In a notice on the Federal Register, 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 Since the release of the first draft guidance on New Dietary Ingredients first published in 2011 and rereleased in updated form just a few weeks ago, the agency has taken the tack that bioidentical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.
No overt safety concerns
The Natural Products Association has taken issue with this filing, noting that there has been no slew of adverse events on vinpocetine, which has been on the market as a supplement ingredient for years. NPA president Dan Fabricant, PhD noted that 5 NDI notifications have made their way through the process without objections from FDA (something which the agency itself acknowledges.) Fabricant said FDA’s action has overstepped its bounds, noting that part of the NDI notification process is not only to determine that an ingredient is safe, but also whether it meets the definition of a dietary ingredient in the first place.
“FDA has statutory authority to re-evaluate any dietary ingredient, old or new, if they have a safety issue with the ingredient. However, FDA does not have the statutory authority to re-evaluate whether an NDI fits into the 201(ff)(1) gate again after it already passed that hurdle. FDA had multiple chances to kick vinpocetine notifications out of the 201(ff) gate and determined that it fit under the definition of a dietary ingredient,” Fabricant told NutraIngredients-USA.
Adding up the amount of time the agency has had to consider the matter via the NDI notifications, Fabricant said that the question of vinpocetine’s status was considered for more than a year by the agency, which came up with a positive conclusion on its legality. Then the agency took yesterday’s abrupt about-face.
“FDA’s actions would create a dangerous legal precedence if gone unchallenged. FDA already has the ability to remove dietary ingredients and/or dietary supplements from the marketplace if they are deemed unsafe. They can rule in an NDI submission whether an ingredient fits under the definition of a dietary supplement. . . in this case, the FDA is attempting to set up a new administrative process where it has the ability to to remove an acknowledged ingredient from store shelves. Not only does it set a dangerous precedence, it will result in fewer new dietary ingredient notifications,” Fabricant said.
McCaskill’s call for removal
Senator McCaskill issued the following statement about vinpocetine: “It’s good news that the FDA is aiming to take stock of the scientific work of third-party researchers. That said, the fact remains that oversight of the dietary supplements that Americans take every day remains alarmingly inadequate.
"We cannot and should not wait around for outside research or tragedy in this space to spur us to action, and I look forward to working with the FDA to improve the health and safety of all American consumers.”
Last year Sen. Claire McCaskill, D-MO, who is the ranking member of the Senate Special Committee on Aging, called for FDA to remove vinpocetine and picamilon supplements from the market. McCaskill’s move was prompted by results of a recent analysis by researchers from the National Center for Natural Products Research at the University of Mississippi and Cambridge Health Alliance / Harvard Medical School published in Drug Testing and Analysis, which found that, of the 23 vinpocetine supplements tested, six (or 26% of the products tested) did not contain any vinpocetine, while 17 contained vinpocetine with quantities ranging from 0.3 to 32mg per recommended daily serving. Fabricant said he couldn’t say with authority that the agency was responding directly to McCaskill’s pressure, but that the timing would support that view.
“I do find it interesting that FDA is taking this approach just 10 months removed from Sen. McCaskill’s request for retailers and distributors to stop selling vinpocetine supplements, pending an investigation,” he said. If push comes to shove and
Potential economic impact
In addition to providing comments to NutraIngredients-USA, NPA has also already sent a letter to Leslie Kux, an associate commissioner on policy at FDA. Fabricant’s brief missive focused on whether the economic impact of removing an ingredient that has been on the market for years was considered.
Fabricant’s letter reads: “The original economic impact analysis on 21 CFR 190.6 never presented a situation where a properly notified ingredient, considered lawful for a period of time, could be removed approximately 20‐years ex post facto. It would appear that removal of this ingredient would bear little incremental public health effect (per the notice) but a significant incremental cost associated with the change in regulatory status, which I believe is generally considered in such actions and how to provide more or other cost‐effective alternatives. Was there a review by the Office of Management and Budget (OMB) review?”
Fabricant said it was important to take a vigorous stand on FDA’s action. Other substances that are the market legally, such as synthetic versions of resveratrol or L-theanine, could be at risk.
“If we let FDA do this, they will most certainly do it again. FDA more than anything likes to follow a course of action if they have been successful with that approach,” he said.