There are plenty of elements set to shake up the regulatory state of play for the dietary supplements market.

A rising tide of state regulations that seek to preempt federal law; marketing by artificial intelligence and influencers; continued calls for lawmakers to revise the core tenets of the Dietary Supplement Health and Education Act (DSHEA); the U.S. Food and Drug Administration’s (FDA) agency-wide reorganization; the U.S. Federal Trade Commission’s (FTC) updated guidance on health and wellness marketing; and updated guidance on New Dietary Ingredient Notifications (NDINs) from FDA are just a handful that have been top of mind lately.

At the 12th annual American Conference Institute (ACI) and Council for Responsible Nutrition (CRN) Legal, Regulatory, and Compliance Forum on Dietary Supplements held in NYC in June, forecasts on these topics and more were shared by top regulatory officials, lawyers, and industry experts.

30 Years Later, Does DSHEA Need Rebalancing?

A perennial topic of discussion is whether the industry should advocate for amendments to DSHEA, which lays out the rule structure for dietary supplements as a unique class of foods. At the core of the discussion in recent years has been confusion surrounding how the agency makes decisions about NDINs.

“This overhaul is a major undertaking, so it might be worth it to continue to try working with FDA to see if they are open to interpreting certain provisions of DSHEA differently, rather than assuming the problem is with the provisions themselves,” said Miriam Guggenheim, partner at Covington and Burling, LLP. “FDA and Congress have completely different ideas than we do,” and the “trade-offs” could be hard to predict.

The industry hopes pending guidance documents will offer clarity on NDINs, particularly on the “drug preclusion” provision, which disqualifies new dietary ingredients from being considered for introduction to the supplements market if they were first researched as drugs. Ingredients like NMN, NAC, CBD, and others have been in regulatory limbo due to confusion about the statute.

Defining “substantial clinical investigations,” and what it means for a study to enter public knowledge are important issues to address since these factors determine whether an ingredient is a dietary substance or a drug, Guggenheim said. “Drug companies have been getting protection up front, while the supplements sector has had to invest in research without knowing if there’s some secret IND (investigational new drug) authorization out there. We want parity here.”

Patrick Runkle, a trial attorney for the consumer protection branch of the U.S. Department of Justice, concurred that clarity is needed even in egregious cases of dangerous drugs being masqueraded as supplement products.

“These are hard cases to prove, and involve novel substances with deep science that most judges have a hard time understanding,” Runkle said. “The tools we have are not effective to address bad actors before it gets to the point of a criminal case.”

While there are many questions that still require answers through pending NDIN guidance, Rend Al-Mondhiry, partner at Amin Wasserman Gurnani LLP, noted some key changes to date. FDA’s new guidance suggests that NDINs must be submitted by supplement manufacturers, rather than the ingredient manufacturer. Further, the agency has noted that whatever position it takes on an NDIN isn’t precluded from future action against a dietary supplement containing an NDI, if the agency walks back its decision.

There are still several unanswered questions surrounding the pending Master File process for NDINs, Al-Mondhiry noted. In order for the Master File program to improve adherence to NDIN requirements, there needs to be assurance that trade secrets will be protected, and that supplement firms won’t have the rug swept out from under them in a drug preclusion-related decision. 

Fireside Chat with Cara Welch

Steve Mister, president and CEO of CRN, interviewed Cara Welch, PhD, director of the Office of Dietary Supplement Programs at FDA, about her top-line perspectives.

Mister noted that there are some perceptions within industry that dietary supplements are perceived by the agency, more or less, as snake oil, and that dietary supplements as a class of products have gotten the short end of the stick in FDA’s reorganization.

Welch said that “feelings don’t hang around very long,” regarding the agency’s overall temperature on dietary supplements writ large, and there’s certainly “no animosity toward dietary supplements. It’s another commodity where we have statutes to implement,” she said.

Regarding the FDA reorganization, “our structure will remain the same. The same number of people will be doing the same work on dietary supplements, within the Office of Food Chemical Safety, Dietary Supplements, and Innovation (OFCSDSI),” Welch said.

“But we’re still deep in the process of trying to figure out how to take a proposal on paper into actuality,” she added. “How does ODSP work with post-market assessment and the Office of Pre-Market Additive Safety together? How will surveillance and risk prioritization work? The discussions about delegating responsibilities are important.”

