As experts in industry continue to delve into the intricacies of FDA's New Dietary Ingredient (NDI) guidance, one thing is becoming clear: It's going to be difficult to nail down all of the possible ramifications this document has for industry and then effectively respond within the 90-day comment window.
"My worst fear was the FDA guidance document would lend itself to providing more questions than answers," said Scott Steinford, president of ZMC-USA. "To that end, at this point, it seems it has. The comment period should be extended as this guidance document is too complex and important for both the FDA and the industry to rush to a conclusion. It has taken 17 years to get to this point and 90 days to fully interpret and comment on this guidance is inadequate."
A big reason for this is the scope of the guidance. It's huge.
"It's more onerous than I was expecting," said Ivan Wasserman, an attorney with the law firm Manatt, Phelps & Phillips. "FDA has interpreted the [NDI portion of] the statute to have as broad an application as possible."
"I don't sense a lot of give in this document as to what ingredients don't need a NDI notification," he said.
Few exceptions for NDI filing requirement
The exceptions are few. An ingredient that has GRAS status for use in food could be used in a supplement without a NDI filing so long as it is used in the same form and in the same dosage. A dusting of powdered oregano to flavor a pizza and an extract of oregano in a capsule are two different things, in other words.
The other exception in the document that exempts substances from a NDI filing states if they have been "present in the food supply as an article used for food in a form in which the food is not chemically altered."
And that last bit is the rub. In a subsequent section, the guidance delineates the ways in which ingredients would considered chemically altered, and they are legion. Distilling an extract to remove some of its constituents, for example. Filtering it through a membrane or via chromatography. Even taking an ingredient from an unripe fruit as opposed to a ripe one is mentioned as constituting chemical alteration.
Another way in which the guidance seems to broadly interpret the NDI portion of the Dietary Supplement Health and Education Act (DSHEA) is that it is calling for NDI filings on finished products as well as ingredients.
"The statement that NDI submission is 'supplement-specific, not ingredient specific' can lend itself to incredible amounts of required research and analysis of each formulation," said Steinford. In other words, if an ingredient manufacturer has submitted a NDI notification, that notification would not apply to the finished good manufacturer, who would, according to the guidance as written, need to do a separate NDI filing.
It has been a cause of concern for some of Wasserman's clients. "I've gotten a few calls that were like, 'Really? But I've only been buying ingredients that had NDIs. Isn't that what I was supposed to be doing?' "
NDI filings could flood FDA
This interpretation would seem to open up floodgate for potentially thousands of NDI filings.
"It is impossible to guess the number of NDI filings that could be required," Steinford said. "I have heard estimates of 65 percent of current consumer offerings could be subject to NDI filings. Extrapolating this figure out, the store shelves could conceivably become quite sparse if the worst case interpretations of this guidance are realized. Consumers will not allow this and it is doubtful the FDA will want that type of burden as well."
Steinford said that FDA has been unable to keep up with the NDI workload during a period in which many companies have been avoiding filing notifications. If the industry reacted to the guidance as written, FDA would be swamped with filings. He noted that a big complicating factor is the position FDA took in the guidance dismissing the lists trade organizations compiled of what ingredients were on the market as of Oct. 15, 1994 and therefore would qualify for Old Dietary Ingredient (ODI) status.
"One of the biggest revisions which would benefit the FDA NDI process would be the adoption of the trade organizations' previously defined ODI lists," Steinford said. "The trade organizations have been working on the projects for years in an effort to assist the industry and presumably the FDA. The FDA could absolve itself and the industry from countless hours of stress and research by changing the singular position that trade organization ODI lists are irrelevant."
Steinford is far from alone in calling for amendments to the guidance.
"If this guidance is truly a safety issue it should be more holistic," said Len Monheit, director of the Supply Network of New Hope Natural Media. "The NDI process is burdensome right now. The process is going to become more burdensome."
How to respond
Comments on the draft guidance can be submitted at www.regulations.gov. Written comments can be submitted to the Division of Dockets Management (HFA-305), Food and Drug Administraion, 5630 Fishers Lane, RM. 1061, Rockville, MD 20852.
In addition, industry associations have been quick to step up to the plate with ways to help understand and react to this guidance. The Amercian Herbal Products Association, which has the industry's most complete, up-to-date database of NDI filings available on a subsciption basis, is planning a webinar on the issue to be scheduled soon.
The Natural Products Association has scheduled a webinar titled, "NDI Guidance: What You Need to Know" on Monday, July 11 at 3:30 p.m. Eastern time.
And the United Natural Products Alliance is holding a two-day conference on the ramifications of the NDI guidance document on July 26 and 27 in Salt Lake City.