At the outset of the 5th wave of corona virus affecting the globe, European Union seems to have drawn useful lessons from the pandemic within the context of the European Union Pharmaceutical Strategy[1], since the importance of ensuring timely access to safe, high quality and affordable medicines on a permanent basis are principles under which the European Commission plans to evaluate and review general EU legislation on medicinal products for human use, with a view to ensuring a long-standing and crisis-resistant regulatory system for medicinal products. The review aims to ensure access to affordable medicines, promote innovation, including in areas where medical supplies are not covered, improve equipment safety, adapt to new scientific and technological ones, and reduce bureaucracy.
On March 2021 the Commission made available the “Combined Evaluation Roadmap/Inception Impact Assessment” document in relation to the evaluation and revision of the general pharmaceutical legislation, while on 21st September 2021, the Commission launched a public consultation on the revision of the general EU pharmaceutical legislation (EU Directive 2001/83 & EU Regulation 726/2004) aiming at creating a future proof regulatory framework and at supporting industry in promoting research and technologies that actually reach patients in order to fulfil their therapeutic needs while addressing market failures. The public consultation ends on 21 December 2021 and any interested party may submit comments and observations.
The revision of the general pharmaceutical legislation is complementary to other initiatives under examination in the same context, such as the European Health Data Center (EHDS), which aims to provide high-quality healthcare while taking advantage of “digital health” and the work of the “European Emergency Preparedness and Response Authority (HERA)”. It is also linked with the “European Green Agreement”, in particular through the impact of medicinal substances on the environment. It is to be mentioned that the revision also follows the adoption of the Health Technology Assessment Regulation which is expected to improve access by facilitating national decisions and creating a more predictable assessment process within the EU.
The consultation is based on the following six (6) pillars: (a) unmet medical needs and market failures for medicines other than medicines for rare diseases and children; (b) unequal access to available and affordable medicines for patients across the EU; (c) the current legislative framework may not be fully equipped to respond quickly to innovation; (d) inefficiency and administrative burden of regulatory procedures; (e) vulnerability of supply of medicines, shortages of medicines; and (f) environmental challenges and sustainability.
1st Pillar: With respect to the first pillar related to the unmet medical needs[2] and commercial failures concerning non-orphan and pediatric medicines. It goes without saying that there is a need for innovation and innovative treatments, especially in the areas where there are needs that are not covered by legislation on rare diseases and pediatric medicines. This includes treating antimicrobial resistance (AMR), as well as avoiding excessive and inappropriate use of antibiotics. It also includes finding the right synergies with HERA’s[3] problem-solving activities. From two European surveys, namely (a) the EU statistics on income and living conditions (EU-SILC) instrument, which collects information on an annual basis covering persons aged 16 and over, and (b) the second wave of the European health interview survey (EHIS), conducted between 2013 and 2015 and covering persons aged 15 and over, the outcome was that more than one quarter of the EU-28 population in need of health care had an unmet health care need in 2014 that was attributed to high costs, distance or waiting lists. It is to be noted that an indicator on the equality of access to health care service, defined as the total self-reported unmet need for medical care for the reason of financial barriers, waiting times and too far to travel, is included in the health services chapter of the European core health indicators (ECHI)[4].
In the above respect and given the need in this area, the initiative for the first pillar aims to identify elements that are important in defining what unmet medical need is and in which areas of unmet medical need innovation should be stimulated. The following criteria shall be considered: (i) seriousness of a disease; (ii) absence of satisfactory treatment authorised in the EU; (iii) therapeutic advantage over existing treatment(s); (iv) lack of access for patients across the EU to an authorised treatment.
2nd Pillar: As far as the second pillar is concerned, the Commission aims at meeting the challenge of the unequal access to affordable medicines for patients across the Union. Innovative and promising treatments are not always available to patients. In particular, due to many factors, pharma companies commercialize their products medicines in different way within the EU markets and, thus, access may vary significantly between EU member states. It is to be noted that, at times, there is no competition in the pharma market. This affects access to generic and biosimilar drugs, which may have a tremendous effect on patient prices and the budget sustainability of health systems.
The initiative of Commission aims to address differences in access to medication between EU member states. This will be done by granting incentives to pharma industry and establishing new obligations, such as (a) introduce incentives for swift market launch across the EU, (b) allow early introduction of generics in case of delayed market launch of medicines across the EU, (c) require companies to place – within a certain time period after authorization – a medicine on the market of the majority of EU countries, including small markets and (d) require companies withdrawing a medicine from the market, to offer another company the opportunity to take over the medicine.
