Despite the five positive NDI notifications for the ingredient in the late 1990s (Amrion Inc (1997), Leiner Health Products (1998 & 1999), GNC (1999), and Pharmavite (1999)), FDA announced on September 7, 2016 that it was seeking comment on the regulatory status of the ingredient after tentatively concluding that vinpocetine is not a dietary ingredient.
Almost six months on from the initial announcement and the agency is still working through the comments submitted.
An FDA spokesperson told NutraIngredients-USA: “We have not yet completed our review on vinpocetine or reached a final position on its regulatory status. To date, we have received more than 800 comments on our federal register notice, and will carefully review the comments before reaching any final determination.”
Agency stance
Vinpocetine, a compound positioned for brain health formulations, is derived from vincamine obtained from the lesser periwinkle plant (Vinca minor L.) and there is evidence to support its role as a vasodilator – or increasing blood flow to the brain. It’s being investigated as a drug in many countries but is not permitted as a pharmaceutical in the US, instead being sold as a supplement.
FDA’s tentative decision that vinpocetine is not a legal dietary ingredient hinges on two factors:
- 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 pre-empts 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;
- Vinpocetine is synthetic. Since the release of the first NDI draft guidance in 2011 and re-released in updated form just a few weeks ago, the agency has taken the tack that bioidentical compounds, or so-called ‘synthetic botanicals’ do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.
The deliberate and careful review of the comments is inline with comments made by Steven Tave, Acting Director of the FDA’s Office of Dietary Supplement Programs, at the Council for Responsible Nutrition’s Annual Symposium for the Dietary Supplements Industry in October 2016.
Tave explained that the Agency has just published an announcement looking for information about vinpocetine. “If it’s not a legal dietary ingredient, what do we do next? We didn’t do an enforcement action, didn’t issue any warning letters, demand any recalls. If it came to us today, it probably wouldn’t get acknowledged, so is there information out there that would change that position?” he asked.
“If it does hold that’s it not an NDI (and we realize we received 5 notifications in the 1990s and companies made business decisions based on those notifications) then what do we do?” he said. “We’ve gone slowly deliberately.”