In a letter dated October 25 and addressed to FDA Commissioner Dr Robert Califf, Senator Hatch states that, while Section 4 of the Dietary Supplement Health and Education Act (DSHEA) provides pathways for withdrawing dietary ingredients based on safety concerns, the agency has not cited any such concerns over vinpocetine.
“Citing no risk of illness or hazard to public health, this Notices [to the Federal Regitser FDA-2016-N-2523] creates uncertainty in the market as to what steps manufacturers can take to sell safe products,” wrote Sen Hatch.
Five (5) NDINs
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.
Vinpocetine is considered a new dietary ingredient (NDI) after the FDA acknowledged notifications in the late 1990s from Amrion Inc (1997), Leiner Health Products (1998 & 1999), GNC (1999), and Pharmavite (1999).
“In 1997, 1998, and three times in 1999, the FDA reviewed New Dietary Ingredient notifications for vinpocetine, each time pulling the product for 75 days and conducting safety and regulatory checks,” wrote Senator Hatch. “Each evaluation was an opportunity to raise concerns about whether vinpocetine was a valid dietary ingredient, yet the FDA did not object to the product during any of the five reviews, allowing it to proceed to market each time.”
The letter also states that the notice raises questions about whether the office of management and budget did a full economic impact review. “Vinpocetine has a large footprint in the dietary supplement market and serves as a component in many common products. As this is the first time that FDA has attempted to pull a product for a definitional reason instead of a public health concern, a complete and thorough economic impact analysis should be completed.”
“I have great trust in the experts of the FDA, as do the American people. By 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.
“Given that FDA has had five previous opportunities to make this change, yet returned the product to market, the agency signaled that the product could be sold in the US. As such, I urge you to withdraw this Notice and conduct cost-benefit analyses when considering the merits of withdrawing dietary and nutritional supplement products when safety in not the predicating reason for withdrawal.”
Despite the five positive NDI notifications for the ingredient, FDA announced on September 7, 2016 that it has initiated a proceeding to take vinpocetine off the market despite a number of successful NDI notifications filed on the ingredient.
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.
Speaking at the recent Council for Responsible Nutrition’s Annual Symposium for the Dietary Supplements Industry, Steven Tave, Acting Director of the FDA’s Office of Dietary Supplement Programs, 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.”
The Natural Products Association has called on the US Food and Drug Administration to extend the comment period on the status of vinpocetine until September 6, 2017. In a letter to the FDA dated October 3, 2016, Dr Dan Fabricant, NPA’s CEO and executive director, wrote: "To sufficiently respond to FDA’s view on vinpocetine, the industry will need time to do additional research as well as identify the extent to which these changes may impact manufacturers, distributors and consumers."