Approaches to assessing the environmental impact of pharmaceuticals (review)

Introduction. The pharmaceutical industry, while ensuring public health, simultaneously creates significant environmental risks. The article discusses modern approaches to assessing the impact of drugs on the environment in various regulatory systems. This impact is manifested through emissions of pollutants into the air, wastewater discharge, solid waste generation and consumption of significant volumes of natural resources as raw materials for chemical and biological substances. In addition, drugs and their metabolites enter the environment after use by patients. The problem of safe collection and disposal of drugs in civil circulation is also relevant. The complex of environmental problems associated with drugs is the focus of international organizations such as the Organization for Economic Co-operation and Development (OECD) or the United Nations Environment Programme (UNEP). Expert groups within their framework assess the situation with environmental pollution by drugs as threatening. The problem of drug pollution requires the use of an approach covering the entire life cycle of drugs – from development and registration to consumption and disposal. The focus should be on pollution prevention measures: developing "green" drugs, limiting the use of substances with high environmental risks, creating drug disposal programs, upgrading treatment facilities, and educational campaigns.

Text. The objective of this review is to conduct a comparative analysis of environmental risk assessment methods used in the European Union (EU), the United States, and Russia. The EU uses a two-stage assessment system (primary screening and detailed analysis) regulated by the European Medicines Agency (EMA). In the United States, the Food and Drug Administration (FDA) applies a categorical exclusion mechanism, which makes the system more flexible. The current environmental legislation in Russia regulates waste management and sets standards for the impact on the environment, while there is no comprehensive risk assessment of the life cycle of drugs.

Conclusion. The use of international experience, including the phased implementation of regulatory requirements for the assessment of environmental risks of drugs, can contribute to the development of a more sustainable pharmaceutical industry in Russia.

1. Sheldon R. A. E factors, green chemistry and catalysis: an odyssey. Chemical Communications. 2008;44(29):3352–3365. https://doi.org/10.1039/b803584a

2. Vestel J., Caldwell D.J., Tell J., Constantine L., Häner A., Hellstern J., Journel R., Ryan J. J., Swenson T., Xei W. Default predicted no-effect target concentrations for antibiotics in the absence of data for the protection against antibiotic resistance and environmental toxicity. Integrated Environmental Assessment and Management. 2022;18(4):863–867. https://doi.org/10.1002/ieam.4560

3. Hayes A., Murray L. M., Stanton I. C., Zhang L., Snape J., Gaze W. H., Murray A. K. Predicting selection for antimicrobial resistance in UK wastewater and aquatic environments: Ciprofloxacin poses a significant risk. Environment International. 2022;169:107488. https://doi.org/10.1016/j.envint.2022.107488

4. Wilkinson J. L., Boxall A. B. A., Kolpin D. W., Leung K. M. Y., Lai R. W. S., Galbán-Malagón C., Adell A. D., Mondon J., Metian M., Marchant R. A., Bouzas-Monroy A., Cuni-Sanchez A., Coors A., Carriquiriborde P., Rojo M., Gordon C., Cara M., Moermond M., Luarte T., Petrosyan V., Perikhanyan Y., Mahon C. S., McGurk C. J., Hofmann T., Kormoker T., Iniguez V., Guzman-Otazo J., Tavares J. L., Gildasio De Figueiredo F., Razzolini M. T. P., Dougnon V., Gbaguidi G., Traoré O., Blais J. M., Kimpe L. E., Wong M., Wong D., Ntchantcho R., Pizarro J., Ying G.-G., Chen C.-E., Páez M., Martínez-Lara J., Otamonga J.-P., Poté J., Ifo S. A, Wilson P., Echeverría-Sáenz S., Udikovic-Kolic N., Milakovic M., Fatta-Kassinos D., Ioannou-Ttofa L., Belušová V., Vymazal J., Cárdenas-Bustamante M., Kassa B. A., Garric J., Chaumot A., Gibba P., Kunchulia I., Seidensticker S., Lyberatos G., Halldórsson H. P., Melling M., Shashidhar T., Lamba M., Nastiti A., Supriatin A., Pourang N., Abedini A., Abdullah O., Gharbia S. S., Pilla F., Chefetz B., Topaz T., Yao K. M., Aubakirova B., Beisenova R., Olaka L., Mulu J. K., Chatanga P., Ntuli V., Blama N. T., Sherif S., Aris A. Z., Looi L. J., Niang M., Traore S. T., Oldenkamp R., Ogunbanwo O., Ashfaq M., Iqbal M., Abdeen Z., O’Dea A., Morales-Saldaña J. M., Custodio M., de la Cruz H., Navarrete I., Carvalho F., Gogra A. B., Koroma B. M., Cerkvenik-Flajs V., Gombač M., Thwala M., Choi K., Kang H., Ladu J. L. C, Rico A., Amerasinghe P., Sobek A., Horlitz G., Zenker A. K., King A. C., Jiang J.-J., Kariuki R., Tumbo M., Tezel U., Onay T. T., Lejju J. B., Vystavna Y., Vergeles Y., Heinzen H., Pérez-Parada A., Sims D. B., Figy M., Good D., Teta C. Pharmaceutical pollution of the world’s rivers. Proceedings of the National Academy of Sciences. 2022;119(8):e2113947119. https://doi.org/10.1073/pnas.2113947119

5. Hoang A. T. P., Do M. C., Kim K.-W. Environmental risk assessment of selected pharmaceuticals in hospital waste-water in northern Vietnam. Chemosphere. 2024;356:141973. https://doi.org/10.1016/j.chemosphere.2024.141973

