By Steve Mister, Esq., president and CEO, Council of Responsible Nutrition

Have you ever taken your grandfather to a doctor’s appointment and waited what seemed like forever in the car?  Waiting for FDA’s interpretation of a “grandfathered ingredient” is becoming a lot like that too. When I’m sitting in the car, there a lot of time to fidget with the radio, read the owner’s manual, and watch traffic. So as the industry sits, waiting for FDA’s long-promised issuance of a guidance on the new dietary ingredient provision, there been a lot of time to muse about what it might contain, and how the industry should respond.

FDA has indicated that it will likely issue a guidance document on the new dietary ingredient provision of DSHEA in early 2011. Industry anticipates that it will address two fundamental questions about the process: First, what is a “new dietary ingredient”? In other words, what is a dietary ingredient “that was not marketed in the United States before October 15, 1994,” according to the statute? And secondly, what does the agency consider to be sufficient evidence to conclude that a dietary ingredient “will reasonably be expected to be safe”?

Although the first question might seem obvious on its face, I predict the answer from FDA will not be so self-evident. For instance, if the method of extraction has changed since 1994 (e.g., from water to alcohol based), is the current ingredient “new” under the law?  What if the concentration being sold has increased in the past 16 years? Or if the ingredient is being standardized to different markers than it was before the passage of DSHEA? Some FDA officials have even suggested in podium policy that a product containing a new combination of “old” ingredients might be considered “new”. Depending on the answers FDA gives, the industry could be in for a real fiasco. What ends up being considered “new” in the guidance would presumably be subject to the requirements for an NDI notification, and the sheer volume of ingredients impacted could create a torturous backlog at the agency to review. 

Complicating this situation is the fact that FDA has never created its own list and never accepted as authoritative any of the lists that were developed by industry as to what ingredients were in fact on the market in 1994.  CRN, along with NPA and AHPA, created such a list by gathering sales data from their members, but FDA won’t accept it.  A few years ago when a drug company petitioned to have FDA declare pyridoxamine a drug, CRN submitted a copy of the grandfathered list to the agency and FDA declared that without actual invoices, sales slips or catalogue data, inclusion on the list was not evidence the ingredient was actually sold.

All of this demonstrates just one more lingering problem from the period after DSHEA was enacted when FDA dragged its heels, put down its enforcement pencils, and failed to implement the law until the agency ultimately determined it was time to see what tools DSHEA made available in its regulatory toolbox.  During that time, company documents that could have verified the ingredients were marketed in the U.S. undoubtedly were destroyed, converted to microfiche (this was before PDF files and scanners) or exiled to off-site storage that is long forgotten. That makes it nearly impossible to defend the grandfathered status of these ingredients all these years later.

So here’s an idea – not fully developed at this point, but perhaps worthy of consideration:  Perhaps we should seek a re-set of the clock for grandfathered ingredients. After all, the point of the grandfathered date (October 15, 1994) was not a magic point in time – it simply was a date for products that were already on the market which to that point had not demonstrated any serious safety risk. Thus, the presumption is on FDA to prove the ingredient is not safe, whereas, for new dietary ingredients, the burden lies on the manufacturer to show a reasonable expectation of safety before the ingredient goes to market.

So what if Congress moved the grandfathered date forward to January 1, 2008? That was when the requirement for serious adverse event reporting became effective. Presumably, if a dietary ingredient is posing a safety risk, then there would be adverse event reports over the past three years that FDA could be acting upon to uphold its side of the pact. The absence of significant adverse event reports should create that same presumption of safety for these ingredients today and place the burden on FDA to show the products are not safe. This is not a punishment for FDA’s foot-dragging over the past 16 years; it’s simply an acknowledgement that because FDA didn’t tell the industry for 16 years what was “old” and what is “new,” it can’t expect now to demand proof of sales from that long ago and hold the industry hostage with the requirement of countless NDI notices for which it is not capable of addressing.   

Our critics will say that too many ingredients were introduced between 1994 and 2008 that don’t have proper safety profiles and that moving the grandfather date forward would sweep many ingredients into a category of presumed safety without sufficient data. The AER data should address that.  But remember that the “grandfather” date of October 15, 1994 was an arbitrary one in the first place; it was simply the date of passage of DSHEA.  And what that did was determine who has the presumption of safety and who has the burden of proof for a particular ingredient.  It certainly was no guarantee of market security, as the subsequent histories of ephedra, Aristolochic acid and comfrey (containing pyrrolizidine alkaloids) will attest. In fact, the critics that point to Consumer Reports’ so-called “dirty dozen” should be reminded that these are grandfathered ingredients anyway – they have been on the market long before 1994. With regard to the steroid-like ingredients that have appeared on the market since then, these are not even legitimate “dietary ingredients,” whether old or new, so FDA already has the tools to remove them from the market regardless of where the presumption of safety lies.

Such a proposal would make it a lot easier for companies to demonstrate what was – or was not – on the market on January 1, 2008 since these records are still readily available. And it would allow FDA to issue a guidance document on NDIs without creating a tsunami of NDI notifications that would hopelessly backlog the agency for years to come, holding consumer desire for new products hostage in the process.  We don’t seem to be able to speed up the FDA’s release of a guidance document on new dietary ingredient notifications, but maybe we can create a way to make it more palpable when it finally arrives.

See what we can think of when the agency leaves us waiting. . .