February 6, 2026 by Olivia Tran

The European Medicines Agency (EMA) held a webinar on the revised guideline for the environmental risk assessment (ERA) of human pharmaceuticals in October 2025, and a summary of the webinar has just been published. Representatives from EMA and members of the ERA guideline drafting group responded to a list of 20 questions submitted by European pharmaceutical industry trade associations representing innovator and generics companies.

Olivia Tran and Richard Maunder from wca attended the webinar. While EMA were able to provide responses to a number of questions during the webinar, the summary contains greater clarification on some topics and additional ERA guidance that has been developed after the webinar. We have pulled out a couple interesting discussion points from the summary:

1. Data access – EMA suggested that Applicants may submit a request to EMA for access to documents under Policy 43. EMA may be able to provide documents containing environmental information, but a Letter of Access is still required from the data owner to reference the data in the ERA. A justification should be included if data-sharing is not agreed.
2. Publicly available data – EMA suggested a couple of information sources that can inform on the availability of data, all of which are checked in wca’s established procedure for pharmaceutical literature searches. However, the data in some sources (e.g., ECHA CHEM portal, FASS and PREMIER databases) may not be accepted if they have not been previously reviewed by a regulator, which means that the study report should be submitted along with a Letter of Access, or the Applicant will need to conduct new testing.
3. EQS dossiers – Some pharmaceuticals have been assessed under the Water Framework Directive (WFD) and environmental quality standards (EQS) for surface water have been derived. EMA suggests that this information can be used in an ERA, e.g., surface water EQS may be used as PNECs. In this case, we would still recommend reviewing the data in the EQS to assess its suitability for use in the pharmaceutical ERA to meet EMA’s revised guidelines.
4. Post-approval commitments – If the ERA is not complete at the time of submission, the Applicant should proactively outline a strategy to fill data gaps (e.g., conducting new testing) as part of a post-approval commitment. Sufficient justification is required, otherwise these applications will be rejected.
5. Refinement of the market penetration factor (Fpen) – EMA reiterated that Fpen refinements based on sales, prescription or monitoring data are no longer possible as they do not account for competitor products and environmental exposure may be underestimated if there is some lag time between market availability and uptake. The Fpen can only be refined based on prevalence and treatment regimen, which gives a realistic worst-case environmental exposure.
6. Ionisable substances – EMA recommends that the octanol-water partitioning coefficient (log Kow) should also be determined at a pH level where the molecule is in its neutral state, even if this is outside the environmentally relevant pH range of 5 to 9. This is a new recommendation that is not alluded to in the revised 2024 guideline. EMA also provide a formula to calculate the log Kow based on the octanol-water distribution coefficient (log Dow) for monoprotic bases; the revised guideline contains only a formula for monoprotic acids.
7. Bioconcentration testing – EMA suggests that OECD 321 (Hyalella azteca bioconcentration test) may be considered as an alternative to testing in fish (OECD 305). However, OECD 305 may still be required if there are any uncertainties in the aquatic bioaccumulation potential. wca works with a network of testing laboratories to ensure:
   • Selection of the most competent laboratory for testing,
   • Appropriate study design for the specific substance (considering any substance properties that may impact the testing outcomes and study reliability, e.g., ionisation, solubility, surface activity),
   • Comprehensive study monitoring to quickly resolve any issues during the experimental phase, and
   • Adequate reporting of all the relevant information to support the study’s reliability.

OECD 321 is a new study which will require careful execution so that the experimental design and results are robust and reliable. Bioaccumulation testing is also relatively costly, so it would be best to avoid the need to repeat the study or conduct further testing in fish.

8. Secondary poisoning via the terrestrial food chain – EMA gives further guidance on calculation of the predicted environmental concentration in porewater and soil and recommends bioaccumulation testing in earthworm following OECD 317. These aspects were not included in the 2024 revised guidance or ERA guidance for veterinary medicines, which the 2024 revised guidance refers to on this topic. Secondary poisoning assessment via the terrestrial food chain is only triggered if a risk to soil is identified, which we rarely see for human pharmaceuticals.
9. Adsorption data – For new ERAs, an OECD 106 study must be conducted with two sludges and three soils, but an evaluation of desorption is not required. If adsorption data from an OECD 121 study are available for a previously accepted ERA, this may only be used to assess the soil trigger and not for calculations of predicted environmental concentrations (PEC).
10. Testing for endocrine active substances (EAS) – The choice of testing depends on the endocrine modality of the substance (oestrogen, androgen, steroidogenesis or thyroid). It may be possible to justify testing (or no testing) depending on screening-level data and mode of action. If testing is required, we would recommend seeking scientific advice from the regulators to agree the experimental design and endpoints. wca are highly experienced in endocrine assessments, with some of our staff having direct lab-based experience in endocrine testing in fish and amphibians.

The webinar and summary give clarity in how Applicants can prepare an ERA to meet EMA’s revised guideline, as well as helpful background to understand the thinking behind some aspects of the guidance. The additional guidance is much appreciated, although it does give Applicants more “food for thought”. We highly recommend taking a proactive approach to completing the ERA to allow sufficient time for literature searches, data gap analysis and assessment of costs if testing is required, which may determine the viability of a new application for marketing authorisation.

If you would like any support in preparing an ERA, literature searches, study monitoring or responding to assessor comments, please get in touch.

Image Credit: iStock.com/kutberk.