6. Rapp-Wright H., Regan F., White B., Barron L. P. A year-long study of the occurrence and risk of over 140 contaminants of emerging concern in wastewater influent, effluent and receiving waters in the Republic of Ireland. Science of the Total Environment. 2023;860:160379. https://doi.org/10.1016/j.scitotenv.2022.160379

7. Riikonen S., Timonen J., Sikanen T. Environmental considerations along the life cycle of pharmaceuticals: Interview study on views regarding environmental challenges, concerns, strategies, and prospects within the pharmaceutical industry. European Journal of Pharmaceutical Science. 2024;196:106743. https://doi.org/10.1016/j.ejps.2024.106743

8. Moermond C. T. A., Puhlmann N., Brown A. R., Owen S. F., Ryan J., Snape J., Venhuis B. J., Kümmerer K. GREENER Pharmaceuticals for More Sustainable Healthcare. Environmental Science & Technology Letters. 2022;9(9):699–705. https://doi.org/10.1021/acs.estlett.2c00446

9. Calderia C. Abbate E. Moretti Chr. Mancini L. Sala S. Safe and sustainable chemicals and materials: a review of sustainability assessment frameworks. Green Chemistry. 2024;26(13):7456–7477. https://doi.org/10.1039/D3GC04598F

10. Leso V., Rydberg T., Halling M., Karakitsios S., Nikiforou F., Karakoltzidis A., Sarigiannis D. A., Iavicoli I. Safety and sustainability by design: An explorative survey on concepts’ knowledge and application. Environmental Science & Policy. 2024;162:103909. https://doi.org/10.1016/j.envsci.2024.103909

11. Fumagalli D. Environmental risk and market approval for human pharmaceuticals. Monash Bioethics Review. 2024;42(1);105–124. https://doi.org/10.1007/s40592-024-00195-1

12. Gildemeister D., Moermond C. T. A., Berg C., Bergstrom U., Bielská L., Evandri M. G., Franceschin M., Kolar B., Montforts M. H. M. M., Vaculik C. Improving the regulatory environmental risk assessment of human pharmaceuticals: Required changes in the new legislation. Regulatory Toxicology and Pharmacology. 2023;142:105437. https://doi.org/10.1016/j.yrtph.2023.105437

13. Harrison S., Barnett C., Short S., Uluseker C., Silva P. V., Pavlaki M. D., Roberts S., Vieira M., Lofts S., Loureiro S., Spurgeon D. J. Continuous improvement towards environmental protection for pharmaceuticals: advancing a strategy for Europe. Environmental Sciences Europe. 2025;37(1):128. https://doi.org/10.1186/s12302-025-01180-z

14. Zinken J. F., Pasmooij A. M. G., Ederveen A. G. H., Hoekman J., Bloem L. T. Environmental risk assessment in the EU regulation of medicines for human use: an analysis of stakeholder perspectives on its current and future role. Drug Discovery Today. 2024;29(12):104213. https://doi.org/10.1016/j.drudis.2024.104213

15. Oldenkamp R., Hamers T., Wilkinson J., Slootweg J., Posthuma L. Regulatory Risk Assessment of Pharmaceuticals in the Environment: Current Practice and Future Priorities. Environmental Toxicology and Chemistry. 2024;43(3):611–622. https://doi.org/10.1002/etc.5535

16. Ahkola H., Äystö L., Sikanen T., Riikonen S., Pihlaja T., Kauppi S. Current uncertainties and challenges of publicly available pharmaceutical environmental risk assessment data. European Journal of Pharmaceutical Sciences. 2024;197:106769. https://doi.org/10.1016/j.ejps.2024.106769

17. Welch S. A., Grung M., Madsen A. L., Moe S. J. Development of a probabilistic risk model for pharmaceuticals in the environment under population and wastewater treatment scenarios. Integrated Environmental Assessment and Management. 2024;20(5):1715–1735. https://doi.org/10.1002/ieam.4939

18. Cannata C., Backhaus T., Bramke I., Caraman M., Lombardo A., Whomsley R., Moermond C. T. A., Ragas A. M. J. Prioritisation of data-poor pharmaceuticals for empirical testing and environmental risk assessment. Environment International. 2024;183:108379. https://doi.org/10.1016/j.envint.2023.108379

19. Ceger P., Garcia-Reyero Vinas N., Allen D., Arnold E., Bloom R., Brennan J. C., Clarke C., Eisenreich K., Fay K., Hamm J., Henry P. F. P., Horak K., Hunter W., Judkins D., Klein P., Kleinstreuer N., Koehrn K., LaLone C. A., Laurenson J. P., Leet J. K., Lowit A., Lynn S. G., Norberg-King T., Perkins E. J., Petersen E. J., Rattner B. A., Sprankle C. S., Steeger T., Warren J. E., Winfield S., Odenkirchen E. Current ecotoxicity testing needs among selected U.S. federal agencies. Regulatory Toxicology and Pharmacology. 2022;133:105195. https://doi.org/10.1016/j.yrtph.2022.105195

20. Van Wilder L., Boone L., Ragas A., Moermond C., Pieters L., Rechlin A., Vidaurre R., De Smedt D., Dewulf J. A holistic framework for integrated sustainability assessment of pharmaceuticals. Journal of Cleaner Production. 2024;467:142978. https://doi.org/10.1016/j.jclepro.2024.142978