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What are the biggest problems in the dietary supplements market, and will changing DSHEA fix them?
Dietary supplement industry leaders acknowledge that certain problems plague the industry. Bad actors selling subpar or even illegal products are front and center, but there are also regulatory weaknesses, a dearth of FDA enforcement resources, and a lack of clarity in the law that hamper even responsible companies who are producing good products. What’s the remedy? For years, industry insiders—and outsiders—have debated whether changing the longtime U.S. law governing supplements, the Dietary Supplement Health and Education Act of 1994 (DSHEA), would help solve some of these challenges. (This hypothetical revision has been dubbed “DSHEA 2.0.”) For the past few years, FDA has also expressed interest in “modernizing” supplement regulations to address residual problems and better meet the needs of today’s growing market—a market that started at around $4 billion in the U.S. in 1994 when DSHEA was signed and is now approximately worth $50 billion, per Nutrition Business Journal estimates.
What are the supplement market’s biggest problems, and would amending the hard-won, founding piece of legislation that’s governed supplements for nearly three decades do good—or do harm? Moreover, realistically speaking, could the law be changed in today’s political environment?
The Council for Responsible Nutrition (CRN; Washington, DC) hosted a joint webcast on April 28 together with Informa, titled “Careful What You Wish For: Pitfalls & Booby Traps of DSHEA 2.0,” during which industry experts discussed the needs and the possibilities.
Among the many problems discussed during the webcast, a few stood out especially.
Generally Recognized as Safe
Notably, the webcast included a speaker from the Center for Science in the Public Interest, a group known to be critical of the dietary supplements industry. Laura MacCleery, CSPI’s director of strategy and program, said one major problem CSPI sees is that many supplement companies are using Generally Recognized as Safe (GRAS) self-determinations for food to get their products into the dietary supplements market instead of submitting new dietary ingredient (NDI) notifications for supplements to FDA—a concept some refer to as an NDI “loophole.”
This route to market seemed to be sanctioned in FDA’s original 2011 NDI draft guidance (the document outlining how FDA intends to regulate supplements per DSHEA). In it, the agency stated that ingredients that are present in the food supply that have either been self-determined by a company to be GRAS—that is, to have “reasonable certainty of no harm under the intended use conditions”—or whose GRAS notifications have been submitted to FDA in turn do not need to submit an NDI notification to FDA before using the ingredient in dietary supplements. (Nutritional Outlook guest authors Robert McQuate and Richard Kraska previously wrote about this process here.) FDA’s updated 2016 version of the NDI draft guidance, it should be noted, was less clear on whether the agency would still allow this route for GRAS self-determinations, something Nutritional Outlook wrote about here.
Nonetheless, many companies today self-determine their supplement ingredients under the GRAS framework. The problem is, MacCleery said, that the dosage of an ingredient that was determined to be safe in food might be much lower than the dosage that would ultimately be used in a dietary supplement. In short, she said, the GRAS safety evaluation a company might have conducted on an ingredient for food use might not reflect the safety of the ingredient used at a higher dose in a supplement.
“I think that GRAS notifications are generally not a great substitute for an NDI because they probably cover food uses and not all the conditions of use in a dietary supplement form,” she said. GRAS determinations “wouldn’t cover and actually shouldn’t be replacing the need for an NDI for other conditions of use that have higher levels of concentration in the product.”
Another webcast speaker, attorney Will Woodlee, partner at Kleinfeld, Kaplan & Becker LLP, pointed out a separate problem. Currently, regulations state that companies do not need to submit an NDI notification if the ingredient is already present in the food supply and would be used in the same form, and not chemically altered, in a dietary supplement. However, he said, the definition of what “chemically altered” comprises is unclear in the law and in FDA’s draft guidance documents. As a result, he said, “there’s been some conflict between what industry thinks chemically altered means, what Congress thought chemically altered meant, and what FDA thinks chemically altered means.”
