FDA has taken a position via the NDI draft guidance that synthetic versions of botanical constituents cannot be dietary ingredients. This position shows FDA at its worst.
By Steve Mister Esq., President and CEO
Wasn't it Shakespeare who said a rose by any other name is still a rose? I wonder if he would feel the same if he had worked for FDA? Given the direction the agency appears headed, he would likely have wanted assurance that it was indeed grown in a garden and not subjected to any artificial processes—no matter how much it looks like the prized flower.
On its current course, FDA seems determined to declare a variety of substances as anything but dietary ingredients, regardless of how much they look like the botanicals on which they are based. I am referring to the agency's determination that DSHEA permits it to declare any synthetic substance that is modeled on an extract of a plant not to be a dietary ingredient, and therefore, not eligible to be used in a dietary supplement. Note that with this death sentence, the ingredient is categorically forbidden from use in a supplement: unlike a new dietary ingredient (NDI), no amount of safety data can save it.
This interpretation of the law has most recently shown up in FDA's draft NDI guidance, but it certainly isn’t the first time FDA has expressed this view. Each time, the industry has tried to correct the agency's misinterpretation of the law, but the agency simply isn’t listening.
In 1994, DSHEA declared a dietary supplement may include (among other things) a vitamin, mineral, herb or other botanical, or a concentrate, metabolite, constituent or extract of any of these substances. Compounds that can be isolated and removed from a botanical are clearly a "constituent" of a botanical.
So what about a synthesized version of a constituent of a plant? When DSHEA was written, the industry already had experienced FDA's attempts to distinguish between synthetic and natural vitamins and other nutrients. During the 1970s, FDA tried to declare synthetically-made vitamins as pharmaceuticals, and the Proxmire Amendment, enacted by Congress in 1976, declared these substances to be eligible for use in supplements regardless of their origin. DSHEA even includes provisions that assure vitamins and minerals, whether natural or synthetic, be treated equally. As a result, synthetic vitamins and minerals appear to be immune from FDA's current efforts. But because we did not ask Congress to be clearer when it passed DSHEA, botanical-based ingredients are not.
Way back in 2004, when the FDA issued its regulation banning ephedra from dietary supplements, one reason it gave for challenging the safety of the herb was that much of the "ephedra" on the market was actually synthetically derived ephedrine. While CRN applauded the agency's ruling (ephedra was becoming a liability to the industry), we disputed FDA's statement that a synthetic version of a botanical extract could not be a dietary ingredient. FDA was silent in response. Earlier this year, FDA denied a petition to use homotaurine in a dietary supplement, declaring that because homotaurine would be produced synthetically, instead of extracted from seaweed, it could not be a dietary ingredient. Again, CRN challenged that reasoning.
It seems to me the fundamental question is whether a synthetically derived constituent of a plant is any less safe than its naturally extracted twin? Otherwise, why should FDA care whether the substance is extracted from a plant material or made in a lab to be bio-identical to the natural counterpart? Just like vitamin and mineral ingredients.
Today, there are any number of supplements in the market that utilize ingredients based on a botanical extract, but created in a lab to mirror the plant constituent. As a result of the synthesis, these substances can be produced with more uniformity of strength, standardized to particular biologically active compounds, and without worry for heavy metals or other contaminants that might plague an extracted compound that was grown in less than pristine soil. Created in a lab, these ingredients have less variability from batch to batch, and provide consumers with consistent high quality dosages of the compounds that offer health benefits.
Now FDA has used the NDI guidance document to declare once again that synthetic compounds, even if they are nature-identical, can't be used in dietary supplements. CRN discovered recently that even before the industry gets to challenge that position in comments to be submitted this fall, that FDA has seized incoming shipments of certain ingredients at the port, and denied entry into the U.S., claiming that these synthetic (or even semi-synthetic) compounds can't be dietary ingredients because they are not "natural" constituents of a plant, and therefore are Active Pharmaceutical Ingredients (APIs).
It's hard to view this as anything except the FDA at its worst. At the same time the agency seems incapable, or at least reluctant, to use its authority to address real dangers to consumers from products that contain illegal pharmaceutical ingredients like sildenafil, sibutramine and anabolic steroids, it pursues this course instead. One can only conclude it is part of a larger effort to impede the maturity and standardization of the supplement industry. If synthetic versions of botanical ingredients can’t be used, and their natural twins cannot be extracted at the scale necessary for viable products, industry growth can be curtailed.
By any other name, this is scandalous. For me, the rose has lost its bloom.
(The CRN Blog represents the view of the author and does not necessarily reflect the view of CRN’s Board of Directors or serve as an official position of the association.)