Changes to NDI process called for in paper that claims DSHEA no longer adequate to regulate industry

By Hank Schultz

- Last updated on GMT

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Related tags Ndi draft guidance Ndi notifications regulations

A paper published today in a prominent medical journal asserts that the law governing dietary supplements is no longer adequate to protect consumers and sweeping changes are needed to keep potentially dangerous new ingredients off the market.

The paper, published in the New England Journal of Medicine​, was written by attorney Scott Bass, of the firm Sidley Austin and Dr Pieter Cohen, MD, of the Harvard Medical School. Bass was closely involved with the drafting of the Dietary Supplement Health and Education Act (DSHEA)​, which was signed into law in 1994 and which is credited with creating the modern dietary supplement marketplace. Dr Cohen, on the other hand, is a critic of the supplement industry of more recent vintage who has railed against what he has characterized as inadequate safeguards.

DSHEA inadequate for new realities, authors argue

The authors assert that DSHEA no longer is adequate to regulate the modern supplement marketplace. The $4 billion market of 1994 bears little resemblance to the more than $40 billion global market of today, they said.

“Today, this law does not adequately protect the public. Since it was written, the supplement industry has been reshaped by Internet sales and an increasingly complex global supply of new substances,” they argued.

Liver injuries episode illustrates risks 

The authors said the flow of new ingredients into the industry sans sufficient safety review is particularly troubling.  They used the DMAA episode as an example of how the public is being put at risk.

DMAA is a stimulant ingredient that had been on the market years ago as a nasal decongestant.  Formulators of products aimed at gym enthusiasts put it into dozens of pre workout products without, the authors said, any review by FDA.  After the military became concerned about the ingredient’s potential to raise the risk of hemorrhagic stroke and sudden death FDA, under pressure, took the ingredient off the market in 2011.

In the search for an alternative to DMAA the formulators of one product, OxyELITE Pro, used a combination of aegeline, higenamine, and caffeine.  The authors said this brew, which entered the market without any safety review of its formulation, included “synthetic versions of botanical constituents not traditionally consumed together.”

The results were fatal, they said.

“Within a year of being introduced, the product, OxyELITE Pro, had been linked to an outbreak of severe hepatitis affecting 69 people; 32 of them were hospitalized, 3 required liver transplants, and 2 died,” ​they wrote.

Unknown number of new ingredients with no safety data

Bass and Cohen noted that since DSHEA, at least 75,000 new products have come on the market, but FDA has received adequate safety information on fewer than 250 new ingredients. Under the current regulatory regime, the authors said FDA has no system to determine how many of those new products contain unreviewed new ingredients and, if so, what those ingredients are.

Bass and Cohen argue that part of the problem has been a lack of enforcement of existing provisions, such as the New Dietary Ingredient Notification process.  But they argue that parts of the law form loopholes that can frustrate a safety review.  Those include the claim by many ingredient innovators that their products ought to be classified as Old Dietary Ingredients as well as the use of the GRAS self affirmation process to sidestep an NDI submission.

GRAS forms ‘exception that has swallowed the law’ 

The authors maintain that the GRAS process was originally envisaged as being something that would be used infrequently.  But in their view it has become a loophole that, “has grown into the exception that has swallowed the law.”

“The exemption was not meant to apply to new chemicals, combinations, or synthetic compounds. Nonetheless, the FDA has appeared to condone the use of this loophole to permit countless substances to be introduced in the absence of submitted safety data,” ​the authors wrote.

To fix this situation the authors advocate for a mandatory submission of all labels to FDA prior to putting a product on the market.  They also say there should be an ironclad provision for premarket safety approval of all new ingredients.  Exceptions to this should be narrowed down to those ingredients that are extracted in the same form and in the same concentration as the source material, using citrus bioflavonoids as an example. And much more aggressive enforcement will be necessary, they said, with new legislation needed to provide FDA with adequate funding to carry out this mission.

Industry: Suggestions are reasonable, rhetoric, less so

Dietary supplement industry stakeholders found much to agree with in the paper, even if they took some issue with the tone of the rhetoric.

“When you look at what they’re proposing, I don’t think it’s that far from where the industry is as far was what we would like to see as improvements to DHSEA. For example, a mandatory products listing is something CRN has strongly advocated for and will be one of our major legislative priorities for the coming year. And we are emphatically in agreement that FDA needs to do more to enforce the law,”​ Steve Mister, president and executive director of the Council for Responsible Nutrition told NutraIngredients-USA.

“It’s not in what they are proposing, it’s in the rhetoric they are using.  I think in general DSHEA is going a good job of protecting the public,”​ he said.

Daniel Fabricant, PhD, president and CEO of the Natural Products Association, said in his view the issue should first be getting enforcement of the existing law up to where it should be before new provisions are considered.

While we don’t agree with all that’s there we certainly appreciate parts of the dialogue, especially around a lack of enforcement on the NDI provision by the agency in recent times. There hasn’t been an import action (import alert or bulletin) related to NDIs in six years, since I left the agency. In that time I’m certain that new ingredients that didn’t file an NDI, which makes the products adulterated under DSHEA, made it to our ports for distribution, and the agency hasn’t enforced the law at the ports where they have clear and strong jurisdiction. After six years I think we’re running out of patience, especially when people want to talk about a new NDI draft guidance or adding new authorities like a mandatory product listing, when the existing statutory protections aren’t being implemented,” ​he said.

Loren Israelsen, president of the United Natural Products Alliance, said his organization supports the notion of a mandatory product listing, but the issue of NDIs is harder to wrap up in a few paragraphs.

UNPA supports the concept of mandatory product registration as a logical step to provide a central database for FDA to know how many products of what kind are available to consumers,” ​he said.

Revising New Dietary Ingredient requirements is a far more complex and nuanced issue. UNPA's view is that the NDI procedure as envisioned and passed in DSHEA provides an important mechanism to evaluate the safety of "new" dietary ingredients that enter the market. It is our view that the study authors did not intend to comprehensively lay out a new NDI mechanism but rather to point out that if there are abuses of the GRAS affirmation process, this should be addressed, as well as to reaffirm the underlying statutory requirement that ingredients that are truly new to the market should undergo FDA review,”​ Israelsen added.

Source: New England Journal of Medicine

Injecting Safety Into Supplements—Modernizing the Dietary Supplement Law
DOI: 10.1056/NEJMp1913004
Authors: Cohen PA, Bass S

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