European Commission Archives - European Industrial Pharmacists Group (EIPG)

The European Medicines Regulatory Network Data Standardisation Strategy


by Giuliana Miglierini The availability of interoperable data is a “must” to ensure the smooth sharing, use and re-use of data along the entire regulatory process. A new document - the European Medicines Regulatory Network Data Standardisation Strategy - has Read more

ICMRA published a Reflection paper on remote inspections


by Giuliana Miglierini Remote inspections have become a widely used approach since the last two years to ensure the oversight of the compliance of pharmaceutical productions to regulatory requirements, as the prolonged lockdown periods determined by the pandemic made very Read more

EMA’s Q&A on the integration of EudraGMDP and OMS


by Giuliana Miglierini A new step in the integration at the central level of data needed to manage regulatory procedures is going to be activated on 28 January 2022: starting from this date, member states’ national competent authorities (NCAs) shall Read more

A study on medicines shortages from the European Commission

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by Giuliana Miglierini

The study on medicines shortages commissioned in March 2020 by the European Commission upon request of the European Parliament and Council has been published; the document, prepared by a consortium led by Technopolis, suggests 16 possible policy measures – both legislative and not-legislative – that the Commission may consider while drafting a new legislative proposal to govern the issue, expected to be announced at the end of 2022.

According to the current EU pharmaceutical legislation (Directive 2001/83/EC), marketing authorization holders (MAHs) have to submit – two months before the temporary or permanent interruption of supply of a certain medicinal product – a pre-notification to the relevant national competent authorities (NCAs) (Article 23a, a part in the case of exceptional circumstances).

The mandate to continue supply to cover the needs of patients, and respective responsibilities of MAHs and wholesale distributors are established by Article 81 of the same directive.

The new study will support some of the achievements set forth in the Pharmaceutical Strategy; another action undertaken to reduce the impact of shortages in the EU is represented by the EU Executive Steering Group on Shortages of Medicines Caused by Major Events, an initiative set up in March 2020 with the contribution of the Commission, EMA and member states.

The Commission study on shortages by Technopolis confirms that current market framework conditions for off-patent medicines play against supply resilience – said Rebecca Guntern, President ad-interim of Medicines for Europe, commenting the release of the study –. As long as healthcare systems only focus on the cheapest possible price for off-patent medicines and do not reward investments to ensure robust supply chains, the only option for companies is to be the cheapest or to leave the market.

The main outcomes of the study

The study on shortages focused its attention on medicines for human use marketed in the EU/ EEA in the period 2004-2020. The main objectives of the exercise include the identification of shortages’ root causes and specific characteristics, the assessment of the adequacy of the current framework (at EU and national level) and of possible solutions to address the problem.

Data from the shortages registries kept by national competent authorities (NCAs) of 22 EU’s countries was only available for years 2007-2020. Commercial data on pharmaceutical sales from IQVIA MIDAS was also used, and extensive consultation with stakeholders was run under different formats.

Central to the 16 recommendations highlighted in the study is the establishment of a centralized and harmonised EU-wide definition of medicine shortages, as well as of harmonised reporting criteria. The latter should aim to collect sufficiently detailed information on key parameters (e.g. product details, MAH, details on the shortage and impact).

Different definitions, systems for notifications and type of information requested are currently in use in the various member states; even the definition of “shortage” agreed in 2019 by EMA and HMA was not considered by stakeholders adequate to differentiate between critical and non-critical shortages. According to the report, this fragmented situation doesn’t allow for the sharing of data and comparative analysis between countries, thus resulting in the overall inefficiency of the system.

Attention should be paid also to the creation of a EU-wide list of medicines subject to critical shortages; specific policies and regulations may be developed on this basis to improve their availability. Medicines typically experiencing shortages are older, off-patent and generics drugs with low profit margins; the main therapeutic areas involved include pain, hypertension, infections and oncology.

The creation of dialogue platforms at the national level is also envisaged, where to exchange the point of view of different supply chain stakeholders (including patients and healthcare providers). The study highlights the high burden shortages create on pharmacists and physicians looking for the best possible treatment alternative for their patients. A possible way to address this issue would see the availability of information about alternative medicines in shortage databases. In many cases, this type of occurrence is referred just to some countries within the EU, thus suggesting inequitable distribution and access rather than global supply issues may play a major role in shortages.

Understanding the root causes

Limited reporting is a key point to be solved in order to improve the understanding of root causes of shortages. According to the study, a reductionist approach to reporting is often used; this makes fully evident just acute causes (e.g. a problem at the production site), but leaves unattended more systemic issues (e.g. consolidation of manufacturing, resulting in a very limited number of production sites) and market-related factors (e.g. single-winner procurement practices).

Quality and manufacturing issues account for approx. half of all cases of shortages, suggest the report; among commercial reasons are market withdrawals and unexpected increases in demand. The information available for the analysis was judged insufficient to exactly asses the potential risks linked to outsourcing of manufacturing activities (including the production of APIs) and parallel distribution.

The proposed recommendations ask for greater transparency of industry supply quotas as well as parallel traders’ and wholesalers’ transactions. Suppliers should establish adequate shortage prevention and mitigation plans; legal obligations for MAHs and wholesalers are suggested in order to maintain a safety stock of (unfinished) products for medicines of major therapeutic interest at EU-level.

A new legislation to tackle shortages

The provisions set forth by Articles 23a and 81 of the Directive have been transposed differently into the single national legislations, often well before the establishment of the shortages registries. Several EU’s countries have acted on their own to strengthen the system, for example establishing mandatory reporting on stock levels and export restrictions. Nevertheless, according to the study available data are not sufficient to draw final conclusions on the costs and efficacy of stock keeping obligations on the level of (notified) shortages in the countries where they were introduced.

