This article discusses FDA's publication of its revised draft of Dietary Supplements: New Dietary Ingredient Notifications and Related Issues: Guidance for Industry (2016 Draft Guidance) and the implications regarding the lack of finalization in the year following its publication. The authors make suggestions regarding what companies may begin doing prior to and in anticipation of eventual finalization.
Regarding how dietary supplements should be regulated, particularly with regard to New Dietary Ingredient (NDI) notifications, there have been a few differences in opinion between the dietary supplement industry and the US Food and Drug Administration (FDA). Yet, industry's reaction to FDA's publication of its revised draft of Dietary Supplements: New Dietary Ingredient Notifications and Related Issues: Guidance for Industry (2016 Draft Guidance) seemed to be measured in comparison to reactions following the previous draft's release.1 Despite this, there was still a scramble to determine what the revisions were and how they would affect each company's products. Many hoped there would be more answers after the "dust settled," but industry is still trying to determine the long-term effect of the 2016 Draft Guidance. Without new information or an anticipated finalization date, questions remain about the impact and what to do about it.
A Trip Down NDI Memory Lane
The Dietary Supplement Health and Education Act of 1994 (DSHEA) formally created the category "dietary supplements" and along with this formal recognition, laid the groundwork for categorizing an ingredient as a NDI and for submitting pre-market NDI notifications.2 Any dietary ingredient marketed after 15 October 1994 is deemed to be an NDI for which a notification is required (unless an exemption applies).3 Conversely, an ingredient marketed before 15 October 1994 is commonly called an Old Dietary Ingredient (ODI) and a notification prior to marketing is not required. FDA first published a draft guidance for industry regarding NDI notifications in 2011 (2011 Draft Guidance).4 Overall, the 2011 Draft Guidance was subject to extensive criticism by industry as it was considered burdensome and overly broad. In August, FDA released an updated 2016 Draft Guidance in response to submitted comments. While it brought many changes and updates (some more desirable than others), there are a handful of particularly noteworthy points.
Acceptable ODI Documentation- additional examples of what documentation is appropriate and what documentation may not be sufficient to establish ODI status were provided.
Potential Authoritative "Grandfathered" List - FDA expressed a willingness to create an authoritative list of ODI or "grandfathered" dietary ingredients, but cautioned creation of the list may be difficult, requiring extensive identity information.
Elaboration on Manufacturing Changes - the 2016 Draft Guidance provides more examples of which processes would be considered a manufacturing change. The examples rely heavily on a 2014 FDA Final Guidance Document – Guidance for Industry: Assessing the Effects of Significant Manufacturing Process Changes, Including Emerging Technologies, on the Safety and Regulatory Status of Food Ingredients and Food Contact Substances, Including Food Ingredients that are Color Additives.5 Note: the manufacturing change standard applies when assessing whether an ingredient that was an ODI or had been changed in such a way that caused it to become an NDI.
Food Supply Exemption Clarification - the 2016 Draft Guidance limits the food supply exemption to inclusion in conventional food; inclusion in a dietary supplement prior to 15 October 1994 would not qualify the dietary ingredient for the food supply exemption.
Acknowledgment of DSHEA's no Chemical Alteration Examples as Non-Exhaustive - DSHEA provides a short list of processes not considered to result in chemical alteration. The 2016 Draft Guidance acknowledges that this list is not exhaustive and that there are other processes that may not result in a chemical alteration. The chemical alteration standard is relevant for determining whether an NDI subject to the food supply exemption has become an NDI requiring a notification.
Synthetic Botanical Explanation - a significant area of concern with the 2011 Draft Guidance was the assertion that synthetic copies of botanicals (synthetic botanicals) cannot be dietary ingredients because they are not considered a "herb or other botanical" under DSHEA's definition of "dietary ingredient."6 This position continues through 2016, although FDA clarified how a synthetic botanical may meet the definition of a "dietary ingredient" if it is lawfully used in the conventional food supply and therefore a "dietary substance for use by man to supplement the diet…" (i.e., it qualifies as a "dietary ingredient" through a different subsection of the definition).7
Examples of When an NDI Notification is Required and Creation of a Master File- FDA added numerous new examples explaining when an NDI notification may be needed and when it is not. And where the 2011 Draft Guidance would have required a separate notification for every product containing an NDI, the 2016 Draft Guidance discusses FDA's willingness to consider a new procedure that allows for a Master File submission that can cover a range of products.
