FDA considers dietary supplements that contain new dietary ingredients and that have not submitted new dietary ingredient Notifications to be adulterated. Any supplement that is considered to be adulterated can be subject to enforcement action by the FDA.

What is a new dietary ingredient?

A new dietary ingredient is a dietary ingredient that was not marketed in the United States in a dietary supplement before October 15, 1994. If a company is using a new dietary ingredient in their product, the onus is on them to provide FDA with evidence of the dietary ingredient’s safety or history of use, presented in the form of a new dietary ingredient Notification¹. When submitting a pre-market notification you must provide data that indicates either: (i) a history of safe use or evidence establishing safety or (ii) data to indicate that the ingredient has been used in the food supply as an article used in food that has not been chemically altered.

How do you determine which ingredients in your product are considered new dietary ingredients?

The FDA does not have an authoritative list of dietary ingredients that were marketed as dietary supplements before October 15, 1994, placing the burden on industry to determine if the dietary ingredient in question was marketed before that date. However, to aid the industry FDA released a guidance document in July, 2011 to better define the process². After October 15, 1994 industry associations such as the American Herbal Products Association (AHPA) and Council for Responsible Nutrition (CRN) published lists of dietary ingredients believed to have been marketed before October 15, 1994. However, these industry association lists are not approved or recognized officially by the FDA but are generally accepted by industry. If the ingredient in question is not contained within these industry association lists you either need to provide evidence to the FDA to prove that it is not a new ingredient or you must file a Notification at least 75 days before introducing the supplement with the new dietary ingredient present into interstate commerce or delivering it for introduction into interstate commerce.

Information required to be submitted in a new dietary ingredient Notification:

As part of the new dietary ingredient premarket notification FDA requires the following information to be submitted:

• The name and complete address of the manufacturer or distributor that is submitting the notification.
• The name of the new dietary ingredient that is the subject of the premarket notification. For botanicals, the Latin binomial name must be given, including the author citation (the name of the scientist who gave the botanical its Latin binomial name).
• A description of the dietary supplement that contains the new dietary ingredient, including:
  • the level of the new dietary ingredient in the dietary supplement, and
  • the conditions of use recommended or suggested in the labeling of the dietary supplement, or if no conditions of use are recommended or suggested in the supplement’s labeling, the ordinary conditions of use of the supplement.
• The history of use or other evidence of safety establishing that the dietary ingredient, when used under the conditions recommended in the labeling of the dietary supplement, will reasonably be expected to be safe.
• The signature of a person authorized by the manufacturer or distributor to sign the notification on its behalf².

How do I determine if my new dietary ingredient is considered “chemically altered”?

A common question regarding new dietary ingredients is determining what are the limits and definition that apply to a dietary ingredient being chemically altered. Currently, there is no set definition for defining a dietary ingredient as chemically altered in any FDA draft guidance documents; however the FDA has provided examples of what they consider to be chemically altered. The following are examples of processes that FDA would likely consider to involve chemical alteration.

• A process which makes or breaks chemical bonds such as hydrolysis or esterification, unless the bonds created by the process are reversed when the ingredient is dissolved in water (e.g., creation of a soluble salt) or during ingestion.
• Removal of some components of a tincture or solution in water (e.g., by chromatography, distillation or membrane filtration), which changes the chemical composition of the mixture.
• Use of solvents other than water or aqueous ethanol (tincture) to make an extract. Water and aqueous ethanol are specifically excluded from processes that chemically alter a food in the official legislative history of DSHEA. Other solvents alter the composition of the extract in significantly different ways, usually by extracting different types of constituents than are extracted using water and aqueous ethanol.
• Changing the manufacturing method for an ingredient such that the chemical composition is significantly different (e.g., changes that alter the composition of materials used to make the ingredient, use of a different solvent, use of a chromatographic matrix instead of a passive filter).
• Application of nanotechnology that results in new or altered chemical properties of the ingredient.
• 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 compounds².

A safe assumption to determine whether your dietary ingredient would classify as a new dietary ingredient due to chemical alteration is to look at the chemical structure of the dietary ingredient that was marketed before October 15, 1994 and compare it with the chemical structure of your compound, if both structures are not completely identical you may have to submit a Notification.

Challenges presented by the new dietary ingredients guidance document:

Although, the FDA has released a draft guidance document on new dietary ingredients there still remains a lot of ambiguity regarding whether an ingredient is a considered new and hence requires a Notification to be submitted. As such trade organizations such as the CRN, Natural Product Association (NPA), AHPA and United Natural Products Alliance (UNPA) have raised the following five issues that the FDA has agreed to address in their next draft of the new dietary ingredients guidance document

1. Whether a synthetic version of a botanical ingredient can be a botanical ingredient.
2. Grandfathered ingredients and who has the burden to prove something is grandfathered.
3. Whether a new dietary ingredient has to be filed for each supplement or whether it can be filed with the ingredient itself.
4. The breadth of the definition of chemical adulteration.
5. What is the appropriate standard of science to match the “reasonable standard of safety”?³

With all of these factors to consider when discovering that you have a new dietary ingredient in your product, reformulation may be a consideration. However, the goal of the FDA is not to slow down industry progress and restrict new and innovative products from the market but to ensure public safety. At dicentra we employ a team of scientific and regulatory experts that are available to help you determine whether your ingredient is a new dietary ingredient and if so are able to aid in the completion of a Notification.

References: 1. http://www.health.gov/dietsupp/ch1.htm 2. http://www.fda.gov/food/guidancecomplianceregulatoryinformation/guidancedocuments/dietarysupplements/ucm257563.htm 3. http://www.naturalproductsinsider.com/news/2012/06/fda-reportedly-to-revisit-ndi-draft-guidance.aspx