A more pro-active approach to the management of medicines shortages by MAHs and distributors may be supported by the availability of a EU-wide and uniform legislation governing financial sanctions to be applied if notification requirements and/or supply responsibilities are not met. Other suggestions include the adoption of common principles for the introduction of national restrictions on intra-EU trade, and the availability of greater flexibilities for emergency imports of specific products in case of market withdrawals and other critical shortages. As for procurement, the study indicates the opportunity to address public procurement tenders also considering the incorporation of requirements for more diversified, multiple tenderers and thereby supply sources.

From a regulatory perspective, the document highlights the opportunity to reduce costs and simplify administrative procedures for the submission of post-approval changes. The availability of an accelerated mutual recognition procedure (MRP) within the EU is also suggested, together with a more efficient use of the Repeat Use Procedure. Improved flexibility should be a target also with respect to the EU-wide regulation governing medicines packaging and labelling, so to allow for the use of digital leaflets and multi-country/multi-language packaging and labelling.


Steps towards the final approval of the IP action plan

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By Giuliana Miglierini

The end of 2021 may see the final approval of many pieces of the new legislative framework announced in November 2020 by the European Commission. An important piece of this puzzle is represented by the IP Action Plan, governing the protection of intellectual property (IP); a step forward in this direction is represented by the resolution of 11 November 2021 on the Own-initiative report of the European Parliament.

The final text licensed in single reading is the result of the examination of the initial draft report – issued in May 2020 by the Committee for Legal Affairs, rapporteur Marion Walsmann – by several other Committees (IMCO, DEVE, CULT, AGRI).

The main points of the resolution

The resolution recognises the importance for the European economy of a balanced protection and enforcement of intellectual property rights (IPR). In years 2012-2016, the knowledge-intensive industries generated almost 30% of all jobs and almost 45% of total economic activity (in terms of Gross Domestic Product, GDP) in the EU; the IPR-intensive industries account for 93% of total EU exports of goods.

Europe’s recovery and resilience capacity is also highly impacted, as demonstrated by the pandemic when shortages of certain medicinal products and vaccines occurred. The EU Parliament acknowledges the role played by intellectual property in increasing the overall value of companies,especially the small-and-medium size ones (SMEs).

A current limitation to IP protection in Europe is represented by the still fragmented situation across different member states, which often leads to parallel national validation procedures and litigation for European patents. To this instance, the Parliament suggests the establishment of an IP coordinator at European level, to harmonise the approach to EU IP policy and enhance cooperation between the different bodies involved in the process (i.e. national IP authorities, Commission Directorates-General, EPO, EUIPO, WIPO, etc).

The Parliament also recognised the role IP plays in the pharmaceutical sector, where the availability of incentives greatly favours the development of new and innovative treatments. The resolution asks the Commission to support the innovative potential of European companies “on the basis of a comprehensive IP regime”, so to guarantee effective protection for R&D investments and favour fair returns through licensing. The availability of open technology standards has been valued as an important competitive element on the wider, global scenario.

Many different types of incentives are suggested by the Parliament’s resolution as useful to support micro-enterprises and SMEs in filing and managing their intellectual property, including IP vouchers, IP Scan and other Commission and EUIPO initiatives to support simple registration procedures and low administrative fees. The newly created European IP Information Centre may represents a fundamental reference point to increase knowledge in the field. The Parliament also suggests to introducing an EU-level utility model protection, not yet available, as a possible fast and low-cost protection tool to protect technical inventions.

Unitary patents and improved market competition

Still missing members states are urged to adhere to the enhanced cooperation scheme for the creation of a Unitary Patent Protection (UPP) and to ratify the Protocol to the Agreement on a Unified Patent Court on provisional application (PPA). The activation of this unique Court in charge of the examination of litigations would allow for a more efficient process and for lowering legal costs and improving legal certainty.

Fragmentation remains an issue also with respect to Supplementary Protection Certificates (SPCs): to this instance, the resolution asks the Commission to issue guidelines for member states and to provide a legislative proposal based on an exhaustive impact assessment. A major criticality to be solved is represented by the unitary patent not providing a unique SPC title valid across the EU; the own-initiative report also suggests the extension of the EPO’s mandate, so that examination of SPC applications could be carried out on the basis of unified rules.

Other important points needing attention to improve the presence of generic and biosimilar medicines in the EU are the abuse of divisional patent applications and patent linkage, which should also see an intervention by the Commission. The Parliament also opened the possibility of a revision of the Bolar exemption, which allows clinical trials on patented products needed to reach marketing authorisation of a generic or biosimilar version not to be regarded as infringements of patent rights or SPCs. This may also support the immediate market entry after the expiration of patent rights and SPCs. The Commission is called also to ensure the effectiveness and better coordination of compulsory licensing in order to provide access to medicines needed in case of health emergencies.

The resolution also addresses the theme of standard essential patents, which currently often leads to litigations, and it calls for the revision of the 20-years old system for design protection. Transparency on results obtained from publicly funded R&D is also recommended. The Parliament suggests artificial intelligence (AI) and blockchain technologies may play an important role in tackling counterfeiting practices and guarantee traceability of goods, as they may contribute to a better enforcement of intellectual property rights along the whole supply chain. The Commission should also work to establish clearer criteria for the protection of inventions created by the AI, without human intervention.

