The old canard against dietary supplements is it is an unregulated industry. The truth of the matter, of course, is supplements are very much regulated, just in a different way than pharmaceutical drugs, which notably need pre-market approval from FDA. Not so for supplements, but that’s because this class of consumer goods is regulated as foods, which carry a presumption of safety.
Supplements still need to be produced in a certified GMP (good manufacturing practice) facility, labels must be in compliance, claims must be of the structure/function variety and not drug-disease claims, companies must submit adverse events reports (AERs), and so on.
These regulations were mostly promulgated in the Dietary Supplement Health and Education Act of 1994 (DSHEA), which established the rules for the modern supplements market.
However, one aspect of DSHEA has still not been finalized by FDA, not even today, 25 years after the governing legislation passed.
That is new dietary ingredient (NDI) rules.
In 2011, FDA rolled out an NDI guidance document—the government’s interpretation of laws—and received such pushback that even Sen. Orrin Hatch (R-UT) wrote the agency to advise them they were way out of line.
In 2016, FDA issued another round of draft rules, and this too was seen as not merely onerous but actually an attempt to rewrite DSHEA. (FDA has never been known to be a fan of supplements.)
Some of the sticking points with FDA’s proposed guidance documents include:
- New extraction methods: Supercritical CO2 extraction is a way of extracting plant components. It came to the market after DSHEA passage. Does using that over a traditional ethanol extract make it a new ingredient? FDA says yes. Industry says no.
- Synthetic botanicals: If a compound is molecularly identical to the plant, yet not grown from soil, does that make it a new ingredient? Issues around this include less cost and sustainability issues. Is a “nature identical” ingredient a new ingredient? FDA says yes. Industry says no.
- New ingredients vs new supplements: In the 2016 round, the agency took the position that virtually every new supplement had to receive NDI notification (NDIN). But the governing legislation is about NDIs, not supplements.
- “Old” dietary ingredients: Ingredients already on the market before DSHEA passage, in October 1994, are grandfathered in and presumed to be safe. Yet FDA has been limited in what it considers evidence of an old dietary ingredient. “We need an advertisement that happens to have the back of the label showing,” said Michael McGuffin, president of the American Herbal Products Association (AHPA). “There are very few of those.” In addition, after DSHEA was passed the world turned digital, and over the years most documents were destroyed. And various industry groups have submitted records and catalogs, most of which have been summarily dismissed by FDA.
And so the standoff continues. It’s notable that most NDI submissions are denied by FDA but on procedural grounds.
“The main failing has always been the FDA saying you did not clearly identify an ingredient,” McGuffin said. “You told it’s an extract, the plant part, but not the concentration level, the extraction process, you didn’t clearly identify the ingredient. So why don’t you give us guidance on properly identifying the ingredient? The FDA has not been a good keeper of the program.”
The result is companies usually take one of two directions when considering this issue. One is to straight-up ignore it. FDA estimates there are as many as 80,000 new supplements on the market since DSHEA passed, and it has granted “good day” letters to a tiny fraction.
The other is the GRAS (generally recognized as safe) workaround. The advantage of filing for self-affirmed GRAS instead of an NDIN is not necessarily cost or science required, but rather the federal agency that is involved.
“Early on I heard lawyers say work with FDA on GRAS and you’ll get a sophisticated, helpful group and they’re not biased against you,” McGuffin said, “or you can deal with people at the Office of Dietary Supplement Programs [ODSP] NDI team and they’re less professional and less experienced and appear to have a bias against you. I’m not saying that’s so, but the perception in the industry was that you didn’t get good service at the FDA NDI team.”
That sentiment seems to be backed up by the legal community.
“In original intent NDI was expected to be ‘easier’ than GRAS,” said Jessica Wasserman, partner with the Greenspoon Marder law firm, “but in the recent past FDA has made the NDI process difficult.”
GRAS filings also offer a two-fer. “With it,” said Ivan Wasserman, partner at the Amin Talati Upadhye law firm, “you can use the ingredient in food as long as you are within the GRAS levels, types of foods, etc., and with supplements. With NDIs you only get supplement use—not food.”
NDIs this year
INSIDER filed a Freedom of Information Act (FOIA) request and was informed that, between Oct. 1, 2017 and Sept 30, 2018, there were 45 NDI notifications, of which 17, or about 45 percent, were acknowledged without an objection.
Former FDA commissioner Scott Gottlieb, M.D., in remarks just before he departed the agency, spoke of “modernizing” DSHEA around the twin issues of access and safety—specifically to “adequately evaluate product safety while promoting innovation” by updating its NDI notification process.
Will this third attempt at an NDI guidance document be more amenable to the supplements industry—especially since 25 years have gone by and supplements remain largely safe, and safety is the primary goal of FDA regulations?
NDIs and CBD
In a Dec. 20, 2018 announcement—the day the Farm Bill was signed that removed hemp and hemp cannabidiol (CBD) from the controlled substance list—FDA said it would consider a legal pathway for hemp CBD “if the agency were able to determine that all other requirements in the FD&C Act [Federal Food, Drug and Cosmetic Act] are met, including those required for food additives or new dietary ingredients.”
Does that mean FDA would consider hemp CBD to be legal only if companies file an NDIN? If that’s the case, one could imagine the vast majority of hemp CBD companies would not able to afford it. To date, only one hemp CBD company, CV Sciences, makers of Plus CBD Oil, has successfully completed a self GRAS filing—at a cost in the high six figures.
“The reason we haven’t seen NDINs for hemp CBD is because FDA has said it isn’t a lawful dietary ingredient,” said Rend Al-Mondhiry, senior counsel at Amin Talati, “so even if a company were to submit a notification, FDA is likely to object and not consider the substance.”
So until FDA confirms the pathway forward for CBD in supplements, NDIs for hemp will remain on the back burner. And although Gottlieb said the agency was going to be looking at both NDIs and hemp CBD in the near future, his departure may create a lull in agency urgency.