On March 27, 2026, the FDA held a public meeting that put dietary supplement regulations under a serious spotlight. The discussion covered what officially counts as a dietary ingredient, how identity is defined, and where the current system is falling short.
For supplement brands, formulators, and distributors, this was not a meeting to overlook.
A Turning Point for the Supplement Industry
Most regulatory meetings produce little more than notes. This one was different. It tackled a question that has gone largely unanswered for over 30 years: what exactly qualifies as a dietary ingredient under U.S. law?
The session brought together FDA officials including Dr. Cara Welch, director of the Office of Dietary Supplement Programs, alongside industry leaders like Dan Fabricant of the Natural Products Association and Jensen Jose of the Center for Science in the Public Interest. Experts from the University of Illinois, Novonesis, CRN, and the International Probiotics Association also joined the conversation.
At the center of the debate was a phrase buried in DSHEA: "a dietary substance for use by man to supplement the diet." How the Food and Drug Administration interprets those words directly affects what dietary ingredients can legally enter the market. This meeting marked the first real push to revisit that definition in decades.
The Core Conflict: What Counts as a Dietary Substance?
The debate came down to one question: does a substance have to already exist in the food supply to qualify as a dietary ingredient? Jensen Jose of the Center for Science in the Public Interest argued for a more cautious approach, emphasizing that dietary substances should stay grounded in the existing food supply. Dan Fabricant pushed back, pointing to the strong safety record of the supplements industry and the need to allow new ingredient categories to develop.
Industry leaders argued that "dietary substance" was always meant to be a broad, flexible term, one that could grow alongside science. The FDA's current interpretation, however, ties eligibility to historical presence in human food. That distinction sounds subtle, but its consequences for dietary supplement manufacturers are significant.
If a substance must already exist in the conventional diet to qualify, truly new ingredients face a much harder road. The result is a system that pushes companies toward indirect regulatory pathways that were never designed for supplements in the first place.
Probiotics and the Innovation Bottleneck
Nowhere is the gap between science and regulation more visible than with probiotics. Despite being widely studied and commercially available, probiotics still occupy an unclear space under current FDA regulations.
Probiotics were not formally defined until 2001, seven years after DSHEA was enacted. That timing matters because it means they were never explicitly recognized as a dietary ingredient category. Many probiotic strains end up directed toward the GRAS pathway, a route built for food additives, not dietary supplements.
Amy Smith of Kerry and President of the IPA highlighted that both intentional and incidental exposure to microbes in the human diet should factor into regulatory recognition. Andrea Wong of CRN added that the statutory language of DSHEA was written broadly on purpose and was never meant to be limited to substances already present in food. The frustration in the room was clear: the science to evaluate probiotics safely is well established, but the regulatory framework has not kept pace.
Ingredient Identity Is No Longer a Simple Concept
Knowing what is in a supplement sounds straightforward. In practice, it has become one of the more challenging areas in modern dietary supplement compliance. Professor Gonzalez de Mejia from the University of Illinois explained that proteins are not just defined by their composition, but by their amino acid sequence, structure, and folding behavior. A single amino acid difference can change how a substance functions in the body and, in some cases, whether it is safe.
Traditional testing methods are no longer always sufficient to establish identity. One example discussed at the meeting involved undenatured collagen type II. Frank Romanski explained that its efficacy depends on maintaining a very small fraction of undenatured collagen, and that validated ELISA testing is required to measure it accurately. Products tested using HPLC methods may carry the same label claims but are not scientifically equivalent, and that gap is both a quality issue and a compliance issue.
Current good manufacturing practice standards require dietary supplement manufacturers to establish and verify ingredient identity as part of the manufacturing process. But as ingredients become more complex, the specifications and testing procedures required to meet that standard need to evolve too.
Delivery Systems and the Redefinition of Efficacy
Delivery technology has moved from a marketing point to a scientific requirement. Frank Romanski and other formulation experts demonstrated that for enzymes, probiotics, and peptides, the question is not just whether an ingredient works, but whether it reaches the right location in the gastrointestinal tract. Without the right delivery system, even a well-characterized ingredient may not produce the intended results.
Advanced encapsulation strategies, including capsule-in-capsule systems, were shown to improve delivery efficiency considerably compared to standard formulations. This raises a new regulatory question: if delivery determines function, should it be considered part of ingredient identity?
Current FDA regulations do not fully address this, but the direction of the discussion suggests that it will need to be part of the conversation going forward. For dietary supplement manufacturers, this is a reminder that the manufacturing process and packaging choices are not separate from compliance. They are part of it.
The Rise of Precision Fermentation and Modern Bioactives
Science has moved faster than regulation. Fermentation, cell culture, and precision fermentation are now being used to produce dietary ingredients at scale, and the FDA raised an important question at the meeting: when a production method changes significantly, does the ingredient itself change enough to require a new review?