Comments from the industry

The European Parliament has clearly voted for a strong and fair IP system by underlining the importance of timely generic and biosimilar medicine competition. The misuse of divisional patents, the need to enlarge the scope of bolar to include API and all regulatory and administrative steps, and the long overdue ban anti-competitive patent linkage are well known problems that the Commission should address in the IP Action Plan. The Parliament has voted; the Commission must act.”, said Adrian van den Hoven, Director General at Medicines for Europe.

A major point in the implementation of the new European policies is represented by the review the Commission is going to conduct in 2024 to assess the effective achievement of goals of the SPC manufacturing waiver, which entered into force in July 2019 and is expected to start producing effects in the second half of 2022.

Many of the themes discussed in the Parliament’s resolution were debated during a webinar organized by Medicines for Europe, with the participation of representatives from the European Commission and the European Patent Office.

EFPIA, representing the innovator pharmaceutical industry, focused its attention on the impact of past EU Free Trade Agreements (FTAs) on drug spending, timing of countries’ access to new medicines after global launch, investments overall and in pharmaceuticals, and clinical trial participation. A report by IQVIA published in the Federation’s website addresses the impact of IP protection on these elements. Results confirm the central role of the pharmaceutical sector as the most R&D intensive industry in the world, with R&D spending averaging over 15% of revenue. A strong IP protection framework available at the level of EU FTAs favours the attractiveness for investments in the EU and its FTA partner countries. According to the report, an expanded IP protection appears not to be linked to the generation of a higher pharmaceutical spending; drugs’ share of healthcare spending is claimed to stay flat or fall after an FTA, and prices for medicines to rise more slowly than the level of inflation. A stronger IP index, adds IQVIA, is also correlated with increased clinical trial activity in a country, bringing both clinical and economic benefits.


Consultation on the reform of the European pharmaceutical legislation

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In November 2020, the Commission published a Communication on a Pharmaceutical Strategy for Europe. The Pharmaceutical Strategy identifies flagship initiatives and other actions to ensure the delivery of tangible results: https://ec.europa.eu/health/sites/default/files/human-use/docs/pharma-strategy_report_en.pdf As part of the implementation of the strategy, the Commission is evaluating the general pharmaceutical legislation and assessing the impacts of possible changes in the legislation as described in the relevant inception impact assessment.

This consultation aims to collect views of stakeholders in order to support the evaluation of the existing general pharmaceutical legislation and the impact assessment of its revision. A summary on the outcome of the public consultation will be published by the Commission services on the ‘Have your say’ portal. The Commission’s questionnaire is under consideration by our Bureau members and the link is as follows: https://forms.office.com/r/EUHkxBN3Sk. The deadline to participate in this consultation call is the 10th December. 

We thank you for your participation.


Commission establishes portfolio of 10 most promising treatments for Covid-19

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by Giuliana Miglierini

The second phase in the development of new medicines to treat Covid-19 – a part of the EU Strategy on Covid-19 Therapeutics launched in May 2021 – has reached a cornerstone with the announcement made by the European Commission of a first portfolio list of ten potential Covid-19 therapeutic candidates likely to be authorised by the European Medicines Agency (EMA). The only medicine authorised up to now at EU-level to treat Covid-19 is remdesivir.

The choice of the molecules to be included in the list was based on independent scientific advice by an expert group, and it is aimed to offer new treatment opportunities for patients affected by the disease in a way complementary to the preventive action of the already available vaccines. The strategy shall contribute to the achievement of the European Health Union, and it has been modelled on the example of the EU Vaccines Strategy.

Once available in the European market, the new medicines are expected to contribute to the reduction of hospitalisations and deaths from Covid-19. “We have already signed four joint procurement contracts for different Covid-19 treatments and we stand ready to negotiate more. Our goal is to authorise at least three therapeutics in the coming weeks and possibly two more by the end of the year and help Member States gain access to them as soon as possible.”, said the Commissioner for Health and Food Safety, Stella Kyriakides.

Three different categories of therapeutics

The initial list of ten candidates includes three different categories of therapeutics, and it may evolve in future according to the emerging of new scientific evidence.

Antiviral monoclonal antibodies have been identified as the most efficacious approach to be used in the earliest stages of infection. This category includes the following medicinal products under development:

  • Ronapreve, a combination of two monocolonal antibodies casirivimab and imdevimab from Regeneron Pharmaceuticals and Roche.
  • Xevudy (sotrovimab) from Vir Biotechnology and GlaxoSmithKline.
  • Evusheld, a combination of two monoclonal antibodies tixagevimab and cilgavimab from Astra-Zeneca.

The second category refers to oral antivirals, in this case too for early treatment; it includes the following candidates:

  • Molnupiravir from Ridgeback Biotherapeutics and MSD.
  • PF-07321332 from Pfizer.
  • AT-527 from Atea Pharmaceuticals and Roche.

Hospitalised patients may also benefit from the use of immunomodulators; four different possible candidates have been selected within this category:

  • Actemra (tocilizumab) from Roche Holding.
  • Kineret (anakinra) from Swedish Orphan Biovitrum.
  • Olumiant (baricitinib) from Eli Lilly.
  • Lenzilumab from Humanigen.

The scrutiny and selection of the most promising therapeutic options took into consideration 82 different molecules in late-stage clinical development. The analysis assumed that different types of products are needed for different patient populations and at different stages and severity of the disease. This scrutiny exercise was completely separate from the standard scientific assessment of the regulatory dossiers submitted for the candidates, that will be performed by EMA in order to issue the recommendation for final marketing authorisation by the EU Commission.

