Active pharmaceutical contaminants in dietary supplements: A tier-based risk assessment approach

Regul Toxicol Pharmacol. 2021 Jul;123:104955. doi: 10.1016/j.yrtph.2021.104955. Epub 2021 May 19.


The presence of active pharmaceutical ingredients (APIs) in adulterated or contaminated dietary supplements is a current product safety concern. Since there are limited guidelines, and no published consensus methods, we developed a tier-based framework incorporating typical lines of evidence for determining the human health risk associated with APIs in dietary supplements. Specifically, the tiered approach outlines hazard identification and decision to test for APIs in products based on criteria for likelihood of contamination or adulteration, and evaluation of manufacturer production standards. For products with detectable levels of APIs, a variety of default approaches, including the use of fraction of the therapeutic dose and the threshold of toxicological concern (TTC), as well as health-based exposure limits (HBELs) are applied. In order to demonstrate its practical use, as well as any limitations and/or special considerations, this framework was applied to five dietary supplements (currently available to the public). We found that the detected levels of APIs in some dietary supplements were above the recommended dose of the drugs, and thus, pose a significant health risk to consumers and potentially workers involved in manufacturing of these supplements. The results support the value of increased product quality surveillance and perhaps regulatory activity.

Keywords: Active pharmaceutical ingredients (APIs); Dietary supplements; Framework; Human health; Nutraceuticals; Risk assessment.

MeSH terms

  • Dietary Supplements*
  • Drug Contamination*
  • Humans
  • Pharmaceutical Preparations
  • Quality Control
  • Risk Assessment
  • United States
  • United States Food and Drug Administration


  • Pharmaceutical Preparations