There's an old saw that says 90 percent of what you worry about won't happen anyway. And in the case of the guidance due soon from the Food and Drug Administration (FDA) on New Dietary Ingredients (NDIs), it might actually be true.
There has been worry aplenty in industry since the process of writing this guidance document began at FDA several years ago. At one point, the doomsayers were envisioning the black day after the issuance of the document, a day on which as many as 60 percent of the ingredients on the market would suddenly be invalidated by the new guidance.
Cooler heads have come forward in recent months. It's still true that no one outside of FDA knows exactly what this document will say. But by taking the temperature of recent podium policy, industry watchers have concluded that while the guidance will certainly be an important milestone in the industry's regulatory history, it is not something to fear.
"If there is any consternation, it would be about whether the issuance of the guidance means that FDA is now going to start enforcing the rule. Will they be going into the marketplace and finding products with ingredients they believe are new, and challenging companies on that?" said Michael McGuffin, president and CEO of the American Herbal Products Association.
The most basic definition of an NDI is something that came into the market after Oct. 15, 1994. Ingredients that were in commerce before that were grandfathered in under the Dietary Supplements Health and Education Act (DSHEA) and are considered safe. If manufacturers have brought new ingredients to the market since that date, they were supposed to have filed an NDI notification with FDA. Many have, and have had a variety of experiences in that process, but some have ignored the requirement or have made their own, extra-broad interpretation of the grandfather clause.
So, having proof that a given ingredient was on the market on that date is a key part of the decision tree regarding whether an ingredient is new, and requires a filing, or is an Old Dietary Ingredient (ODI) as defined by DSHEA. Having that proof delves into the days of dusty old ledgers and dated photographs.
Another branch of that decision tree concerns the clause in DSHEA about whether an ingredient should be considered new because it has been "chemically altered" from the state in which it was sold in 1994. Having that phrase more carefully defined is one of the things that may come out of the new guidance.
The potential impact of the new guidance will depend to a large degree on how inclusive the definition of an NDI might be, assuming the guidance goes a step beyond the current language of DSHEA. Industry experts contacted for this article were in broad agreement that a large number of ingredients will fall into the new category as a result of this guidance.
Take for example a botanical extract. A manufacturer might say, "This extract was on the market in 1994, so we're good to go." But what if some aspect of the extract is different, be it potency, extraction method or what have you?
"There are scores of examples of that kind," said Loren Israelsen, president of the United Natural Products Alliance. "Take something that has been on the market for decades and decades. What we have seen over the years are changes in potency, changes in extraction methods, changes in solvents used, changes in the ratios of key constituents. Does that make these ingredients new? Now that's the big question."
The purpose of the whole NDI filing procedure revolves around the safety of a new ingredient. An NDI filing is not about the ingredient's fitness for its intended use (e.g. for immune support, cardiovascular system support, etc.). The process makes no judgments about efficacy, a point that has eluded a number of filers. NDIs are exclusively about safety.
GRAS status and NDIs
That issue of safety figures into the world of ingredients that have achieved Generally Recognized as Safe (GRAS) status for use in foods, and the relation of that status to NDI filings. A clause in the NDI wording states if a new ingredient has GRAS status, whether through self-affirmation or via a no-objection letter from FDA, and has been sold on the market as an ingredient in foods, it can be used in supplements without going through an NDI filing. And, while GRAS status is valuable in and of itself, killing two regulatory birds with one stone has been one impetus for the large number of GRAS filings in recent years, said John Endres, chief scientific officer of Seattle-based scientific and regulatory consultancy AIBMR.
"What companies are doing is going GRAS and then selling that ingredient as a functional ingredient in foods and then potentially having that door opened for both medical foods and dietary supplements," Endres said. "They save money that way, too, because to do a GRAS self-affirmation and an NDI notification to the FDA is about the same price."
And, in theory, the consumer might be even better protected because the safety bar for GRAS status is higher. GRAS ingredients have to be "reasonably certain to be safe" whereas an NDI filing requires a "reasonable expectation" of safety.
A key point here is the quality of the GRAS certification. A big part of Endres' job is counseling companies on their GRAS certifications. A self-affirmation can be a shoddy job or a solid, reliable document depending on the quality of the data and the expert panel assembled by the company to vet the data. The wide variety in the quality of GRAS self-affirmations is one of the reasons why big food and drink manufacturers looking to source new functional ingredients are almost universally requiring a no-objection letter from FDA before using a given GRAS ingredient.
Getting ready for NDIs
Companies can do several things to get ready for the issuance of this document, which, according to a rider in the recently passed Food Safety Act, must come out no later than the end of June. If you're confident your ingredient fits the ODI definition, review your historical proof. Review your safety data, and consider whether additional information will be needed if an NDI filing becomes necessary. And consider budgeting for an NDI or GRAS filing, even if you think your ingredient is an ODI.
Whatever the guidance will say, industry watchers are eager to have it issued so that companies can get on with business.
"At its core the NDI process is about safety, and no one has an argument with that. What is at issue, though, is the chilling effect this uncertainty is having on innovation," said Scott Steinford, president of ZMC-USA.
NDI failures and successes
Industry buzz indicates that the NDI filing process is difficult and could result in ultimate failure for a company's ingredient. It's a detailed, potentially expensive process, but not as fraught with peril as it might seem at first glance.
AHPA president Michael McGuffin, in a recent broad-brush review of the association's NDI database, came up with the following numbers:
Of 414 unique NDI notifications filed with FDA as of February 2010, 64 were erroneous submissions. That leaves 350, of which 147 met with no objection from FDA. Of the approximately 60 percent of filings that did not sail through on first reading, a small, but significant proportion were "junk," as McGuffin terms it.
McGuffin said he has not finished the analysis of the data to see how many submissions succeed on their second or third tries, but the assumption is that a majority does.
Some common mistakes that can lead the FDA to kick back a filing:
The inclusion of safety studies that refer to an ingredient that is similar, but not identical, to the ingredient that is the subject of the NDI filing.
The ingredient is insufficiently characterized, which can be a challenge for some botanical ingredients.
The ingredient is referred to by different names in various documents, making it hard for FDA to be sure that the safety info pertains to the ingredient in question. Kevin Boot, regulatory counsel for Iowa-based Embria Health Sciences, said this problem can crop up when companies begin the development of an ingredient under a code name that differs from its eventual market name.
The inclusion of health claims in NDI filing documentation. Some companies have made this error, leading FDA to conclude that the substance is a drug, not a dietary ingredient. NDI filings should be about safety. Period.