Removal of Redbook References- the 2016 Draft Guidance lacks any of the references to FDA's Toxicological Principles for the Safety Assessment of Food Ingredients (Redbook) that the 2011 Draft Guidance had included and instead, provides other references for toxicological studies.8
A year later, industry's general feeling seems to be that while a step in the right direction, the 2016 Draft Guidance leaves significant concerns from the 2011 Draft Guidance that are inadequately addressed. The primary criticism is that the 2016 Draft Guidance blurs the edges between safety standards for foods, supplements, and drugs, and seems to be applying a higher standard than what Congress and DSHEA intended. Another prevalent criticism is that NDI notification requirements are still unwieldy and cost-prohibitive.
Since its release last August, the 2016 Draft Guidance has had a surprisingly minimal regulatory impact. Many companies and commentators feared a potential "uptick" in regulatory action against potential NDIs with unsubmitted notifications. Some also were concerned there would be a swift review period and the 2016 Draft Guidance would be finalized with little time for meaningful review and updates. Neither concern has materialized within the first year.
Perhaps the biggest worry regarded the potential for increased regulatory actions against ingredients currently in the market, but may now require a NDI notification. However, among the Warning Letters FDA sent since August 2016, only two appear to discuss ingredients being potential NDIs.9, 10 Both letters involved to Acacia rigidula, which was the subject of a wave of Warning Letters sent in March 2016, months prior to the release of the 2016 Draft Guidance. Therefore, it appears no new NDI-related Warning Letters have been issued since the 2016 Draft Guidance's release, indicating that NDI notification compliance may not be currently an enforcement priority.
There appears to also be no significant changes in NDI notification submissions. At a presentation, FDA recently commented that the variation in the number of NDI notifications received has not significantly changed from the years prior to the 2016 Draft Guidance. However, data indicate the percentage of NDI notifications accepted by FDA prior to the 2016 Draft Guidance's release was steadily increasing.11 Data on acceptance post-2016 Draft Guidance are still being collected and analyzed, but the outcome seems promising, given the lack of increase in volume and higher acceptance rate.
Finalization of the Draft Guidance
FDA is now reviewing comments submitted during the comment period following the 2016 Draft Guidance's release. More than 7,000 comments had been submitted when the extended comment period closed on 12 December 2016.12 Such a large volume will certainly take time to evaluate, although initial murmurings suggested FDA would be looking to finalize the 2016 Draft Guidance within a calendar year. However, there has been no indication of when FDA expects to have its review completed and when finalized guidance will be published.
There has been a push by the Senate for FDA to finalize the 2016 Draft Guidance sooner rather than later. In December 2016, Senator Claire McCaskill (D-MO) sent FDA a letter urging reconsideration of parts of the 2016 Draft Guidance and to finalize it as quickly as possible.13 More recently, in July 2017, the Senate Appropriations Committee Report requested FDA to meet with stakeholders regarding the 2016 Draft Guidance,14 signaling they likely want the matter to be finalized soon as the theme of the Senate's Report seems to be encouraging FDA to wrap up pending regulatory matters. Despite these political pressures, there is no information as to when the 2016 Draft Guidance will be finalized or if there will be a chance to provide more comments to FDA.
Current Regulatory Climate
While the past year has shown next to no movement toward finalization on the 2016 Draft Guidance front, it is unclear whether this is only temporary or will continue for an extended amount of time. While there was a several year gap between the previous 2011 Draft Guidance and the 2016 Draft Guidance, with the Trump Administration's de facto freeze on regulatory action and attempts to scale back current regulations, there are serious questions regarding the 2016 Draft Guidance's fate in the near future.
One of those questions is whether the 2016 Draft Guidance is even on the FDA agenda. As with other federal agencies, FDA is required to create a regulatory agenda each year, called a Unified Agenda.15, 16 Currently, FDA's Unified Agenda does not list the 2016 Draft Guidance as an active, long-term, or even inactive item.17 However, this is not dispositive as the current Unified Agenda lists regulations, but not guidance documents, despite several draft guidance documents pending finalization.
Another hurdle is Executive Order 13771 (EO) for reducing regulations.18 This EO requires two regulations to be eliminated for every new regulation enacted. According to the guidance provided to the federal agencies on implementing the EO, new "significant" guidance documents "will be addressed on a case-by-case basis" as to whether they are covered.19 How a "significant" guidance document is defined is unclear, but a "significant regulatory action" that would be subject to the EO is one that, among other things, has "an annual effect on the economy of $100 million or more or adversely impact in a material way the economy, a sector of the economy, productivity, competition, jobs, the environment, public health or safety, or State, local, or tribal governments or communities."20 Based on this definition, it is unclear whether the 2016 Draft Guidance would be considered "significant," although it is not impossible that it would meet the monetary threshold. Because NDI notifications are manufacturer-specific, the costs of safety testing and producing a dossier can add up quickly, depending on the number of ingredients affected. Therefore, in addition to finalizing the document, FDA may face challenges in calculating marketplace effect, consulting with the Office of Information and Regulatory Affairs to determine whether the 2016Draft Guidance is covered by the Executive Order, and if so, identifying regulations to subsequently eliminate.
