Key takeaways for the environmental risk assessment (ERA) in the proposal for new EU pharmaceutical legislation

On 10 April 2024, the European Parliament adopted its position on a proposed revision of the EU pharmaceutical legislation covering medicinal products for human use. The proposed revision was put forward by the European Commission in April 2023 and includes a new directive and a new regulation that would replace inter alia Directive 2001/83/EC and Regulation (EC) No 726/2004. Setterwalls has previously reported on the reform here.

Introductory remarks

The overarching objective of the proposals is to enhance the availability, accessibility and affordability of medicines in Europe, while simultaneously supporting the competitiveness and appeal of the pharmaceutical sector in the European Union. Additionally, the pharmaceutical package aims to introduce higher environmental standards inter alia by tightening the requirements for assessing environmental risks through the entire lifecycle of medicines in order to limit the considerable impact on the environment associated with the manufacture and use of medicinal products.

In this article, we will discuss the recently proposed legislative changes, particularly focusing on their impact on the environmental risk assessment procedure. We will also explore the amendments concerning the ERA introduced by the European Parliament.

Under the existing regulatory framework, the submission of an ERA is a mandatory component of all new applications for marketing authorisation (MA). However, this requirement does not extend to marketing authorisations granted prior to 30 October 2005. Furthermore, the scope of the ERA is limited to specific stages of the medicinal product’s lifecycle, focusing primarily on the usage, disposal and labeling of the product. It is important to note that within the current system, the environmental impact of a medicinal product is not considered a valid ground for the refusal of a marketing authorisation.

Extended scope of the ERA

With the proposed revision, the ERA faces a significant expansion in its scope. Under the proposed amendments, the ERA would adopt a broader definition, as it would not only include the evaluation of the risks to the environment. It would also encompass an evaluation of public health risks associated with the environmental release of medicinal products through their usage and disposal.

Moreover, the concept of “risks related to the use of the medicinal product” is set to be redefined to include not only quality, safety, efficacy and environmental risks, but also the potential adverse effects on public health due to the release of the medicinal products in the environment. A particular point of emphasis will be the issue of antimicrobial resistance (AMR). The scope of the ERA will be extended to specifically address the risks of AMR that arise from the manufacture, usage, and disposal of antimicrobial agents.

Furthermore, it is suggested that the ERA would cover measures aimed at mitigating the release of pollutants into the environment (that is, the air, water and soil) and whether the product, or any of its constituents, is an endocrine disruptor,[1] or falls into specified chemical hazard classes relevant to human health and the environment.

Changes to the procedure

In the proposed Directive, refusal of a national marketing authorisation is governed by Article 47. One of the grounds for such refusal concerns the adequacy of the environmental risk assessment provided by the applicant. Specifically, an authorisation may be denied if the assessment is deemed incomplete or insufficiently substantiated, or if the risks identified in the ERA have not been sufficiently addressed by the applicant.

The authority may request supplementary information within a set deadline. Failure to provide the requested information within the stipulated period would be considered a withdrawal of the marketing authorisation application.

Following approval of marketing authorisation for a medicinal product, the ERA must be continuously updated to remain current and reflect any new data that may affect the previous conclusions. Such new information may include, but is not limited to, the emergence of new ERAs, new data on environmental exposure or findings from recent environmental monitoring and eco-toxicological research.

Regulatory authorities may also require additional post-authorisation ERA studies should concerns emerge pertaining to an already approved medicinal product or to others that contain the same or a similar active ingredient(s). In instances where a significant threat to environmental safety or public health is identified and not sufficiently addressed by the marketing authorisation holder, the authorities may suspend, vary or revoke the marketing authorisation, as well as prohibit the supply and request the withdrawal of the medicinal product from the market.

Amendments introduced by the European Parliament

The European Parliament has introduced several amendments regarding environmental oversight of medicinal products. With regard to Article 22, which addresses the ERA, the European Parliament has provided further guidance. It is now clarified that the requirement that applicants must incorporate risk mitigation strategies within the ERA to prevent, or when prevention is unfeasible, to minimize the release of pollutants into the air, water and soil extends over the entire lifecycle of the medicinal product, that is, its manufacture, use and disposal.