Steps towards the approval of the selected candidates

As announced by Commissioner Stella Kyriakides, half of the selected candidate therapeutics may reach approval by EMA by the end of 2021. These include products for which the rolling review is already ongoing or that have applied for marketing authorisation to the European Medicines Agency. Pre-requisite for the approval is the final demonstration of their quality, safety, and efficacy; there is still the possibility some of the products in the list shall not be authorized should the scientific evidence provided to EMA be considered not enough robust to meet the regulatory requirements.

Four other candidates are still in early phase of development and have already received scientific advice from the Agency; their rolling review shall begin as soon as enough clinical data will be available. The further development of these products will benefit by an innovation booster to support development activities.

As said, this is just a first list of promising therapeutics to treat Covid-19; some other approaches are expected to be identified as a consequence of the activation of several new initiatives by the EU Commission. Among these are the setting up of the interactive mapping platform for promising therapeutics which represents one of the first targets of action for the newly created Health Emergency Preparedness and Response Authority (HERA) (we wrote about this in October’s newsletter). The Commission also announced the activation within few weeks of the HERA website, where contact details and practical guidance for interested companies shall be found.

A pan-European matchmaking event for therapeutics industrial production has been also announced; this effort will focus on the development of new and repurposed Covid-19 therapeutics and it is aimed to mobilise the EU’s pharmaceutical manufacturing capacity.

The criteria used to select the candidate therapeutics

The European Commission published also a Q&A note to better explain the process that led to the selection of the ten promising therapeutics to be included in the list.

The portfolio of the selected products (authorised and under development) has been established by the expert sub-group on Covid-19 therapeutics (part of the expert group on SARS-CoV-2 variants) upon request of the Commission. The criteria used to run the analysis were approved by Member States in the Human Pharmaceutical Committee.

They include the evaluation of the pharmacological rationale on the basis of the available evidence of the potential role played by the single medicinal product in the treatment of Covid-19, its stage of development and availability of relevant data from clinical trials, the absence of (new) major identified safety issues, and the ability to answer to unmet clinical need and/or bring therapeutic added value. For some product categories, the efficacy against new SARSCoV-2 variants has been also evaluated.

Other points included in the assessment refer to the route of administration, treatment regimen, and formulation, and the company’s intention to access EMA’s early stage scientific advice procedures. The analysis run by the expert group did not focused on more industrial aspects, i.e. manufacturing, production volumes, prices and access conditions; these will be part of the considerations made by the Commission in order to activate its support instruments.

As for the three different categories of selected products, antiviral monoclonal antibodies are intended to mimic the action of natural antibodies generated by the immune system against coronavirus. They can exert both a curative and a preventive action against the infection, in particular in the earliest stages of the disease. They are usually administered by injection.

Oral antivirals are small molecules aimed to block the activity and replication of the virus. These too are early interventions targeted to prevent damage in tissues and organs and offer the advantage of administration as tablets or capsules, thus favouring compliance. Other plus identified by the expert group are a higher resistance to variants, and the therapeutic action maintained also in vaccinated patients.

Immunomodulators aim to regulate the excessive reaction of the immune systems against the virus, thus preventing the risk of hospitalisation. They represent a symptomatic treatment option for patients at severe stage of progression of the disease despite vaccination and antiviral therapy.


First steps of the HERA Authority and comments from industrial and medical associations

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by Giuliana Miglierini

The new European Health Emergency preparedness and Response Authority (HERA) has started its operative phase. Initially launched in February 2021, HERA has been modelled by the European Commission on the example of the US’s DARPA agency, and it will be in charge of anticipating threats and potential health crises.

The first three calls for tender to support HERA’s setup have been published on the Commission’s website and will remain open until 29 October 2021. They are targeted towards addressing different aspects of the management of Covid-19 therapeutics and antimicrobial resistance.

A total sum of €7 million from the EU4Health programme will fund these activities. An info session on the three calls was delivered on 14 October 2021 by European Health and Digital Executive Agency (HaDEA) in collaboration with DG Santé (see more at this link). A summary of HERA’s activities in the field of crisis preparedness and emergency response is also available here. A budget of €6 billion from the current Multiannual Financial Framework 2022-2027 is available to fund HERA’s setup and activities, plus additional support from other EU programmes, for a total of almost €30 billion. HERA will be part of the internal Commission structure, and it is expected to become fully operational in early 2022.

HERA’s role is to improve the EU’s development, manufacturing, procurement and distribution of key medical countermeasures said the Commissioner for Health, Stella Kyriakides, following the recent Informal Meeting of Health Ministers in Ljubljana, Slovenia -. HERA will also be crucial in ensuring accessibility and availability of medicines. As I said to Ministers today, HERA is a joint undertaking, with Member States, EU Agencies, the European Parliament and other concerned stakeholders, including industry and civil society. HERA’s strength and success will come from our joint preparedness and joint response, and our capacity to bringing joint solutions. HERA is now operational and should be fully up and running early next year.

HERA’s first activities

The call for tender on antimicrobial resistancerefers to a service contract to run a study comprehensive of a technological review of the latest AMR medical-countermeasures (e.g.; medicines, medical devices, vaccines) and a gap analysis and assessment of needs amongst the EU Member States and key stakeholders. The study shall also include options for possible actions, funding and provision of support mechanisms, and exploration of available tools suitable to ensure the availability of safe and effective products in the European market. These products are expected to be immediately available to the EU and member states in the event of a public health emergency. The estimated total value of the tender is €1 million.

