The New Dietary Ingredient (NDI) Notification Guidance draft released by FDA earlier this month has touched off a flurry of activity among nutritional supplement trade associations eager to advise their industry constituents on the complex process of submitting notifications and how to interpret FDA’s response.
 
An NDI is defined as any substance that was not marketed as a dietary supplement ingredient in the U.S. prior to October 15, 1994 (ingredients used in dietary supplements before this date were “grandfathered in.”) Any manufacturer intending to market an NDI must submit evidence-based documentation to FDA that proves the safety at least 75 days before introduction of the product into commerce.

With around 80% of NDI notifications rejected by the FDA since 1994, a properly prepared NDI notification is critical. Most are rejected due to insufficient evidence for safety, the absence of required elements, as well as lack of knowledge and experience as it relates to preparing such notifications.


The Natural Products Association Weighs In
 
The Natural Products Association (NPA), Washington, D.C., recently hosted an informative webinar about the NDI Guidance and how it can impact a company’s business. Speakers included Dr. Daniel Fabricant, director of the Division of Dietary Supplement Programs at the FDA’s Center for Food Safety and Applied Nutrition (CFSAN); Scott Bass, head of the Global Life Sciences Team at Sidley Austin LLP; Dr. Cara Welch, NPA vice president of scientific and regulatory affairs; and John Gay, NPA executive director and CEO.
 
The speakers discussed how the Guidance clarifies when a premarket safety notification is necessary and what type information is expected for NDI notifications.
 
Dr. Fabricant framed the situation aptly, noting that there are about 55,600 dietary supplement products currently on the market. However, despite the 1000 new products introduced annually, FDA has only received about 700 NDI notifications since it began reviewing them about 16 years ago. On average, Dr. Fabricant said, FDA receives about 50 NDI notifications annually. “We believe, as I hope the industry believes, that consumers should have access to supplements that meet quality standards, are free from contaminants, accurately labeled and have an assurance of safety that is accurately described in terms of their safety and identity,” he said.
 
NPA’s Dr. Welch summarized NPA’s position on the NDI Guidance when she stated: “NPA believes FDA’s current thinking on what documentation is required for establishing pre-DSHEA ingredients is much more stringent than Congress intended when it wrote the Dietary Supplement Health and Education Act of 1994 (DSHEA). Congress wasn’t looking to make this provision so hard to meet that it essentially becomes unattainable. Additionally, the safety testing FDA believes is necessary for an NDI notification is on par with the food-additive petition process, but this is another example of FDA seemingly disregarding the intent of DSHEA. Congress clearly differentiated an NDI notification requirement from a food-additive petition by using different language.”
 
To order a copy of NPA’s webinar presentation, follow this link.
 

The American Herbal Products Association Offers Its Position
 
The American Herbal Products Association (AHPA), Silver Spring, MD, also held a webinar, titled “FDA’s NDI Guidance: What It Means for Your Business,” which addressed the implications to the dietary supplement and ingredients trade, while reviewing each of the controversial sections of the guidance on a variety of dietary ingredients and classes of ingredients.
 
AHPA’s presentation featured an assembly of speakers, including: Vasilios (Bill) Frankos, PhD, former FDA-CFSAN director, Division of Dietary Supplements; Tony Young, Esq, Kleinfeld, Kaplan & Becker & AHPA General Counsel; and Michael McGuffin, president, AHPA; as well a panel of attorneys comprised of Ashish Talati, Esq., Amin Talati; Jim Prochnow, Esq., Greenberg Traurig; and Paul Rubin, Esq., Patton Boggs.
 
Prefacing the discussion by emphasizing that the Guidance is still in draft form and not yet finalized, AHPA’s Mr. McGuffin stated that it represents FDAs thoughts on what a dietary ingredient is, what “marketed” means, etc.
 
The panel answered questions about how new NDI’s would impact innovation, how the new rules would affect dietary supplement marketers, what FDA was trying to accomplish with this guidance document, and the opportunities for the industry to amend the Guidance.
 