One of the biggest changes for dietary supplements, structurally, will be that ODSP will have closer contact with the Office of Regulatory Affairs (ORA), and there will be fewer steps involved in policy implementation, Welch said.

“That means there will also be more opportunities for us to talk to inspectors, and we’re not waiting for the reorganization to do this,” she noted. “We’re getting closer to field staff already to make sure they understand our policies and make sure we understand the challenges they’re dealing with.”

Welch said she’s optimistic that Jim Jones, deputy commissioner for FDA’s Human Foods Program, will bring “a renewed focus on chemicals in foods and dietary supplements.”

“I know the word (chemical) isn’t something that some folks are comfortable with, but we understand that all ingredients are chemicals. We want a good structure to our review and management activities to regulate chemicals in foods and supplements, all through the appropriate statutory authorities. We’re not going to conflate supplements with additives,” she noted. 

One of the biggest issues lately has been a rise in products with questionable safety that aren’t technically being marketed as dietary supplements. While FDA’s hands aren’t tied, its resources are limited, Welch said.

“Bad actors are completely ignoring what FDA is saying. We’ve been doing seizures of kratom products for 7 or 8 years now, and it’s still being sold widely. In an ideal world we’d completely clear the market of kratom, but in 6 months we’d be right back where we started, because the responsibility is unclear. I’m not throwing up my hands, we’ll continue taking action and notifying the public, but we need to step back and ask what the issue is here, and what the appropriate fix might be.”

State laws regulating the sale of kratom are serving to legitimize the current products on the market, Welch noted. “Our position is that the ingredient is not appropriate for dietary supplements, based on DSHEA. There are specific safety standards and adverse event requirements. There needs to be a reasonable expectation of safety and we just haven’t seen that,” Welch said. “When the supplement regulatory structure works, it’s great, but there are so many situations in which people try to shoehorn inappropriate constituents into the supplement framework.”

Therefore, the agency is asking for more explicit authority in ruling against products that don’t meet the technical definition of a dietary supplement, Welch said. “The definition of a supplement is very specific … if a capsule is called a supplement but only has sildenafil, it’s excluded from that definition.”

As the agency continues rolling out more guidance documents to clarify points of confusion about how it interprets NDI rules, it’s difficult to estimate when those answers will come, said Welch, such as whether amnesty for late NDI notifications will be granted, whether a synthetic version of a botanical can be a dietary ingredient, or what constitutes “substantial alteration” of an ingredient.

FTC and NAD Priorities

In a conversation with Megan Olsen, senior vice president and counsel at CRN, Christine Delorme, an attorney in FTC’s Division of Advertising Practices, discussed the agency’s priorities for regulating dietary supplement marketing.

When it comes to health claims that aren’t FDA-qualified, a question always remains as to whether the existing clinical evidence is appropriate, noted Delorme.

For instance, New York Attorney General Letitia James’ trial against Quincy Bioscience, which marketed Prevagen supplements as a way to reduce memory problems, is in line with FTC’s present stance on health-related claims. The jury, Delorme noted, found that “all claims had a tendency to deceive and constitute fraud” under New York Executive Law § 63(12), as the court determined the health claims were based primarily on post-hoc analysis of studies.

“In Quincy, we found dozens and dozens of claims based on post-hoc analysis. But failing to pre-specify a hypothesis in a study is like betting on the horse race after it’s over. Lots of clinical trials have things happen by chance, and have lots of false positives,” said Delorme.

She noted that FTC’s focus remains on egregious cases “not even close to the realm of structure/function claims.”

“The 2022 guidance was written from personal experience in the cases we’ve litigated over the past two decades, involving very serious health claims, and those areas are where we focus our limited time and resources.”

Eric Unis, senior attorney at BBB National Programs’ National Advertising Division (NAD), said he didn’t find FTC’s guidance to be “earth-shattering.”

“There was strong continuity between it and what NAD had already been doing,” he said, noting that unlike FDA, “we don’t get into distinctions between structure/function and disease claims. It’s not our role.”

Unis noted recent NAD litigation that targeted substantiation issues, such as studies without controls or with clear confounding factors, studies on diseased populations, and more. NAD has also focused on a lack of substantiation in claims that a product is environmentally friendly, such as overly broad and vague claims of some environmental benefit, or claims about net zero emissions with a lack of evidence. 