Moreover, the European Parliament has broadened the scope of requirements for the ERA. Applicants must not only offer a comprehensive explanation that the proposed mitigation measures are both appropriate and sufficient in addressing the identified environmental risks, but they must also, where necessary, include information on the available techniques and on the techniques that will be used to reduce the discharges and emissions of the medicinal product. In particular, those relating to effluents in manufacturing and their treatment before leaving the production facilities.

In the case of ERAs conducted prior to a period of 18 months after the date the new Directive entered into force, holders of marketing authorisations will be requested to update their ERAs to reflect the aforementioned risk mitigation measures.

The European Parliament has also introduced a requirement that the results of the ERA, along with the data provided by the marketing authorisation holder, is to be made publicly available. However, any commercially confidential information contained within these documents will be redacted by the relevant regulatory authority prior to public disclosure.

Lastly, the European Parliament has introduced a balanced approach between environmental protection and ensuring patient access. Under the revised Article 195 of the Directive, the European Commission’s initial proposal that marketing authorisations for medicinal products may be subject to change, including suspension or revocation, should a significant environmental or public health risk arise that has not been adequately managed by the authorisation holder, has been amended. The Parliament has clarified that such actions would only be considered if the risks in question cannot be mitigated through the grant of the conditions specified in in Articles 44(1), first subparagraph, point (h) or 87(1), first subparagraph, point (c). Namely, the requirement for marketing authorisation holders to conduct inter alia post-authorisation environmental risk assessment studies. Importantly, any such decision must take the clinical benefits of the medicinal product and the needs of patients into account, including the availability of alternative treatments.

Marketing authorisations granted prior to 30 October 2005

The proposed revision includes specific amendments for medicinal products granted marketing authorisation prior to 30 October 2005. Under the new Directive, these products will be subject to an ERA if the European Medicines Agency (EMA) deems them to pose a potential risk. The EMA’s prioritisation process will hinge on the level of risk associated with the product or its active ingredients.

Concerning these products, the European Parliament clarified in the preamble that, where the environmental risk assessment is incomplete or insufficiently substantiated for a medicinal product authorised before 30 October 2005, it should be possible for the national marketing authorisation to be revoked. However, due consideration to avoid restricting patient access to such medicinal products should be given before any decision is taken on revocation.

Regarding environmental risk assessments of medical products granted marketing authorisation prior to 30 October 2005, the European Parliament has further proposed that the European Medicines Agency must ensure public access not only to the data in these assessments but also to a summary of the ERA studies, including their results, as provided by the holder of the marketing authorisation.

Moreover, the European Parliament proposed to extend the scope of Article 47 by adding that the national marketing authorisation of medicinal products, where the reference medicinal product received its first marketing authorisation before 30 October 2005, may be refused if the view is taken that the environmental risk assessment is incomplete or insufficiently substantiated and the medicinal products concerned can be identified as potentially harmful to the environment.

Summary and conclusions

In summary, the proposed legislative changes to the European Union’s pharmaceutical regulatory framework aim to significantly enhance the role of the environmental risk assessment in the process for obtaining marketing authorisations for medicinal products, while still securing patient access to medicines. The amendments seek to broaden the ERA’s scope to include a comprehensive evaluation of risks to the environment and public health. Additionally, the amendments provide for the refusal of MAs where ERAs are inter alia incomplete or insufficiently substantiated by the applicant and revocation of MAs if a serious risk to the environment or public health has been identified and not sufficiently addressed by the marketing authorisation holder.

The proposal and the European Parliament’s adopted position reflect the EU’s focus on environmental impact and public health in the context of pharmaceuticals, while also considering the implications for the availability of medicinal products.

Setterwalls looks forward to seeing how this develops and is continuing to monitor the process. Further discussions in the European Parliament following the summer elections are now awaited.

[1] Natural or human-made chemicals that may mimic, block or interfere with the body’s hormones, which are part of the endocrine system.