Council for Responsible Nutrition to request FDA guidance on drug preclusion issues

The Council for Responsible Nutrition (CRN) is planning to file a citizen petition with FDA that requests guidance around standards for determining circumstances in which an ingredient meets the definition for “drug preclusion,” CRN’s president and CEO, Steve Mister, said.

The forthcoming petition reflects an effort to obtain greater certainty for dietary supplement brands who are concerned about their investments in ingredients that FDA may determine are precluded in supplements as a result of the “articles” being the subject of FDA drug approval or “substantial clinical investigations.”

“We understand why the drug preclusion provision is in the statute to begin with,” Mister reflected during an April 18 interview at the SupplySide East trade show in Secaucus, New Jersey. “It was a reasonable concern in 1994 that drug companies who spend millions—tens of millions of dollars, really—on drug research have some assurance that at the last minute a supplement is not going to come in using the same ingredient and undercut all of those years of research.

“But what has happened over the last several years at FDA has totally upset that balance between protecting innovation on the drug side and protecting innovation on the supplement side,” Mister argued. “That needs to be righted, and I think that kind of is the focus of our citizen’s petition.”

CRN’s petition will “look at the language of the drug preclusion issue and where FDA is misinterpreting the statute either based on the plain reading of the language or based on the original intent,” Mister said.

Among the frustrations expressed by industry trade groups: FDA’s conclusion that it cannot disclose the date that an investigational new drug application (IND) takes effect. This reality may complicate business planning and investments in novel dietary substances since the IND date is critical in determining whether an ingredient is excluded from dietary supplements.

FDA doesn’t reveal information related to INDs if the information is deemed part of a pending application, and the IND is still considered pending once it takes effect, FDA’s Center for Drug Evaluation and Research (CDER) confirmed in an Oct. 4, 2022 story published by Natural Products Insider. Several federal statutes and regulations preclude FDA from discussing details of an IND application, CDER said, including the Freedom of Information Act, Trade Secrets Act and Federal Food, Drug & Cosmetic Act (FDCA).

“That is certainly not what Congress intended drug preclusion to do,” Mister said, commenting on FDA not revealing the IND dates. Lawmakers “wanted to give a date certain so that you know what you’re shooting against. You know, ‘OK this is the date the drug went into the market, or the clinical investigation was published.’ So now we know if we don’t have evidence of marketing as a supplement prior to that date, we should leave [the ingredient] alone.”

CRN’s citizen petition, Mister said, will assess “FDA’s reading other words into the statute to try to limit the dietary supplement side of the marketplace and make some recommendations on how FDA might reconsider its interpretation.” The petition, he added, is focused on drug preclusion broadly versus a specific ingredient like NMN, which is the subject of a citizen petition filed by the Natural Products Association (NPA) and Alliance for Natural Health USA.

Mister shared he recently met with the CEO of one of his member companies and asked them, “What’s keeping you awake at night? And the response was drug preclusion.”

Mister then asked the CEO if the concerns were related to FDA’s decision that NMN is excluded from supplements.

“And they said, ‘No. I am concerned about the other big ingredients in my portfolio, and now I don’t have confidence that I’m going to be able to sell that product in a year or five years. How do I know FDA won’t take that off the market?’” Mister recounted. “So, for us, that was a reminder this can’t be about any one ingredient. It has to be about returning the level of certainty to the marketplace.”

[Steve Mister (below, left) of the Council for Responsible Nutrition being interviewed by Josh Long at SupplySide East on April 18, 2023].