Mr. Frankos overviewed the origins of NDI Guidance draft as it related to DSHEA. Unfortunately, he noted, there are no documents available that refer to Congressional intent, as all discussion was expunged from the record regarding DSHEA. “We were hoping there would be more discussion of congressional intent from people who were there,” he said.
 
Mr. Prochow said he felt that Congressional intent was to stress the “importance of making new dietary ingredients and supplements available to public with primary focus on safety.”
 
Mr. Rubin expressed discontent with the draft Guidance document, calling it “inconsistent with Congressional intent.”
 
“[It] goes far behind what is legally justified or necessary,” he said. “It is overbroad and pushes companies unnecessarily to NDI submissions.”
 
He called upon the industry to be vocal and submit comments to help shape the draft guidance.
 
Mr. Frankos spoke about the possibility of phasing in the eventual Guidance. “This needs to be part of the dialogue with FDA,” he said. “How do you implement this so that it’s not totally disruptive to the industry?”
 
Mr.Young disagreed with the phase-in premise, and instead argued that FDA should use its enforcement priorities. “From an enforcement perspective, FDA has to make cases the old fashioned way: seizure, injunction, and prosecution. That’s a lot of work. They will pick cases carefully,” he said, defining those cases as “low hanging fruit,” those products with potential safety issues.
 
Among the speculated “low hanging fruit” most vulnerable to the NDI process could be products in the sports nutrition categories. “Sports nutrition ingredients try to be new, different and exotic. They seem to be at risk,” Mr. Prochow agreed. “Sports nutrition products are probably more at risk (of rejection) than other products because of the novel ingredients in those products.”
 
Also bound to be in FDA crosshairs would be products with marketing language like “new, patent-pending, never before available,” as well as imported products. “You have to show product is lawful,” noted Mr. Young. “FDA is the judge and jury.”
 
Two other categories the panel felt would fall into a gray area would be probiotics and nanotechnology. Probiotics are of particular concern because they are not vitamins, minerals or botanicals but are still considered to be dietary supplements. “FDA has indicated concern about probiotics,” said Mr. Young. “We all know probiotics are in dietary supplements. They were in before DSHEA. And there have been NDI notifications.”
 

The United Natural Products Alliance Sounds Off
 
The United Natural Products Alliance (UNPA) held a two-day seminar in Salt Lake City, UT, titled “The NDI Guidance: Understanding and Responding to FDA’s New Safety Paradigm for Dietary Supplements” late last week.
 
UNPA approached the new NDI Guidance draft as an essential part of a four-piece puzzle, which they termed a “new paradigm of dietary and functional ingredient safety.” They asserted that the NDIs go hand in hand with GRAS Affirmation, the Food Safety Modernization Act of 2010 and new food importation and detention regulations as it relates to confirming ingredient safety status, Section 111, GMP HACCP compliance, supplier qualification management and new importation regulations.
 
Loren Israelsen, executive director of UNPA said while his organization supports the role of the NDI process to provide a mechanism for FDA to evaluate the safety of truly new dietary ingredients, the Guidance, however, placed the focus on the dietary supplements and not the dietary ingredients as the law intended. “This single change created a system that would require a every DS company to adopt a drug-like review and approval process for most of their currently sold products,” he said. “FDA wants to review each product, new combinations of ingredients, manufacturing process changes as well as new ingredients. In each case the company must wait a statutory 75 days for an FDA response, in addition to all of the documentation preparation that FDA now asks for.” 
 
He went on to explain the implications of the NDI process, which he stressed stands for new dietary ingredient, not new dietary supplement. “The burden on industry is vastly different, and from our view would not materially contribute to improvements in product safety, just fewer products and fewer companies,” he said. “We will be working closely with FDA to offer changes to this draft Guidance with the goal of finding the proper balance of government oversight and industry safety control procedures that allows consumers to enjoy broad access to safe and high quality supplements, at affordable prices.”       
 
For an FDA backgrounder on NDI Guidance, follow this link.