Pan-European insights on pharmaceutical use and removal patterns based on wastewater analysis for more than 400 compounds.

Pharmaceuticals and their human metabolites are widely detected in municipal wastewater, serving as indicators of both population-level use and wastewater treatment performance. Within the PARC project, a coordinated pan-European wastewater monitoring campaign was conducted at 30 wastewater treatment plants (WWTPs) in 15 countries, integrating multi-laboratory targeted analysis of >400 pharmaceuticals and metabolites, covering a broad range of relevant compounds. Influent pharmaceutical load profiles indicate that regional prescribing practices contribute substantially to pharmaceutical patterns in municipal wastewater, whereas seasonal variability contributes only modestly, and sewer catchment size has little influence. These patterns were driven by complex mixtures of pharmaceuticals across multiple therapeutic classes rather than individual compounds. Comparison with national prescription statistics highlighted substantial limitations in the comparability of pharmaceutical use data across Europe, underscoring the value of wastewater-based epidemiology as an independent and complementary data source. Case studies demonstrated the interpretative power of wastewater data: Sacubitrilat was detected in all 30 WWTPs, enabling the first quantitative pan-European assessment of its increasing use and widespread occurrence across 15 countries, including its loads and removal. In contrast, sartan profiles varied markedly between countries, reflecting national prescribing preferences and demonstrating that indicators based solely on defined daily doses can misrepresent environmental relevance. For the sartan case study, wastewater-derived consumption estimates based on the summed loads of seven sartans agreed well with reported national statistics, generally within a factor of three across the investigated countries despite uncertainties inherent to wastewater-based back-calculation. Across treatment technologies, mean pharmaceutical removal efficiencies were comparable (41-53%). However, pronounced variability among WWTPs suggests that treatment performance may be influenced by site-specific operational factors (e.g., process configuration, hydraulic retention time, and sludge age), although these effects could not be robustly disentangled from differences in treatment technology and other site-level characteristics in the present dataset. Overall, this study represents one of the largest multi-compound and multi-country wastewater monitoring efforts to date and demonstrates that harmonized wastewater monitoring can provide reliable, actionable insights into pharmaceutical use and fate across Europe, supporting both epidemiological surveillance and identifying pharmaceuticals that may warrant further environmental risk assessment.