Strong cause-and-effect claims, for outcomes like weight loss, are riskier territory in which strong clinical research is needed, said Katie Bond, partner at Keller and Heckman LLP. “But what about other claims found on a multivitamin, such as ‘supports eye health’ or ‘supports heart health?’ Statements from FTC in its 2022 guidance that randomized, controlled trials are almost always required for claims is really troubling. There’s a lot of tension between the 2022 guidance and case law.”

Bond noted that DSHEA states there is “no requirement that health claims be derived from clinical trials,” and “evidence from a broad range of reliable scientific sources should be considered in determining the adequacy of scientific support. FDA will be expected to take full advantage of the flexibility of the standard to maximize the availability on food and dietary supplement labels and labeling of disease-related information consumers can prudently use to affect their disease risk.”

Additionally, in FTC’s concerns about whether an ingredient versus a finished product was assessed in clinical research, “all of a sudden they’re concerned about interactions between ingredients that can change their physiological activity, which would be holding these products to a drug standard,” Bond said. 

Aside from a renewed focus on substantiation in health and wellness marketing, FTC is also concerned with other aspects of business conduct.

Testimonials and endorsements are an area highlighted in a proposed rule introduced last summer. This includes failing to disclose material connections, or falsifying reviews and/or filtering and censoring reviews in a way that misrepresents overall consumer sentiment, Delorme said.

When it comes to leveraging positive reviews in advertising, “consumers will take away that this experience is typical, even with the presence of certain disclaimers. Advertisers need to substantiate everything, including what is communicated through a testimonial. Testimonials might be useful for advertising, but they’re very hard to present in a way where consumers understand the limited nature of that evidence …”

“Opinions that are expressed, if they’re manipulated in any way, can be deceptive, including cherry picking reviews. Generally, if you just leave reviews alone, you’re not responsible for what they say. But if you retweet a review, or promote it in some way, you’ve adopted it and you’re responsible for that,” Delorme said.

State Age Restriction Laws and FDA Deference

With an influx of state laws placing unique restrictions on the dietary supplement marketplace — most notably a New York law banning the sale of “muscle building” or “weight loss” supplements to minors — companies need to navigate both federal rules and a patchwork of new, state-specific regulations.

New York passed the first law placing an age restriction on supplements, and likely won’t be the last. Just recently, Michigan became the 11th state to propose a similar ban.

The lack of clarity across each of these bills makes it difficult to determine which products might be covered in each respective ban, noted Paola Clavijo, head of policy and risk management at Unilever, and each state will likely have a different set of criteria from all others. “Every vitamin and mineral is part of a metabolic process,” she said, and “these laws could theoretically touch every product in this market.”

Even if New York’s law stands following a lawsuit by CRN, and if California continues to pursue a similar bill, “the policy discussion is far from over in those states. We’re constantly looking at laws already on the books and discussing how to make them better,” said Meghan Stoppel, member of Cozen O’Connor.

For now, it’s important to “understand your product lines and categorize them according to legislation,” said Clavijo, and it’s important that product development, sales, and supply chain teams are fully aware of the company’s determinations.

For finished product companies, a lot of work goes into ensuring affected products aren’t inadvertently sold to minors, said Patricia Kim, senior regulatory counsel at Growve. “Lots of retailers are asking for brands to indemnify them and ensure they’ve in compliance with New York’s law. It’s hard to not sign those agreements and lose out on a retailer’s business, and right now, it seems like most brands will sign indemnification letters saying that they comply with New York’s law, or California’s law, if that passes.”

Broadly, state laws such as New York’s erode the standard-setting accomplished by DSHEA, Kim noted, asking, “how will FDA respond to this erosion of their authority?”

“Further, if we think DSHEA is being eroded, who should be responding, FDA? Congress? When it comes to lawmaking, I’m not sure it’s FDA’s job to do much beyond come to the table when invited,” said Stoppel.

She noted that the California age restriction bill, which failed to advance in the current legislative session, would have placed especially strong pressure on FDA to take a stance, as it would require California’s Department of Health to consult with FDA in creating a list of affected supplement ingredients.

Class Action Trends

To protect against the plaintiff’s bar, regulatory experts said it’s important to think like a plaintiff’s attorney.

