Why gluten-free claims, precision fermentation, and emerging dietary ingredients are forcing manufacturers to think beyond the Certificate of Analysis.
Walk through the supplement aisle and you'll see claims that appear straightforward:
Gluten-free.
You'll see enzymes marketed for digestive support, probiotics identified by species and strain, proteins, peptides and an expanding number of ingredients manufactured using fermentation and biotechnology.
From the consumer's perspective, the obvious question might be:
Was it tested?
But modern dietary supplement manufacturing is making that question increasingly complicated.
Sometimes the better questions are:
What exactly was tested? At what stage was it tested? Was the analytical method appropriate for that particular material? And what happened to the ingredient during manufacturing?
Those questions aren't merely theoretical.
In March 2026, FDA's Office of Dietary Supplement Programs held an entire public meeting examining how scientific and technological advances are changing the dietary supplement ingredient landscape. FDA specifically asked stakeholders to discuss emerging manufacturing methods such as precision fermentation, cell culture, and recombinant production, along with the identity of proteins, peptides, enzymes, and microorganisms.
The meeting provides a fascinating window into a problem the supplement industry increasingly faces:
Our ability to manufacture sophisticated ingredients is advancing faster than some regulatory concepts were originally designed to describe.
The Gluten-Free Problem Is a Perfect Example
Consider a dietary supplement containing an ingredient produced through fermentation.
A manufacturer wants to make a “gluten-free” claim.
The obvious Quality response might seem to be:
Test the finished ingredient for gluten.
But FDA specifically recognizes that this may not be sufficient.
FDA's gluten-free regulation applies to FDA-regulated packaged foods including dietary supplements. Foods bearing a gluten-free claim must meet FDA's definition, which includes having less than 20 ppm gluten when any unavoidable gluten is present.
Fermented and hydrolyzed ingredients present a special analytical problem.
During fermentation or hydrolysis, proteins can be broken into smaller fragments. FDA explains that currently available conventional methods cannot adequately detect and quantify gluten in these materials because the gluten proteins are no longer intact.
That changes the Quality question dramatically.
A finished-product result isn't necessarily the entire answer.
For a fermented or hydrolyzed food—or a product containing such an ingredient—that carries a gluten-free claim, FDA requires manufacturers to maintain records providing adequate assurance that the material met the gluten-free definition before fermentation or hydrolysis. Manufacturers must also evaluate potential gluten cross-contact and document controls where a risk exists.
Those records must generally be retained for at least two years after the food is introduced or delivered for introduction into interstate commerce and made available to FDA during inspection upon request.
That is an important distinction:
Testing is evidence. But evidence is only useful when the analytical method is capable of answering the question you're asking.
Fermentation Is Changing the Ingredient Landscape
This becomes even more interesting when we move beyond traditional fermentation.
FDA's March meeting specifically examined new methodologies for producing dietary ingredients, including precision fermentation, cell culture technology and recombinant production.
The concept itself isn't completely new. One presenter noted that microbial fermentation has been used to manufacture vitamins for decades. What is changing is the sophistication with which microorganisms can now be used to manufacture specific proteins, enzymes and other bioactive compounds.
A microorganism can essentially become a biological manufacturing system.
But that raises new Quality questions.
What organism produced the ingredient?
What strain was used?
What fermentation medium was used?
What impurities or byproducts might be produced?
How was the target compound separated from the fermentation biomass?
Does the resulting molecule have the same structure and biological characteristics as the substance we're comparing it with?
FDA essentially put these questions on the table.
Its memo for the meeting asked when a production change involving synthesis, cell culture, precision fermentation or recombinant production meaningfully changes an ingredient's identity, composition or safety profile enough to justify additional regulatory scrutiny or data. FDA also asked how manufacturers should characterize potential byproducts, impurities, and structural or functional variations. U.S. Food and Drug Administration
That's Ingredient Intelligence at a much deeper level.
An Enzyme Isn't Just a Name on a Label
Enzymes illustrate the problem particularly well.
An enzyme is a protein, and proteins aren't defined merely by the ingredient name attached to them.
During FDA's meeting, scientists discussed characteristics including amino-acid sequence, molecular weight, folding, post-translational modifications, stability and biological activity. One presentation emphasized that amino-acid sequence helps determine how a protein folds and ultimately behaves biologically.
FDA's previous review questions concerning enzymes have similarly considered attributes including post-translational modifications, folding, structure, stability and enzyme activity.
That creates a fascinating Quality question.
