Would FDA’s NDI Guidance Really Cost Industry Billions of Dollars?

September 14, 2016
Michael Crane

While some industry experts warn FDA is calling for tens of thousands of new NDI notifications, others anticipate the burden on industry will be more manageable.

It’s the million-dollar question-or maybe even the billion-dollar question-raised by FDA’s revised new dietary ingredient (NDI) draft guidance; how much would it cost the dietary supplement industry to meet the requirements outlined in the draft guidance? In the weeks since the new NDI guidance first dropped, industry experts have proposed vastly different estimates for both the total number of NDI notifications (NDINs) that would be required and the cost for each separate NDIN.

On the high end, the United Natural Products Alliance (UNPA; Salt Lake City) suggested a preliminary estimate of the total NDIN cost burden on industry could range from $2 billion to $6 billion. Those figures, which UNPA noted were a very early and tentative assessment, are based on a reading of the guidance that requires a separate notification be submitted for every manufacturing process change and every combination of different NDI ingredients. If that turns out to be the case, it’s easy to imagine tens of thousands of instances when a separate NDIN would be necessary.

“It’s a spawning effect,” said Loren Israelsen, president of UNPA, in UNPA’s August 25 webinar on the new NDI draft guidance. “If FDA really means this, then you will have a constantly generating set of new dietary supplement products that require notification.” And if the cost burden on industry really does extend into the billions of dollars, many companies may simply find it too expensive to submit the required NDINs, Israelsen cautioned, for fear of going bankrupt.

Other industry experts, however, foresee a less daunting future under the revised NDI guidance. Perhaps it’s only hundreds of new NDINs that will be necessary, instead of thousands, or maybe some NDINs can be submitted at relatively low cost. Much of the potential cost may also depend on what type of ingredient a firm is working with, and how strong its researched safety profile is already.

 

How Many New NDINs?

There’s at least one certainty in the new NDI draft guidance; FDA believes the supplements industry is currently underreporting NDIs. 

“Over the past 20 years we’ve received over 900 notifications. We have not yet reached 1000,” said Cara Welch, PhD, senior advisor at FDA’s Office of Dietary Supplements, during a September-7 NDI webinar hosted by the Council for Responsible Nutrition (CRN; Washington, DC). “Now we don’t have all the information as to how many notifications should have been submitted that have not submitted, but our impression is we should have received more than the 50 or so we receive a year.”

Though Welch declined to estimate whether it was closer to hundreds or thousands of NDINs that needed to be filed, she did note that there are tens of thousands of supplement products on the market. Not all require notifications, Welch said, but many do. And while she chose not to guess at the total number of new notifications that would be required under the revised draft guidance, Duffy MacKay, ND, CRN’s senior vice president of scientific and regulatory affairs, took a stab at the question.

“If I were to read the document literally and look at every manufacturing change considered both for old ingredients as well as new ingredients, I would hedge a bet that there are thousands of finished products that would require a notification,” MacKay said. Going one step further, UNPA arrived at its preliminary cost estimate by figuring in tens of thousands of new NDINs.

 

But other industry leaders, including Dan Fabricant, CEO and executive director of the Natural Products Association (NPA; Washington, DC), said estimates based on such high NDIN numbers are just “fearmongering tactics.” He noted that the addition of a “master file” provision in the latest draft guidance, which allows ingredient firms to create a single NDIN for a broad range of product formulations, would enable fewer NDINs, especially with regard to ingredient combinations.

“You can’t say we got a master [file] list and then [say] the FDA is requiring a new submission for each independent NDI,” Fabricant told Nutritional Outlook. “It doesn’t work. There’s clearly a way that you can do a cube submission if you build [an NDIN] that covers a broad range of combinations and defends amounts of ingredients to the agency.”

Michael McGuffin, president of the American Herbal Products Association (AHPA; Silver Spring, MD), also pushed back against the idea that thousands or tens of thousands of new NDINs would be necessary, even if that’s what the guidance may seem to imply as currently written.

“I don’t believe we’re going to actually see that every dietary supplement that contains an NDI is going to be subjected to a notification if we can continue to focus on where the assurance of safety to the public is needed, a clear reading of the law, and some guidance on how to put your notification together so that it does have a broad application against broad conditions of use,” McGuffin told Nutritional Outlook.

 

How Much Will Each NDI Cost?

Aside from the sheer number of new NDINs proposed under the revised draft guidance, the question of how much each NDIN costs is just as important in arriving at an overall cost estimate.

During NPA’s August-17 “emergency” webcast on the NDI guidance, Corey Hilmas, MD, PhD, NPA’s senior vice president of scientific and regulatory affairs, shared NPA’s estimate that a single NDIN may cost up to $500,000. That’s based on the estimate that a toxicology study may cost $178,000–$328,000, on top of an estimated $162,500 in consultant fees and other added costs.

“Those are real costs,” NPA’s Fabricant told Nutritional Outlook. “Those are costs we got from quotes from contractors, research organizations, and the labs themselves that do the animal testing and those sorts of things.”

However, not all outstanding NDINs will require such large fees, AHPA’s McGuffin suggested. For ingredients that already have much of the supporting research work complete, it could be a fraction of that cost. McGuffin said he has spoken with companies that paid less than $25,000 for their NDINs, and in at least one case, less than $10,000.

“We’re not going to have to do a [toxicology] study except for truly novel new ingredients,” McGuffin said. “We’re going to have to do some work, but this isn’t intended to be a ‘start over, assume it might be poison’ approach for ingredients that are reasonably expected to be safe at the beginning of the review. I’m not saying we can ignore it and staple a bunch of pieces of paper together, but this idea that it’s going to cost billions, that’s in a worst case scenario.”

Part of a given ingredient’s NDIN cost calculation may also depend on what category it falls in. Some ingredient types, such as synthetic botanicals or probiotics, may require considerably more work than other ingredients.

Clearly, industry cost estimates for the NDI draft guidance are all over the map. Several trade associations have announced plans to call on FDA to conduct its own economic cost burden for NDIN submissions in their public comments, which will be submitted in the coming weeks.

 

Read more:

Is GRAS Still a Viable NDI Workaround?

FDA’s NDI Guidance and GRAS Rule: Stop Fighting, and Move Forward

How FDA’s NDI Guidance Could Paralyze Industry

 

Michael Crane
Associate Editor
Nutritional Outlook Magazine
michael.crane@ubm.com

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