Summer is in full swing here in the Northern Hemisphere and FDA is heating things up for the US dietary supplement industry. On Friday, July 1, 2011 FDA published the long-anticipated Draft Guidance for Industry on Dietary Supplement New Dietary Ingredient Notifications. You can read the whole guidance at http://www.fda.gov/Food/GuidanceComplianceRegulatoryInformation/GuidanceDocuments/DietarySupplements/ucm257563.htm. The issuance of this guidance was mandated by the Food Safety Modernization Act signed into law in January of this year. The goal is to clarify when a New Dietary Ingredient Notification should be submitted. New Dietary Ingredients are substances intended for use in dietary supplement products which both meet the definition of ‘dietary ingredient’ and which were not marketed as dietary ingredients prior to October 15, 1994, the day that the Dietary Supplement Health Education Act became law.
Our team routinely checks ingredients in dietary supplement products we review for their regulatory status and we also work on New Dietary Ingredient Notifications. As the lead consultant for our group, I work hard at keeping up with FDA guidance documents and warning letters. Nevertheless, I was surprised and even shocked by some of the things I found in the guidance upon first reading today and thought you might be interested in them also.
Dietary supplements are regulated as a special class of foods in the US and prior to issuance of this guidance, my team and I understood that conventional food ingredients that met the definition of dietary ingredients and that were not chemically altered were not new dietary ingredients and would not require a notification (NDIN). According to the guidance, there are circumstances in which an NDIN would not be required BUT the product could be considered adulterated under certain circumstances if no NDIN has been filed. Frankly, I need to read these sections a few more times and probably draw a diagram to figure these details out because the various exceptions are confusing.
It has been common practice for dietary supplement manufacturers to rely on NDINs made by other companies, trusting that once an NDIN had been filed and FDA had no objections, anyone could market the ingredient. However, the NDIN draft guidance makes it clear that EVERY manufacturer must submit an NDIN if they plan to market a dietary ingredient that was not marketed prior to October 15, 1994. This interpretation, once enforced, could readily result in branding two thirds of the dietary supplements currently on the market as adulterated. Clearly, companies and consultants will be very busy filing NDINs for ingredients and products that have been sold for years.
This next issue that got my attention was not really surprising, since FDA has been applying this standard to recent NDINs, but still breathtaking to see spelled out: The draft guidance unequivocally states that synthetic versions of naturally occurring substances ARE NOT dietary ingredients unless they were marketed as dietary supplements prior to October 15, 1994. Most vitamins are safe since synthetic versions were used prior to that date but what about indol-3-carbinol, limonene, resveratrol, various isoflavones and countless other phytochemicals that are valuable for maintaining health but occur in amounts too small to make extraction with water and ethanol feasible and affordable. (Note that water and ethanol were the only solvents the guidance listed as not chemically modifying an ingredient.) Seems that ingredient manufacturers need to hustle and see if they have sufficient data to obtain GRAS status for use of their ingredients in dietary supplements.
Similarly, naturally-occurring metabolites and other biochemicals that have been stabilized by adding esters or other chemical moieties are not considered dietary ingredients. It is clear from the guidance document that FDA has reviewed some supplements that are on the market and determined that they have been “chemically altered” and do not meet the criteria to be sold as dietary ingredients. One example of this is high selenium yeast. The guidance states that chemical alteration includes, “Changing agricultural or fermentation conditions to alter the chemical composition of the ingredient, such as by sprouting garlic or fermenting yeast using a medium containing large amounts of sodium selenite to create large amounts of organic selenium compounds.” It also appears that FDA would consider some probiotics as chemically altered by “use of a defined commercial growth medium to produce a microorganism previously made by fermenting milk into dairy products like yogurt or cheese.”
The draft guidance on New Dietary Ingredient Notifications will undoubtedly have a tremendous impact on the US dietary supplement industry. We will continue to review the guidance and provide you with insights in the coming weeks. In the meantime, contact us with questions regarding New Dietary Ingredient Notifications (NDINs); Generally Regarded As Safe (GRAS) designation or your other regulatory affairs needs.
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Evelyn and Team
Bioscience Translation & Application