Lawsuits attacking structure/function claims have been evolving, in the wake of FTC’s 2022 guidance, newsworthy studies questioning the health benefits of certain ingredients, and more. Even structure/function claims authorized as qualified health claims by FDA, such as fish oil promoting heart health, are being challenged as false benefit claims, noted Christine Burdick-Bell, vice president and general counsel at Pharmavite LLC, and Lori B. Leskin, partner and co-chair of the consumer products practice group at Arnold & Porter Kaye Scholer, LLP.

While case law has largely determined that a lack of substantiation of structure/function claims isn’t legally actionable, class action suits have been “repackaging” substantiation-related challenges with words like “lack of credible evidence,” or arguments that structure/function claims lead consumers to believe that a given product had been researched.

Class action suits are also targeting certain label claims, such as whether a multivitamin is “complete.” Ongoing cases are currently challenging “free from preservatives” and “natural flavors” claims; at issue is whether malic acid constitutes a natural flavor, and whether citric acid qualifies as a preservative if used for flavoring purposes.

Class action lawsuits are also targeting undisclosed ingredient overages, alleging they present safety issues, due in part to a 2023 study that highlighted widespread variations in doses of melatonin products, and a CDC report that cited a sharp uptick in Poison Control Center calls related to children ingesting melatonin.

Most class action lawsuits take advantage of areas where the law is less clear, noted Veronica Colas, counsel at Hogan Lovells. “Most lawsuit claims aren’t subject to express preemption by federal law,” she said, and “claims about rules defined in FDA regulations usually don’t come up unless those rules are being clearly violated,” which is why claims that a product is “natural” or “not artificial” make for easy targets. 

While using disclosures on the back panels of products to explain ambiguous statements can be helpful, contradictions between front-of-pack claims and disclosures provide an easy argument that consumers were misled, Colas noted. 

Other “low hanging fruit” on the plaintiff’s bar radar include: quantifiable claims that lack sufficient evidence to support an exact number; claims made on social media by those less attuned to how dietary supplement marketing is regulated; product recalls; allegations that auto-renewals for subscription programs are difficult to opt out of; and degrees of bias or unreliability in scientific evidence, noted Claudia Lewis, partner at Venable.

The Rise of AI

Generative AI will quickly be deployed in a range of applications in the supplement industry, including marketing, sales, product development, packaging designs, and corporate insights, noted Bezalel Stern, partner at Manatt, Phelps, & Phillips LLP.

“FTC’s approach to AI in advertising is robust,” he said. “Sam Levine, director of FTC’s Bureau of Consumer Protection, stated that AI isn’t bad and America should lead it. FTC will and already is using tools to challenge unfair or deceptive practices related to the technology, and FTC has issued a proposed rule to address harms caused by AI, such as fake reviews or impersonators.”

Already, there are several outstanding cases of direct and indirect copyright infringement, DMCA violations, breach of contract, state law claims, trademark infringements, and right of publicity violations associated with generative AI, noted Candice Kersh, partner at Frankfurt Kurnit Klein & Selz. “These platforms scraped the entire web and took everything in, and the big question is whether it constitutes copyright infringement,” Kersh said. “For our purposes, as advertisers, the outputs are more important.”

Courts generally aren’t buying into certain challenges that all content generated by AI is derived from copyrighted content, Kersh said. “There’s no final decision yet, but courts largely are looking to see if outputs are substantially similar, which is a risk that’s always inherent in these platforms.”

On the other side, “In the U.S., only human authorship is protectable and ownable,” Kersh said. The U.S. Copyright Office has already taken the position that AI-generated images can’t be protected. In the case of something partially-done by AI, one can only copyright human-made portions of a product, and AI-altered photographs also cannot be protected.

In the future, if an AI-generated image or voice is similar enough to a real person, that person may have a claim that their right of publicity was violated. In addition to AI-related right of publicity laws passed by states, the Senate also proposed the NO FAKES Act, while the House has proposed the No AI Fraud Act.

There is also concern, and legislative action at the state level, regarding lack of transparency around the use of chatbots for customer service or for the sale of a product. Laws are largely centered around preventing actors from divorcing themselves from the consequences of an AI platform violating consumer protection law, engaging in discrimination, and more.

What Does ‘Healthy’ Mean?

