The long waited new Pharmaceutical Strategy for Europe was finally published on 25 November 2020 by the EU Commission: a fundamental act that will inspire legislative and non-legislative actions in this key sector for the European economy for coming years. The Strategy builds upon four different pillars, including access to affordable medicines and attention to unmet medical needs, supporting competitiveness, innovation and sustainability of the EU’s pharmaceutical industry, enhancing crisis preparedness and response mechanisms, and promoting a high level of quality, efficacy and safety standards worldwide.
“The coronavirus pandemic has highlighted the vital need to strengthen our health systems. This includes access to safe, effective and high-quality medicines at an affordable price. In the challenging economic and social times the EU is currently facing, the strategy adopted today will ensure that Europe and Europeans will continue to benefit from such medicines. I call on member states and the Parliament to endorse this approach which will be rolled out in the next three years, and beyond”, said President Ursula von der Leyen.
“With our Pharmaceutical Strategy for Europe, we are delivering on our commitment to create a future-proof and patient-centred pharmaceutical environment in which the EU industry can innovate, flourish and continue to be a global leader. It is our long-term vision for open strategic autonomy, and our response to the challenges of today and the vulnerabilities exposed by Covid-19”, added Stella Kyriakides, Commissioner for Health and Food Safety.
Breaking down all barriers
Despite the many advances in pharmacological treatments made in the EU during the past 20 years, still many barriers prevent a sustainable access to medicines. Unavailable or unaffordable products continue to represent an issue for many people, and further vulnerabilities emerged as a consequence of the Covid-19, e.g. data availability, shortages and manufacturing capacities. The pandemic has also represented a sort of testing exercise for improved forms of cooperation among stakeholders, for example in the case of the advance purchase agreements for vaccines signed by the Commission on behalf of member states.
The new Pharmaceutical Strategy aims to overcome these barriers, and to fully enable the additional potential arising from the implementation of the digital technologies to further increase competitiveness. According to the Commission, the European pharmaceutical industry provides 800 thousand direct jobs and a €109.4 billion trade surplus, and saw over €37 billion contribution to research investment in 2019. The starting point for the future evolution of the second pharmaceutical market in the world is represented by the very robust European regulatory framework, which already supports drug development and commercialisation.
The Pharmaceutical Strategy will act in synergy with other pieces of legislation from the von der Leyen Commission, including the Europe’s Beating Cancer Plan, the Zero Pollution ambition part of the European Green Deal, the strategy on Shaping Europe’s digital future, the creation of a European health data space and the European One Health Action Plan.
New approaches for unmet medical needs
The development of new antimicrobial agents is the priority area of unmet medical need addressed by the Pharmaceutical Strategy, together with rare diseases (in the field of neurodegeneration, paediatric and rare cancers) which are often not attractive for the industry to invest on.
The 2021 should see the launch of the first flagship initiative aimed to testing new approaches to provide incentives for the development of novel antimicrobials and new public procurement schemes for this type of medicines. Planned actions include the proposal to revise the paediatric and rare diseases legislations to include tailored incentives. EMA’s PRIME scheme for priority medicines may be included in the regulatory framework in order to expedite the approval of new products in areas of unmet need. Joint meetings with participation of existing committees/networks of regulators, health technology assessment (HTA) bodies and payers should favour a better collaboration between different institutions. In particular, a parallel scientific advice on clinical study design by EMA and HTA bodies may be considered in the context of the new HTA Regulation.
The promotion of investment and the coordination of R&D, manufacturing, deployment and use for novel antibiotics will be managed by the newly established European Health Emergency Response Authority (HERA, see below). The EU’s pharmaceutical legislation may be also reviewed to restrict and optimise the use of antimicrobial medicines. Non-legislative tools that might be used to tackle antimicrobial resistance include harmonisation of product information, draft evidence-based guidance on existing and new diagnostics, promotion of the prudent use of antibiotics and communication to healthcare professionals and patients.
The Commission also supports early collaboration between scientific disciplines on R&D, including regulators, academia, healthcare professionals, patients’ organisations and healthcare providers and payers. This should facilitate the breaking of the still existing silos that slow down the development and approval processes of new medicines. New forms of information sharing, such as horizon scanning, are advised as useful tools to complement cross-country collaborative approaches in public procurement and joint pricing and reimbursement negotiations, while waiting for the adoption of the proposed HTA Regulation.
