The 2024 revision of the EMA guideline on the environmental risk assessment (ERA) of human medicinal products (EMA, 2024)[1] replaces practice-based approaches with a clear, harmonised methodology. It retains the tiered approach introduced in 2006, clarifies how it operates, and—above all—aligns it with ECHA’s proven methodological framework, notably the REACH Regulation (EC) No 1907/2006 and the Biocidal Products Regulation (EU) No 528/2012.
The ERA applies to active substances, and to their metabolites and environmental transformation products where these contribute to exposure or hazard. Excipients fall outside the scope of the guideline.
The life-cycle stage covered begins after administration to the patient, following the down-the-drain pathway (excretion → sewer → sewage treatment plant), then the receiving environmental compartments: surface waters with possible transfer to sediments, soils via sludge application, and into biota through bioaccumulation/biomagnification.
Two assessment phases
Phase I is a screening step based on calculating a PEC (Predicted Environmental Concentration) for surface water. This PEC is compared with the 0.01 μg/L threshold to decide whether to proceed to Phase II. Note that for certain substance classes (endocrine-active substances, antibacterials, antiparasitics) Phase II is required regardless of the PEC.
Phase II offers opportunities to refine the ecotoxicological profile of the substance. It relies on generating and assessing data on (i) environmental fate and behaviour; (ii) chronic ecotoxicity to reduce uncertainty in PNEC (Predicted No-Effect Concentration) derivation for relevant compartments; and (iii) release estimates resulting from patient use. Risk is characterised for each relevant compartment via a Risk Quotient (RQ = PEC / PNEC):
- If RQ < 1, the risk is acceptable.
- If RQ ≥ 1, the risk is not controlled; further refinements and/or risk-management measures are required to ensure RQ < 1 across all relevant compartments.
In parallel, EMA (2024) details the assessment of PBT/vPvB potential, aligned with REACH methodology and criteria.
Beyond the technicalities, the revision shows how EU chemicals regulations interact. By integrating ECHA tools and methods, the EMA strengthens coherence, reduces methodological uncertainty, and avoids unnecessary, costly duplication. It also turns marketing authorisation holders (MAHs) into producers of robust, shareable data (studies, modelling, PBT assessments) that can be useful under other regulatory frameworks such as REACH.
The EMA 2024 revision sits within a broader wave of regulatory reform in Europe. As highlighted by Harrison et al. (July 2025, Environmental Sciences Europe)[2], forthcoming pharmaceutical regulation is expected to go further: potential refusal of a marketing authorisation on environmental grounds, obligations to assess legacy medicines, and greater transparency via open data. The signal is clear: the environment is becoming a central and durable criterion in medicines regulation.
A clear roadmap for industry:
- Anticipate in R&D signals of persistence, bioaccumulation and modes of action with concern;
- document Phase I and, where needed, build a robust, targeted Phase II;
- convert conclusions into communicable risk-management measures; and,
- reassess when use changes.
The required skill set mirrors this convergence: ecotoxicology, environmental chemistry and fate/kinetics, exposure modelling, and PBT/vPvB expertise.
EQUITOX can support you with the ERA for human medicines under the EMA’s 2024 guideline.
More information: contact@equitox.eu