previously-notified NDIs, that are manufactured differently than they were previously. The revised draft guidance indicates that even slight manufacturing changes that do not impact the safety of an ingredient would trigger the notification requirement. FDA’s broad interpretation of “manufacturing changes” would likely trigger numerous NDI notifications and exhausting cycles of innovating, filing, and waiting for FDA’s acknowledgment, with each new improvement in manufacturing techniques. The result would create a backlog of notifications for industry and FDA alike and constrain innovation while increasing the costs to bring new technology to market.
- FDA interprets the statute to require that almost every product that contains an NDI would require a separate notice to FDA with a separate demonstration of safety. DSHEA says the dietary supplement containing the ingredient must “reasonably be expected to be safe,” but does not demand a separate filing for each product. FDA wants each finished product containing an NDI to have its own notification on file. Although the NDI master file would allow an ingredient supplier to “do the science” for their customers, it would not likely anticipate every supplement formulation. FDA deems that adding another dietary ingredient, even an old one with a history of safe use, creates a new formulation that would require a separate NDI notification. This would result in redundant notifications for similar products, creating increased costs to industry and more backlog at FDA. Furthermore, the FDCA adulteration provision already requires that manufacturers provide a reasonable assurance in the safety of a finished dietary supplement that contains an NDI and other dietary ingredients.6
The revised draft guidance is intended to help dietary supplement companies determine whether a substance is a dietary ingredient at all; when it is a new dietary ingredient; when a NDI notification is required; and how to prepare and submit a notification. CRN welcomes such a document, but has concerns that sections of the revised draft guidance may inappropriately narrow the scope of legal dietary ingredients and re-characterize many old dietary ingredients as NDIs, which would allow FDA to conduct pre-market review of these ingredients. The NDI provision of DSHEA was never intended to permit FDA to assert premarket approval over the dietary supplement marketplace—in fact, one of the objectives of BACKGROUNDER continued: New Dietary Ingredients for the Dietary Supplement Industry DSHEA was exactly the opposite. However, an eventuality of the guidance is that as ingredients become the objects of manufacturing improvements, they would be converted to NDIs requiring notification even if the manufacturing changes did not impact the safety of the ingredients.
If the revised guidance is enforced, and FDA’s thinking does not continue to evolve, it could restrict innovation and product improvements, and would likely overwhelm FDA with submissions. Should responsible industry members begin to act in accordance with the guidance’s more onerous demands, the sheer number of NDI submissions for ingredients for which there have been manufacturing changes and improvements would be both a drain on FDA’s limited federal funds and a barrier to market, slowing down innovation by industry. FDA may inappropriately use its scarce resources to enforce this guidance against safe products containing ingredients FDA considers to be “new” instead of focusing on egregious actors who illicitly defraud the consumer by spiking dietary supplements with illegal prescription drugs and anabolic steroids. It is certain that the negative economic impact of this revised draft guidance on the dietary supplement industry would be substantial (e.g., additional bureaucratic filing requirements, redundant safety testing for ingredients already demonstrated to be safe, loss of manufacturing jobs, reduced availability of ingredients, less access to innovative products).
CRN believes the revised draft guidance is a significant improvement from FDA’s stated position on NDIs in 2011; however, it has not moved far enough to provide a workable framework for distinguishing between old and new dietary ingredients. It still requires clarification, and in some cases, additional refinement and evolution. The revised draft guidance still fails to acknowledge the wide margins of safety for dietary supplements and the Congressional mandate that dietary supplements are to be regulated as “food.” Rather, it sets a course towards reclassifying many time-honored ingredients into pre-market review. Vigorous oversight and supervision by Congress will be required to assure that FDA does not exceed the authority DSHEA provided or misinterpret the NDI provision of the law.
1 See, e.g., United States v. Two Plastic Drums...Black Currant Oil (Traco Labs, Inc.), 984 F.2d 815 (7th Cir. 1993).
2 Food, Drug & Cosmetic Act (FDCA) §402(f)(1)(A), 21 U.S.C. §342(f)(1)(A).
3 Food, Drug & Cosmetic Act (FDCA) §413(a), 21 U.S.C. §350b(a).
4 21 CFR 190.6.
5 P.L. 111-353 (2011).
6 Food, Drug & Cosmetic Act (FDCA) §402(f)(1); 21 USC §342(f)(1).