NDI Regulations: Challenges Facing Botanicals

Anticipating FDA’s eventual release of new dietary ingredient (NDI) guidance, the greatest challenge the botanicals industry will face depends on whether the new guidelines will allow ingredients to be grandfathered in simply by ingredient name, or if they will be grandfathered in by specific production method.

If ingredients are grandfathered in by ingredient name, the ruling will be much simpler to execute and more likely to be supported by the industry. However, if FDA gets very specific and only grandfathers in products that were produced via a specific method prior to 1994, this could open up Pandora’s box.

Production methods have changed greatly over the last 17 years, and there are numerous variables FDA would have to contend with. For example, ingredients could be considered “new” if they used to be extracted with alcohol but are now extracted with water. Ingredients could also be considered new if they now have higher assay concentrations or greater bioavailability.

Unfortunately, we do not know how specific the new NDI guidance will be until the draft is released. The good news is that former FDA principal deputy commissioner Joshua Sharfstein, MD, had emphasized that the release will be a draft only and that it is meant to be a starting point, open to industry feedback. Industry members would do well to keep tabs on the release of this draft, review it fully, and vocalize their opinions of what is most ideal and why.

Unfortunately, determining which ingredients should be grandfathered in is a fundamental challenge even for FDA. There is no credible source or list of ingredients that were actually on the market in 1994. And, understanding the extent to which an individual ingredient’s identity or function in the body may change due to changes in manufacturing or other inputs also becomes complicated. It will be interesting to see with whom the burden of proof will lie in determining the nature of new dietary ingredients.

How to Prepare

Of course, it may be wise for finished-product manufacturers to get ahead of the curve as much as possible and prepare for the release of the NDI guidance. Some ways to prepare could include:

• Think about what you’re doing differently now versus in 1994-both in terms of ingredient offerings and production processes.

• Prepare a list and supporting documentation proving that your ingredients were in fact on the market prior to 1994. This will help identify which ingredients should be grandfathered in.

• For ingredients for which information is not available confirming their presence on the market prior to 1994, ask your vendors to help you locate any relevant documentation.

• Identify evidence confirming the safety of new dietary ingredients. For those that seem questionable, consider expanding safety data or executing safety studies.

Complications Involved with ID Testing

A major problem in ID testing of botanical ingredients is that you can only test for what you know is there. So, when dealing with a new botanical, it is important to have a reference standard to compare to. These can be acquired through third-party labs. If they do not have reference standards on file, the next step may be to have the lab contact a local nursery to provide an authenticated plant to study; however, this can be an expensive process.

Once you have the correct reference standard to work with, you must also have a staff knowledgeable about botanical identification. While chemical ID tests may be fairly straightforward and easy to decipher, sometimes there is a need to interpret microscopic data, which requires more expertise. It is also imperative that the right identity tests be used, as different tests yield varying identity results. You must have the right combination of tests to ensure you are correctly identifying a botanical ingredient.

Also, the form and preparation of a botanical need to be considered in order to choose and interpret the identity tests correctly. For example, excipients or carriers can interfere with testing results unless you correctly account for them. Finally, adulterants can sometimes mimic the identity of a true ingredient, or contaminants can sneak into the product. A sophisticated lab will be aware of and prepared to identify these types of problems.

Best Testing Methods

It is best to implement comprehensive ID testing, as one test is usually not enough. For example, BI Nutraceuticals offers Identilok testing, which includes the following tests: Thin layer chromatography (TLC), Fourier transform infrared spectroscopy (FTIR), microscopic image analysis, organoleptic testing, and macroscopic taxonomy. Additionally, the following tests are completed as required: High-performance liquid chromatography (HPLC) and gas liquid chromatography (GC).

Interpretation of test results also requires consideration of the product form being tested. For example, powders provide a complete, naturally occurring matrix. Extracts, however, have been processed into a liquid or powder and then concentrated (leaving behind fibers, starches, or sugars), so you have changed the composition and are now looking for a different concentration of markers. Common markers will be there, but in greater intensity. As such, the reference standard would also be different. For example, with an extract you will no longer see the cell structure, so macroscopic and microscopic ID testing would no longer apply.

Liquid botanical products may also have solvents such as glycerin that can interfere with ID testing. If the solvent creates interference, it could overshadow the marker. The solution for this it to separate out this interference and understand how to test accordingly.