How to favour access to medicines
The fragmented availability of a certain medicinal product in different EU’s national markets is due to many different factors, from market size to pricing and reimbursement policies, from size of the population to type of healthcare systems. High pricing of innovative medicines is often related to a lack of transparency in R&D costs or return on investment, and it may be tackled by mean of innovative payment approaches, such as risk-sharing arrangements and deferred payment schemes.
The Commission also aims to revise the system of incentives to possibly include greater ‘conditionality’ in relation to intellectual property rights to support broader access for patients and increase competition. Root causes of deferred market launches will be investigated in a pilot project; attention will also be paid to favour greater generic and biosimilar competition through interchangeability and clarification of the ‘Bolar’ provision to conduct pre-approval clinical studies on patented products.
Review and enforcement of EU competition rules and innovative procurement procedures seeing a closer cooperation of buyers (as already done in the Big Buyers initiative) are other tools announced by the Pharmaceutical Strategy. Competent authorities will also be called to share their best practices on pricing, payment and procurement in order to improve affordability, cost-effectiveness and sustainability of healthcare systems. Guidelines on principles and costing methods for establishing R&D costs may also favour better access for patients.
The support to innovation
The Pharmaceutical Strategy closely complement the Commission’s Intellectual Property (IP) Action Plan with regard to the review and simplification of EU’s pharmaceutical IP system, with a particular attention to supplementary protection certificates (SPCs) which are expected to become more transparent and efficient.
Access to interlinked systems of comparable and interoperable health data will prove key to sustain research and innovation, as well as evidence generation and efficient regulatory processes. The European health data space and its related interoperable data access infrastructure go in this direction to allow secure cross-border analysis of health data while safeguarding individuals’ rights to privacy and data protection.
Specialised skills are needed to advance towards these goals, and they will benefit of the initiatives planned under the new European Education Area (see the dedicated article in this newsletter). Funding will be provided through different sources, including the EU4Health programme, Horizon Europe, Cohesion Policy, the European Defence Fund, and public-private and public-public investment partnerships. Special initiatives to support small and medium sized companies are included in the SME strategy for a sustainable and digital Europe and Startup Europe.
New tools for innovative therapies
Gene and cellular therapies and vaccines will continue to represent key factors of innovation in the pharmaceutical pipelines. New business models may be required to accommodate the increasing trend of more personalised, one-time treatments of patients under a “bedside” manufacturing of individualised medicines perspective. Platforms based on data sharing agreements shall support the identification of new therapeutic approaches and data analysis, also assisted by artificial intelligence (AI). Access to genetic data is planned in order to develop new prevention strategies; the secure federated access to 10 million genomes across EU’s borders should become possible by 2025 in order to use them for R&D, clinical application and personalised medicine.
Artificial intelligence may also support the identification of new drug substances and the repurposing of the already existing ones, thus reducing the risk of failure for the pharma industry. Digital therapeutics and app-based platforms may be especially useful to treat chronic diseases from remote; the combination of medicines and medical devices is another rapidly expanding area needing a better tuning of the relevant legislation and clarification of roles and responsibilities of the different parties involved in the development and approval processes.
The full implementation of the Clinical Trials Regulation will allow to reach a harmonised, more transparent and coordinated approach to the assessment of clinical data. New study designs will also be explored, including pragmatic trials, where the treatment is prescribed and used as in normal daily practice.
New roles for the regulatory agencies
The role of the robust network formed by the European Medicines Agency and national competent authorities under the Heads of Medicines Agencies may receive a full, formal recognition by the Commission. The reviewing of the regulatory legislation may lead to new approaches to assess scientific evidence supporting applications while reducing approval times. The experience with the rolling reviews for Covid-19 treatments is just a first example, that will be used to further expand the initiatives in this key area.
A study on the authorisation and monitoring of medicines for human use is also planned as a prerequisite for the simplification of procedures (e.g. for variations management) and regulatory costs. EMA fees system should be revised. A critical area in regulatory assessment to be evaluated during the review of the current legislation is represented by the requirements needed to authorise medicines for human use containing or consisting of genetically modified organisms (GMOs).
Other planned actions include the possible introduction of a single active substance master file for substances to be used in different generic medicines, so to run a single assessment process across member states, and the upgrade of the Commission’s Union Register of centrally authorised products to include a statistical dashboard and make data fully available for secondary use. Electronic product information (ePI) should also become the standard for all EU medicines.
Secure supply chain to prevent new crisis
The Covid-19 has highly stressed the resilience of the European pharmaceutical supply chain at a grade the EU Council has recognised that “achieving strategic autonomy while preserving an open economy as a key objective of the Union”.