So far, unfortunately, FDA has taken a very narrow definition of chemically altered to mean that any process that breaks chemical bonds, including boiling, baking or, cooking, would render an ingredient chemically altered—meaning many companies might need to submit NDI notifications to use ingredients in supplements. Woodlee urged that the regulatory definition of chemically altered be clarified further to resolve ambiguities about whether an ingredient does or does not need to file an NDI.
Not a Supplement
Another big problem speakers outlined was the fact that FDA currently doesn’t have an easy way to enforce against products that are not actually dietary supplements by definition because they contain non-dietary ingredients such as drugs. This puts the agency in a difficult position to get such products off the market.
FDA needs more explicit authorities for dealing with such products, said speaker Julia Gustafson, CRN’s vice president of government regulations. And, in fact, at last year’s CRN virtual conference, “NOW, NEW, NEXT,” Steven Tave, then-director of FDA’s Office of Dietary Supplement Programs, acknowledged this problem, noting that FDA is currently not able to crack down on such violative products under existing supplement laws because the products aren’t, by definition, dietary supplements at all.
During the webcast, Gustafson said, “It seems that, right now, FDA is somewhat reticent to go after too many products that are out there if they don’t know for sure that they’re going to be able to win [an enforcement case],” she said. This can lead to a long, winding, and resource-intensive path for FDA to ultimately remove these products from the market, she pointed out.
One way to improve the situation would be to “clarify” the definition of a dietary supplement in the Food, Drug, and Cosmetic Act (FD&C Act). This week, CRN announced its support of such an effort.
The law also needs to make clear the route by which FDA can remove such non-supplement products from the market, including seizing the products or barring their import, Gustafson said. “FDA needs to have very, very, very clear authority to act and enforce on that product,” she said. Woodlee noted that the “Hemp and Hemp-Derived CBD Consumer Protection and Market Stabilization Act of 2021” (HR 841) recently reintroduced in Congress included suggestions to amend several provisions—the prohibited act provision, the seizure authority provision, and the import refusal provision—in order to “give FDA a more straightforward way to take action against these products.”
He added: “Today, under existing law, if a product is labeled as a dietary supplement but doesn’t meet the definition of a dietary supplement because it contains undeclared active pharmaceutical ingredients, the agency has to approach the situation somewhat indirectly. So, for example, the agency could take action against the product because it’s an unapproved new drug based on its intended use, and then via cooperation with the Center for Drug Evaluation and Research proceed against that product on those grounds. But that requires developmental evidence of a drug-intended use and would be administratively more complicated than simply saying, ‘This product doesn’t meet the definition of a dietary supplement’—and that in and of itself permits FDA to refuse entry of that product if offered for import.”
Another standout discussion centered on FDA-issued warning letters. Gustafson said FDA sometimes doesn’t provide much clarity to the public after issuing a warning letter, and doesn't always make public how the issue was resolved, which can in turn detrimentally affect the broader market beyond just the company who received the warning letter itself.
For instance, Gustafson said, after FDA recently issued warning letters to some companies selling N-acetyl cysteine (NAC) that were specifically making false hangover-remedy claims for their products, large retailers began banning NAC supplements en masse, “erring on the side of caution.”
In addition, after FDA issues a warning letter to a company, the warning letter can often be left “unresolved,” Gustafson said. Companies dealing with unresolved warning letters and any detrimental fallout aren’t provided any course of redress. Due to this, she said, “CRN would like to have FDA provide clarity around these types of warning letters and whether these warning letters serve as a final agency action for the purposes of declarative relief for industry.”
Another webcast speaker, Patricia Knight, senior political advisor for the United Natural Products Alliance, called the notion that warning letters could represent final agency action “fascinating” but also said more discussion is needed to determine how that might change FDA’s behaviors. “Would it make the agency less likely to send a warning letter, because maybe an individual or inspection or inspector then takes on a policy significance?” she asked.
Finally, FDA resources for enforcement: Everyone agreed FDA needs more resources. Woodlee even floated the idea of “third-party GMP inspector programs to give companies who want to be inspected the opportunity to be inspected if FDA is otherwise not knocking at the door.”
