The EU pharmaceutical package: Environmental aspects

On 26 April 2023, the European Commission published its proposal to reform the EU's pharmaceutical legislation. The package includes two legislative proposals: a new Directive and a new Regulation, which together will replace the existing pharmaceutical legislation and aim to address a huge challenge among the key objectives of the new framework: make medicines more environmentally sustainable.

Indeed, residues of medicines may enter the environment during their manufacturing, use by patients and disposal. Another issue is the emissions and discharges of antimicrobials to the environment from manufacturing sites, which may lead to antimicrobial resistance (“AMR”).

The pollution of waters and soils with pharmaceutical residues and the AMR are emerging environmental problems across the EU and this new framework tries to reduce these risks.

To achieve the goal of reducing the environmental impact of the pharmaceutical product lifecycle while promoting innovation, the package proposes a broader environmental risk assessment (“ERA”), which would have a reinforced role before granting the marketing authorisation (1) alongside with other concrete measures post-marketing authorisation (2).

Please note that these measures are designed to complement other EU legislation regarding protection of the environment:

• the Water Framework Directive (2000/60/EC13) ;
• the Environmental Quality Standard Directive (2008/105/EC14);
• the Groundwater Directive (2006/118/EC15);
• the Urban Wastewater Treatment Directive (91/271/EEC16);
• the Drinking Water Directive (2020/218417);
• the Industrial Emissions Directive (2010/75/EU18).

1. A reinforced environment risk assessment (ERA) to obtain a marketing authorisation (MA)

As the current ERA has been criticized regarding its scope, content and compliance, including the gaps in timely enforcement and possible risk minimisation measures, the scope of the ERA would be significantly extended to limit the potential adverse impacts of medicines on the environment and public health.

Therefore, the new scope would be extended to cover the entire product lifecycle, the manufacturing and the risk for AMR selection in the environment due to the manufacturing, use and disposal of medicinal product with an antimicrobial mode of action.

The ERA has been mandatory since 2006 for all pharmaceutical companies placing their medicines on the EU market. However, incompleteness of the ERA in the MA application has no real consequence under the current legislation.

To strengthen the role of the ERA in the MA procedure, this new legislation would sanction the lack of seriousness of the ERA. If the applicant fails to submit a complete or sufficiently substantiated ERA or does not propose risk mitigation measures to sufficiently address the risks identified in the ERA, the MA should be refused.

The ERA must be prepared by the MA applicant in accordance with scientific guidelines on ERA to be drawn up by the European Medicines Agency (EMA), where appropriate in collaboration with the European Chemical Agency, the European Food Safety Authority and the European Environmental Agency.

ERA procedures of other EU legal frameworks should also be taken into account by MA applicants : Regulation (EC) No 1907/2006 (REACH) for industrial chemicals, Regulation (EC) No 528/2012 for Biocides, Regulation (EC) No 1107/2009 for Pesticides and Regulation (EU) 2019/6 for Veterinary medicines.

For generic, biosimilar and hybrid medicinal products, the MA applicant must refer to ERA studies conducted for the reference medicinal product.

The European public assessment report (EPAR), describing the evaluation of an authorised medicine and published by the EMA, would now include a summary of ERA studies and their results as submitted by the MA holder and the assessment of the ERA by the EMA.

Finally, some articles in the proposed legislation are also designed to cover the environmental risks which may arise from medicinal products containing or consisting of genetically modified organisms, with a specific ERA.

2. Reducing the environmental impact post-marketing authorisation

After the granting of the MA and in any case, the ERA should be updated with new information without undue delay.

The MA may be granted subject to conditions with a deadline to fulfil them. 10 conditions have been established in the proposed Directive and one of them is related to the ERA. Indeed, the MA holder may be required to conduct post-MA ERA studies, collect monitoring data or information on use, if there are concerns about risks to the environment or public health, including AMR need to be further investigated after the medicinal product has been marketed.

Competent authorities may also request information from the MA holder about the implementation of any measures previously imposed regarding risks to the environment or public health, including AMR. The MA holder would have the obligation to respond fully and within the time limit set by the authorities.

Moreover, to reduce the environmental impact of pharmaceuticals, the MA may be suspended, revoked or be subject to a variation if a serious risk to the environment or public health is identified for a medicine and not sufficiently addressed by the MA holder.

The MA holder may also decide to suspend the marketing of the product, withdraw the product from the market or request the withdrawal of the MA if he identifies a serious risk to the environment or to public health via the environment and if he does not sufficiently addressed this risk. In such a case, the MA holder should notify without undue delay this action to the EMA, the reasons of such action and declare that this action is based on a serious environmental risk.

If urgent action is required to protect public health or the environment, a Member State may, at the Commission’s request or on its own initiative, suspend in its territory the use of the concerned authorized medicinal product.

For medicinal products authorised before 30 October 2005, as they have not been subject to any ERA and if the EMA has identified them as potentially harmful to the environment, the EMA would establish a specific programme for the ERA to be submitted.

Lastly, the new Directive proposes that the EMA sets-up an active substance based review system of ERA data (physiochemical data, fate data and effect data) for authorised medicinal products, called “ERA monographs”. This new database of information and risk assessments would be based on a risk-based prioritisation of active substances.

The initiative to improve the environmental sustainability of medicines by this proposed EU package can be welcomed. However, it is to be hoped that these new administrative burdens will not be to the detriment of marketing medicines and patient access and that the balance will be found between the interests involved.