FDA’s draft New Dietary Ingredients (NDIs) guidance has swept like a hurricane-driven storm surge over the dietary supplement industry. As summer gave way to fall, the troubled waters have started to recede and some of the high points have started to emerge.
In early September FDA granted the request of a coalition of five major trade groups for an extension on the comment window. The coalition had called for a 45-day extension and FDA went one better by granting 60 days. The new deadline for comments is now Dec. 2.
The key points in industry’s reaction so far
1. Supplements vs. ingredients: Is FDA right in interpreting the NDI section of the Dietary Supplements Health and Education Act (DSHEA) as applying to the safety of formulations as opposed to the ingredients of the formulations?
2. Scope: Is the guidance overbroad?
3. Old vs. new: What’s grandfathered? How do you prove that? What changes a grandfathered ingredient into a new one?
4. Probiotics: What does the future hold for this category?
Since the guidance was issued in early July, Daniel Fabricant, PhD, director, Division of Dietary Supplement Programs, FDA, has repeatedly cited the following statistics: An estimated 55,600 supplement products are on the market, yet FDA has received fewer than 700 NDI notifications, or an average of about 55 per year. It seems clear that no matter what the interpretation of the law turns out to be, more notifications should have been filed in the 17 years since DSHEA was signed into law.
Ingredients or finished products?
So does FDA have it right that this is about supplements, not the ingredients of those supplements? As so often is the case when considering points of law, it depends on whom you ask. The majority of industry sources, including some of those who helped write the original bill, think FDA erred in coming down on the side of requiring safety information on finished product formulations.
Loren Israelsen, executive director of the United Natural Products Alliance, is one who believes FDA got it wrong when it focused on the finished product side of the equation. Most sources in industry contacted for this story agree with him that the intent of DSHEA was to call for notifications on new ingredients, not on new products containing those ingredients. That’s what the “I” in NDI stands for, after all.
To bolster his view, Israelsen, who was on Sen. Orrin Hatch’s (R-Utah) staff when DSHEA was crafted, has shown a draft version of the law in which the heading of the NDI section had the word “supplement” crossed out and replaced with “ingredient.” Wording lower down in the section is less clear-cut, however.
That leads Todd Harrison, an attorney with Venable LLP and the chair of its Food and Drug Group, to conclude that FDA is likely on solid legal ground with its position that the law says this process is about the safety of the finished product.
“FDA’s reading of the law is reasonable and court is unlikely to disagree with the agency. I don’t think that is what Congress intended. The law was poorly drafted—like a host of laws. Unfortunately you’re stuck with the language as written,” he said.
Harrison noted, as others have, that to cleave to this position in practice could set the agency up for an untenable flood of NDI notifications. The agency, which has a staff of 10 that spends part of its time dealing with these filings, has been processing an annual average of 55 NDI notifications up to now.
“FDA should use exercise its enforcement discretion and only require submission of the ingredient rather than the finished product,” Harrison said.
As far as the scope of the guidance is concerned, natural products attorney Marc Ullman of Ullman, Shapiro and Ullman LLP is unequivocal.
“This is ‘rulemaking by guidance,’ which is frowned upon by Congress and the courts,” Ullman said. “It is well beyond that which the agency had previously made clear in 1996, which clearly applied only to ingredients rather than supplements containing ingredients.”
Ullman noted that legal options are few under the guidance procedure. A formal rulemaking could be challenged in court before it goes into effect, which is why he said regulatory agencies often prefer to go the guidance route.
“To implement this change they have to do it formally,” he said.
Ullman has also clearly staked out the position that the NDI procedure is a notification process, not a premarket approval procedure. Fabricant is on the record as saying that NDI notifications are the only way FDA has of exerting “preventive control” over supplements.
“All I have to do is notify. FDA is still obligated to take an enforcement action and prove in a court of law that my product is adulterated or misbranded. It’s not a preapproval process. But there are implications in the marketplace that make this procedure very coercive,” Ullman said.
Everything old is new again
Another part of the guidance that continues to cause consternation in industry is the portion dealing with Old Dietary Ingredients and how to determine the status of an ingredient. In the guidance FDA dismissed out of hand industry lists of what was on the market in late 1994. Also excluded are any affidavits that might be filed by companies as to what they were selling at the time DSHEA was passed. This puzzles Michael McGuffin, president of the American Herbal Products Association, who wondered why affidavits aren’t good enough for FDA when they form an important and accepted part of court procedure. And there is a lengthy list in the guidance of what might constitute “chemical alteration” of an ODI such that it becomes an NDI.
This issue still needs some clarity. Among other things, it seems to place most or all extracts obtained with supercritical CO2 extraction into the NDI category. Manufacturers who use the process say that it merely results in a purer, higher-quality extract, but not one that alters the material on a molecular level.
Probiotics in peril?
One huge segment of the industry that seems especially vulnerable as a result of this document is the probiotics category. Strains of gut bacteria that have been long studied and manufactured, such as some strains of lactobacillus and bifidobacterium that can be shown with some certainty to have been in the food supply in 1994, seem to fit reasonably safely into the ODI realm. But newer strains seem to be in limbo.
“I think the designer strains of probiotics may be in jeopardy, but this should hardly be news to the industry as FDA has been telegraphing this possibility for at least a few years ” Harrison said.
“If I’m on the market [with a probiotic] and I’m selling and I haven’t had a problem, based on this draft guidance document, legally I’m not doing anything,” Ullman said. “What I’m worried about is what’s going to happen with my insurance coverage, and that’s where there is a big coercive element here.”
A number of probiotics manufacturers have achieved GRAS status on their ingredients, which removes the need for filing a NDI notification. But, Harrison said, without an FDA no-objection letter, that status might not be as powerful a protection as it would seem.
“Taking a self-determined GRAS position is not the panacea that many in the industry appear to believe if FDA would disagree with that self-determination. Indeed, some in the industry appear to believe that an expert report is sufficient to establish a self-determined GRAS position rather than convening an expert panel. Such a report will not pass FDA muster and leaves the company vulnerable. Basically, if you have a solid self-determined GRAS position, it should be readily converted into a GRAS Notification. If it cannot, the self-determination is not worth the paper it is written on,” he said.
Now that the draft guidance has been filed and the comment period is over (or nearing its end) there is a months-long procedure for FDA to respond to comments and (possibly) alter the guidance in response. The guidance is unlikely to be finalized before the end of the first quarter in 2012. But the battle lines have been drawn.