Linda Nechmer of Novonesis described how fermentation-derived ingredients are already fully characterized at the sequence, structure, and function level. These are not experimental substances. They are produced through well-documented processes with thorough analytical testing and have been used across food, supplements, and healthcare for decades.
The gap is between what science can now define with precision and what the regulatory system is currently set up to handle. As noted by the FDA's Office of Dietary Supplement Programs, the agency is actively seeking input on how to treat ingredients produced through emerging technologies like precision fermentation, cell culture, and recombinant production.
Microbial Identity: Genus, Species, and Strain
For probiotics and other microbial dietary ingredients, identity is not a single data point. Gregory Leyer and other experts at the meeting explained that microorganisms are classified at three levels: genus, species, and strain. Each level carries different scientific and regulatory implications.
Clinical results are typically tied to a specific strain. Two strains within the same species can produce completely different outcomes in the body. Safety, on the other hand, is usually assessed at the species level, drawing on historical use as the foundation.
Current FDA regulations do not always reflect this distinction. Requiring strain-level presence in the food supply sets a bar that many well-supported strains cannot meet, even when the science behind their safety and intended use is solid. This creates a growing disconnect between how ingredients are actually developed and how they are evaluated.
The NDI Pathway and the Economics of Innovation
The New Dietary Ingredient Notification process was designed to give dietary supplement manufacturers a clear, responsible path to introduce new dietary ingredients. When it works as intended, it also protects companies that invest in safety data and scientific evidence by giving them a form of regulatory recognition that others cannot easily replicate.
The issue raised at the meeting is enforcement. Dan Fabricant and others pointed out that when companies bypass the NDIN process without consequence, it puts compliant manufacturers at a disadvantage. Stronger FDA actions in this space are not just about consumer safety. They are about maintaining a level playing field.
A well-functioning NDIN pathway sets a quality bar, supports dietary supplement compliance across the industry, and gives responsible manufacturers a reason to keep investing in proper documentation, testing, and identity verification.
FDA Capacity Under Strain
One issue that surfaced throughout the day was resources. The Office of Dietary Supplement Programs reviews NDI notifications under real time and staffing constraints. The 75-day review window creates pressure on both the agency and the manufacturers submitting safety data.
As ingredients become more complex, especially those produced through precision fermentation or cell culture, the volume and depth of what needs reviewing grows. Multiple speakers flagged this as a practical constraint that will limit how quickly any regulatory change can actually be implemented.
The Department of Health and Human Services oversees the FDA, and addressing capacity will likely need to be part of any serious effort to expand the scope of what qualifies as a dietary ingredient. Without that, the intent of updated regulations risks outpacing the ability to act on them.
What Comes Next for Dietary Supplement Compliance
The public comment docket remains open until April 27, 2026. This is a direct opportunity for dietary supplement manufacturers, formulators, and distributors to influence how the FDA defines "dietary substance" going forward.
Loren Israelsen of UNPA was clear: the more substantive comments the FDA receives, the stronger the mandate for change. He called for thousands of responses. Comments can be submitted at regulations.gov, docket number FDA-2026-N-2047.
For brands and companies in this space, staying silent is also a choice. Those who engage now through data submissions, NDI notifications, and public comments will be better positioned when updated dietary supplement regulations take shape.
Reviewing Your Manufacturing Process and Compliance Checklist
Here is what supplement brands and manufacturers should be looking at right now:
- Review your ingredient list for anything that may fall into a gray area under current dietary ingredients rules
- Check your NDI status for any ingredients introduced after October 1994
- Audit your manufacturing process against manufacturing practice standards
- Confirm that your labeling accurately reflects the intended use and identity of each ingredient
- Submit a public comment before April 27, 2026 if your products are affected by how these definitions are drawn
- Monitor upcoming FDA actions and guidance that follow this meeting
Where the Supplement Industry Goes from Here
The supplement industry has grown well beyond vitamins and capsules. It now includes fermentation-derived bioactives, precision-designed amino acids, and microbial ingredients that did not exist when DSHEA was written in 1994. The science has moved forward. The regulations are catching up.
The FDA oversees everything from how dietary ingredients are identified to how products marketed as supplements make health claims. As that scope expands, so does the responsibility for manufacturers and distributors to comply with standards that are still being defined. Regulatory action tends to follow when the gap between what the science allows and what the rules permit gets too wide to ignore.
What the March 27 meeting showed is that the FDA is asking the right questions and is open to input. The outcome will depend on how clearly the industry can demonstrate that safety and innovation are not in conflict, and that modern science provides the tools to evaluate both with real precision.
For the full breakdown of what was discussed, review the official FDA meeting agenda.
