EMA: Discussions on the Revised ERA Guideline

During the second industry stakeholder webinar on the revised guideline on environmental risk assessment (ERA) for medicinal products for human use, the European Medicines Agency (EMA) addressed key implementation challenges observed during the first year of application. The discussions focused on data sharing, literature review practices, exposure assessment and methodological as well as technical requirements for ERA dossiers, with the aim of clarifying regulatory expectations.

The EMA made recommendations to the following issues:

Data sharing and generic applications
Each application must include a complete and standalone ERA. Existing ERAs may be referenced even without a formal data-sharing agreement, provided it is scientifically justified that their conclusions remain applicable. Additional studies are required if existing ERAs are incomplete or not compliant with the revised guideline.

Literature review
Literature data may be used only if quality, relevance and reliability are demonstrated. The literature search strategy must be transparently documented. No additional EMA guidance on literature review is currently foreseen.

Use of sales and consumption data
Sales, monitoring or consumption data may no longer be used to refine exposure estimates. In Phase I, a 100% market share must always be assumed. Exposure refinements are acceptable only in Phase II, for example via wastewater treatment modelling.

Technical and methodological clarifications
Effect concentrations corresponding to a 10% effect level (Effective Concentration 10%, EC10) are generally preferred when scientifically robust. For ionisable substances, experimental determination of the octanol/water partition coefficient (logarithmic octanol/water partition coefficient, log Kow) is recommended. For new ERAs, an OECD 106 adsorption study up to Tier 3 is required, while previously accepted studies remain valid.

Tailored testing strategies and the 3R principle
Tailored testing strategies aimed at replacement, reduction and refinement of animal testing (3R principle: Replace, Reduce, Refine) may be applied where scientifically justified, but must fully comply with regulatory requirements.

Source:

EMA: Industry stakeholder webinar on revised environmental risk assessment guideline for medicinal products for human use - 1 year experience