Six priority areas will characterise the work of the network of European medicines agencies (EMRN) for the next five years. The goals have been established by the new joint regulatory strategy to 2025 published in December 2020 by the European Medicines Agency (EMA) and the Heads of Medicines Agencies (HMA).

Areas of activity will include the availability and accessibility of medicines; data analytics, digital tools and digital transformation; innovation; antimicrobial resistance and other emerging health threats; supply chain challenges; and the sustainability of the network and operational excellence. The strategic objectives, which also underwent a phase of public consultation from July to September 2020, will be transformed into concrete actions by EMA and the network of European national competent authorities.

The Covid-19 pandemic has highlighted the pivotal role of medicine regulation for the protection of public health,said Emer Cooke, EMA’s Executive Director. “Lack of availability of medicines, either because they are not marketed or due to supply disruptions, has shown to pose serious threats to patient and animal health, animal disease control programs and sustainable livestock production. This strategy ensures that we join forces across the EU to effect tangible improvements for citizens.

The EMRN network is expected to grow further in the next five years in order to achieve an improved sustainability and operational excellence. The actions planned in this direction are part of the sixth priority discussed in the joint strategy, and will be based on the availability of adequate resources (financial, expertise, competence, and skills), business processes, IT capabilities, as well as of an efficient governance structure.

The new EU’s pharmaceutical legislation is growing

EMA-HMA’s joint strategy aims to provide a medium-to-long term reference framework to coordinate all actions of the complex network of stakeholders working at the development, approval and commercialisation of pharmaceuticals. The 27 national competent authorities (plus those of Iceland, Liechtenstein and Norway), the EMA and HMA are represented by the European medicines regulatory network (EMRN); other stakeholders include among others the associations representing the pharmaceutical industry, patients, payer and health technology assessment (HTA) bodies.

The challenge is double: on one hand, the need to ensure a steady supply of already available medicines, on the other one, the opportunity to exploit new technologies in the medical, biomolecular and informatics fields to develop new approaches to treat unmet medical needs. The Pharma 4.0 paradigm is becoming the new normal under the manufacturing perspective, and it has to cope with new European and global policies addressing sustainability, climate change and green economy.

The Covid-19 pandemic has highlighted the need to ensure a better governance of the global supply chains providing the European pharma industry with APIs and excipients. These issues have been also addressed by the new Pharmaceutical Strategy for Europe (see the article in the December newsletter), and are now complemented by the more operative goals set by the EMA-HMA joint strategy.

Availability and accessibility of medicines

Access to medicines is the first priority to ensure patients can always find in the market the medicines they need. The strategy plans to run a deep analysis to better identify the multifactorial root causes of unavailability of patented and off-patent products, for example with reference to authorised but not marketed products, or low volume paediatric medicines. “It is important to differentiate shortages caused by safety, efficacy or quality/supply chain issues from availability issues for commercial reasons, where political engagement may be necessary”, states the joint strategy.

Shortages shall be addressed by the improved sharing of data and the inclusion of marketing status data in the SPOR programme; it needs a coordinated action across different countries to find sustainable solutions and avoid unilateral actions which may further exacerbate the problem. A better understanding of the different roles played by the various stakeholders along the supply chain is also foreseen in order to improve transparency of the overall process and favour the better monitoring by regulatory authorities. The removal of national barriers still limiting the free flow of medicinal products in the EU market is another area of attention, which might include the implementation of the electronic Product Information (ePI), the sharing of best practices and increased coordination of the EMRN. The final adoption of the new Veterinary Medicines Regulation is also expected to resolve many availability issues in the field of medicines for animal health.

Processes leading to regulatory approval shall be improved to ensure a better collaboration between medicines regulators and other decision makers along the entire pathway (including political actors and international organisations), from evidence planning, to reviewing of evidence and methodologies. Participation to horizon scanning activities, also at the international level, and an improved collaboration with HTA bodies on scientific advice procedures (including pre-planning and generation of post-licensing evidence) represent useful tools to favour a rapid access of patients to innovation. It is also important to ensure transparency in the communication of scientific evidence and regulatory assessment of new products, as emerged during Covid-19 vaccines and treatments development.

