What’s guidance without enforcement, asks industry in response to FDA’s recently issued final NDIN guidance


Without proper enforcement, the NDI notification process does not effectively safeguard consumers, nor does it incentivize manufacturers to invest the time and money to submit.

Photo © iStockphoto.com/ Kuzma

Photo © iStockphoto.com/ Kuzma

The U.S. Food and Drug Administration recently published its final guidance on new dietary ingredient notification (NDIN) procedures and timeframes, with plans to roll out more final guidance documents that are targeted in their subject matter. This format was suggested by a number of industry stakeholders, and while the targeted guidance documents are more easily digestible, the agency did not offer any clarity on how soon or how often the next guidance will be published. The core takeaway from this current guidance is that FDA expects a finished product approach to NDINs, in which finished product manufacturers using a NDI are responsible for notifying FDA even if the ingredient manufacturer submitted their own NDIN. This is contrast to an ingredient-specific approach advocated by industry, which would be less burdensome.

Based FDA’s guidance a manufacturer would have to submit a separate notification for each product containing the NDI. This can be difficult and costly for brands who may use a NDI in a number of product formulas. While the guidance does state the FDA accepts NDINs “that cover multiple dietary supplements and include safety data for a range of doses, daily intake levels, or other variations in conditions of use (e.g., serving size, duration of use, frequency of intake, target population, dosage form),” products that contain NDIs in combination with different ingredients would have to be filed separately. By requiring every company selling a NDI to submit a notification, you could say that they bear equal responsibility and that manufacturers cannot legally market a NDI based on someone else’s notification. However, where’s the enforcement?

“It is curious that FDA seems fixated on this requirement, but we cannot point to a single incidence where FDA has taken enforcement action against a firm for marketing an NDI where another company successfully received a no objection letter and then another company seems to be piggybacking—either legitimately or illegitimately—on that notification,” says president and CEO of the Council for Responsible Nutrition (CRN; Washington, D.C.). “CRN has raised the need for this enforcement with FDA when we submitted our master file proposal. It’s simply wasted breath – and ink – for FDA to demand each manufacturer submit a separate NDI for each product when it seems clear the agency has no intention of enforcing this requirement.”

The master file framework, suggested by CRN, the Consumer Healthcare Products Association (CHPA; Washington, D.C.), and the United Natural Products Alliance (UNPA; Salt Lake City, UT) would create some ease of use while also helping to protect the intellectual property of ingredients manufacturers whose ingredients are used in multiple finished products. However, this framework is not useful without enforcement from FDA.

“The combination of a Master File system to safeguard the intellectual property of innovative ingredients, combined with a requirement for each company that uses an NDI to file a separate notification, raises the bar for market entry, while also benefitting companies investing in science-based formulation and ingredient development. Without FDA enforcement, consumer safety can be compromised, and market progress becomes hindered because there are no protections for innovators who are compliant with regulations,” says Duffy MacKay, senior vice president, Dietary Supplements, for CHPA. Essentially there is no incentive to comply.

As an example of FDA’s lack of enforcement, The Natural Product Association’s (NPA; Washington, D.C.) president and CEO, Daniel Fabricant, PhD, points to a letter received by the Natural Alternatives International (NAI) in response to its request that FDA take enforcement action against generic beta-alanine products being imported into the country without having submitted NDINs. NAI’s beta-alanine, by contrast, did have a successful NDIN in compliance with FDA regulations. In response, FDA’s Cara Welch, PhD, Director of FDA’s Office of Dietary Supplement Programs in the Center for Food Safety and Applied Nutrition, wrote: “the fact that a dietary ingredient is not covered by NAI’s NDIN, or any NDIN, does not automatically render the dietary ingredient adulterated under section 402(f) of the Federal Food, Drug & Cosmetic Act (FD&C Act).”

She also wrote: “While our review of the safety information included with NAI’s NDIN did not raise any safety concerns, our response should not be interpreted as a conclusion about whether beta-alanine generally is subject to the requirements in section 413(a)(2) of the FD&C Act.”

Essentially, Welch explains that the generic beta-alanine is not considered adulterated unless it is subject to the NDIN requirements, meaning it was not present in the food supply prior to the passage of DSHEA. According to Welch, FDA had not yet determined whether beta-alanine even required a NDIN. In response to assertions that the generic beta-alanine posed a safety risk to the public, Welch said that FDA was not aware of any evidence that supported the assertion, and NAI did not furnish such evidence. Therefore, FDA did not know if beta-alanine even required a NDIN, and the lack of evidence of safety issues did not incentivize the agency to take any immediate action. So, did NAI waste its time and money on submitting a notification? Again, without enforcement, industry lacks incentive to comply.

“In practice [FDA has] shown they really don't value the NDI process, which is the life blood of our industry and 30 years after the fact, not having a clear process is just disgraceful,” says Fabricant to Nutritional Outlook. “I think we've seen FDA’s more than willing to go to the bat for pharma IP, look at NMN,” adds Fabricant, while pointing out that final NDI guidance has taken eight years to publish since the most recent draft.

FDA has indeed been actively enforcing the drug preclusion clause which restricts ingredients from being sold as dietary supplements if they’re being studied or have been approved as a novel drug. This is the case with N-acetyl cysteine (NAC) and nicotinamide mononucleotide (NMN), both of which are examples of FDA retroactively enforcing the clause, despite evidence that NAC was on the market as a dietary supplement prior to passage of DSHEA, and despite NMN having already been subject of a successful NDI notification. FDA is currently exercising enforcement discretion on NAC following numerous citizen petitions and a lawsuit by NPA, which has since been withdrawn. FDA has not yet reached a decision on citizen petitions submitted in response to FDA’s NMN conclusion.

While the current guidance offers some clarity on what FDA expects from industry, it still does not address the larger issues plaguing the NDI notification process.

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