So how is the industry doing 30 years after the passing of the Dietary Health and Education Act of 1994? Is it complying with the statute? Is there room for improvement?
Before launching into a rapid-fire series of slides, Dr. Welch reminded industry that her office, which currently sits within Center for Food Safety and Applied Nutrition (CFSAN) at the Food and Drug Administration (FDA), sets the policies and programs for FDA’s oversight of dietary supplements. This includes providing guidelines, regulations, safety assessments and compliance strategy.
Always at the center of its strategic priorities, she emphasized, is consumer safety.
“The products should be what they say they are, contain what they say they contain, only in the amount that they say they contain,” she said, adding that informed decision-making at all levels from manufacturer to consumer is also key.
For the report card, she focused on scoring three main areas: new dietary ingredient notification requirements, good manufacturing practices and structure-function claim notifications.
New dietary ingredient notifications
New dietary ingredient (NDI) notifications are FDA's only premarket review opportunity for dietary supplements. NDIs are defined as those not marketed prior to Oct. 15, 1994 or present in the food supply.
Published in 1997 to enable industry to comply with DSHEA, the requirement for NDI notification is codified in 21 CFR 190.6. It establishes that a manufacturer or distributor of dietary supplements containing a new dietary ingredient submit a safety notification at least 75 days prior to marketing.
Dr. Welch noted that the number of notifications varies in any given year—peaking at close to 100 in 2017 and now averaging somewhere between 40 and 50 but that perhaps more telling is the type of FDA responses to those NDINs since 1995.
These include an acknowledgment without objection (also known as the “good day” letter); a notification that an NDIN is incomplete; an objection to the identity and safety information provided; and a notice that the ingredient does not meet the definition of a dietary or supplement and is therefore beyond ODSP purview.
Looking back over the last 10 years, there has been an uptick in the percentage of “good day” letters.
“This is a direction I really hope we continue to see because acknowledgement letters mean the notifications are coming in, and they're giving us a nice substantive review of what the ingredient is, what's the basic kind of safety event,” Dr. Welch said. She added that the numbers also show a higher percentage of acknowledgement letters when companies engage ODSP through a pre-NDI meeting.
FDA previously estimated that compared to the approximate 1,350 received, as many as 3,400 additional NDINs should have been submitted.
Steps being taken to strengthen the regulation of NDIs: publishing NDIN guidance, education and engagement with notifiers, and increased enforcement.
Good manufacturing practices
Regarding compliance with product quality, purity, consistency and safety standards through Current Good Manufacturing Practices established in 21 CFR 111, FDA confirms adherence through facility inspections, which have settled around 500 to 600 a year after pandemic lows.
Here, FDA classifies inspection determinations as no action indicated (NAI), voluntary action indicated (VAI) and official action indicated (OAI). The latter, Dr. Welch said, probably results in an FDA warning letter or even subsequent action but that by-and-large the percentage of these determinations is decreasing.
“What we have not really seen a change in is the top observations when we are inspecting facilities,” she said, categorizing the repeat citations as “pretty serious systemic issues” that ODSP is working to address through education, improving inspectional coverage, exploring the value of external audit programs and enforcement.
Top observations since 2007 include violations of 21 CFR 111.70 (e), 21 CFR 111.205 (a) and 21 CFR 111.103—related to establishing product specifications for quality assurance, maintaining a written master manufacturing record to ensure uniformity, and following written procedures for the responsibilities of the quality control operations, respectively.
Structure-function claim notifications
Last up was structure-function claim notifications as found in section 403(r)(6) of the Food, Drug, and Cosmetic Act. FDA published final rule 21 CFR 101.93 in 2000 requiring that manufacturers or distributors provide the Agency with product name, claim made and the text of the claim within 30 days of marketing a dietary supplement.
Of the 3,000 to 4,000 notifications received a year, the FDA is objecting to a minimal percentage, however Dr. Welch noted, “The problem is we don’t know what we’re not getting.”
To examine this unknown, her office estimated the compliance rate using one month of export certification data since firms must procure these certifications prior to exporting products. This data was compared to the last 10 years of structure-function claims notifications received, and it appeared that only 28% of the firms had any history of submitting these claim notifications to FDA.
“There's any number of ways in which this is a qualified estimate, but it's something, and I don't think it demonstrates a very great picture,” Dr. Welch said. “So, I'm going to be working on increasing the conversation about the importance of structure-function claim notifications and really seeing what we can do with it.”