Stockpiling of medical countermeasures in the area of AMR is the subject of the second feasibility study (estimated total value €1 million). The study shall analyse physical stockpiling solutions compared to other options, providing identification and assessment of all available opportunities. The needs and availability of AMR countermeasures shall be also assessing, both at member states and EU level, as well as the mapping of relevant stockpiling systems currently operated at EU and/or global level (e.g. WHO). Possible funding mechanisms (including procurement options), identification and assessment of operational deployment mechanisms and considerations on liability and regulatory aspects and/or constraints are also to be included in the study.

The third feasibility study has the higher estimated total value (€5 million) and will focus on the design and prototype development for a mapping platform on Covid-19 therapeutics in the EU. The platform is expected to map the production capacity and supply of products intended to treat Covid-19, both already on the market and in R&D phases. Possible examples include ICU medicines, heparin, dexamethasone and antibiotics, in vitro diagnostics devices and/or companion diagnostics.

Comments from stakeholders

Many stakeholders released their comments to welcome the creation of the new Authority.

The creation of HERA is a first step to putting Europe on the front foot in addressing global health threats.”, said EFPIA Director General, Nathalie Moll. “The speed at which Europe became the epicentre of the Covid-19 crisis meant, as a region, we were simply reacting to issues as they arose, working together to find solutions as quickly as possible”.

The lessons learnt during the pandemic revealed a number of weaknesses in Europe’s ability to respond to a public health crisis. HERA’s ability to balance coordination and unity with agility and responsiveness as threats emerge shall be central to its success, according to EFPIA. The Federation, together with Vaccines Europe, supports an end-to-end approach to govern HERA’s activities, and a collaborative, partnership-based model to maximise the strength of each stakeholder in a highly coordinated approach.

The association representing the generic and biosimilar industry, Medicines for Europe, wrote in a note that HERA should “be an efficient agency with strong links to healthcare industries”. A joint industrial cooperation forum to coordinate interactions of manufacturing associations and EU authorities, a regulatory framework able to prioritise the supply of essential medicines and the elimination of the proposal for redundant manufacturing capacity are just some suggestions made by the Association, which is more favourable towards manufacturing investment in a wide range of medicine production types, as outlined in the Structured Dialogue.

Reserve policies should be also revised in order to avoid waste, costly destruction, and distorting supplies of medicines to certain (smaller) EU countries. The functioning of joint procurement system should be also addressed and improved by the Commission, to avoid distortions in the internal market and provide accurate demand estimates.

The Federation of the European Academies of Medicine (FEAM) published in May 2021 a report jointly prepared with the Wellcome Trust, highlighting the opportunity in the short term not to overstep HERA’s role in relation to others European authorities (e.g. the European Centre for Disease Prevention and Control) as a pre-requirement to ensure its success.

The new-born Authority should also try to harmonise the European research and development landscape for pandemic preparedness and response, in order to remain “relevant and active between emergencies”.


Consultation on the reform of the European pharmaceutical legislation

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by Giuliana Miglierini

A new step in the review of the overall framework governing the pharmaceutical sector has been announced by the European Commission on September 28th: the launch of a first phase of public consultation will enable to collect opinions from all the stakeholders of the pharmaceutical sector as a pre-requisite for the revision of the existing general pharmaceutical legislation on medicines for human use.

The initiative builds on the previous public consultation which represented the basis for the drafting of the Pharmaceutical Strategy for Europe released by the Commission in November 2020. The final target is the creation of a future-proof and crisis-resilient regulatory framework for the pharmaceutical sector. The pharmaceutical industry represents one of the main contributors to the European economy, with 800.000 direct jobs and €109.4 billion trade surplus in 2019, and €37 billion contribution to research investment.

Today we take an important step for the reform of EU’s pharmaceutical legislation by the end of next year. A regulatory framework for pharmaceuticals, which is modernised and fit for purpose, is a key element of a strong European Health Union and crucial to addressing the many challenges this sector is facing. I call on all interested citizens and stakeholders to help us shape EU rules for the future, responding to patients’ needs and keeping our industry innovative and globally.”, said the Commissioner for Health and Food Safety, Stella Kyriakides.

Details of the consultation

The consultation is open until 21 December 2021 and is published in the form of an online questionnaire to be filled in by stakeholders and members of the general public, including patients and patient’s organisations, pharmacists and doctors, associations active in public health, healthcare professionals and providers, academia, researchers, regulators, EU’s institutions and the pharmaceutical industry. A combined evaluation roadmap/Inception Impact Assessment published in April 2021 is also available at the consultation’s webpage, together with a document on the consultation strategy (link).

The main issues touched by the consultation include all the 4 pillars of the Pharmaceutical Strategy, for each of which both legislative and non-legislative actions are envisaged.

A main area of interest looks to address unmet medical needs and ensure access to affordable medicines for patients, namely in the areas of antimicrobial resistance and rare diseases. The commitment to respond to environmental challenges is another key point of attention. New incentives for innovation and future-proofing the regulatory framework for novel products shall support the availability of next-generation therapeutics for European citizens and the competitiveness of the European markets. Quality and manufacturing of medicines, and the repurposing of older products are other topics looking for innovative approaches to be defined within the revision of the pharmaceutical legislation.

The Covid pandemia showed the importance to developed measures to enhance crisis preparedness and response mechanisms in all European countries, and to ensure diversified and secure supply chains are in place to reduce dependency of supply from extra-EU countries. A stronger EU voice on the theme of medicines shortages shall be also pursued by promoting a high level of quality, efficacy and safety standards.

