Editorial: Do prior FDA responses shed light on forthcoming new dietary ingredient (NDI) guidance?

May 24, 2011

Do prior FDA responses shed light on forthcoming new dietary ingredient (NDI) guidance?

Do prior FDA responses shed light on forthcoming new dietary ingredient (NDI) guidance?

Granted, there’s nothing industry can do to change things between now and when guidance is released in July. And, guidance is not law. Still, at SupplySide East, Vasilios Frankos, PhD, now Herbalife’s senior vice president of global product science, safety, and compliance-and the previous director of FDA’s Division of Dietary Supplement Programs-cited two citizens’ petitions whose formal FDA responses detail agency thinking regarding nature-identical ingredients and ingredients originally studied as drugs.

For nature-identical ingredients, Frankos mentioned the case of a citizens’ petition made by OVOS Natural Health Inc. (OVOS) in 2009, to market the company’s homotaurine in dietary supplements. In its response this February, FDA stated that although homotaurine occurs naturally in some plants, including in the seaweed Rhodymenia palmate, OVOS’s homotaurine is synthetically derived and could not be considered a dietary ingredient by the agency.

“This is the second time FDA has formally said you can’t be a constituent of a botanical unless you’re actually extracted from the botanical,” Frankos told Nutritional Outlook. (The first time was when FDA disallowed ephedrine as a dietary ingredient because it’s synthetic and not extracted from the Ephedra plant. Also, informally, in a recent poster about NDI notification objections, FDA noted it had objected to synthetically derived phytosterol esters.)

“This is pretty much the position FDA has taken,” Frankos says. “It’s going to have a significant impact on industry because there are a lot of products that say they’re synthetic and nature-identical. This could raise questions about whether those can be sold as dietary supplements, period.”

(On a side note, in the OVOS case, FDA also declared that the company’s homotaurine did not meet the agency’s definition for a dietary amino acid-marking the first time FDA formally defined dietary amino acid. Will more NDI submissions force the agency to formally define other nutrients as well?)

Back to the citizens’ petitions, Frankos also pointed out that the agency has stated that ingredients originally developed as drugs, based on Investigational New Drug (IND) applications, cannot be considered dietary ingredients.

This was the stance FDA took in the case of Biostratum Inc., maker of Pyridorin. Pyridorin’s active ingredient is a salt of pyridoxamine, part of the vitamin B6 family. Biostratum had studied pyridoxamine under an IND for diabetic nephropathy and petitioned FDA to disallow pyridoxamine from being marketed in supplements. FDA did so, citing the fact that no evidence could be found to prove that pyridoxamine had been marketed as a supplement ingredient prior to being studied as a drug.

Moreover, in its formal response in 2009, the agency stated that its decision applied not just to the actual pyridoxamine molecule that was tested per the IND, but also to any other similar molecules, including other salts, chelates, or complexes, because the active moiety is the same.

A few exceptions to the IND/NDI clause exist. Per the Dietary Supplement Health and Education Act, companies can petition that a drug-IND ingredient be considered as an NDI. A company can also try to prove that the ingredient was previously marketed in a dietary supplement.

OVOS’s homotaurine, in fact, had been intended for study as a drug first, for Alzheimer’s disease. The company submitted the first-ever citizens’ petition of its kind, seeking the exemption. However, the petition was stopped short when FDA stated that homotaurine can’t be considered a dietary ingredient, for the reasons mentioned earlier.

“So, to date, no one has gone through the process of getting an exemption,” Frankos notes. “Once you start down the drug path, you may exclude yourself from going down the dietary supplement path.”

These cases offer concrete evidence of how FDA has defined new dietary ingredients in the past. Their implications should not be taken lightly, Frankos says.

“These are two cases that went through a very rigorous review by the agency, including legal review. For pyridoxamine, there was actually publication in the Federal Register, requesting comment from the industry. Therefore, the conclusions are very defensible, from the standpoint of the FDA not being accused of being arbitrary and capricious. They have stature from a legal/regulatory standpoint. And that’s why they’re strong.”