Imagine two ingredients carrying the same enzyme name.
If one is isolated from a traditional biological source and another is produced through an engineered microorganism using fermentation, when should regulators consider them the same dietary ingredient?
That's one of the questions FDA is now examining.
FDA's own meeting memo asked what scientific criteria should establish identity for peptides, proteins, enzymes and microbials, and what criteria should determine whether two substances are sufficiently similar to be considered the same dietary ingredient for regulatory purposes.
There isn't a simple one-test answer.
Probiotics Make Identity Even More Complicated
Microbial ingredients create another layer of complexity.
With a botanical, Quality professionals may ask about genus, species and plant part.
With a probiotic, we may need to think about:
Genus → species → strain
FDA's meeting discussed questions surrounding microbial identity down to the strain level. Industry participants also debated whether food-use history should sometimes be established at the species level while safety for the intended use is evaluated at the strain level. That was an industry position presented to FDA, not an FDA conclusion, which is an important distinction.
FDA is still considering broader questions about how these ingredients fit within DSHEA.
That's precisely why the meeting occurred.
FDA opened docket FDA-2026-N-2047 and accepted public comments through April 27, 2026. The agency said it would review both the meeting testimony and docket submissions in determining its next steps.
FDA — Public Meeting: Exploring the Scope of Dietary Supplement Ingredients
The FDA page includes something unusually useful for anyone interested in supplement science: the full meeting transcript, slide deck, agenda and memo to the docket.
The Manufacturing Process Can Be Part of the Quality Story
This is probably the biggest lesson.
Consumers understandably focus on what's written on the bottle.
Quality professionals have to think much farther upstream.
For a modern fermented ingredient, understanding Quality may require knowing the production organism, raw-material inputs, fermentation medium, process controls, downstream purification, potential contaminants or byproducts, specifications, analytical methods and supporting safety information.
One meeting presentation described evaluating fermentation inputs, potential hazards, downstream processing and the final ingredient's identity and specifications. Another discussed checking potential hazards associated with production organisms—for example, considering mycotoxins with certain yeast or mold systems or endotoxins with certain bacterial systems.
This doesn't mean every fermented ingredient is questionable.
Quite the opposite.
Fermentation can be an extraordinarily sophisticated and controlled manufacturing technology.
The point is that the manufacturing process matters when determining what evidence is necessary to establish identity, purity, safety, and compliance.
Why a COA Isn't the Entire Quality System
A Certificate of Analysis is important.
So is finished-product testing.
But neither document can answer every Quality question by itself.
The gluten-free example demonstrates this beautifully.
If the analytical method cannot reliably quantify fragmented gluten after fermentation, receiving a finished-product result doesn't erase the need to understand what entered the fermentation process in the first place.
Likewise, an enzyme assay may demonstrate activity without necessarily answering every question about the protein's identity.
And identifying the species of a probiotic doesn't automatically answer every question about the characteristics or safety of a particular strain.
Quality isn't simply asking whether something was tested.
It's asking:
Does the evidence we have actually answer the question we're trying to answer?
Supplement Quality Is Becoming Ingredient Intelligence
This is one reason I find the intersection between supplement manufacturing, regulatory science and ingredient science so interesting.
The industry is moving beyond relatively simple questions like:
“Is ingredient X present?”
Increasingly, Quality professionals need to understand:
What exactly is ingredient X?
How was it produced?
Did manufacturing alter it?
Which analytical method can actually characterize it?
What documentation supports the claims being made about it?
And perhaps most importantly:
What don't we know yet?
FDA's March 2026 meeting didn't settle all of those questions. FDA itself described the meeting as an early step and invited additional public input before deciding what should come next. U.S. Food and Drug Administration
That may actually be the most interesting part.
The science of dietary supplements isn't standing still.
Neither can Quality.
The Primal Hacking Takeaway
A supplement label may contain only a few square inches of information.
Behind it can be an enormous chain of science:
source → organism → manufacturing process → ingredient identity → specifications → analytical method → testing → documentation → finished product → label claim.
Understanding that chain is what separates simply reading a supplement label from actually understanding the ingredient behind it.
Evidence over hype also means understanding what the evidence can—and cannot—prove.
Sources & Further Reading
- FDA — Public Meeting: Exploring the Scope of Dietary Supplement Ingredients (March 27, 2026)
- FDA — Memo to the Docket: Exploring the Scope of Dietary Supplement Ingredients
- FDA — Questions and Answers on the Gluten-Free Food Labeling Final Rule