Understanding The New EU Pharmaceutical Directive: A Comprehensive Guide To Environmental Risk Assessment (ERA) For Pharma Companies

The growing awareness of the environmental risks posed by pharmaceuticals is leading to legislative changes that aim to reduce the impact of medicinal products on the environment. These changes are becoming increasingly relevant for pharmaceutical companies, as new regulations and guidelines are proposed and set to come into effect in the European Union. At Maven, we understand the challenges that pharmaceutical companies face in adapting to these evolving requirements, and we are here to help navigate these complexities.

The Proposed New Directive: Key Changes

In April 2024, the European Parliament presented a proposal for a new directive on medicinal products for human use, with the goal of making medicines more environmentally sustainable. Key changes in this proposal significantly impact the environmental risk assessment (ERA) requirements for marketing authorization applications (MAA).

Environmental Risk Assessment as a Marketing Authorization Requirement

While the current Directive 2001/83/EC requires the submission of an ERA during MAA, the proposed directive introduces more stringent conditions. Specifically, the MAA may be refused if the ERA is incomplete or lacks sufficient substantiation, or if proposed risk mitigation measures are deemed insufficient. This change aligns the EU’s approach more closely with the practice in the United States, where an inadequate environmental assessment is a common reason for MAA rejection.

Broader Scope for Environmental Risk Evaluation

The new directive expands the scope of the ERA, addressing not only traditional environmental compartments like water, soil, and sediment, but also tackling emerging concerns such as antimicrobial resistance. The revised legislation aims to ensure that pharmaceutical products have a minimal impact on the environment throughout their lifecycle.

Regular Updates and the Role of Marketing Authorization Holders (MAH)

One of the most significant changes under the proposed directive is the requirement for regular updates to the ERA, like the pharmacovigilance process. MAHs will be held responsible for ensuring timely updates based on new environmental data, which further highlights the growing importance of environmental monitoring in the pharmaceutical sector.

Environmental Information Monographs

The proposal also outlines the establishment of a monograph system, which will collect available environmental data on active pharmaceutical ingredients (APIs). This system will allow other applicants to refer to existing information, streamlining the ERA process and promoting greater consistency in submissions.

Revised ERA Guideline: What It Means for Pharmaceutical Companies

In line with the proposed directive, a revised version of the "Guideline on the Environmental Risk of Human Pharmaceuticals for Human Use" came into effect in September 2024. This updated guideline, which has expanded from 12 pages to 64 pages, offers greater detail and clarity on the ERA process. While many aspects remain like the previous version, there are several key changes that pharmaceutical companies need to be aware of:

• Elimination of the Waiver for Generic Products
  The revised guideline removes the possibility of waiving ecotoxicological studies for generic products. This change places a significant burden on generic manufacturers, who now must conduct a full environmental risk assessment, including a complete set of study reports. However, companies may still rely on scientific literature or data from competitors to meet certain study requirements, offering some cost-saving opportunities.
• Tailored Assessment for Compounds with Specific Toxicological Profiles
  The new guideline provides clearer definitions for compounds that require a tailored assessment due to their specific toxicological profiles. This will help ensure that environmental risks associated with these compounds are adequately addressed and mitigated.
• Encouraging Use of Existing Literature
  The updated guideline emphasizes the use of existing literature to avoid unnecessary repetition of studies, a move that can save both time and resources for pharmaceutical companies.
• Options for Waiving or Reducing Study Requirements
  Several options are available for pharmaceutical companies to reduce the required study set. These include referring to available literature or providing detailed information on the epidemiology of the target indication, treatment regimen, or specific properties of the drug substance.

Regulatory Guidelines: Navigating the New ERA Framework

As part of the evolving regulatory landscape, companies must adhere to updated guidelines, such as the European Medicines Agency (EMA) guidelines on the environmental risk assessment of medicinal products for human use and the new EU environmental sustainability directives. These guidelines aim to ensure that pharmaceutical companies adopt environmentally responsible practices in their product lifecycle, from development to post-market monitoring.

Key Regulations for Pharmaceutical Companies:

• Directive 2001/83/EC and the Proposed New Directive: These provide the framework for marketing authorization and environmental risk assessment.
• EU Regulation 726/2004: This regulation governs the marketing authorization of medicinal products within the EU, emphasizing the importance of an environmental risk assessment.
• OECD Guidelines on Ecotoxicology: The OECD guidelines play a significant role in determining testing procedures for the environmental risk assessment of pharmaceutical products. These guidelines are instrumental in ensuring compliance with global environmental standards.
• Pharmacovigilance and ERA Updates: As part of regular pharmacovigilance requirements, the proposed directive mandates continuous monitoring and updating of environmental risk assessments.

How Maven Can Help

Navigating the new regulations and ensuring compliance with updated guidelines can be complex. At Maven, we specialize in providing comprehensive toxicology risk assessment and regulatory services, helping pharmaceutical companies meet both the new ERA requirements and broader sustainability goals.

Our services include:

• Environmental Risk Assessment (ERA) Consulting: We offer guidance on how to conduct comprehensive environmental risk assessments in line with the latest EU regulations and the revised ERA guidelines.
• Regulatory Strategy and Compliance Support: We help navigate the regulatory landscape by providing insights into the EMA’s guidelines, ensuring that marketing authorization applications meet all environmental criteria.
• Tailored Assessment for Specific Toxicological Profiles: Our experts provide in-depth support for compounds that require customized assessments, ensuring that your product complies with the latest standards.
• Monitoring and Updates: We assist in setting up monitoring systems to ensure regular ERA updates, helping you stay compliant with the pharmacovigilance-like requirements for environmental data updates.
• Streamlined Study Submissions: We offer advice on how to effectively use available scientific literature and data from competitors to fulfill environmental risk study requirements, saving your company time and resources.
• Customized Mitigation Measures: Maven helps design and implement environmentally sustainable strategies that go beyond the standard requirements, including pollution reduction measures for air, water, and soil.

Conclusion

The future of pharmaceutical regulation is shifting towards greater emphasis on environmental sustainability, and companies must be prepared to meet these evolving challenges. With the proposed directive and the revised ERA guideline already in effect, the time to adapt is now. Partnering with experts in toxicology and regulatory affairs, like Maven, can simplify this transition and ensure that your company remains compliant with new regulations while minimizing environmental impact.

For more information on how Maven can assist you in navigating these changes, contact us today.