Overall, given the current regulatory climate, there is a legitimate question as to whether the 2016 Draft Guidance will be finalized in the near future. Although no one has a crystal ball, today the signs are pointing toward there being procedural concerns that may delay FDA's finalization. Considering the first revision took five years, and without the current regulatory "chill," there is the potential for a substantial delay in finalization.
Marketplace Impact Since the Draft Guidance's Release
While there has been minimal movement on the regulatory end, the 2016 Draft Guidance has begun to have a marketplace impact. The most notable instance is the retailers' reaction and incorporation of NDI examinations into product reviews. But the good news is that a lack of NDI notification compliance does not seem to provide a smooth path for consumer class actions.
Although FDA may not be actively citing the 2016 Draft Guidance in enforcement actions, its release put NDIs back onto the "radar" for dietary supplement retailers. Many retailers already review products for compliance with FDA labeling requirements. However, there is a growing trend for a heightened review of ingredient safety. Retailers are more often inquiring into each dietary ingredient's regulatory status and specifically asking whether the ingredient is an NDI, and if so, whether it is the subject of a notification. Many retailer's questions regarding NDI status can be answered through information on the ingredient's source and manufacturing, but being prepared with appropriate documentation is critical.
Of course, the 2016 Draft Guidance may not be the sole factor for the increased examination by retailers. Enforcement actions by state Attorneys General also may be an important trigger as well, such as the Oregon21 action against GNC and the New York botanical allegations against Walgreens, GNC, Walmart, and Target.22 Additionally, attorney general allegations usually start with a private letter and may include potentially years of discussions prior to any public announcement or filing of a case. Therefore, it is possible that there are attorney general allegation actions pending.
In a rare situation in the ever-increasing consumer class actions in the industry, NDI notification violations are likely a difficult argument for a consumer class action suit. Attorneys general are in a position to directly enforce ingredient safety compliance via their state's analog of the Federal Food Drug and Cosmetic Act (FD&C Act) because they are state authorities enforcing a state law. However, this is a position generally not available to private consumers. The FD&C Act does not provide a private cause of action, meaning that private individuals are unable to bring legal actions seeking to directly enforce compliance with its provisions. This is why when a private consumer brings a class action regarding supplement products, they do so usually under state consumer protection laws and "piggy back" allegations off of FD&C Act violations. Put another way, a consumer cannot sue by only alleging that a product is adulterated/misbranded under the FD&C Act; instead, the consumer needs to allege that the product is adulterated/misbranded under the FD&C Act and this adulteration/misbranding caused them to be deceived. It is this second part that can cause a "hiccup" for a potential plaintiff asserting an NDI notification violation. However, how is the failure to comply with the NDI notification requirement deceptive to a consumer? If a consumer cannot thread this needle, they are merely alleging a violation of the FD&C Act, an allegation they have no legal right to privately assert.
A California court recently agreed that private citizens had no legal right to allege such a violation and dismissed a consumer class action that alleged failure to comply with the NDI notification requirement for certain nitrate ingredients.23 In attempt to link this claim through a state consumer protection statute, the plaintiffs alleged that the failure to comply made the products worthless as a matter of law, and also that they would not have purchased products if they had known FDA had not approved the products as safe. The plaintiffs also tried to link their claim through state "adulteration" statutes instead of the FD&C Act. However, the court ultimately found these state law claims unpersuasive and determined that the consumers were essentially alleging only a violation of the FD&C Act. The court reasoned the alleged failure to submit a notification would only violate the FD&C Act and not any state laws and, thus, was an attempt to privately enforce the FD&C Act. The claim was dismissed because the court found there is no private right to enforce the NDI notification requirement of the FD&C Act.
The above case only applies where the allegation is merely a failure to submit a notification for an NDI. If FDA has affirmatively stated an ingredient is not a dietary ingredient (such as picamilon or BMPEA), this is a different matter and different laws apply.
Despite little regulatory movement, some marketplace impacts have been seen regarding compliance with NDI notification requirements. Arguably, the most important impact has been on the retailers' closer attention to an ingredient's regulatory status prior to selling a dietary supplement. Companies must begin preparing for heightened questions from retailers and, hopefully, preparation for the retailers now will be fruitful when the 2016 Draft Guidance is finalized.
