Comparison of regulatory frameworks of environmental risk assessments for human pharmaceuticals in EU, USA, and Canada

Highlights: • Current ERA procedures for human pharmaceuticals worldwide were compared. • EU and USA assess the products, while Canada assesses the substances. • Lack of ERA on existing drugs or those already in DSL may cause environmental risk. • ERA system incorporating total pollution load and based on a substance is warranted. • Implementing mitigation measure based on ERA is warranted. -- Abstract: With the growth of the aging population and increasing prevalence of chronic diseases, more medicinal products are expected to be used in growing amount. Consequently, numerous pharmaceutical residues have been detected in aquatic environments worldwide. Because of the potential impacts of pharmaceutical residues on the ecosystem, ensuring the environmental safety of the pharmaceutical products before marketing is warranted. Several countries have implemented environmental risk assessment (ERA) procedures for the regulation of human pharmaceuticals. The purpose of the present study is to compare existing ERA procedures for human pharmaceuticals and to highlight their strengths and limitations. Currently, the EU, the USA, and Canada operate the ERA for human pharmaceuticals. Legislation, guidelines, and directives related to these ERA frameworks were gathered and analyzed. A major difference among the current ERA systems is that the EU and the USA assess the products, while Canada assesses the substances. A major limitation of the current systems lies in the lack of consideration for existing products or substances that lead to significant underestimation of their risks. In addition, even when ecological risk is expected, any examples that banned the marketing of the pharmaceutical are not available. Existing ERA systems for human pharmaceuticals have played significant roles in enhancing environmental awareness of the pharmaceutical industries and in protecting environmental health. However, to better serve the intended purposes, the current systems have rooms to improve. 1) To perform ERA at the active ingredient level rather than at the product level, 2) to establish a system for evaluating the environmental risks of existing drugs, 3) to consider the total amount of discharge of a given ingredient, and 4) to develop effective risk mitigation measures are among those identified areas. These suggestions can be helpful for countries which consider the development of ERA systems for human pharmaceuticals.