The consultation aims to better understanding of all implications of the possible policy options, and to provide evidence to the Commission on the functioning and delivery of the current legislation with respect to its initial objectives. The impact of new potential options on the different stakeholders shall be also assessed. The exercise aims to identify areas of broad agreement among stakeholders as well as differences of views on other topics, and the causes of contention.

A brief overview of the legislative process

The revision of the pharmaceutical legislation is just one of the many legislative actions undertaken by the von der Leyen Commission in order to completely innovate the reference framework for medicines’ development, production, authorisation, commercialisation and postmarketing monitoring. The last revision of the pharmaceutical legislation occurred almost 20 years ago.

The Pharmaceutical Strategy defines the general targets, to be then synergistically implemented by mean of actions specific to the different fields. The revision of the general pharmaceutical legislation is one of the main flagship initiatives towards this target, and it is also being supported by an ongoing study run by an external contractor and expected to close in Q1 2022.

Among other actions which shall contribute to the goals of the Strategy are the proposal of the new regulation on Health Technology Assessment, the EU Health Data Space, the revision of the current legislation on rare diseases and paediatric medicines and actions to address shortage of medicines in the EU’s market.


The Pact for Research and Innovation in Europe

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by Giuliana Miglierini

The roadmap to support the implementation of the new vision of the European Research Area (ERA) made a concrete step forward on 16 July 2021, with the adoption by the European Commission of the proposal for a Council Recommendation on “A Pact for Research and Innovation in Europe”. The chosen form of a Recommendation supports the final adoption of the Pact in the form of a single non-binding initiative.
The Commission’s proposal was drafted taking into consideration the results from the public consultation ran between 15 April and 13 May 2021, the views generated within the ERA Forum for Transition (set up as an informal Commission expert group), and the out-comings of workshops involving selected stakeholders.
“The pandemic has shown us the importance of uniting research and innovation efforts that swiftly bring results to the market. It has shown us the importance of investment in jointly agreed strategic priorities between Member states and the EU. The Pact for Research and Innovation we propose today, will facilitate better collaboration, and join our efforts to tackle research and innovation objectives that matter the most for Europe. And it will allow all of us to learn from each other”, said Margrethe Vestager, EU Commission’s Executive Vice-President for a Europe Fit for the Digital Age.
According to Mariya Gabriel, Commissioner for Innovation, Research, Culture, Education and Youth, “The objective of the Pact is to foster the future dialogue process with key actors putting a clear emphasis on sharing best practices and facilitating the collaboration of Member States to invest in and coordinate on common research and innovation objectives”.

The main features of the document
The goal of the Commission is to update the approach used to manage the European Research Area to the most recent models of R&I and financing of scientific research. The new model for ERA was already described in the “Communication on A New ERA for Research and Innovation” (COM(2020) 628 final) adopted on 30 September 2020.
Integration of national policies instead of a simple collaboration is one of the main points to achieve sharing of key principles and values and to guide joint actions in priority areas. These values and principles are now better detailed in the new Pact for Research and Innovation (R&I), which shall represent the basis for national authorities to reform their internal R&I frameworks in the direction of an improved harmonisation between different member states.
Coordination of efforts at the central and national level should benefit from a Union-level coordination and support mechanism, a common ERA policy agenda of jointly agreed ERA actions to be implemented, a dedicated ERA policy online platform for reporting, and a ERA score- board to monitor progress towards common objectives. Regular bilateral and multilateral policy dialogues between member states and the Commission is expected to favour the sharing of best practices and mutual learning exercises.

The inspiring values
Three different dimensions characterise the declination of the principles and values called to inspire future R&I activities. The “upholding values” include ethics and integrity of research and innovation, freedom of scientific research, gender equality and equal opportunities.
“Working better” values target the free circulation of researchers, excellence and value creation as a tool to support European excellence in science generation, together with early sharing of scientific knowledge through open science practices, attractive and merit-based careers, enhanced framework conditions for mobility and exchanges between academia and industry, and open access to research infrastructures, technology infrastructures and their services. The common goal of all these actions refers to the achievement of the highest quality of R&I activities, to be supported by new models of selection and funding; re-use of previous results should be also pursued during research management activities.
The “working together” dimension is based on the key principles of coordination, coherence, and commitment. Member states are called to coordinate their R&I policies and programmes in areas of common interest and to direct research and innovation investments and reforms to- wards achieving the ERA and speed up the green and digital transition. Global outreach should base on collaboration with partners from third countries and regions, while inclusiveness should support the exploitation of ERA’s full potential to compete at the global level. Furthermore, societal responsibility should aim to increase public trust in science and innovation.

