Former FDA inspector offers insight into identity testing procedures

AHPA:​  What responsibilities do manufacturers have when it comes to verifying the identity of ingredients?

TC:​ For dietary ingredients, the manufacturer has the responsibility to verify the identity of any dietary ingredient by at least one appropriate test or examination per 21 CFR 111.75 (a)(1). In some cases, a single test or examination may be all that is required, but other cases may require conducting more than one test or examination.

For non-dietary ingredients (i.e. components), the manufacturer has the responsibility to conduct appropriate test or examination or rely on a Certificate of Analysis (C of A) from the supplier per 21 CFR 111.75 (a)(2) contingent on the following:

• The manufacturer establishes the reliability of the C of A through confirmation testing
• The C of A include description of test or examination methods used, limits of test/examination, and actual results of test/examination
• The manufacturer qualifies the supplier with documentation of how the supplier was audited/qualified. Quality control personnel reviews and approves the documentation noting the basis for qualification or re-qualification of the supplier
• Periodically reconfirming the supplier’s C of A

AHPA:​ Are there any identification verification responsibilities that are specific to botanicals?

TC:​ Manufacturers are 100% responsible for the identification of the botanical ingredients using scientifically valid methods for authentication. The manufacturer also has to ensure that valid method is appropriate for the intended purposes (i.e. whole herb versus powder).  The manufacturer should exercise due diligence to know their suppliers and the supply chain to help determine appropriate confirmation testing of the botanical ingredient. A verified botanical reference standard (e.g. American Herbal Pharmacopoeia) is also critical in the identification verification process.

In the case of individual botanicals not in whole form (e.g., powder or extract), confirming the botanical identity can be a challenge. It becomes even more difficult with botanical blends in a dietary supplement. Distinguishing key marker compounds can be almost impossible if ingredients contain the same marker from closely related species. In extracts, small trace amounts can also be hard to detect. Manufacturers should focus on identifying the blend as a whole rather than each ingredient once it is a blended finished product.

AHPA:​ What are some of the strengths and weaknesses of the current technologies available to help verify the identity of ingredients?

TC:​ Chemical and molecular methods (e.g. HPLC) can provide good “indicators” of identity if known conditions (e.g. marker compounds) are            met. Results are fairly rapid due to automation capabilities and sensitivity to some known marker compounds. However, these methods often exhibit limitations when attempting to differentiate closely related species which becomes an issue when a finished product blends two or more closely related botanical ingredients; dirt and/or insects are present; or when trying to distinguish different plant parts that share similar composition.

Macroscopic and organoleptic examinations are among the most useful and appropriate tests because the unique identifying features of the botanical ingredients (whole plant parts) are intact and readily distinguishable.

AHPA:​ Are certain tests more effective for verifying the identity of ingredients in different forms -- whole vs. powder vs. extract?

TC:​ Yes, certain technologies are more useful depending on the form of the ingredient. For example:

• TLC/HPTLC are good for identifying botanical ingredients in a single test run versus high-performance liquid chromatography (HPLC). This is also an appropriate test of botanical extracts (via constituents).
• Macroscopic exams are very good in identifying botanical ingredients in whole parts/plant parts (stems, leaves, roots etc.) because you distinguish the “true” identity of an ingredient. Once botanicals are highly processed (powders, extracts etc.), it can becomevery difficult or impossible using this method to verify identity.
• Microscopic exams are good for highly refined materials identification testing and common botanical ingredients in powered form. They are not appropriate to identify botanical extracts.
• FTIR/NIR are good for highly refined materials, but not appropriate for botanicals. These are often inappropriately used as a “one size fits all” instrument.
• HPLC/GC/Spectrophotometer can be used for detecting different key marker compounds, but is limited if the different ingredients contain the same marker or markers are widely distributed in nature as is the case in botanicals. These canalsobe used for verifying the identity of fish oils in finished products.
• Organoleptic can be a very good identification test if an experienced/ trained individual is involved (e.g. botanist) but should not be used as a stand-alone test. This approach has limitations associated with visual examination confirmation for powdered and processed botanical ingredients
• ICP, ICP-MS is good for heavy metal detection and mineral detection.

AHPA:​ Given all the technology available, is there still a role for organoleptic analysis?

TC​: Yes, organoleptic analysis is still very effective in identifying whole form plant (root, stems, leaves, fruit etc.) by trained individual (e.g. botanist) who can recognize the ingredient (e.g. goldenseal) and its common adulterants. It can also be a good indicator something is wrong with the ingredient per expected sensory evaluation (e.g. smell) for processed ingredients and/or finished product. There are differentiation limitations associated with chemical and molecular methods in regardsto identification verification which would make the organoleptic evaluationbemore of an appropriate choice but, it should be used in conjunction with chemical/molecular methods.