The Dietary Supplement Health and Education Act (DSHEA) formed a strong framework for the regulation of New Dietary Ingredient (NDI) notifications as a pre-market safety review process.

NDI is defined as “a dietary ingredient that was not marketed in the United States before October 15, 1994 and does not include any dietary ingredient which was marketed in the United States before October 15, 1994”. The dietary supplements marketed before October, 1994 are categorized as grandfathered or old dietary ingredients (ODI). Therefore, as per the new NDI draft guideline, the manufacturer or distributor of NDI required a submission of a premarket notification to FDA before introducing the product into market. A new dietary ingredient will be exempted if the dietary ingredient is present in the food supply as a food and has not been chemically altered during the manufacturing process.

So how do various manufacturing processes and chemical alterations make an ODI an NDI? As per the new FDA draft guidance document, we have summarized a few preliminary points below to get you started on classifying your old dietary ingredients into a NDI.

• Any changes in your manufacturing process that alter the identity of the ingredient will convert a previously marketed dietary ingredient into an NDI.
• Any manufacturing changes that alter the physicochemical structure or properties, purity and impurities, or biological properties (such as bioavailability or toxicity) of the ingredient result in an NDI.
• Any changes in manufacturing process which changes the ingredient in a way that leads to alteration of the serving level or conditions of use of the product is likely to create an NDI.
• Any changes that alter the identity of the source material for an ingredient may create an NDI.
• If the ingredient produced by the new manufacturing process is an NDI.

Moreover, below are some examples of processes that FDA would likely consider to involve chemical alteration during the manufacturing process. These methods would also be likely to affect the safety profile of a dietary ingredient.

• A process that makes or breaks chemical bonds, unless the bonds created by the process are reversed when the ingredient is dissolved in water.
• Removal of some components of a tincture or solution in water, which changes the composition or structure of the mixture.
• Use of solvents other than water or aqueous ethanol to make an extract or tincture.
• High temperature baking or cooking of an ingredient that has not previously been baked or cooked, unless the process causes only minor loss of volatile components with no other changes to the chemical composition or structure.
• Changing the manufacturing method of an ingredient.
• Application of nanotechnology that results in new or altered chemical properties of the ingredient.
• Changing agricultural or fermentation conditions to alter the chemical or molecular composition or structure of the ingredient.
• Fermentation using a fermentation medium different from the one used to make conventional foods in the food supply.
• Use of botanical ingredient that is at different life stage than the life stage of the botanical ingredient used as a conventional food.

In contrast to the above examples, the term “chemically altered” does not include the following physical modifications: minor loss of volatile components, dehydration, milling, tincture or solution in water, slurry, a powder, or solid in suspension.

Overall, the draft NDI guidance can be viewed as a variety of exercises by FDA to describe as many dietary ingredients as possible as NDI, and to implement a standard of proof for their safety that manufacturers would be able to meet. Moreover, FDA strongly believes that this new guidance will provide consumers with access to safe and affordable dietary supplements. Contrariwise, if the draft guidance were implemented, it might restrict innovation and product improvements, and would likely overwhelm FDA with submissions as food industries begin to comply with the new guidance. Besides, food industries have expressed a contradictory view that the NDI guidance FDA is interpreting doesn’t go far enough to protect consumers.

Ultimately, as federal policies are influenced by the food industry in most part of U.S, the food industry and FDA should have a common goal to guarantee that NDI notifications, when they are required, are clearly presented and comprehensive in providing to FDA the safety information that is required under the law. This would be a real victory for public health in the U.S.

dicentra is a professional consulting firm that specializes in addressing all matters related to safety, quality and compliance for all product categories in the health sciences and food industries. We evaluate, implement, and provide all the necessary support for your products and operations to gain market access and build confidence in your brand.