Synergies of action
The Pact for R&I is expected to act in synergy with many other pieces of European legislation to achieve its goals. Challenge-based ERA actions should support the increased integration of the Commission and member states, including their regions, cities, and municipalities. The operative tools may be represented for example by collaborative projects to be run as a part of Horizon Europe Missions, European partnerships including EIT Knowledge and Innovation Communities (EIT KICs), joint programming initiatives or multilateral alliance. Inspiration can be obtained also from existing coordination initiatives, such as the Strategic Energy Technology Plan (SET Plan) or the ERAvsCorona initiative.
Integration with the EU Skills Agenda is also important to ensure the alignment of R&I with higher education, and synergies are expected between ERA and the European Higher Education Area (EHEA). Not less important are possible synergies with the EU’s Industrial Strategy, for example in the field of technology infrastructures, industrial Alliances, and common industrial technology roadmaps. A more active citizen and societal engagement in R&I is another target of the Pact.
At the financial level, the EU Commission looks at improved synergies between EU’s, national and regional funding programmes, with attention to favour the excellence-based integration of research-performing organisations from countries with lower R&I performance into EU’s scientific networks and innovation ecosystems.
The proposal adopted by the Commission provides insights on the expected level of investments in R&D: the total expenditure on research and development should reach the 3% target of EU GDP by 2030, with a total public effort on R&D up to 1.25% of EU GDP. The share of national public R&D expenditure committed to joint programmes, research infrastructures and European Partnerships should also reach 5% of national public R&D funding by the same year.
Voluntary targets for investments
A possible weak point in the vision of the Commission for the future of ERA may be represented by the voluntary adhesion member states are called to with respect to the expected level of expenditure on R&I activities. According to Science Business, the 3% target was achieved in 2019 only by Germany, Sweden, and Austria, while the EU average (2.2%) is below that of US, Japan, and Korea.
Critics to the current EU’s “boom and bust” approach to basic research funding came by the outgoing president of the European Research Council (ERC), Jean-Pierre Bourguignon, during a meeting of EU science ministers in Slovenia in July (see Science Business).
According to Bourguignon, basic R&D should be not necessarily targeted towards topics which represents the priority of action of the EU Commission, such as the green and digital agenda. Sufficient funding for bottom-up research should be always available in order to support curiosity-driven research.


The new vision for the European research landscape

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by Giuliana Miglierini

The new European framework for research and innovation, Horizon Europe (HE, 2021-2027), is now operative. A great deal of work has been accomplished in the recent months in order to define the possibility for third countries to participate to the new projects that will be activated. The List of Participating Countries in Horizon Europe was published by the European Commission at mid-June; it includes eighteen third countries associated to the framework programme, according to the provisions set forth by Regulation 2021/6951.

Eighteen third countries associated to Horizon Europe
The list also includes the United Kingdom, which became a third country after the Brexit, but with the exception of its participation to the EIC Fund (which is part of the EIC Accelerator that provides investment through equity or other repayable form).
The status of associated country makes its legal entities entitled to participate to HE’s projects under equivalent conditions as legal entities from the EU member states, unless specific limitations or conditions are specified in the work programme and/or call/topic text. All the sixteen non-EU countries associated to Horizon 2020 have expressed interest to continue the collaboration with the EU’s researchers. Transitional arrangements are in place to govern their participation to HE while waiting for the definitive closure of the negotiations.
Israel, Iceland and Norway are other components of this list, together with the majority of East European countries, Turkey, Morocco and Tunisia. Among not associated countries, Liechtenstein openly expressed its intention not to become an associated country. Further negotiations can lead to the expansion of the list.
Non-associated countries and international organisations can participate to most Horizon Europe’s calls, unless specific limitations or conditions apply; particularly interesting from this point of view are topics of research specifically directed to improve international cooperation.
Participants from not associated countries are not automatically eligible for funding, thus have to participate to the research activities at their own cost. Some exceptional circumstances allow them to access funding, i.e. in the case of outstanding competence/expertise, or if access to particular research infrastructures, data or geographical environment is needed. Automatic funding is available to a selected list of low- to middle-income countries from Africa, Asia, South America and Oceania.

The case of Switzerland
Switzerland is currently excluded from the pool of associated countries to Horizon Europe.
This is the result of the decision of the Swiss Federal Council occurred at the end of May to stop the seven years-long negotiations with the EU Commission (see more on Science Business).
Significantly, scientific research and the status of associated country within HE was not part of this negotiation, that was focused instead on bilateral agreements for the free movement of persons and mutual recognition of industry standards, agricultural products, air transport and land transport, as reported by Science Business.
The exclusion of Switzerland immediately caused a vivid debate among European scientists, worried for the possible consequences of the inability of their Swiss colleagues to take part to HE’s projects. An Open Letter signed by many different European Science,Technology & Innovation (STI) Councils and Advisory Bodies and other Science organisations (among which Science Europe and Cesaer) urges for the full association of Switzerland with Horizon Europe.
The signatories of this letter would like to underline the importance of continuing the long established and mutually beneficial cooperation between the EU and Switzerland in the domain of research and innovation”, states the letter. Many are the past contributions from the Helvetic country to the success of European research, starting with the hosting of the European Organisation for Nuclear Research (CERN) up to the foundation of the European Space Agency. “Downgrading Switzerland to a third country would severely limit its expertise being brought into Horizon Europe projects tackling today’s and tomorrow’s global challenges. We are convinced that this would lead to a lose-lose situation, putting successful cooperation in strategic areas at risk and ultimately weaken the ERA as a whole”, write the scientific organisations.

The situation with respect to China, the US and Canada
The “open strategic autonomy” is the new paradigm of action the von der Leyen Commission shall apply also in the field of research and innovation. According to Science Business, this approach will represent the basis for the negotiations with countries like China, that might require a higher level of attention with respect to the need of providing adequate protection for the intellectual property developed by European scientists.
Preliminary discussions to solve legal issues that prevented the participation of US universities to EU research projects in the past years are also undergoing. In the meantime, the high level EUUS Trade and Technology Council (TTC) was launched by US president Joe Biden and EU Commission president Ursula von der Leyen during the US-EU Summit in Brussels on June 15, 2021.
The TTC will meet periodically at the political level to coordinate approaches to key global trade, economic, and technology issues and to deepen transatlantic trade and economic relations commitment to strengthen our technological and industrial leadership and expand bilateral trade and investment. It also gives us tools to address threats such as unfair competition and the misuse of new technologies. This is a top priority for the EU, and we warmly welcome the fact that it is now also at the top of the transatlantic trade agenda”, said Valdis Dombrovskis, European Commission Executive Vice-President and EU Trade Commissioner.
The TTC will operate through several working groups, responsible to translate the political decisions into deliverables, coordinate the technical work and report to the political level. Among the first topics for its action is cooperation in the field of technology standards and secure supply chains.
Preliminary negotiations took place also with Canada in the course of the European Union-Canada summit, in June (See more here). Specific points in the field of health mentioned in the final joint statement include the launch of a new Canada-EU dialogue on health under the Strategic Partnership Agreement to improve health cooperation in multilateral contexts, and an enhanced bilateral cooperation under Horizon Europe. This last action should see some exploratory discussions towards a possible association of Canada to the framework programme, particularly with respect to the green and digital transitions and AI and quantum cooperation.