Preparing Your Company for the Next Steps
As with the 2011 Draft Guidance, the aftermath of the 2016 Draft Guidance seems to be heading into a long period of "wait-and-watch." But the waiting does not need to be idle. Many companies have started preparing for when the 2016 Draft Guidance is finalized. A prudent approach would be to make a risk-based analysis entailing compiling a list of all dietary ingredients in all products and categorizing each based on its level of risk. A simple method would be a three-color system (red = high risk, yellow = medium risk, and green = low risk), although more complex scales can be used as necessary. To accurately categorize an ingredient's risk requires a frank assessment of an ingredient's potential regulatory status. Important questions to consider in this analysis include:
- Does this ingredient meet the definition of dietary ingredient?
- Is there adequate documentation of this ingredient's ODI status?
- Has the product undergone a manufacturing change?
- Does some food supply exemption apply, and if so, has the ingredient been chemically altered?
- Has my supplier submitted a NDI notification or is there a GRAS affirmation?
Once all products have been categorized, the next step is to determine action plans for the highest risk ingredients. It may be judicious to focus on ingredients in the "bread and butter" products first as well. No matter which way the list is analyzed, the objective is to have a picture of the company's current exposure and an understanding of steps to take to minimize potential risks. This will help locate ingredients that may require an NDI notification so that a company can be fully prepared to submit a notification if it is determined to be ultimately necessary for regulatory compliance.
Beyond preparing for the 2016 Draft Guidance's inevitable finalization, this risk assessment also would be a tool helpful in preparation for retailer inquiries. By proactively conducting an assessment, a company will be in a position for informed discussions with retailers and have appropriate documentation on-hand for answering any questions.
While the past year has not provided greater insight into the long-term effects of the 2016 Draft Guidance, it has been helpful to have the time to digest the revisions and strategize future compliance. Although there is no indication as to when FDA will finalize the 2016 Draft Guidance, the industry has started to adopt the more significant aspects and started to determine how it will comply when the finalization rolls around. It is expected that there will not be any large changes in the final guidance, so the best step is to begin planning now in order to minimize potential pitfalls. Early planning also will be helpful in assuring retailers of a continued commitment to full compliance with all dietary supplement regulations.
- Dietary Supplements: New Dietary Ingredient Notifications and Related Issues: Guidance for Industry. August 2016. FDA website. http://www.fda.gov/downloads/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/UCM515733.pdf. Accessed 16 October 2017.
- Dietary Supplement Health and Education Act of 1994 (Public Law 103-417, 103rd Congress).
- 21 USC § 350b.
- 76 FR 39111 (5 July 2011).
- Guidance for Industry: Assessing the Effects of Significant Manufacturing Process Changes, Including Emerging Technologies, on the Safety and Regulatory Status of Food Ingredients and Food Contact substances, Including Food Ingredients that are Color Additives. June 2014. FDA website. https://www.fda.gov/downloads/Cosmetics/GuidanceRegulation/GuidanceDocuments/UCM300927.pdf. Accessed 10 October 2017.
- 21 USC § 321(ff)(1)(c).
- 21 USC § 321(ff)(1)(e).
- Guidance for Industry and Other Stakeholders: Toxicological Principles for the Safety Assessment of Food Ingredients. July 2000; revised July 2007. FDA website. https://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/IngredientsAdditivesGRASPackaging/ucm2006826.htm. Accessed 10 October 2017.
- Warning Letter to Nutrishop d/b/a Natural Generation Nutrition. 24 February 2017. https://www.fda.gov/iceci/enforcementactions/warningletters/2017/ucm545775.htm). FDA website. Accessed 10 October 2017.
- Warning Letter to Xcel Sports Nutrition, LLC, 8 June 2017. https://www.fda.gov/iceci/enforcementactions/warningletters/2017/ucm564584.htm). Accessed 10 October 2017.
- Long, In FY16, FDA Objected to Fewer Dietary Supplement Ingredient Notices, 10 July 2017. Natural Products Insider website. https://www.naturalproductsinsider.com/blogs/insider-law/2017/07/in-fy16-fda-objected-to-fewer-dietary-supplement.aspx).Accessed 10 October 2017.
- Docket ID: FDA-2011-D-0376. US Regulations.gov website. https://www.regulations.gov/docketBrowser?rpp=25&so=DESC&sb=commentDueDate&po=0&dct=N%2BFR%2BPR%2BO&D=FDA-2011-D-0376). . Accessed 10 October 2017.
