Pharmacology and Toxicology Concerns of Impurities

Abstract

Botanical drugs are complex mixtures of natural constituents with potential for product impurities that could impact the efficacy or safety profile of the finished product. Botanical health products are regulated under diverse national and international regulations which identify these natural substances as botanical drugs, medicinal foods, or dietary supplement ingredients. Regulatory agencies take consideration of historical and intended use to set expectations for characterization of the botanical material, including quality, safety, and efficacy. For conventional drugs, specific regulatory guidelines from the FDA, ICH, and other global regulatory bodies exist for all aspects of development, such as sourcing, formulation, stability, impurity characterization, and overall product usage guidelines. Many of these guidances pertain to botanical drugs except for impurities, where a similar level of guidance does not exist, relying instead on adherence to Good Manufacturing Practices (GMPs). Botanical drug impurities have the potential for significant impact on the safety or efficacy of the finished product. Adequate analytical characterization, quantitation of potential exposure to sensitive population(s), and a thorough safety evaluation of the impurities are necessary. With many botanical drugs and dietary supplements being developed and marketed, application of guidelines pertaining to drug impurities in combination with Good Agricultural Practices and GMPs will ensure efficacious and safe botanical products. With the unique complexities of sourcing, harvesting, extraction, and formulation of botanical drugs, the risk of contamination and impurities has increased, and development of botanical pharmacopeia monographs is a critical area for better ensuring safe and efficacious botanical drugs.