Dietary supplement manufacturers are required to notify the FDA in advance when they intend to add a NDI to their products. However, in certain situations when the ingredient has been part of the food supply (and is still considered an NDI), an NDI notification to the FDA is not required if it has not been chemically altered for use in supplements.
Under the guidance, minor loss of volatile components, dehydration, lyophilization, milling, and formation of a tincture or a solution in water, a slurry, a powder, or a solid in suspension do not chemically alter an ingredient.
However, the following are examples of processes that the FDA would 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.
- 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 of the ingredient.
- 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 compounds.
- Fermentation using a fermentation medium different from the one used to make conventional foods in the food supply (e.g., use of a defined commercial growth medium to produce a microorganism previously made by fermenting milk into dairy products like yogurt or cheese).
- Use of a botanical ingredient that is at a different life stage than previously used (e.g., making an extract from unripe instead of ripe apples or using the mycelium instead of the fruiting body of a fungus.)
The guidance also states that if the manufacturing process alter the chemical composition or structure of an "old" dietary ingredient, the resulting compound is probably an NDI and an NDI notification to the FDA would be required. For example, using a solvent to prepare an extract from a "old" dietary ingredient creates a NDI because the final extract contains only a fractionated subset of the constituent substances in the original dietary ingredient. In addition, changes that alter the composition of materials used to make the ingredient, such as using a different part of a plant (e.g., using an extract of plant leaves where the root extract from the same plant is an "old" dietary ingredient), would create a NDI.
The 53-page guidance document could greatly impact your business. It is recommended that you read it carefully and discuss it with your legal and regulatory team.
The FDA is inviting the public to submit comments about the draft guidance. Although you can comment on any guidance at any time, to ensure that the agency considers your comments on the draft guidance before it begins work on the final version of the guidance, you should submit your comments by October 3, 2011.
For more information: Federal Register Notice for New Dietary Ingredient Notifications and Related Issues (link for submitting comments; Docket ID: FDA-2011-D-0376): http://www.regulations.gov/#!documentDetail;D=FDA-2011-D-0376-0001.