Several speakers, including CSPI's MacCleery, also expressed support for the concept of an FDA-mandated product registry that would require all supplements on the market to be registered in an FDA database, giving FDA sharper eyes on the market. FDA itself has entertained this notion. The agency currently does not track all of the products in the market.
CSPI’s MacCleery, it should be noted, also conveyed CSPI’s existing wish that rulemaking would see FDA designate certain categories of supplement products as “posing a high risk to consumers” and that these “high risk” products be subject to “some additional certifications of purity or supplement quality that would be presented with the listing/registration requirement.” She did specify, however, that CSPI is not calling for FDA premarket review of all supplements. “It’s not really a premarket review….it’s a different concept,” she said.
Will Change Come?
Fixing many of these problems would require legislative change, but is disturbing DSHEA as it stands the right move?
Changes need to be made carefully, Gustafson advised. “We know there are some tweaks that can be made,” she said, but “changes need to be made responsibly, because we believe the law is mostly working.”
Speaker John Dutton, principal at Veritas Advocacy LLC, pointed out, “We’re talking about a potential rewrite of a bedrock piece of legislation for the industry and for others that are interested in this space.”
Knight, the former chief of staff for Senator Orrin Hatch when he and Sen. Tom Harkin introduced DSHEA back in 1994, said that when DSHEA originally passed, there was great enthusiasm supporting the legislation from both the public and lawmakers. Today, however, there isn’t an overwhelming public grassroots effort driving change for supplements, and lawmakers are juggling other, non-supplement priorities that might supersede concerns about overhauling DSHEA. Also, she said, unlike when DSHEA was passed and strongly supported by industry, “now, industry doesn’t always speak with one voice.”
Due to these reasons, she said, her organization, UNPA, “is skeptical of the ability of Congress, at this point in time, to look at a large DSHEA 2.0 bill.”
Amending DSHEA “is a big project,” Dutton said. “It’s almost like eating an elephant one bite at a time—but it might be too big, in the current climate, to make any kind of overhaul at this point.”
Dutton said that perhaps the focus should be on smaller changes, one at a time, as opposed to one large DSHEA overhaul. “Sometimes, smaller is better than larger,” he said. “The big authorizing bills are difficult to move…” For instance, he said, “the appropriations process would be one potential avenue to move either the bill in its totality—or pieces of it that are extracted that would be more narrow and just smaller in its scope.” Lawmakers would also likely be more interested in certain aspects, such as addressing bad actors, he said.
There’s also no escaping CBD. While a big DSHEA overhaul might not be on lawmakers’ radars, the issue of legalizing hemp CBD in supplements and food certainly is. To this day, FDA has not carved out a legal pathway for CBD in food and supplements, and many (not all) would like to see that change, as evidenced by the numerous bills already introduced in Congress, past and present.
In fact, said Dutton, any move to reform supplement regulations are “going to be viewed in a way that’s largely in the context of CBD.” In fact, he believes the topic of CBD will be a very influential force on who ends up supporting revising supplement regulations at all. The issue of CBD could very much hurt, or drive, efforts toward change.
“Now, in isolation, looking at those potential reforms”—such as to the GRAS process—“is very important, obviously," he said. "But, the politics would be very different if it was absent CBD. You add CBD into this and now you’re looking at a situation where every reform that goes forward that could potentially impact CBD, pro or con, will be viewed through a lens that first asks, ‘What is the impact on CBD? Is it pro-CBD or con-CBD?’ And advocates for either side are going to have an instinctive reaction to that.”
He continued: “It could work either way. With this larger bill, the problem is that CBD could define it. And so unless you truly reach a consensus or at least some kind of compromised position on CBD, you’re undermining passage of the bill rather than incentivizing it….[I]f CBD is a resolvable issue within the context of this legislation, it is actually potentially a driver to move it through as well as all the, frankly, lower-profile issues that would be addressed in the bill. But the concept of trading CBD for other non-CBD issues in the bill may not placate the CBD opposition in Congress because the other issues that are being traded are simply of less interest to them. Most members don’t follow this issue set particularly closely.”