Inconsistencies between NDI, GRAS raised in letter to FDA

By Hank Schultz contact

- Last updated on GMT

FDA photo
FDA photo

Related tags: New dietary ingredients, Gras

A letter from a member of Congress to FDA calls into question the inconsistencies between the NDI process and how GRAS submissions are evaluated and the lack of communication between the staffs working on these issues.

Rep. Tim Burchett, R-TN, sent a letter in mid December raising questions about the situation concerning various forms pyrroloquilonine quinone (PQQ) on the market.  PQQ is a redox cofactor found in small quantities in some plant materials such as kiwifruit as well as within animal tissues. PQQ has been studied for its growth-promoting activity, anti-diabetic effect, anti-oxidative action, and neuroprotective function.

The first form to come to market is called BioPQQ, manufactured by Japanese company Mitsubishi Gas Chemical.  Burchett’s letter noted that Mitsubishi filed a successful New Dietary Ingredient Notification on the ingredient in 2008 (‘successful’ in that the company received a no-objection letter from FDA).

Successful GRAS following NDI failure

In 2010, Burchett’s letter notes, new versions of the ingredient appeared on the market without filing their own NDINs.  When they got around to doing so, the letter says, these notifications were rejected because, among other things, “[T]he notifier failed to address organ damage (e.g., renal lesions) in the consumption of PQQ in an experimental animal model.”

Yet, according to Burchett’s letter, the manufacturers of these same ingredients subsequently submitted successful GRAS notices to FDA without addressing the kidney damage issue.

“The inconsistency between these reports issued from two offices under FDA is concerning,” ​Burchett wrote.  His letter said that a FOIA request issued by the law firm Rivkin Radler on behalf of Mitsubishi uncovered documentary acknowledgement that the Office of Dietary Supplement Programs (which handles NDINs) did not consult the Office of Food Safety (which has jurisdiction over GRAS submissions) concerning prior NDI or GRAS submissions on PQQ ingredients.

“Furthermore, the FDA acknowledged that it does not have a procedure by which either office can flag concerns for the other office’s review,”​ Burchett wrote.

Burchett requested that FDA address that lack of internal communication channels to ensure consistency in agency rulings on products coming to market.

Lack of internal communication

“The genesis of the letter remains ongoing frustration with FDA and its refusal to address the presence in the market of products that we believe that are unfairly competing with Mitsubishi, the innovator of PQQ,”​ said attorney Marc Ullman, of counsel with Rivkin Radler.

“That’s our narrow concern.  But globally the issue that Rep. Burchett identifies is the absence of any mechanism for the folks the NDI program and the GRAS programs to communicate with each other and flag issues. That should be alarming to any consumer,” ​Ullman added.

Daniel Fabricant, PhD, president and CEO of the Natural Products Association said the issue is one he’s familiar with from his time running ODSP at FDA (which at the time was called the Division of Dietary Supplement Programs).

“You clearly have some discrepancies at FDA.  The manufactures of these ingredients went shopping and got themselves a GRAS notice and there was no discussion between the NDI side of the house and the GRAS side of the house,”​ he said.

“There are not a lot of good answers from the agency on this one,” ​Fabricant added.

Import alert option

Fabricant noted that in his view it would be fairly easy to enforce the NDI provision via an import action as opposed to a formal enforcement action that would take the warning letter/injunction route.

“This goes back to the meeting we had in May on NDI enforcement. No one at FDA is paying attention to these products coming into the country.  We should actively be protecting our borders at a minimum.  On import alerts FDA has a much broader jurisdiction, but the last import alert concerning an NDI was six years ago on kratom,”​ he said.

Related topics: Regulation

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