The Council for Responsible Nutrition and the Natural Products Association both submitted comments before the deadline yesterday. FDA declined to extend the comment period on its administrative action as initially requested by NPA. While FDA couches its action as tentative, NPA at least views the die as pretty much cast. “It is clear from their intent that FDA currently concludes that the dietary ingredient, in the absence of any additional information provided to them, is not a dietary ingredient for use in dietary supplements,” the organization wrote in its comments.
In a notice on the Federal Register in early October, FDA requested comment on, “our tentative conclusion that vinpocetine is not a dietary ingredient and is excluded from the definition of dietary supplement in the Federal Food, Drug, and Cosmetic Act (FD&C Act).”
Vinpocetine was first synthesized in the mid ‘70s by Hungarian researchers. FDA itself says “vinpocetine is a synthetic compound, derived from vincamine, an alkaloid found in the Vinca minor plant, or tabersonine, an alkaloid found in Voacanga seeds.” The ingredient has vasodilation effects and is said to increase blood flow to the brain, which is why it has been used in nootropic formulations. It has been in the market as a drug in Germany under the name Cavinton. One newspaper story from the Los Angeles Times called it a “new memory drug.”
Factors in conclusion
FDA’s tentative decision that vinpocetine is not a legal dietary ingredient hinges on two factors. First, FDA said a search of its files reveals that the ingredient was the subject of an Investigation New Drug application in 1981 and that multi center trials on the substance were conducted in the mid 1980s. Under Federal law a compound can first be marketed as a dietary supplement and then developed into a drug, but not vice versa, so an IND filing preempts a supplement application. One view of this provision of the law is to protect the huge investment that pharmaceutical companies must make to bring new drugs to market.
FDA’s second bone of contention on vinpocetine has to do with its synthetic nature. Since the release of the first draft guidance on New Dietary Ingredients first published in 2011 and rereleased in updated form just a few weeks ago, the agency has taken the tack that bioidentical compounds, or so-called ‘synthetic botanicals’ do not qualify as dietary ingredients because synthetic compounds, even if they are identical in all respects to their botanical progenitors, did not themselves arise from plants and therefore don’t meet the definition of a dietary ingredient. “Vinpocetine is not found in V. minor, Voacanga, or any other botanical, but rather is a synthetic derivative of vincamine or tabersonine,” the agency said.
Trade organizations disagree with FDA
In their comments, CRN and NPA both maintained that FDA’s action is inappropriate for an ingredient that has five successful NDI filings (two of which were filed by major firms such as GNC and Pharmavite) and for which there is a long history of safe use. Both organizations questioned the action on legal grounds and procedural grounds and requested that FDA lay out more solid explanations for its decision and provide industry an additional period of comment to respond to those reasons.
“Such a reversal on the status of a dietary ingredient is inappropriate when, as here, there are no safety concerns,” CRN said. NPA noted that the ingredient’s long history in the market means that it now has “over 19 years of safe historical use in the U.S. as a food and over 38 years of safe historical use as a functional food/drug in Europe and Asia. Therefore, vinpocetine possesses greater than the 25 years adopted by both FDA and the European Union that is required for safe historical use.”
On the question of the ingredient’s drug status, NPA noted that an IND review is, or ought to be, part of the agency’s evaluation process on NDI notifications. If all five filings are taken together, the agency had more than a year to consider the IND information. NPA maintains the the mid ‘80s IND filing on vinpocetine had become “inactive”, and therefore the agency’s initial rulings in the NDI filings were correct.
Both NPA and CRN noted that the agency has not taken the potential economic ramifications of the removal of vinpocetine from the market into account. CRN noted that, “According to a database maintained by the National Institutes of Health, more than 300 hundred dietary supplements contain vinpocetine, although this number is likely an underestimate.Before changing its position on vinpocetine for reasons unrelated to safety, FDA should assess the number of products its decision would affect and the economic costs to industry, including possible reformulations or recalls of products.”
Finally, both organizations said the reversal for an ingredient that is not associated with a public health concern sets a bad precedent that could undermine the confidence in the integrity of the NDI process. Why invest invest the time and money if FDA can reverse itself on purely definitional grounds? NPA, in its comments, quoted a letter sent to FDA by Sen. Orrin Hatch, R-UT in which Hatch said “[b]y removing a product from market without safety concerns, FDA would be taking a precedential step that could shake the confidence that manufacturers maintain in the FDA process.”