Rockville, MD — Since the U.S. Food and Drug Administration (FDA) released its Revised Draft Guidance for New Dietary Ingredient (NDI) Notifications in August, industry has been working hard to understand how exactly it has changed since 2011, where it has improved and where further revisions should take place. It has been a major talking point at industry trade shows and conferences, with finished product manufacturers and suppliers desperate to understand what they might be in for, considering the potential costs involved with submitting notifications on products and ingredients they have been selling safely for years.
While FDA appears to have taken industry’s comments from the 2011 draft into consideration, there are still major points of contention that have been consistently cited by trade groups in the industry. This week, trade groups that included the Natural Products Association (NPA), United Natural Products Alliance(UNPA), Council for Responsible Nutrition (CRN), the American Botanical Council (ABC) and the American Herbal Products Association (AHPA) submitted their comments to FDA and here are some of the major takeaways.
Defining Dietary Ingredients
One major point industry takes issue with in the new guidance is that according to FDA, synthetic copies of herbs or other botanicals do not qualify as dietary ingredients. CRN describes this as a very narrow interpretation of Section 201(ff)(1) of the Federal Foods, Drug and Cosmetic Act (FD&C), which the Dietary Supplement Health and Education Act of 1994 (DSHEA) as an amendment of FD&C defined as “a dietary substance for use by man to supplement the diet by increasing the total dietary intake; or a concentrate, metabolite, constituent, extract, or combination of any [vitamin, mineral, herb or other botanical, amino acid]” under Section 201(ff)(1)(E)(F).
“Congress did not include limitations on synthetic ingredients, or any requirement for historical use of a substance to supplement the diet under Section 201(ff)(1)(E), and FDA therefore should not exceed its authority by imposing its own limitations through guidance,” states CRN in its comments.
ABC concurs, stating, “DSHEA does not explicitly prohibit a synthetic or semi-synthetic compound as a dietary ingredient nor has FDA set forth data to support a safety concern for the use of a synthetic or semi-synthetic copy of an herbal or botanical constituent. ABC continues to emphasize that the safety of an ingredient is the primary consideration and if a synthetic or semi-synthetic compound is chemically identical to the natural compound and has the same level of safety as the natural compound, then ABC supports the availability of the synthetic or semi-synthetic version as a legitimate dietary ingredient.”
Additionally, FDA is essentially contradicting itself. “Botanicals are the only type of ingredients listed in section 201(ff)(1) for which the draft guidance attempts to differentiate between synthetic and non-synthetic forms of a ‘concentrate, metabolite, constituent, extract, or combination’ under part (F),” states NPA in its comments. “This attempt stands in stark contrast to a long line of statutory and regulatory precedents that expressly reject distinctions between synthetic and ‘natural’ forms of the other ingredient types listed.”
Ingredient vs. Supplement Notifications
Another aspect of the new guidance industry opposes is FDA’s supplement-focused approach to notifications. UNPA, for example, points out that DSHEA “created an NDI review system focused on the ingredient as the gateway to assess the safety of future dietary supplements,” but FDA has instead interpreted in a way that “subjects over 75,000 dietary supplements and nearly 10,000 dietary ingredients to persistent re-review for safety at an economic cost that is unjustifiable to the industry.” Complicating the matter further, UNPA cites a review by Healthnotes, Inc. in which they analyzed 51,286 dietary supplement SKUs and found that on average, dietary supplements sold in the U.S. contain 9.5 dietary ingredients. This would be an immense logistical and financial burden on any company but smaller manufacturers in particular.
CRN acknowledges where FDA sought to work with industry by providing specific scenarios where multiple NDIs would not be necessary but maintain its original stance that “the statute does not authorize FDA to require a separate NDI notification for each finished product using that NDI unless the finished supplement utilizes the ingredient in a manner that is inconsistent with the serving size range or restrictions on use indicated in the earlier notification, or in combination with other dietary ingredients that may adversely affect the safety profile of the finished supplement.”
CRN recommends that ingredient manufacturers and distributors submit NDI notifications to serve as a basis for establishing safety of an NDI across a range of dietary supplements. Firms would then self-determine whether additional notifications are required.
NPA also believes that finished products manufacturers should not be burdened with submitting notifications when ingredient manufacturers and distributors would have submitted notifications for the individual ingredients. They add however, that DSHEA places the burden on FDA to prove a supplement as unsafe and that they should “rather than requiring notifications for each and every supplement containing an NDI, FDA should, in a transparent fashion, publish combinations of ingredients from successful NDI filings that either do or do not require a subsequent filing.”
Similarly, AHPA suggests that FDA “encourage, in any subsequent draft or final NDI guidance, manufacturers or distributors of dietary ingredients to make sure to provide general descriptions of the many dietary supplements that may contain the NDI.” The “general descriptions” would be exactly that, such as describing the form dietary supplements containing the NDI would be marketed as (ie. tablet, capsule softgel, gelcap, powder, or liquid). ABC for their part challenges FDA to “provide specific examples of cases where the combination of duly notified NDIs have resulted in a problematic situation from a human safety perspective,” as they are unaware of any such occurrence.
The previous draft of the guidance placed the burden on industry companies to prove that the ingredients they are marketing are pre-DSHEA and therefore do not require a notification. This would prove enormously difficult considering that DSHEA’s passage was 22 years ago, when companies did not keep computer records, many companies that would have those records are now defunct and newer companies have no reasonable way to access these records and generate proof. The revised draft calls for compiling a list of pre-DSHEA products that will serve as a reference, but the task is still not much easier even with cooperation between industry and FDA.
The revise guidance still requires industry to provide objective proof of pre-DSHEA marketing, when documentation is hard to come by, and refuses to accept the lists of pre-DSHEA ingredients compiled by trade groups familiar with formulations prior to DSHEA. The trade groups agree that this in an unreasonable demand on the industry and will likely fail if FDA does not change its approach.
This is but a small taste of what our industry trade groups have to say about the revised guidance, but it makes clear the disparity between how FDA and industry interpret the law as well as science. Industry generally agrees that NDIs are important for consumer safety, and while we were probably expected worse from this new guidance, as it stands now, there is still an undue burden placed on dietary supplement manufacturers and overstepping of regulatory authority by FDA.