- Letter From Senator McCaskill to Dr. Califf, FDA Commissioner, 12 December 2016. US Senator McCaskill website. https://www.mccaskill.senate.gov/imo/media/doc/Mccaskill%20Comment%20re%20NDI%20Draft%20guidance%2012.12.16.pdf. Accessed 10 October 2017.
- Senate Report 115-131, Appropriations Committee Report on Agriculture, Rural Development, Food and Drug and Administration, and Related Agencies Appropriations Bill 2018, page 92. July 2017. US Senate website. https://www.appropriations.senate.gov/imo/media/doc/FY2018%20Agriculture%20Appropriations%20Bill,%20Report%20115-131.pdf). Accessed 10 October 2017.
- Unified Agenda-TRACK. FDA website. https://www.fda.gov/AboutFDA/Transparency/track/ucm351742.htm. Accessed 10 October 2017.
- FDA-TRACK. FDA website. https://www.accessdata.fda.gov/scripts/fdatrack/view/index.cfm. Accessed 10 October 2017.
- Current Unified Agenda of Regulatory and Deregulatory Actions. FDA website. https://www.reginfo.gov/public/do/eAgendaMain. Accessed 10 October 2017.
- Executive Order 13771 – Reducing Regulation and Controlling Regulatory Costs, 30 January 2017. US Government Publishing Office website. https://www.gpo.gov/fdsys/pkg/FR-2017-02-03/pdf/2017-02451.pdf. Accessed 10 October 2017.
- Mancini, "Reducing Regulation and Controlling Regulatory Costs." February 2017. Interim Guidance Implementing Section 2 of the Executive Order of 30 January 2017. White House website. https://www.whitehouse.gov/sites/whitehouse.gov/files/briefing-room/presidential-actions/related-omb-material/eo_iterim_guidance_reducing_regulations_controlling_regulatory_costs.pdf. Accessed 10 October 2017.
- Executive Order 12866 – Regulatory Planning and Review, September 1993. US Office of Information and Regulatory Affairs website. https://www.reginfo.gov/public/jsp/Utilities/EO_12866.pdf. Accessed 10 October 2017.
- Oregon Files Lawsuit Against GNC for Selling Nutritional Supplements with Ingredients not Approved in US, 22 October 2015. Oregon Department of Justice website. https://www.doj.state.or.us/media-home/news-media-releases/oregon-files-lawsuit-against-gnc-for-selling-nutritional-supplements-with-ingredients-not-approved-in-u-s/. Accessed 10 October 2017.
- A.G. Schneiderman Asks Major Retailers to Halt Sales of Certain Herbal Supplements as DNA Tests Fail to Detect Plant Materials Listed on Majority of Products Tested, 3 February 2015. New York Attorney General website. https://ag.ny.gov/press-release/ag-schneiderman-asks-major-retailers-halt-sales-certain-herbal-supplements-dna-tests. Accessed 10 October 2017.
- Dabish and Bohr v. MusclePharm Corp., 15-CV-03848, Document 37 – Order Granting Motion to Dismiss First Amended Complaint (S.D. Cal. 26 September 2016).
About the Authors
Jennifer M. Adams is an attorney at Amin Talati Upadhye LLP and focuses on regulatory and advertising matters for food, beverage, supplement, cosmetic, drug, and animal products. She advises clients on issues such as NDI requirements, claim substantiation, labeling, and cGMPs, as well as advocates for clients in challenges by FDA, USDA, FTC, CBP, State Attorney Generals, consumer class actions, and the National Advertising Division. With a background in food science, she provides a unique prospective to assist companies with their regulatory needs. Adams may be contacted at firstname.lastname@example.org.
Ashish R. Talati is a partner and chair of the Food and Drug practice at Amin Talati Upadhye LLP. He primarily counsels clients on matters of regulatory compliance, helps them anticipate and address regulatory issues in their day-to-day business operations and strategic planning, and advocates on their behalf before the FDA, FTC, Customs, USDA, DEA, and other federal agencies, and in court.
He works with companies all over the globe and is a trusted advisor at every step of the product lifecycle, including product formulation, safety and efficacy studies, product launch, and ongoing marketing and sales. He has written extensively on topics related to New Dietary Ingredients (NDI) and has successfully filed many NDI notifications with FDA. Talati may be contacted at email@example.com.
Cite as: Adams, J.M. and Talati, A.R. "NDI Guidance: the Waiting Game." Regulatory Focus. October 2017. Regulatory Affairs Professionals Society.