The dietary supplements and nutritional ingredient supply industries have long awaited updated guidance from the U.S. Food and Drug Administration (FDA) concerning New Dietary Ingredients (NDIs) for dietary supplements. This is yet another step in the long march toward full implementation of all the provisions of 1994’s seminal Dietary Supplement Health and Education Act (DSHEA) legislation. Finally, FDA's NDI guidance is expected to be released by the end of next month.
Much has been written in this space and elsewhere about what this document might contain and what it might mean. The range of possibilities seems to be bordered on one hand by a clarification of some of the vague portions of the existing rules on NDIs, or on the other by the introduction of a new, broader interpretation of what constitutes an NDI, thereby invalidating many of the ingredients on the market.
Preparing for FDA's NDI guidance
No one can be sure what this new guidance will contain, but there are some commonsense things a company can do to prepare in the meantime. One of these is to make sure that evidence supporting a "grandfather" claim for an ingredient is as solid as it can be. (Such a claim states that an ingredient was in commerce prior to October 15, 1994, thereby obviating the need to file an NDI notification). Or a company can arm itself with information in preparation for an NDI filing, should one become necessary.
One of the best sources of information on NDIs has been tended for years by the American Herbal Products Association and its president, Michael McGuffin. AHPA's subscription-based, searchable NDI database contains full documentation on every NDI filing starting with the first in 1995 and ranging up to the present – 575 submissions in all.
"We wanted to learn from how FDA responded. We thought the best idea to learn how this thing works it to watch how the regulators responded," McGuffin said.
NDI database fills need
"If you are going to file an NDI notification (the database) can be very useful," McGuffin said. "One, you can see if anyone has filed a notification for that same or similar ingredient. And two, it can help to study how companies are submitting those notifications, to see whether FDA is agreeing the information is sufficient.
"It's really a learning tool for companies when they file so that they can do a better job," he said.
Several trends have arisen from looking at the data that AHPA has compiled. FDA raises concerns generally on two primary areas:
- The company has not clearly identified the ingredient to FDA's satisfaction. For example, an ingredient may be named as an extract of a given botanical, but there is insufficient information on the solvent used, the extract ratios, etc.
- The other primary objection arises when a company supplies information on a similar substance but is not clearly about the exact ingredient that is the subject of the notification.
In addition to the database, AHPA produced a guidance document for members back in 2006. The document, which was updated in June 2011, sets up a decision tree to help a company decide whether an ingredient warrants filing an NDI notification.
NDI case study: POM Wonderful
Of the 575 total submissions, McGuffin said, 118 were duplicates, leaving 437 unique submissions covering 466 ingredients (some submissions included more than one ingredient). Another 64, or about 15 percent, were erroneous submissions; poorly done, filed on finished products rather than ingredients, etc.
That leaves 373 suitably well-prepared submissions. Of those, FDA responded to a majority of submissions with a letter saying the agency had concerns about the submission. The others "succeeded," in that they received a note saying "Filed by FDA without substantive comment."
One set of filings by a high-profile company – POM Wonderful LLC – illustrates that persistence in this process can pay off. It took POM three tries to receive the desired "filed by FDA" response. It also illustrates the pitfalls of the process; POM fell into the two traps mentioned above before finally prevailing.
POM first filed an NDI notification for its Pomegranate (Punica granatum 'Wonderful') fruit polyphenol extract on July 21, 2006. FDA responded with the concern that the ingredient was insufficiently characterized. The agency said it was "unable to determine the identity [of the NDI] other than the statement that it consists of polyphenols." POM filed an amended notification on August 31, 2006, and received a response from FDA that stated that the information POM had supplied applied to pomegranate juice, whereas the NDI in question was an extract. The agency stated that it was "therefore . . . unclear how your ingredient is qualitatively or quantitatively similar to the substances described in the information that you rely on for the safety" of the NDI.
Finally, on Dec. 13, 2006, POM submitted a notification that included enough information to allay FDA concerns and the company received its "filed by FDA" communiqué in at the end of February 2007.
The NDI bargain
A company that referred to cases like POM's in AHPA's database could likely avoid some of the same mistakes. This would save money in staff time and in bringing an ingredient to market faster. (It's worth adding that while a simple NDI notification, regardless of FDA's response, fulfills the letter of the law, in practice few if any companies have chosen to go to market with an ingredient that has an FDA objection letter hanging over it.)
AHPA operates the database on a subscription basis in cooperation with NPI Center of New Hope Natural Media's Supply network. The cost is $125/year for AHPA members, and $495/year for nonmembers. With fees for top-flight attorneys in the natural products business hovering at about $350 an hour, it seems a bargain.