Environmental Risk Assessment (ERA) in Drug Products: Understanding the EMA Guideline

Regulatory Affairs Pharma & Biotech Toxicology

Monday, 06 October 2025

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Mae Ann Belandres, Senior Consultant Toxicology

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Learn how the EMA guideline defines Environmental Risk Assessment (ERA) for drug products, including its structure, key phases, and implications for pharmaceutical development.

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Environmental Risk Assessment: EMA Guideline 2024 Update | QbD Group

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Balancing human health, regulatory compliance, and environmental protection is becoming increasingly complex for pharmaceutical companies. While drug safety for humans is rigorously assessed throughout development and approval, the potential impact of pharmaceuticals on the environment — particularly on non-target organisms — has long been less scrutinized.

That is changing. As environmental concerns rise globally, regulatory bodies like the European Medicines Agency (EMA) have updated their expectations. Environmental Risk Assessment (ERA) has become an essential part of the marketing authorization process in the EU, the US, and beyond. The latest revision of the EMA guideline, in effect since September 1, 2024, reflects a more holistic and science-based approach to managing the environmental footprint of medicinal products.

In this blog post, we explore the purpose and structure of Environmental Risk Assessments (ERA) and how the EMA guideline shapes their design and expectations for pharmaceutical companies.

Why Environmental Risk Assessment (ERA) matters

An Environmental Risk Assessment evaluates the potential impact of active pharmaceutical ingredients (APIs) on the environment. After human consumption, pharmaceuticals often enter wastewater systems via excretion. Because many treatment plants cannot fully remove these compounds, APIs may end up in surface water, groundwater, and soil.

Over time, this can lead to:

Disruption of aquatic ecosystems
Endocrine effects in fish and amphibians
Antimicrobial resistance
Bioaccumulation in the food chain

How the ERA works: Phase I and Phase II

The updated guideline retains the two-phase structure but adds clarity and flexibility.

Phase I: screening and exposure estimation

Phase I determines whether a product's environmental exposure warrants further investigation. This begins with calculating the Predicted Environmental Concentration (PEC) in surface water, based on dosage, excretion rates, and market use.

If the PEC is below the threshold of 0.01 µg/L, the product is generally considered low-risk.
If the PEC exceeds the threshold, refinements can be made—e.g., using real-world prevalence data, worst-case treatment regimens, or market consumption estimates.
If PEC remains above the threshold after refinement, the product proceeds to Phase II.

Phase II: detailed ecotoxicological assessment

Phase II involves a tiered evaluation of the product’s impact on:

Aquatic and sediment species
Terrestrial ecosystems
Species at risk of secondary poisoning
Microbial processes in sewage treatment plants (STPs)

This phase also considers persistence, bioaccumulation, toxicity, and specific modes of action, such as antimicrobial or endocrine effects.

How the EMA guideline shapes ERA practice

Since the first version in 2006, our understanding of how pharmaceuticals behave in the environment has advanced significantly. The revised EMA guideline (EMEA/CHMP/SWP/4447/00 Rev. 1 — Corr.) reflects this evolution and supports broader initiatives like the European Green Deal and the One Health concept. Key elements include:

1. Enhanced tiered approach

The two-phase model remains, but the decision tree is clearer, with more guidance on progression between tiers and when to apply refinements.

2. Tighter exemption rules

Exemptions for generics, OTCs, or products with established APIs are more limited. Products with new indications or routes of administration must undergo full ERA.

3. Assessment of specific modes of action

The guideline now explicitly requires assessments for specific mechanisms of concern, such as endocrine disruption and antibacterial effects.

4. Updated data requirements

New endpoints for aquatic and sediment species improve ecological relevance. The guideline also supports read-across and data reuse to reduce unnecessary animal testing.

5. Lifecycle environmental responsibility

The EMA encourages ongoing environmental monitoring and post-approval obligations for high-risk compounds, shifting toward a lifecycle risk management approach.

Why this matters for the pharmaceutical industry

Conducting a thorough ERA is no longer a formality — it’s a regulatory expectation and a public responsibility. The updated guideline:

Establish robust communication channels: Leverage collaborative tools like Microsoft Teams or Slack, Jira to maintain transparency and streamline coordination.
Set clear expectations and KPIs: Define quality benchmarks, turnaround times, and success metrics from the outset to align both internal and external teams.
Implement secure processes: Adopt data encryption, access control, and regular audits to ensure that sensitive information is protected.

Recommendations may include specific disposal methods, routine environmental monitoring, or post-market follow-up actions—all of which require forethought during development.

Conclusion: a new era for environmental accountability in pharma

Environmental Risk Assessment is now a vital component of drug development, marketing authorization, and long-term sustainability. With the EMA guideline in place, companies are expected to go beyond basic compliance to anticipate, assess, and manage environmental risks proactively.

At QbD Group, we support pharmaceutical companies in navigating complex regulatory changes, including ERA requirements. Need help aligning your product development with the latest EMA expectations? Let’s talk.

Don't hesitate to contact us.

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