Environmental Risk Assessment(ERA) [Europe Submission]
In the development and approval of human medicines, the focus is typically on ensuring the product is safe and effective for patients. However, there’s another critical dimension that cannot be ignored—the impact of pharmaceuticals on the environment. This is where the Environmental Risk Assessment (ERA) comes into play. ERA is a regulatory requirement in many regions, including the European Union, and forms a crucial part of the marketing authorisation application (MAA) for any new medicinal product.
What is an Environmental Risk Assessment (ERA)?
An Environmental Risk Assessment evaluates the potential impact that a medicinal product may have on the environment when it is used, excreted, and ultimately disposed of. Specifically, the ERA looks at:
The fate of the active pharmaceutical ingredient (API) in various environmental compartments like water, soil, and sediment.
Toxic effects on organisms such as fish, algae, and aquatic invertebrates.
The potential for the compound to be persistent (P), bioaccumulative (B), and toxic (T), collectively referred to as PBT/vPvB substances.
The ERA is mandatory for all new MAAs submitted through centralized, mutual recognition, decentralized, or national procedures in the EU. It must be included in Module 1.6 of the Common Technical Document (CTD).
Why is ERA Important?
- Protecting Ecosystems Drugs can enter the environment through patient excretion, improper disposal, or Manufacturing waste. Without proper risk assessment, harmful residues could affect aquatic life, pollute drinking water, and disrupt ecosystems.
- Regulatory Compliance In the EU, submission of an ERA is legally mandated under Directive 2001/83/EC. An incomplete or inadequate ERA can delay or block market authorisation of your product.
- Sustainable Development Conducting an ERA ensures your pharmaceutical product aligns with global goals for environmental sustainability and responsible production, especially under the EU Green Deal framework.
When is an ERA Required?
An ERA is required for:- All new Marketing Authorisation Applications
- Line extensions that may increase environmental exposure (e.g., new route of administration or expanded indications)
- Type II variations, if they increase environmental impact
However, renewals of existing authorisations do not require a new ERA unless significant new data have emerged.
How is an ERA Conducted?
The ERA process is stepwise, consisting of Phase I and Phase II assessments:- Phase I: Initial Screening
This stage determines whether a full Phase II assessment is necessary. A predicted environmental concentration in surface water (PECsw) is calculated. If the PECsw is below 0.01 μg/L, no further testing is required, unless the substance is flagged for special concerns (e.g., antibiotics, endocrine disruptors).
- Phase II: Detailed Assessment
If Phase I shows that a product may pose a risk, a more detailed investigation is carried out, involving:
- Physicochemical properties: solubility, log Kow, degradation rate
- Ecotoxicological studies: toxicity to fish, algae, and aquatic invertebrates
- Environmental fate studies: adsorption to soil, biodegradability, potential for bioaccumulation
- Risk mitigation strategies, if needed
- Special Cases
- Endocrine active substances (EAS) and antibacterials always require a tailored risk assessment, even if PECsw is low.
- Biologic and peptide-based products may qualify for simplified justifications if they are shown to degrade rapidly or pose minimal risk.
What Must Be Included in an ERA Submission?
Your ERA report, as part of the MAA dossier, should include:
- Identification of the active substance(s)
- Results of PEC and PNEC (Predicted No Effect Concentration) calculations
- Detailed study reports or scientific justifications
- PBT/vPvB screening outcomes
- Risk characterisation and, if applicable, risk mitigation measures
- Data search and literature reviews (to follow 3Rs principles and reduce unnecessary animal testing)
The ERA should adhere to GLP standards and OECD test guidelines, and data must be sufficiently robust for scientific evaluation by regulatory authorities.
How Masuu Global Can Help You Navigate ERA :
At Masuu Global Quality and Regulatory Consultants, we understand that the environmental assessment of pharmaceuticals is a complex, evolving area of regulation. Our team of experts can support you in:
- Assessing ERA applicability and scope for your product
- Designing and managing Phase I and Phase II ERA studies
- Calculating PEC/PNEC ratios, log Kow, and environmental fate
- Preparing full ERA reports aligned with EMA guidelines
- Advising on data waivers or literature-based justifications
- Interfacing with EMA or national competent authorities to resolve ERA queries or request scientific advice
We ensure your ERA submission is not only compliant but strategically optimized to support your product’s approval and sustainable lifecycle.
Frequently Asked Questions
An Environmental Risk Assessment (ERA) evaluates the potential impact of a medicinal product and its active pharmaceutical ingredient (API) on the environment. It considers environmental exposure, the fate of the substance, and potential effects on organisms in environmental compartments such as water, soil, and sediment.
Yes. An ERA is required for applicable new Marketing Authorisation Applications (MAAs) in the European Union and forms part of the regulatory dossier. The ERA is included in Module 1.6 of the CTD and should address the applicable EU regulatory and scientific requirements.
An ERA is generally required for new MAAs and may also need to be updated for certain line extensions or Type II variations when they could increase environmental exposure or impact. A new ERA is generally not required for routine renewals unless significant new environmental information becomes available.
An ERA evaluates the environmental fate and potential effects of pharmaceutical substances. This can include degradation, adsorption, persistence, bioaccumulation, toxicity to aquatic organisms, and assessment of whether a substance may meet PBT/vPvB criteria.
Phase I is an initial environmental exposure assessment that includes calculation of the predicted environmental concentration in surface water (PECsw). If further assessment is warranted, Phase II provides a more detailed evaluation using physicochemical, environmental fate, and ecotoxicological data to characterize potential risks.
Phase I focuses primarily on estimating environmental exposure and determining whether additional assessment is necessary. PECsw is calculated and compared against applicable regulatory thresholds, while substances requiring special consideration, such as certain antibiotics or endocrine-active substances, may require further assessment regardless of the initial exposure estimate.
Phase II can involve physicochemical information such as solubility and log Kow, environmental fate studies, degradation and adsorption data, and ecotoxicological studies involving organisms such as fish, algae, and aquatic invertebrates. The assessment may also consider bioaccumulation and appropriate risk mitigation measures.
An ERA report can include active substance identification, PEC and PNEC calculations, environmental fate and ecotoxicology data, PBT/vPvB screening, risk characterization, scientific justifications, and applicable risk mitigation measures. Relevant literature searches and existing data should also be considered to support a scientifically robust assessment.
Certain substances may require specific or tailored environmental assessments because of their potential environmental effects. Antibiotics and endocrine-active substances may require additional consideration, while biologic and peptide-based products may, where scientifically justified, qualify for simplified assessments based on their environmental degradation and characteristics.
ERA studies and reports should be scientifically robust and aligned with applicable EMA requirements, GLP principles, and relevant OECD test guidelines. Existing scientific information and literature should be appropriately evaluated to support the assessment and avoid unnecessary testing where justified.
Masuu Global can assess ERA applicability, define the appropriate assessment strategy, support Phase I and Phase II studies, and perform PEC/PNEC and environmental fate evaluations. Our team can also assist with literature reviews, data waivers, scientific justifications, and preparation of the final ERA report.
Yes. Masuu Global can support communication with the EMA and relevant national competent authorities regarding ERA-related questions, scientific justifications, and regulatory queries. Our goal is to help ensure the ERA is appropriately documented, scientifically defensible, and aligned with the requirements for the product’s European regulatory pathway.