In this respect, these suggested ways also target to eliminate existing barriers for medicines entering the EU market. The measures concern mainly generics and biosimilars, which are seen as a means of ensuring accessible and affordable treatments, and increasing competition on the market by: (i) stimulating earlier market entry through a broader possibility to authorize generics/biosimilars despite ongoing patent protection, (ii) creating a certain (regulatory) incentive for a limited number of biosimilars that come to the market first, (iii) introducing an EU-wide scientific recommendation on interchangeability for specific biosimilars and (iv) introducing joint procurement practices.
3rd Pillar: On the third pillar, the Commission pointed out the luck of the current legislative system to respond quickly to innovation.
Pharmaceutical legislation has been developed within an era of technologies, where genomic sequencing, genome editing technologies or artificial intelligence did not exist or were at a very early stage. Given that, innovative solutions continue to challenge the understanding of a “medicinal product” with low volume, and cutting-edge products (e.g. medicines combined with self-learning artificial intelligence) becoming a new reality.
Since technological progress and digital transformation lead to the development of complex product combinations by affecting the discovery, development, manufacture, evidence generation, assessment, supply and use of pharmaceutical products, the current legislation needs to be fully harmonized to cover new scientific and technological advances and models. These include systems based on artificial intelligence for prevention, diagnosis, better treatment, therapeutic monitoring and data for personalised medicines and other healthcare applications. In addition, for medicines containing or consisting of genetically modified organisms (GMOs), the environmental impact assessment must be adapted to the specific characteristics of these products.
Some very innovative solutions fail to see the light of day because of regulations which might be outdated or poorly adapted for fast evolving technologies. One way to address this is through regulatory sandboxes which enable innovative solutions to be live-tested with supervisors and regulators, provided that the appropriate conditions are in place, for example to ensure equal treatment. Hence, the challenge is to create more flexibility for medicines that are manufactured from substances of human origins, as well as for substances that are donated by humans such as blood, plasma, cells, gametes, tissues and organs that are applied as therapy and better coordination among clinical trial, marketing authorization, health technology assessment bodies, pricing and reimbursement authorities and payers for integrated medicines development and post-authorization monitoring.
4th Pillar: In relation to the fourth pillar of the Consultation, it is to be mentioned that the Commission acknowledged that there may be room for simplification and streamlining of procedures and internal processes in terms of reducing administrative and regulatory barriers. The EU pharmaceutical system must remain attractive in a competitive global environment, which requires regulatory attractiveness and flexibility, while adhering to the fundamental principles of safety, efficacy, quality and ensuring that innovation reaches to those in need.
It is also to be pointed out that there is room for optimizing interaction with other frameworks (such as the framework for medical devices and substances of human origin) by using all available digital tools. There is a need to further strengthen the power of regulators to adjust the terms of marketing authorizations on the basis of scientific evidence.
5th Pillar: With respect to the fifth pillar, it is to be mentioned that shortages of medicines and the vulnerabilities in the pharmaceutical supply chain remain concerns in the EU. Shortages of medicines may lead to serious impacts on patient care. Under the current pharmaceutical legislation, pharma industry and wholesalers should ensure a continued supply of medicines once they are placed on the market in the EU.
Still, there are significant challenges to overcome and the exiting legislation fail to ensure that patients have adequate access to medication. Thus, the Consultation aim at enhancing security of supply through stronger procurement and transparency obligations, timely information on drug shortages and withdrawals, stock transparency and stronger EU coordination and mechanisms for monitoring, managing and avoiding shortages.
In this respect, the transparency and oversight of the supply chain should be improved, in particular in relation to aspects of the international supply chain, by reviewing the provisions of pharmaceutical legislation concerning the manufacture and distribution and clarifying responsibilities for quality assurance of medicines per category within the supply chain as well as by ensuring readiness for new manufacturing technologies. The following measures are considered: (i) earlier reporting of shortages and market withdrawals, (ii) prevention plans implemented by companies, (iii) safety stocks by the companies, (iv) effective monitoring of supply and demand at local level, and (v) diversification of the supply chains.
6th Pillar: With respect to the sixth pillar and given that the environmental risk assessments (ERAs) shall be taken into account in the overall benefit/risk analysis, the main challenge that the Commission sets to the revision of the EU pharmaceutical legislation is to enhance the environmental sustainability of the production, use, disposal of medicines and strengthen the requirements of environmental risk assessment to ensure support for greener production in terms of improving the responsibility of bodies and achieving risk mitigation measures, where appropriate.
