Speaking to NutraIngredients-USA.com following the publication of the Food and Drug Administration's (FDA's) long-awaited draft guidance document on New Dietary Ingredient (NDI) notifications, Ullman, Shapiro & Ullman partner Marc Ullman said it was “horrifically broad, anti-innovative, incredibly burdensome,” and “likely to bury FDA under a mountain of paperwork”.
Under the 1994 Dietary Supplements Health & Education Act (DSHEA), firms are required to notify the Food and Drug Administration (FDA) if they intend to market a dietary supplement in the US that contains a ’new dietary ingredient’ (which has not been marketed in the US dietary supplements market before October 15, 1994) and demonstrate that it is safe.
The draft guidance document clarifies what an NDI is, and what evidence the FDA expects to demonstrate it is safe.
‘Absurdly broad’ view of what is ‘new’
As many stakeholders had feared, however, the FDA has taken "an absurdly broad view of when a NDI notification is required and an overly narrow view of what is considered to be a ‘dietary ingredient’", claimed Ullman.
“It really is beyond my comprehension that every new combination of ingredients that happens to include one new ingredient that was not on the market before 1994 in supplements will require an NDI notification. This flouts the statutory intent of DSHEA.”
The strict new safety requirements on microbial ingredients were also completely unexpected, he added: ”The probiotic category could be wiped out if they follow through with this.”
Companies – as well as associations - must respond
While he had no doubt that the key trade associations in the sector would come out very strongly against the guidance, individual companies in the trade needed to respond too, he said.
“It’s no good if the FDA gets five strongly worded letters from the associations. It should be receiving a flood of well-considered comments directly from industry on this.”
On the other hand, the fact that the FDA said an NDI filing was not required for a material that had got only self-affirmed GRAS had left him speechless: “I am flabbergasted that FDA apparently will accept a self-GRAS without notification to FDA in lieu of the NDI filing.”
Meanwhile, as feared, it appeared that many old ‘grandfathered’ ingredients could be subject to new NDI filings because the guidance document says new extraction technologies that could alter the chemical composition of the ingredients in question (such as supercritical CO2 fluid extraction) should trigger an NDI notification, he said.
“But surely the question they should be asking is, is the change material? Does it result in something that a toxicologist would be interested in?”
The guidance notes: “If the changes in your manufacturing process alter the chemical composition or structure of the ingredient, the resulting compound is probably a NDI and a notification to FDA would be required.
"For example, using a solvent to prepare an extract from a pre-DSHEA dietary ingredient creates a NDI because the final extract contains only a fractionated subset of the constituent substances in the original dietary ingredient.”
In a long list of processes that FDA would likely consider to involve chemical alteration, it includes:
- a process which makes or breaks chemical bonds such as hydrolysis or esterification;
- use of solvents other than water or aqueous ethanol to make an extract;
- high temperature baking or cooking of an ingredient that has not previously been baked or cooked;
- the application of nanotechnology that results in new or altered chemical properties of the ingredient.
Meanwhile, separate NDI notifications for supplements containing the same NDI will be required if the other dietary ingredients in the supplements were not included in the original NDI notification; if the target populations are different, or the conditions of use materially differ, says the FDA.
The Alliance for Natural Health USA noted: "Not only does each supplement require its own notification, a separate notification must be submitted by each company that offers it. Additionally, notification must be submitted again if the supplement is reformulated in any way or offered in combination with any other supplement or ingredient."
‘Chilling’ effect on new products
Scott Bass, who heads the global life sciences team at law firm Sidley Austin, said the guidance – if strictly enforced – would have a “major impact on products already on the market and a chilling effect on new products”.
Meanwhile, the level of documentation required by companies to prove that ‘old’ dietary ingredients were on the market in supplements in the US before October 15, 1994 was also unrealistic, he said.
“It will really be impossible for many companies to meet these requirements, because the FDA is not just looking for proof that they were on sale, but also expects very specific records on dosages, and other things.”
Meanwhile, the timetable for assessing NDI notifications had also changed, he said. "Currently, firms must notify FDA at least 75 days before the dietary supplement containing the NDI is marketed in the US. However, the new guidance says that the 75 day period will not start until the FDA is satisfied that the submission is complete."
This meant that the clock did not effectively start ticking until FDA said it did, meaning firms might have to wait much longer than originally anticipated before putting products on the market, he said.
NPA: A deep impact on the market
Natural Products Association chief executive John Gay added: “Our first reading is that this could have a very deep impact on the market.”
The level of information required by the FDA to prove ingredients were sold in the US as dietary ingredients in supplements prior to 1994 was completely unrealistic, and inconsistent with DSHEA, he added. “We’re talking about documentation that’s at least 17 years old.”
Meanwhile, the level of information required by firms to prove the safety of NDIs was far stricter than anticipated, and inconsistent with the intent of Congress to provide a “reasonable mechanism for new materials to come into the market”, he said.
Stakeholders have 90 days in which to comment on the draft guidance, which is available here.