Pharmaceuticals in the environment

Environmental risk assessment

To assess the environmental risks of medicinal products, an Environmental Risk Assessment (ERA) is performed (Maack, 2019). This can be done at the time market authorisation is being sought, or when pharmaceutical residues are actually detected in the environment. For the latter, regulations such the EU Water Framework Directive is used (Verdonschot, 2019).

For market authorisation, in Europe the European Medicines Agency (EMA) requires the submission of an ERA that needs to be performed according to formal guidelines (EMA, 2024). The ERA contains both a risk assessment and a hazard assessment for a product. Many ERAs and the data submitted to regulatory agencies are in the public domain and can also be found by searching the websites of the respective regulatory agencies. As stated in the aforementioned guideline:

The PBT terminology is further explained in the following section.

General principles of risk assessment

Chemical risk assessment is typically organised into stages, which may vary depending on the regulatory context. Here, we distinguish four steps (Ragas, 2019):

Environmental risk assessment for pharmaceuticals

For a regulatory ERA, the assessment procedure involves two phases. In Phase I, an exposure estimate is made based on the predicted use of the product. If the calculated Predicted Environmental Concentration (PEC) of the API in the environment (water) is below the trigger value of 0.01 µg/L (EMA, 2024), it is assumed that there will be no risk and no further assessment is necessary (with some exceptions). In Phase II, a full environmental risk assessment is performed, including tests to determine fate and degradation of the API and its ecotoxicity. The PEC may then be refined based on actual use data and metabolism in the patient.

An important aspect of exposure assessment is the determination of an exposure scenario. An exposure scenario describes the combination of circumstances needed to estimate exposure by means of models. Exposure scenarios are often conservative, meaning that the resulting exposure estimate will be higher than the expected average exposure, leading to a worst-case risk estimate. In a non-regulatory ERA, the exposure assessment may also be based on a Measured Environmental Concentration (MEC). 

For the effects assessment, the results of the ecotoxicity studies are needed. For regulatory purposes, studies must be provided for at least three trophic levels (foodchain levels): algae, daphnia (water fleas) and fish. If other relevant and reliable information is available, e.g., in public literature, this should also be taken into account. The lowest, most critical, ecotoxicity result is combined with an assessment factor to obtain a Predicted No Effect Concentration (PNEC). 

Finally, the risk characterisation is based on a comparison of the PEC (or MEC) and the PNEC. When the PEC exceeds the PNEC, a potential risk is indicated.