The Pharmaceutical Strategy third pillar aims to better identify root causes for shortages and dependencies in health. Diversification of manufacturing and supply, and strategic stockpiling are two options available to improve the current situation, to be operated in parallel with the support to new investments in Europe. Reinforcing the obligation for continuous supply is also envisaged, based on a revision of current legislation; earlier notifications, enhanced transparency of stocks, and a stronger coordinating role for EMA in monitoring and managing shortages may represent possible future actions.
Enhanced cooperation between member states, for example for joint procurement for critical medicines, and making available at the EU level tools and instruments on prices and reimbursement to be used by countries are other examples.
The importance of GMPs
A major criticality emerged during the pandemic is represent by the fact many technologies needed to manufacture pharmaceutical active ingredients and intermediates are no longer available in the European Union, thus supplies come from extra-EU countries (e.g. China and India). Lack of access by regulators to complete information about the structure of the manufacturing and supply chains proved to be a critical issue to be solved during the Covid-19 emergency.
A structured dialogue with all stakeholders will initially be pursued by the Commission in order to gain better understanding of the functioning of global supply chains and identify specific causes and drivers of vulnerabilities. Results from this exercise will support the proposals of new measures and policy options useful to secure the supply of critical medicines, active ingredients and raw materials. Dialogue with WTO members will also help to improve the predictability of the trading environment in health products, on the basis of increased cooperation of trade partners to avoid unnecessary disruptions. A better transparency of the supply chain will be encouraged by favouring the voluntary adhesion of its different actors. Funding within the EU4Health programme will support the development of guidelines and the availability of tools to address structural shortages.
HERA will add to EMA and the ECDC
The European Health Union package, the first response of the Commission to increase preparedness and resilience to cross-border health threats, redesigns the landmark of European agencies in the health sector.
EMA will expand its role to act also as central hub for scientific excellence in order to better coordinate all scientific advice and evaluation procedures, and to prevent shortages by mean of an improved assessment and monitoring of the supply capacity.
The European Centre for Disease Prevention and Control (ECDC) will also find a new vocation in providing support for epidemiological surveillance and scientific recommendations for appropriate health measures to be implemented.
The new European Health Emergency Response Authority (HERA) shall be established within the announced Regulation on serious cross-border threats to improve preparedness and response; this agency will act as a coordinator of operations along the entire value chain in case of a new crisis. Horizon scanning and foresight will be its main tools to anticipate new threats and enable new technologies. HERA will also be involved in production capacity monitoring and pooling and in the development of crosscutting technological solutions (e.g. vaccine platform technologies). In order to set up HERA’s activities and organisation, the Commission will run a preparatory action focused on emerging threats to human health, and will launch an impact assessment and consultation on the establishment of an EU authority, with the target to release the mandate proposal in 2021.
An eye to the Commission’s green agenda
Looking at the Commission’s green agenda, the robust implementation of good manufacturing and distribution practices is considered essential to prevent new occurrences similar to the nitrosanime’s one, which led to an extensive risk assessment (and in some case testing) of all medicines present in the European market. Increased capacity for inspection and audit programmes and a better collaboration with international partners is mentioned in the Pharmaceutical Strategy, as well as a feasibility study to improve information in existing databases or linked repositories pertaining the status of production sites.
Decentralised and continuous manufacturing are emerging technologies that will be strictly monitored to better assess their regulatory impact. A stronger Environmental risk assessment may become integral part of the regulatory documentation in support of a marketing authorisation.
Waste management is another priority of action which complements the EU Green Deal zero-pollution target in order to limit emissions or residues of pharmaceuticals in the environment. Separate collection of household hazardous waste, reduction of pack sizes and realignment to real use, and use of safer chemicals as raw materials for production are among the foreseen actions.
Strengthening of EU’s international leadership
The European framework governing pharmaceutical development and commercialisation often represents a leading standard to inspire other countries in setting up and operate their own systems. The leading role played on different levels by the Commission, EMA and national competent authorities will continue in future years, for example to make more attractive the procedure for issuing opinions on medicines intended exclusively for markets outside the EU. and convergence will be pursued through participation to the International Pharmaceutical Regulators Programme (IPRP) and the International Coalition of Medicines Regulatory Authorities (ICMRA). Higher quality levels, efficacy and safety standards should be the common target in order to facilitate global development of pharmaceuticals.