Before we discuss the FDA’s Draft Guidelines for the New Dietary Ingredient (NDI) notification process we need to recap the way dietary supplements are regulated in the USA. Contrary to much of what you may have read recently in the media, the dietary supplement market in the USA is not unregulated but largely falls under a specific piece of legislation called the Dietary Supplements Health Education Act of 1994 (DSHEA). In addition to outlining items such as how a dietary supplement is made, what claims can be made about the supplement, and the need for the reporting of adverse events, DSHEA defines exactly which dietary ingredients can be included in a dietary supplement. Key to the NDI process is determining when should a company inform the Food & Drug Administration (FDA) when they what want to bring a new dietary ingredient to market.
If there is a NDI, does that mean that there is an Old Dietary Ingredient (ODI)?
Not officially but for practical reasons when DSHEA came into effect on October 15, 1994 any dietary ingredients on the market prior to this date were “grandfathered in”, that is considered to be legally available. Any ingredients introduced to the market after that day required that the FDA be notified via the NDI notification process.
What’s happening to the FDA’s NDI notification process now?
In August 2016, the FDA published draft guidelines — “Draft Guidance for Industry; Dietary Supplements: New Dietary Ingredient Notification and Related Issue”. The purpose of these guidelines was to 1. improve compliance with these notification requirements and 2. to help improve the quality of the information sent to the FDA.
If DSHEA came into force in 1994, why is it necessary to publish these guidelines now?
The best answer to that is to look at the current dietary supplements market and the number of notifications made to the FDA to date. When DSHEA came into effect in 1994, it was estimated that there were 4,000 products on the market. The estimate number of products on the market in 2012 was just over 55,000 with almost 6,000 new ones entering annually. Between 1994 and 2014, the FDA had received less than 1,000 NDI notifications. So you can see that there is something of a disconnect between the FDA and industry and when a notification was required.
What do I need to know about these new draft guidelines?
The draft guidelines published in 2016 are an updated version of draft guidelines previously published. As you can imagine the 2016 draft guidelines are very detailed but largely focus on when a NDI notification needs to be made, how it will be processed including anticipated timelines, and what sort of information needs to be included in notification itself. More information about the draft guidelines can be found at www.fda.gov/food/guidanceregulation/guidancedocumentsregulatoryinformation/dietarysupplements/ucm257563.htm
What has been industry’s reaction to these draft guidelines?
Given how important NDI notification is to the industry, it is not surprising that the FDA has received many comments from both individual companies as well as the main industry associations. Key industry members have been supportive of the need for improved guidelines to strengthen the FDA’s ability to support public health and the safety of products. However, they have also raised a number of important concerns.
Industry’s concerns with the proposed guidelines:
How do you precisely identify what was on the market before October 15, 1994?
This question is commonly seen as one of, if not the, most important one to be answered. Though many different forms of evidence such as sales records, sales contracts and even product catalogs can be used to show that an ingredient was on the market before October 15, 1994, there is a need for an authoritative list of the grandfathered ingredients to allay confusion and ambiguity. Also, since prior to DSHEA the legal status of dietary supplements was unclear, it may be difficult to identify all the dietary supplements on the market at that time.
Is a NDI notification required when you combine two or more dietary ingredients?
Though the NDI guidelines apply to dietary ingredients and not finished dietary supplements, there is some debate whether the 2016 draft guidelines would and should require the combination of two or more NDIs in a finished dietary supplement to require a specific NDI notification. There is much debate as to whether or not this is contained within the intent of DSHEA. Given the number of dietary supplements on the US market that contain more than one NDI, this topic could have a significant impact.
Within the draft guidelines, what exactly do “manufacturing changes” and “chemical alteration” mean?
The dietary supplements industry is very dynamic and innovative, and many changes in extraction and manufacturing techniques have been developed since the passing of DSHEA in 1994. There is much debate as to whether the use of these “newer” techniques (e.g. super critical CO2 extraction) should trigger a NDI notification, particularly when these techniques are now considered to be the norm or best practice. It is one thing if changes and chemical alteration pose a safety issue, but quite another if they make for a superior quality dietary supplement. One option may be to create a list of approved processes used in manufacturing, another may be to focus on situations where safety may be compromised.
How should synthetic copies of botanical and herbal ingredients be addressed?
When DSHEA was passed in 1994 there were synthetic versions of a number of vitamins and minerals on the market, however, the advent of synthetic plant equivalents is a relatively new phenomenon. Though congress did not distinguish between natural and synthetic versions in DSHEA, the FDA has taken the position that synthetic copies of botanicals are not dietary ingredients at all. Some industry members have said that this is the wrong approach and that requiring companies to submit a new NDI notification may be the best way to ensure that dietary supplements containing synthetic versions of ingredients are appropriately regulated.
What kind of impact will this have on the dietary supplement industry?
This, of course, depends on what is contained in the final guidelines. In many ways, adoption of these guidelines could provide for an updated and more appropriate regulation of dietary supplements.
That being said, the impact could be significant and very resource intense for both the industry submitting the notifications and the FDA in dealing with them. If the current draft guidelines are approved as they are, the costs involved would be very substantial for the industry.
Have any decisions about the draft guidelines been made yet?
No, the FDA is still considering all the comments it has received and is continuing to consult with all members of the sector. One of the main questions — How to deal with the creation of an authoritative list of dietary ingredients available pre-DSHEA? will be explored at a workshop set for the Fall of 2017. When finalized, details of this workshop will be posted on the FDA Workshop page at www.fda.gov/Food/NewsEvents/WorkshopsMeetingsConferences/default.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery
About the author: Dr. Michael Smith is trained as a pharmacist and a naturopathic doctor and is recognized internationally as an expert in Natural Health Products and Complementary and Alternative Medicine. For more than 10 years, he worked in senior regulatory positions at the then Natural Health Products Directorate, Health Canada and the Therapeutic Goods Administration in Australia. In addition to his work as a consultant, he is an Adjunct Professor at the National Center for Natural Products Research at the University of Mississippi in the USA and an Adjunct Fellow at the National Institute of Complementary Medicine at Western Sydney University in Australia. Michael is a member of ISURA’s Scientific Advisory Committee.