In view of the abovementioned, this revision of the current EU pharmaceutical legislation constitutes a complex process which may have significant practical impact on key areas for the pharmaceutical sector. In this respect, any structural challenges shall be considered essential for effective crisis management supplementing the enhanced role of the European Medicines Agency (Core) in times of crisis.
The impact on the European economy as a whole is expected to be positive. Elements such as regulatory flexibility to facilitate rapidly emerging scientific and technological developments, the use of new evidence-making tools and simplification will make the EU more attractive for investing and marketing innovative medicines. A more tailored incentive system to increase access and innovation for unmet needs will promote private participation in areas where the market does not attract investment. In addition, the adjustment of incentives in areas where the market attracts investment will allow competition, which is expected to reduce pharmaceutical costs. The long-term positive economic impact on the global drug market is likely to balance the initial one-off negative economic impact that will result from additional liabilities to operators. The economic benefits for the EU pharmaceutical sector in reducing administrative burdens will be further enhanced through the protection of legislation over time and new opportunities to accelerate product development by using real data and artificial intelligence (AI) applications to generate evidence with customizable decisions based on new evidence within the context of R&D.
Furthermore, targeted introduction of public service obligations (such as the obligation to access products when an enhanced incentive is used) and customized incentives are expected to have a positive effect on patient availability and accessibility across the EU. These results will be combined with profits which will help reduce the cost of medicines and have a positive impact on health spending. Provisions that enhance security of supply chain will enhance social protection and assist health systems provide the society with a steady supply of essential medicines. Data on the flexibility associated with long-standing legislation will allow the EU pharmaceutical system to be up-to-date and ready to deal with modern solutions that would in turn be available and put at the service of society.
As far as the environmental aspect is concerned, it is to be noted that policy options suggested to be implemented will strengthen supply chain oversight, transparency of environmental information and clarification of responsibilities to ensure the sustainability of the environment, combined with rules for environmental risk assessment requirements and conditions for the use of medicines would lead to a safer environment for the production, use and disposal of medicines. This would have a positive impact on the environment per se, since it would contribute to the reduced presence of residues in the natural environment and protect the biodiversity and ultimately human health. These results would contribute to the Europe Green Agreement, the Chemicals Strategy, the Zero pollution ambition and the Industrial Strategy.
Last but not least, it is to be highlighted that this initiative aims also to improve the access and availability of medicines as well as to protect the environment. Thus, it is expected to have a positive impact on access to health care and to help improve health and environmental protection as described in Articles 35 and 37 respectively of the EU Charter of Fundamental Rights. According to the “Combined Evaluation Roadmap/Inception Impact Assessment” document made available by the Commission, the final form of the legislative instrument for the revision of the EU Directive 2001/83 & EU Regulation 726/2004 has not been decided yet. The intended review of both the EU Directive 2001/83 and EU Regulation 726/2004 imposes challenges on the EU legislator, especially as to whether the Community Code’s (EU Directive 2001/83) legal form should be maintained or if a transposition of the Community Code into a Regulation and the respective adaptation to a new EU Regulation is practicable for the member states. In our opinion, the legislator should review the general EU legislation on medicinal products for human use in a manner that will preserve the existing balance and will not set new burdens for the stakeholders involved.
Amalia Xeini, MSc, Senior Associate at POTAMITISVEKRIS
Anastasia Georgiopoulou, LL.M. Associate at POTAMITISVEKRIS
[1] On 25 November 2020, the Commission published the “Pharmaceutical Strategy for Europe”. According to the announcement, this is a patient-centered strategy, which aims at the quality and safety of medicines, while strengthening the international competitiveness of the industry. It is one of the main pillars of the Commission’s vision for building a stronger European Health Union, which was presented by the President of the Commission, von der Leyen, in her speech on the state of the Union in 2020.
[2] Article 4 of Regulation (EC) No 507/2006: “….2. For the purposes of paragraph 1 (c), “unsatisfied medical need” means a condition in which there is no satisfactory method of diagnosis, prevention or treatment approved by the Community or even if it exists such a method, in relation to it the drug in question will bring significant benefit to the sufferers….”.
[3] European Emergency Preparedness and Response Authority
[4] The European Core Health Indicators (ECHI), formerly known as European Community Health Indicators, is the result of long-term cooperation between EU countries and the European Commission. Three ECHI projects (1998-2001, 2001-2004, 2005-2008) funded under the EU Health Programmes established the first lists of ECHI indicators, aiming to provide comparable health information and knowledge system to monitor health at EU level.