A new Strategy for Science Europe
Science Europe, the organisation representing major national research performing organisations (RPOs) and research funding organisations (RFOs) in Europe, has published its new Strategy 2021-2026 and the related Action Plan.
The central vision of the news Strategy is that “for a European Research Area with optimal conditions, to support robust education, research and innovation systems”. This goal will be pursued by defining the long-term perspectives for European research and selecting the best-practice approaches. Scientific knowledge as a common good, research as a public service, freedom of scientific inquiry, responsibility of all actors in ensuring the highest possible standards of quality, ethics, integrity, inclusivity, and openness in the conduct and management of research are just some of the values that have inspired the Strategy.
Three priorities will guide members organisations, starting from the role RPOs and RFOs can play in shaping future developments of the European research policy. Open science will continue to represent the paradigm of choice in order to ensure sustainability of the R&I system. A possible evolution of the current framework may result in the proposed European Framework Programmes for Research and Innovation. Science Europe will support its members in promoting investment in R&I and in closing the performance divide between different national R&I systems in Europe. Complementarities shall constitute the basis of bilateral and multilateral collaboration between member organisations, as well as of cross-border collaborations at a global level.
The diffusion of a solid, quality-driven research culture is a fundamental requirement for its success. Science Europe plans to play a central role with other European institutions in jointly define and implement the positive culture shift needed to create sustainable research ecosystems. This goal will take advantage of the different approaches and values that are used by researchers from different EU countries, taking also into consideration the global challenges and societal expectations and the degree of self-organisation of the European R&I system. Incentives and rewards are foreseen as a way to improve the sustainable development of research systems, together with a better coherence between policy areas.
According to Science Europe, the European research framework is called to an effort to develop new, long-term solutions for the current challenges that affects society. Interdependencies between curiosity-driven and challenge-oriented approaches should be addressed in order to boost this target, together with the support to Open Science models. A stronger engagement between researchers, policy makers and society, and improved support to trans-disciplinary research are key objectives set forth by Science Europe’s Strategy.

A Strategic Agenda from five industrial associations
From the industrial point of view, the activation of the new Horizon Europe research framework will correspond to the end of the Innovative Medicines Initiative (IMI), that characterised the public-private partnerships for research in the pharmaceutical and life sciences sectors in the past decade.
A new framework is expected to take its place, the proposed Innovative Health Initiative (IHI), which should be activated in the context of Horizon Europe. While the European Commission is still working to define the legislation governing the new partnerships, a Strategic Agenda for Research & Innovation in Healthcare has been released by five European industry associations representing the pharmaceutical, biotech and medical technologies industries (COCIR, EFPIA, MedTech Europe, EuropaBio and Vaccines Europe).The Agenda has been jointly drafted by the prospective IHI Joint Undertaking member industry associations and the European Commission services (based on the results of a public consultation ran in 2019) and it should represent the basis for the final, formal adoption of the new IHI framework after the partnership legislation has been adopted and the partnership is operational. A new tool is planned within Horizon Europe to run the IHI, the institutionalised Public-Private Partnerships, which are expected to help de-risking the pre-competitive public-private collaboration.
The vision illustrated by the document reflects the new models of cross-sectorial integration of technologies, know-how, products, services and workflows in order to build true new peoplecentred healthcare systems. The development of new solutions for the prevention, diagnosis and treatment of diseases should aim to sustain the good health of EU citizens, and decrease the disease burden for patients, care givers and healthcare professionals.
The new European ecosystem for R&I should aim, according to the document, to facilitate translation of scientific knowledge into innovation, so to respond to the strategic unmet public health needs in a cost-effective way.
Five specific objectives to be achieved by 2030 are envisaged by the Strategy, from a better understanding of the determinants of health and priority disease areas to the integration of fragmented health R&I efforts, up to the development of tools, data, platforms, technologies and processes for improved prediction, prevention, interception, diagnosis, treatment and management of diseases. Projects will be also targeted to demonstrate the feasibility of peoplecentred, integrated healthcare solutions. Digitalisation and data exchange will be central activities to achieve this goal, and will also support the development of new and improved methodologies and models for the comprehensive assessment of the added value of integrated healthcare innovations.
Examples of the activities that may be part of the new IHI projects are the discovery, development and testing of new molecules, and the study of their mechanisms of action; the development and testing of new processes and technologies, and new methodologies for the assessment of safety, health outcomes or for health-economic evaluation. Development may be run up to the pre-standardisation activities or pilots/proofs of feasibility scale, including in-silico trials. Contributions to the development of regulatory science are also an expected outcome. The pharmaceutical and medical technology sectors will be engaged in multi-sectorial activities, moving from product- and pathology-centric goals to patient-centric development. Priorities of research shall be set forth by early engagement with public sector stakeholders, through the establishment of a new Innovation Panel.