Published 11th July 2023
On the 26 April 2023, the European Commission presented their draft proposals to simplify and update the current pharmaceutical legislation. This blog discusses the proposed environmental changes to the reform and how these will support the Commission in meeting its objective to make medicines more environmentally sustainable whilst safeguarding the environment for future generations.
This reform comprises of a revision to the Directive and community code relating to medicinal products for human use, which will repeal Directives 2001/83/EC (community code relating to medicinal products for human use), directive 2009/35/EC (on the colouring matters which may be added to medicinal products). In addition, the regulation of medicinal products for human use will amend regulations (EC) No 1394/2007 (advanced therapy), EU No 536/2014 (clinical trials regulation), (EC) No 726/2004 (community procedures for the authorisation and supervision of medicinal products) , (EC) No 141/2000 (orphan products). and (EC) No 1901/2006 (medicinal products for paediatric use).
The issue of pollution attributed to the production, use and disposal of medicinal products, and the detrimental effect that this is having on the environment is a rising global problem. As scientific data continues to be collected, there is increasing evidence that the lifecycle of a pharmaceutical poses not only a risk to the environment, but the health of the population. Of particular concern is the detection of antimicrobials in environmental systems that could ultimately increase antimicrobial resistance (AMR) and present a global health risk to the population in the treatment of infection.
To address these challenges, the reform has revisited the Environmental Risk Assessment (ERA) process as detailed in the ‘Guideline on the environmental risk assessment of medicinal products for Human Use.’
Previously, the guideline had stipulated that the environmental impact of medicinal products should be ‘assessed and on a case-by-case basis, specific arrangements to limit this impact shall be considered.’ However, ‘in any event this impact should not constitute a criterion for refusal of a marketing authorisation.’ Moving forward, the Directive proposes that those applicants who do not complete or provide insufficient evidence or explanation to support their evaluation of environmental risk and/or mitigation measures to reduce environmental impact, should now expect to see their application for a marketing authorisation rejected. As further information becomes available to support the ERA, this may then be updated for subsequent review.
The reform also advises that risk mitigation measures to ‘avoid or where it is not possible, limit emissions to air, water and soil pollutants’ should be included within the ERA and considered in line with Directives 2000/60/EC, establishing a framework for community action in the field of water policy, 2006/118/EC,on the protection of groundwater against pollution and deterioration, 2008/105/EC, on environmental quality standards in the field of water policy, and 2010/75/EU, on industrial emissions integrated pollution prevention and control.
The reform continues that the applicant should discuss appropriate detailed mitigation measures which should be considered suitable to address those risks identified in the environment. In addition to the directives listed above, the reform advises that consideration should also be given to other ERA procedures within the EU legal framework that could also be applicable to the chemical under review, depending on its ultimate intended use.
A significant emphasis has been placed on the assessment of antimicrobial resistance (AMR) within the environment and the associated effects this may have as a consequence of manufacturing production. As a result of this, the reform proposes that the ‘entire lifecycle of an antimicrobial,’ including the whole manufacturing supply chain, both within and outside of the EU, its use and ultimate disposal, are to be taken into consideration and where relevant, assessed against established predicted no effect concentrations (PNECs) specific for antibiotics.
The packaging of antimicrobials will also be required to include an ‘awareness card’ in addition to the product information leaflet, which will provide a patient with information on antimicrobial resistance and the appropriate use and disposal of antimicrobials.
Following approval of a marketing authorisation, the reform stipulates that any new information that may become available as a result of the examination of a marketing authorisation application by the competent authorities, and could affect the conclusion of an ERA, should be provided to the national competent authorities without delay. The update should include information relating to for example, environmental monitoring, ecotoxicity studies, exposure data, and information from new or revised ERAs within other European legislation. Those marketing authorisation holders whose ERAs have been conducted prior to the approval of the legislation will be required to update their ERA if information is missing that has been identified to be potentially harmful to the environment.
Article 23 of the proposed Directive discusses the creation of a programme to assess those medicinal products authorised before 30 October 2005, that could potentially cause harm to the environment. Prioritisation of products for assessment will be via a risk-based approach and agreed upon scientific criteria. As a result, further information may be requested from the marketing authorisation holder in order to allow the agency to determine the risk prior to any ERA being submitted for review. Where an active substance has been utilised in several medicinal products and the risk to the environment is considered to be the same, marketing authorisation holders will be encouraged to conduct joint studies to support their ERA which will avoid the unnecessary duplication of data. This recommendation will not be without its challenges and requires further direction from the commission as to how such studies could be undertaken whilst ensuring that company data remains protected, as the reform highlights that following assessment of an ERA, the outcome and any supporting data provided by the marketing authorisation holder will be made publicly available.
The proposal also discusses within Article 24, a collaboration in the establishment of an active substance review system or ‘ERA monographs’ for those medicinal products already authorised prior to 30 October 2005. An ERA monograph would enable applicants to access physiochemical, fate and effect data for a specific active substance to assist with a new application for an ERA. Following the acceptance of the Directive, a proof-of-concept pilot will be conducted which upon completion, the Directive will be updated to provide further information.
The environmental impact of medicines and their production is an increasing global problem. The proposed legislative reform aims to address these issues by improving ERA requirements for marketing authorisation applicants and current holders, broadening ERA scope to include assessment of AMR, and to implement further measures to assist applicants with the creation of a new ERA application.
The reform will further support initiatives under the EU green deal which is working towards zero pollution for air, water, and soil with the aim to achieve no net greenhouse gas emissions by 2050. The reform is also aligned with the EUs strategic approach to pharmaceuticals in the environment.
The proposal will help reduce the environmental impact of medicinal products by steering pharmaceutical companies into adequately assessing and limiting where possible, potential adverse effects into the environment thus safeguarding its future and protecting public health. Industry will need to consider how best to tackle these requirements moving forward and what if any, further investment may need to be considered to support a smooth transition.