By Steve Mister Esq., President and CEO
Washington has always been a city of initials and acronyms: FBI, CIA, POTUS, etc. And these days, with texting and tweeting, the artful use of abbreviations has led to an almost secret language among those in the know, leaving outsiders dazed and befuddled by the profuse use of letters instead of words. OMG!
But FDA’s recent denial of the petition to recognize homotaurine demonstrates how important it is that we understand the differences among these acronyms and what they stand for. I’m referring, of course, to the petition by OVOS to have FDA recognize that homotaurine – a synthetically created amino acid that is bio-identical to one found in red algae and kelp – is a legitimate “dietary ingredient” (DI), and would therefore qualify for consideration as a “new dietary ingredient” (NDI).
An original provision of DSHEA requires that if an ingredient has previously been the subject of an investigational new drug application (that would be an IND), then it may only be considered as a DI by petition and the issue of a regulation by FDA. So in June 2009, OVOS did just that and asked FDA to issue such a rule for homotaurine that would turn an IND into an NDI.
In the 20 intervening months, three things have happened that are relevant to this situation:
FDA has been strangely silent about its understanding of section 912, a little-known provision of FDAAA – the Food & Drug Administration Amendments Act – that Congress passed in 2007 that prohibits the use of an ingredient in food if the ingredient has already been the subject of substantial clinical investigation as a drug and those clinical trials have been made public. More curiously, that provision seems to be at odds with a similar provision in DSHEA, yet the agency has not told the industry whether it applies specifically to dietary supplements.
Second, and I think, even more important, FDA issued draft guidance last December offering the agency’s thoughts as to when researchers should be required to properly file an IND to support the clinical research they perform on a substance. In fact, more and more independent review boards (should I say, IRBs?) at universities are demanding INDs for human research because the information necessary to support the IND gives the IRB cover that the substance being studied is not likely to cause harm to the human subjects. What’s not to love about an IND application? (I guess they are just minding their Ps and Qs.)
While this guidance is not surprising for substances being studied for the drug-like clinical endpoints, what is concerning is FDA’s expectation for researchers to file IND applications when they are studying what the industry would consider to be nutrition endpoints – or, at the very least, biomarkers that could be used to support structure/function claims or even health claims and qualified health claims (that’s HCs and QHCs for those now speaking only in initials).
INDs can be particularly problematic because so much of the research performed on dietary ingredients is not controlled by the companies marketing the ingredient, but takes place in university or government labs in which industry does not have the ability to shape the study’s designs, the outcomes being assessed or the way the results are interpreted.
Third is the agency’s intransigence to issue a guidance expounding on the requirements for NDIs (remember, that’s a new dietary ingredient, not an IND). The industry successfully inserted a requirement into the recent food safety law, which passed in December, that FDA must issue this guidance within six months, so we’ll see if that speeds the agency along. But at this point, we have no clear message from FDA as to when a dietary ingredient can be considered “grandfathered” – that is, on the market prior to October 1994 when DSHEA was enacted – and no authoritative statement as to how much science is needed to demonstrate a reasonable expectation of safety. (Should we call that an REOS?)
What we have seen are indications that FDA views any refinements of an ingredient – any changes in extraction methods, increases in concentrations, new standardizations of materials or combinations of old ingredients – as sufficient to recast the substance as an NDI. When that document is released, we can expect it will tighten the chokehold of what can be considered grandfathered, and push many current products, long presumed to be grandfathered, into the camp of being NDIs instead.
So the real crux of my “initial” concern is this: I think the agency has stealthily found a way to stifle innovation in the dietary supplement industry through the use of INDs, DIs and NDIs.
It goes like this: If the agency coaxes more researchers to develop IND applications that describe their proposed findings in drug-like ways, and to put their IND notices and research results on the public record at PubMed; and if at the same time, it refuses to grant license to companies to develop the substances as dietary ingredients by taking a formalistic view of the definition of a dietary supplement – as it is has done in the homotaurine case; and if FDA aggressively enforces the requirement that an ingredient already subject to IND research can only be marketed as a drug; and further, if it freezes the industry’s extraction, concentration and manufacturing techniques at 1994 practices (by forcing anything different into an NDI notification with insurmountable requirements for safety); then the result is a dietary supplement industry that can’t get new ingredients to market as dietary ingredients. All that is left is the route of an NDA – that’s a “new drug application.” That means several hundred million dollars in research and pre-market approval for our ingredients.
If that should happen, the future of our industry is DOA.
(The CRN Blog represents the view of the author and does not necessarily reflect the view of CRN’s Board of Directors or serve as an official position of the association.)