Compendial Monographs Enhance Supplement Safety

Adherence to a strong compendial monograph, developed and “approved” by appropriate stakeholders and accepted by manufacturers and regulators, could complement and complete the cGMPs (current good manufacturing practices) promulgated for dietary supplements. Components of a compendial monograph include analytic testing methodology, acceptance criteria, allied reference materials and standards. The use of ingredients that have been characterized and standardized against these monographs, and signaled on the label or in the attendant literature, bring assurances to the consuming public that known ingredients are being used and define the degree of risk/benefit the individual may wish to assume.

One model that may be appropriate to decrease the potential risk from uncharacterized and unspecified dietary supplements and dietary supplement ingredients would be the U.S. Pharmacopeial Commission (USPC) compendia’s approach to pharmaceutical ingredients, both active drug moieties and excipients. For dietary supplements, there has been a section within the United States Pharmacopeia (USP), but it has been neither complete nor widely utilized by this industry segment. In 2008, USPC is creating a separate compendium for dietary supplements cloned from the USP that not only contains the detailed ingredient monographs, but also the general chapters providing test methods, acceptance criteria, reference standards and relevant information to assist the formulator and manufacturer. USPC also provides two additional compendia with relevant monographs for some dietary supplement components. One of these is the National Formulary (NF), a book of excipient monographs; the other is the Food Chemicals Codex (FCC), a compendium of specifications for food ingredients.

FDA’s new dietary supplement cGMPs allude to components, which include the dietary supplement itself as well as other ingredients that enter into the finished dietary supplement. Taken together, these standards support the overall quality of the finished dietary supplement, which must have an identity, relative to a customary or usual name, as well as specifications for purity, strength and composition, with limits on contaminants, all translating into safety.

Unfortunately, FDA’s dietary supplement cGMPs call for standards without standardization. This is particularly problematic for botanicals. Individual specifications, including identity, are established by each manufacturer. The customary or usual name of the dietary supplement is not necessarily consistent across manufacturers, regarding plant part, plant extractive and even the plant identifying binomial. In contrast, USP’s standards for identity, purity and strength of a dietary supplement ingredient, with limits on contaminants, are exquisitely detailed. USP monographs for botanicals also provide requirements for a broad range of contaminants including those arising from microbes, heavy metals, organic volatile impurities and pesticides.

The dietary supplements cGMPs dance around the term “specifications,” without ever really defining what is meant by that word. Both USP-NF and the FCC define ingredient specifications in terms of Description, Requirements and Tests. USPC is advancing the USP-NF, including its dietary supplements section, toward the ICH1 definition of specifications, which include four universal tests—Identification, Description, Assay and Impurities. Specifications for components in the dietary supplement cGMPs leave it to the manufacturer to define appropriate specifications for components other than the dietary supplement ingredient itself.

The Dietary Supplement Health & Education Act (DSHEA) created a new class of foods. This is less problematic for vitamins and minerals, but more so for botanicals other countries typically handle as traditional medicines. Issues of quality-versus-benefit have been the subject of much controversy. A particular point of debate has been the task of developing sound benefit and risk information for herbal dietary supplements, absent standards that would lead to a consistent product suitable for clinical investigation. FDA’s new cGMPs advance standardization of dietary supplement manufacturing in positive ways. Yet these standards, for the most part, are privately developed and separate from an approval process and are agreed to by inspectors working with manufacturers.

A key hope for USPC’s dietary supplement product standards might lie in the fact they provide a clear cut mechanism for dietary supplement manufacturers to meet many of the component and finish dietary supplement “specifications” stipulations described in the FDA cGMPs. 

James C. Griffiths is the vice president of food and dietary supplement standards, and Darrell R. Abernethy is the chief science officer with the U.S. Pharmacopeia (USP). Contact the authors at (301) 998-6811 or online at www.USP.org.