Few dietary supplements are consumed “naked.” Instead, nearly all dietary supplements are administered in a dosage form that includes inactive ingredients known as “excipients.” Excipients include binders, fillers, capsules and coating agents. At one time, it was thought that these excipients could include substances from the Center for Drug Evaluation and Research’s (CDER) Inactive Ingredient List, as well as: GRAS substances, those substances regulated as direct food additives, and prior sanctioned substances (21 CFR 181).
As per a recent contact with FDA, this appears to no longer be the case. That is, CDER inactive ingredients are no longer permitted in supplements. All excipients must be direct food additives, GRAS substances or prior sanctioned substances. Presumably, use of any GRAS substances not listed in 21 CFR 182 or 184 would require some sort of documentation as to the GRAS status of the excipient substance to be included in an NDIN submission. The same would be true for any supplement delivery system, even for those supplements marketed before October 15, 1994.
The same logic of approved food ingredients would prohibit the use of D&C (Drug and Cosmetic) colors (which are only approved for drug or cosmetic use), thereby requiring all colors used in dietary supplements to be FD&C (Food Drug & Cosmetic) colors.
The next obvious questions include: What does a manufacturer do if the amount of the GRAS or food additive substance to be used as an excipient exceeds the Acceptable Daily Intake (ADI)?
What does a manufacturer do if the aggregate consumption of the proposed excipient when consumed as a food ingredient and in a dietary supplement exceeds the ADI? Another perplexing question is: If the excipient is determined GRAS, what category of use (21 CFR 170.3 (n)) would be identified as the functionality of the ingredient and what food category (21 CFR 170.3(o)) can be used for excipients?
With these questions in mind, Burdock Group welcomes input from industry professionals about this changing landscape. Please send any feedback or questions via e-mail to email@example.com with “Dietary Supplement Excipients” in the subject line. As this topic unfolds, Burdock Group will keep the industry posted.