The target publication date for FDA’s proposed rule that would define “healthy” and regulate which product labels could carry the term has passed.

Al-Mondhiry noted that, in recent news, there have been concerns about the potential for increased class action suits and other litigation against supplement and food companies based on the precedent this rule would set.

The 2024 Consolidated Appropriations Act, signed into law in March 2024, appears to preempt lawsuits based on state laws about “healthy” claims while FDA is still implementing its rule, she noted.

Will Future Nutrition Research Be Subject to IND Requirements?

Another potential debate on the horizon, which would impact how the nutrition world conducts research, involves a proposed “de-regulatory” rule creating a process for nutrition researchers to either self-exempt or seek FDA-determined exemption from Investigational New Drug (IND) requirements in certain clinical studies.

Per a 2013 final rule which FDA eventually put a “stay” on, researchers are required to apply for IND authorization for nutraceutical studies involving infants, immunocompromised individuals, or those with serious medical conditions, or studies evaluating outcomes beyond classical functions of nutrients.

“IND regulations are written around safety and drug approvals,” noted Jena Rostorfer, MS, RD, director of U.S. and Canada regulatory affairs at Abbott. “Studying the maintenance of health is very difficult and we often look at disease endpoints and biomarkers which would be subject to IND requirements under this proposed new rule. This will deeply impact the industry-academia partnerships advancing nutrition science.”

“The IRBs (Institutional Review Boards) would be left to enforce this process, but they’d just push everything to FDA because they don’t want the liability, and FDA won’t have the resources for this … and those writing a research protocol aren’t worried about the legal or regulatory consequences of the products they’re researching,” she continued. 

Emerging Contaminants

How litigators think about what constitutes a “contaminant” is changing substantially, as newly-reported risks for certain additives that have historically been considered safe come to light, noted Seth A. Mailhot, partner at Husch Blackwell.

Preservatives, colors, and flavors also get added to ingredients or raw materials, and those additions can go unknown to a finished product manufacturer, or contract manufacturer.

“Finally, you have true contaminants. These include cross-contamination from shared lines, allergens, or something created through an ingredient production process, or from degradation,” said Mailhot, also noting environmental heavy metals, toxins created through heat or light exposure, and more.

Having an in-house chemist that participates in industry-wide discussion about emerging contaminants, who can walk through test results from independent labs, is important for companies to validate that these results do, in fact, meet their own standards.

The addition of PFAs to food packaging has been of particular concern lately, with state governments and FDA taking certain steps to reduce their presence in food products on the market.

Importantly, in both regulations and case law, FDA defined adulterants as added or man-made substances. “If you can control deleterious substances through the process of GMPs, or through something else that’s required in production, that’s treated differently than environmentally present contaminants,” Mailhot said.

“Suppliers have changed their containers to be PFA-free in 2022. That happened for the most part,” said Aliza R. Karetnick, partner at Morgan, Lewis, and Bockius LLP.

“But no one has any idea how to assess the millions of containers still sitting in a warehouse that may have contained PFAs. Are they grandfathered in? That question was never answered in legislation, and it will be litigated.”

“In 2022, Consumer Reports tested products for PFAs, and it inspired several lawsuits,’ Karetnick said. “Typically, there are no allegations of physical injury, only of economic ones. Defendants need to lean on FDA’s guidance and regulatory support at times, and show that trace amounts have been considered acceptable.”

Starting in the early 2000s, FDA became aware of studies raising safety concerns about long-chain PFAs and began working with manufacturers to remove these products from the market, but oversight of food packaging in other countries is minimal.

As of 2016, long-chain PFAs are no longer used in food contact applications, following extensive studies of the U.S. food supply, and additional safety concerns. This year, the agency announced that all grease-proofing agents containing PFAs are no longer being sold in the U.S., and the agency intends to continue testing with the goal of estimating the average U.S. consumer’s exposure to PFAs from foods.

Several states have passed laws prohibiting food packaging with “intentionally added” PFAs, and there are important distinctions in how each of these laws defines what intentional addition means. While the extent is uncertain at this time, states will likely enforce against PFAs in actual food products, and not just in packaging. 

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About the Author: Mike Montemarano has been the associate editor of Nutraceuticals World since 2020. He can be reached at mmontemarano@rodmanmedia.com.