ERA for human medicinal products under the revised EMA guideline and FDA NEPA framework — Phase I and Phase II assessment, metabolite handling, EAT-active substances, and CTD Module 1.6 reports built on a foundation of REACH and biocides environmental work.
Pharma ERA, built on environmental regulatory foundations.
Our pharmaceutical ERA work is grounded in fate, exposure and ecotoxicology developed under REACH and biocides — the foundation now demanded by the revised EMA guideline and FDA environmental assessments. We structure files around the questions an evaluator actually opens an ERA for: are PECs refined, not formulaic; are metabolites assessed for environmental relevance, not just listed; are PBT/vPvB and EAT-active properties screened early; and does Module 1.6 read as one coherent narrative? Phase I, Phase II, metabolites, special substance classes — one integrated assessment.
Phase I, Phase II, metabolites, special substance classes — one integrated assessment under the regulatory framework that applies.
From early Phase I screening through to FDA query response — concrete points where senior pharmaceutical ERA input shapes the file.
From Phase I screening to CTD Module 1.6 report — one ERA team across the full submission.
An open PBT and PMT screening tool for industrial and pharmaceutical substances — Annex XIII criteria, R.11 logic and 2023 CLP PMT / vPvM overlay, ready for ERA narrative use.
Innovators preparing marketing authorisation applications who need full Phase I and Phase II ERA under the revised EMA guideline. Generic and biosimilar manufacturers facing ERA requirements that did not apply under the previous guideline. Pharmaceutical companies with metabolites, antimicrobials or EAT-active substances requiring specialist assessment. We also support clients responding to EMA or FDA queries on ERA-related elements of submitted dossiers.
A pharmaceutical client preparing a marketing authorisation application had a Phase I PECsurface water above the action limit using the default Fpen. The question was whether refined, indication-specific exposure modelling could reduce the PEC sufficiently to remain within Phase I, under the 2024 EMA ERA guideline.
A Phase I PECsurface water above the 0.01 µg/L action limit using the default Fpen of 0.01, triggering Phase II Tier A chronic aquatic testing under the revised guideline. The estimated Phase II programme would have delayed dossier submission by 12–18 months.
Outcome. Refined PECsurface water below the Phase I action limit, supporting a defensible conclusion that Phase II ecotoxicology testing was not required under the 2024 EMA ERA guideline. Submission proceeded on the original timeline.
Most pharmaceutical ERA conversations start in one of these five places. If yours doesn't fit, send it through anyway — we'd rather hear the question than guess at it.
The Phase I action limit framework remains, but the revised guideline places greater emphasis on realistic exposure refinement before progressing to higher-tier testing. This includes refined Fpen calculations, updated market penetration assumptions, and improved wastewater removal modelling. Conservative default assumptions at Phase I are now less defensible where refinement data are available.
The revised framework places stronger emphasis on systematic evaluation of human metabolites. Metabolites present at ≥10% of parent systemic exposure are typically screened for environmental relevance, but metabolites below this threshold may still require consideration if they are persistent, structurally concerning or pharmacologically active. Each is assessed case by case for formation levels, predicted environmental exposure, intrinsic properties and ecotoxicity data.
Yes. The revised guideline reinforces early consideration of persistence, bioaccumulation and toxicity properties within the ERA framework. Even where PEC-based risk is low, intrinsic PBT/vPvB concerns may trigger further evaluation. Intrinsic property screening is integrated alongside exposure-based risk assessment, not addressed as a separate exercise.
The revised framework requires careful consideration of substances with specific pharmacological modes of action, including estrogenic, androgenic and thyroid activity. Where pharmacological targets may be conserved across species, additional scrutiny of environmental relevance is warranted. We assess biological plausibility and environmental exposure together to avoid mechanistic over-interpretation.
Often yes, case by case. The revised guideline encourages proportionate refinement of exposure before progressing to chronic aquatic testing — through refined Fpen, sewage treatment plant removal modelling, and improved usage data. ERA strategies designed to apply appropriate refinement early reduce the risk of disproportionate testing while remaining regulator-aligned.
Tell us the substance, the route of administration and the submission timeline. We'll come back with an initial scope and a fit assessment.
