The Council for Responsible Nutrition (CRN) submitted a citizen petition to the United States Food and Drug Administration this week requesting that the agency reconsider its interpretation of the Drug Preclusion Clause, which CRN asserts has been misapplied to dietary supplement ingredients.
Unlike other recent citizen petitions, CRN’s petition does not address specific ingredients but asks the FDA to address its position on how it interprets a number of DSHEA provisions, specifically those related to Investigational New Drug (IND).
“The public health benefits from robust innovation in both the supplement and pharmaceutical categories, ensuring consumers have access to a wide array of safe and beneficial ingredients for a number of purposes," the petition stated. "Drugs occupy an important lane allowing ingredients to be studied and used to treat disease under very specific conditions and often at higher doses than can be found in supplements; while supplement use preserves access to ingredients for general non-disease uses, ensuring consumers are not unnecessarily barred from using safe and beneficial ingredients."
"The demands to appropriately balance these interests are clear based on Congress’ purpose in enacting DSHEA and what we ask FDA to do here. Reversing the agency’s position as we have requested here and providing guidance for the discretionary use of rulemaking under drug preclusion help ensure DSHEA is read consistently and fairly to the benefit of public health."
Background
The Food, Drug, and Cosmetic (FD&C) Act’s definition of a dietary supplement includes several provisions that limit what can be a legal dietary supplement based on the ingredients used and delivery form but also whether a substance has a history of drug use, an issue that has become increasingly problematic for the industry.
Congress passed the Dietary Supplement Health and Education Act (DSHEA) in 1994, which amended the FD&C Act and carved out a unique category for dietary supplements as a regulated product. This positioned supplements as a food subcategory governed under the food regulatory framework and a new set of requirements specific to dietary supplements. However, in recent years, trade organizations within the industry have suggested that FDA's interpretation of the DSHEA provisions has been too broad.
When enacting DSHEA, Congress sought to ensure supplements would not limit drug research and development and also aimed to prevent companies from using the supplement category to bypass the drug approval process. With this in mind, Congress enacted a “race-to-market” provision to prevent loopholes and protect incentives for drug research and development. Ultimately, the provision sought to balance drug interests with this new regulatory category where ingredients from both categories could overlap.
“To be clear, ingredients—supplement ingredients and drug ingredients—already coexist," explained Megan Olsen, senior vice president & general counsel at CRN. "If an ingredient is on the market first as the supplement, it's not being pulled off because of a drug. It's the opposite way with the race to market. So you have things like fish oil, for example, that in a highly refined, very high dose is approved as a prescription drug, but of course, access to omega-3s, EPA, DHA, through fish oil products, is readily accessible through any drug store and marketplace selling supplements. So, this is the intent of Congress, that there was a way for these ingredients to coexist.”
Going in blind
CRN noted that one of the most concerning issues regarding FDA’s current interpretation of DSHEA is that a dietary supplement company has no way of knowing if or when a drug company has started the process of preclusion because the date is confidential. This means that companies are unable to verify if the ingredient is being investigated as a drug and risk spending millions of dollars on research, development and marketing only to hit a roadblock.
“That outcome is certainly not what Congress intended when it wrote the law,” CRN said, adding that for years, there have been numerous instances of the preclusion law being misused. Case in point: NAC and NMN.
Olsen highlighted NAC as a prime example of an ingredient that was sold as a supplement for decades.
“We know that FDA was aware of it because we've seen documentation where FDA acknowledged that NAC was being sold as a dietary supplement," she said. "And then as we saw in 2020 how FDA arbitrarily essentially pulled it from the market and said it was subject to drug preclusion. So really just concerning examples of where anything that you're selling, there's uncertainty there now at this point with the way that FDA is not only interpreting it, but these examples of where they allowed companies to sell the ingredient for decades, years, etcetera and then take up a position contrary to their actions that it's a drug precluded ingredient.”
CRN expressed concern over FDA's removal of ingredients like NAC and NMN from the market without offering legally sound reasoning, consistent with DSHEA and prior FDA interpretations of drug preclusion.
“It’s akin to conducting a title search on a house, determining there are no liens, only to be told after you’ve bought the house that there were actually secret liens on the property, and you’ll have to forfeit your investment,” said Steve Mister, president and CEO at CRN. “Yet that is exactly what is happening to supplement companies, which are acting in good faith and in accordance with publicly available information, in what could be perceived as an effort by the agency to unfairly protect the financial interests of pharmaceutical companies over those of supplement manufacturers. We continue to engage the agency on this critical issue.”
Innovation block
CRN hopes the citizen petition will prompt FDA to reconsider its interpretation of the Drug Preclusion Clause, which it says threatens future innovation in the supplement marketplace.
“We are deeply distressed by FDA’s decision to revoke the status of these ingredients as dietary supplements, which threatens future innovation, because by doing so, they’ve flipped the script on how drug preclusion is supposed to work, leaving all parties—manufacturers, retailers and consumers—in a sort of regulatory limbo going forward,” Mister said. “Without a reexamination of FDA’s position, and guidance that lends clarity and predictability to the process, manufacturers are discouraged from continued innovation of new ingredients, and retailers are not sure whether they should, or are able to, continue to make these products available to the public for fear of selling ‘illegal’ supplements.”
Olsen agreed that removing an ingredient has a significant and concerning impact on innovation, adding that "companies that have the ingredients on the market that have met the race to market against any drug approvals or drug investigation have a reason to be concerned as well."
Consistency, balance and guidance
Olsen said the citizen petition has a couple goals in mind: “We are asking for FDA to reconsider its position on a number of interpretations of drug preclusion—IND preclusion date in particular, and we really hope that FDA would look at their record for interpreting drug preclusions. The concerns we've pointed out with inconsistency, and we hope they can clarify their positions in a way that is fair, consistent and meets the purpose that Congress set out for DSHEA and use of drug preclusion in particular.”
“With drug preclusion, Congress wanted to put in some limited controls to help ensure that a bad actor didn't try to put a supplement on the market, essentially as a way to get around the drug approval process, and they didn't want to unfairly limit and disincentivize drug research, but there are ways to ensure that consumers can have access to both ingredients. And our petition really lays that out, that this is about certainty for supplement companies and access and certainty for consumers,” she said.
Timeline
FDA has 180 days to answer the petition, but Olsen said that the answer provided within that period does not have to be substantive.
“We would hope they would, but unfortunately and historically, FDA tends to kick the can down the road by indicating that they're continuing to review and likely will need additional resources to provide an answer or it's just not something the agency is willing to dedicate resources to at the time. So it's really anyone's guess as to what we might see with regard to a response from FDA.”
Pressure applied
While the petition may not lead to an immediate response, Olsen said the petition does raise awareness within the industry, in Congress and among consumers.
“So not only do we intend to continue to put pressure on FDA to answer these questions, move forward with the rulemaking process as they promised with NAC, for example, but this is just another way that we can work with allies in Congress and stakeholders," she added. "We know that one member of Congress has already called on hearings about drug preclusion and so we know this is something that they're interested in. And really what our citizen petition does is help lay out our concerns and arguments to FDA, it's also a document that can be used with stakeholders in Congress to help them understand the real problems here that have been caused by FDA’s interpretation.”
