How to Prepare a Submission-Ready Environmental Risk Assessment (ERA)

The  Environmental Risk Assessment (ERA) should be planned as part of the overall CMC development strategy, not left to the end of dossier preparation. Early involvement allows Regulatory Affairs, CMC, and Non-clinical teams to align on data requirements, responsibilities, and timelines. Integrating the ERA process from the beginning ensures consistency between quality documentation, impurity data, and environmental exposure assessments — helping to avoid delays and data gaps later in development.

The 2024 EMA guideline revision places strong emphasis on transparency in data collection and evaluation. Applicants are expected to clearly describe how information was sourced, screened, and selected. A robust ERA typically combines data from literature reviews, validated databases such as ECHA, OECD eChemPortal, or PubChem, and internal study reports.

Documenting search strategies, databases, and keywords used — as well as the rationale for excluding or replacing data — is essential. When information is missing, data gaps must be identified and justified scientifically.

The ERA follows a tiered approach. Phase I involves calculating the predicted environmental concentration (PEC) to determine whether it exceeds the 0.01 µg/L trigger threshold. If it does, Phase II testing is required. The extent of this testing — standard or tailored — depends on the substance’s use, metabolism, and persistence.

Regulators value clarity and traceability in how these decisions are documented. Well-structured PEC/PNEC summaries and concise rationale statements are preferred over lengthy, unorganized datasets.

The final ERA should be presented as a structured, standalone document within CTD Module 1.6, with cross-references to other modules where relevant. It must include an executive summary, methodology, data sources, results, and justification for any assumptions made. Where applicable, environmental risk statements should also be reflected in the SmPC or product labeling.

Proper report formatting and consistent terminology make it easier for reviewers to assess and validate the conclusions.

Typical issues in ERA submissions include incomplete data documentation, inconsistent search methods, unnecessary experimental testing, and lack of justification for not advancing to Phase II. Using predefined templates, checklists, and quality reviews helps maintain alignment with regulatory expectations and ensures that all required elements are addressed.

Practical, well-documented reasoning often leads to faster approvals and fewer regulatory queries.