In June 2006, the CHMP adopted the European Medicine Agency guideline on environmental risk assessment of medicinal products for human use evaluation guideline (EMEA/CHMP/SWP/4447/00). The latest version of the guidance incorporates the questions and answers published in 2011 and 2016 (EMA/CHMP/SWP/44609/2010 and Rev. 1), changes some of the triggers, and provides greater detail. The draft was published in November 2018, with a review period ending in June 2019.
Although still utilizing a tiered approach, the revised guidance includes changes that remove the need to conduct ERAs for non-natural peptides/proteins that are ready biodegradable, but does now require an assessment for generic drugs for which no ERA exists that covers exposure following from the intended application for authorization. Furthermore, all testing has been moved to Phase II Tier A, with Tier B focusing on refining exposure calculations. Due to changed triggers, soil testing is expected to be needed in more cases. Finally, the bioconcentration study may now trigger the need for an assessment of secondary poisoning.
PBT assessments are still considered in Phase 1, but the trigger for testing has been slightly altered and, to address concerns for ionizable substances, pH ranges are required both in the PBT and bioaccumulation assessments. Endocrine activity (less focus on action limit and more on mode of action) and antibiotics are now addressed with specifically tailored assessment and testing strategies. Sediment organism toxicity is now also assessed much earlier in the process and is needed without first conducting a degradation study in aquatic sediment systems.
Our white paper covers the many changes proposed in the draft guidance and the results of a comparison study conducted by Charles River, which assesses the potential impact these changes would have on those substances assessed under both the old and new ERA guidance criteria.