European Medicines Agency provides Clarity on the Updated Guidelines for Environmental Risk Assessment of Human Pharmaceuticals
Towards the end of 2025 the European Medicines Agency (EMA) held a webinar to discuss the revised environmental risk assessment guidelines with stakeholders after 1 years’ experience with the new guidelines. The notes from this meeting were recently published1 and provide clarity on some aspects of the revised guidelines. A summary of the main topics discussed is presented below. Over the coming months these topics will be further explored in additional posts, with the interpretation and impacts of the updated EMA guidelines and the clarification provided in the EMA webinar notes being discussed.
Procedural Topics
- Data sharing is strongly encouraged but lacks specific legal incentives. For generics where an earlier satisfactory ERA exists, repeating ERA studies is generally unnecessary even when data sharing cannot be agreed.
- European Public Assessment Reports (EPARs) cannot replace underlying study data; other databases may inform but are not regulatory substitutes. Some data from European Environmental Quality Standard (EQS) dossiers can be directly used in the risk assessment.
- Applicants relying on third-party data must provide accurate letters of access, and the EMA emphasises the importance of complete, justified ERAs at submission.
- Literature searches should be thorough, using relevant search terms and quality standards; industry suggested guidance documents for standardisation, though EMA currently sees no need for formal guidance.
Technical & Methodological Topics
- Use of sales or consumption data for PEC refinement is no longer permitted.
- EC10 values are preferred over NOECs.
- For ionizable substances, log Kow can be estimated from log Dow at relevant pH, but experimentally determined log Kow of the neutral molecule is more reliable. The Applicant was advised to determine the log Kow of the neutral molecule even if this requires testing a pH outside the environmentally relevant range of pH 5 - 9.
- The OECD 321 (invertebrate BCF testing) was highlighted as a potential alternative to the fish bioconcentration test (OECD 305) to reduce vertebrate testing.
- Some technical assumptions were clarified for terrestrial food chain risks, such as equivalence of certain exposure metrics.
- For adsorption data the studies should be performed up to Tier 3 of the OECD 106 guidelines (i.e. generation of KF and KFOC values) in three soils and two sludges. Desorption testing is no longer required. Old studies with only Tier 2 data and/or fewer substrates tested are still acceptable in the context of the previously accepted ERA.
Tailored Testing Strategies
- For endocrine active substances (EAS), a tailored testing approach can avoid full lifecycle fish tests if screening assays (OECD 229/230) are negative or if molecular mechanism data (e.g., receptor binding) demonstrate no endocrine activity.
- The approach emphasises mechanistic understanding, with in vitro assays used for initial screening, especially for estrogenic or androgenic activity, and in vivo tests reserved for confirmation.
- For EAS substances it is possible to waive the OECD 209 and OECD 201 tests based on the justification that microorganisms generally do not have the biomolecular targets associated with an EAS mode of action (e.g. steroid receptor proteins).
Overall, the webinar clarified procedural expectations, methodological standards, and ongoing developments to optimise environmental risk assessments, emphasising data integrity, scientific justification, and efforts to reduce animal testing. It has raised some interesting scientific and regulatory issues which warrant further explanation and will be discussed in future blog posts.
If you'd like to discuss any specific queries relating to environmental risk assessment of human pharmaceuticals, call or email and speak directly with one of our specialist regulatory consultants pharma ERA expertise.