Support to the digital transformation

The digital transformation represents a cross-sectorial area planned for the actions of the von der Leyen Commission for next years, to be supported also through the creation of the new European Health Data Space. The EMA-HMA joint strategy aims to enable access and analysis of the great amount of routine healthcare data available both at the point of care (e.g. electronic health records, eHR) and by use of smart devices, including the analysis of individual patient data from clinical trials. Artificial intelligence and machine learning will represent fundamental tools to achieve this goal, and will contribute to generate evidence from real world data to be used for regulatory and decision-making purposes, particularly with reference to post-approval clinical studies.

A goal that requires a better standardisation of targeted data (as reflected in the EC’s policy on Open Data and the Public Sector Information Directive); modernisation of regulators’ internal processes and the creation of a suitable infrastructure within the Network to deal with statistics, epidemiology, real world data and advanced analytics are other planned actions. The wide integration of medicines and medical devices calls for a collaborative effort with HTA bodies to jointly map the current status of the digital regulatory infrastructure and plan its upgrading. The analysis of real world data will also represent the basis for the creation and implementation of dynamic regulation and policy learning policies within the current regulatory framework, taking into consideration also aspects referred to data security and ethical considerations.

Europe as a leading hub for innovation

The regulatory science developed by European agencies historically represents a leading reference at the international level. Four new goals have been identified to improve the action of the EMRN network in order to support innovation in the pharmaceutical field, starting from the integration of science and technology in medicines development. This requires the Network to develop suitable competences to support innovators during medicines development. Research and innovation is also expected to play an enabling role in regulatory science. Advanced Therapy Medicinal Products (ATMPs) coupled with new biomarkers are supporting the rapid expansion of personalised medicine. This also correspond to the development of new formulation strategies (including the use of nanoparticles) and of small batches manufacturing techniques (e.g. 3D printing).

Collaborative evidence generation should represent the final target, and should see the cooperation of all stakeholders along the lifecycle, including HTAs, and pricing and reimbursement authorities. Large, multicentre and multinational clinical trials with a shared protocol and standard are foreseen by the strategy in order to produce robust evidence in support to decision makers.

Antimicrobial resistance and other health threats

Antimicrobial resistance (AMR) continues to represent the first priority of action to prevent possible risks for the public health. High quality information on antimicrobial consumption and surveillance data on AMR in animals and humans is needed, according to the strategy, to better support policy development and proper implementation of Regulation (EU) 2019/6 on veterinary medicinal products.

Multi-drug resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) are the main two areas to be addressed as for AMR, using a One Health approach. Emerging health threats will also require great attention in order to prevent the occurrence of new possible epidemics.

EMA and HMA have planned to continue the actions supporting the responsible use of antimicrobial agents both in the human and veterinary sectors. Reduction of antimicrobial use and misuse is considered critical to decrease the burden of AMR. This should be paralleled by development of new antimicrobials or other therapeutic options and the maintenance of a sufficient production of older products to cover the EU’s market needs.

Ensure the sustainability of the supply chains

An enhanced traceability along the global, highly complex supply chain of human and veterinary medicines, from manufacturing of APIs and excipients in third countries to their importation and final use, is the main target set forth by EMA and HMA. It will require to improve inspector capacity building and extensive cooperation at the international level, particularly with reference to APIs production in extra-EU countries (e.g China and India). “For example, the network should make optimum use of mutual recognition agreements (MRAs) through expansion of scope to include more product categories where appropriate or recognition of inspections by MRA partners in third countries where GMP certificates are available from those partners”, states the document. Pre-approval inspections of APIs facilities may be also addressed, leading to routine assessor-inspector joint inspections.

Dependency on a limited number of manufacturers and sites is a critical issue to be solved to ensure continuity of supply and availability of medicinal products in the European market. A risk-assessment evaluation detailing the supply capacity and measures for mitigation of any potential disruption may be required to manufacturers of the API and finished product for inclusion in the application for a marketing authorisation. Measures to favour manufacturing in the EU are also possible.

A more coherent approach by regulators and industries to the standards for medicinal products for human and veterinary use is indicated by EMA and HMA in order to reinforce the responsibility for product quality. Good distribution practices (GDP) and guidances may be revised to support a better standardisation among member states and to promote synergies among GDP actors.

The regulatory framework is also expected to evolve to accommodate new manufacturing technologies based on artificial intelligence and the Internet of Things (IoT), as well as innovation in manufacturing and distribution of medicinal products. An example made by EMA and HMA is that of tabletop-sized machine with integrated production and purification, that  might turn useful to run decentralised manufacturing in a hospital pharmacy or operating theatre, or in mobile clinics to provide personalised medicines for the individual patients.