HERA Archives - European Industrial Pharmacists Group (EIPG)

Generative AI in drug development


by Giuliana Miglierini Generative AI is perhaps the more advanced form of artificial intelligence available today, as it is able to create new contents (texts, images, audio, video, objects, etc) based on data used to train it. Applications of generative Read more

PGEU annual medicine shortages report


by Giuliana Miglierini The situation of medicine shortages is getting worse, with many countries which in 2023 experienced more issues than the previous years, according to the PGEU annual report on medicine shortages. Community pharmacists are on the front line Read more

EMA’s pilot scheme for academic and non-profit development of ATMPs


by Giuliana Miglierini Advanced therapy medicinal products (ATMPs) are often developed by academic and non-profit organisations, because of their high level expertise in the biotechnological techniques that underpin many new therapeutic approaches. On the other hand, these organisations often lack Read more

EC Communication (part 2): a Critical Medicines Alliance to support European pharma supply chain

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by Giuliana Miglierini

After last week’s examination of the first part of the Commission’s Communication, specifically targeted to short-term actions to prevent and mitigate critical medicine shortages, in this second post we will address the announced mid- and long-term structural measures, focused on the creation of the Critical Medicines Alliance, the diversification of supply chains and the role of international partnerships.

The Critical Medicines Alliance

The second part of the Commission’s Communication details the structural measures to strengthen the secure supply of pharmaceuticals in the EU, with particular reference to critical medicines. An objective that, according to the Commission, may require the development of new pieces of legislation, such as the EU Critical Medicines Act. To this instance, the preparatory study should be launched by the end of 2023, and followed by the impact assessment.

In the meantime, the improved coordination of the industrial approach to the management of shortages in the EU should be pursued by the Critical Medicines Alliance, to be created in early 2024. The Alliance will bring together all involved stakeholders; its activities should start from a shared analysis of vulnerabilities in the supply chain of the critical medicines on the Union list (i.e over-dependency on a limited number of external suppliers, limited diversification possibilities, limited production capacities, etc).

The result of this exercise should be the identification of useful tools to address vulnerabilities of a limited number of critical medicines with the highest risk of shortages and impact on healthcare systems. To this regard, several lines of actions are identified in the Communication, starting from the issuing of a dedicated guidance and common criteria for the coordinated procurement of critical medicines (e.g. green production and prioritisation of supplies in Euro-pe at times of critical shortages). A better quantification of demand and the consequent possibility to compensate and incentivise industry for its effort in these directions are other expected outcomes.

Medium-term contractual incentives are proposed as a tool to improve predictability of supply and to attract new manufacturing investments in Europe, together with the use of capacity reservation contracts modelled on EU FABs. These last instruments were launched by the HERA Authority during the pandemic in order to reserve manufacturing capacities for vaccines and obtain a priority right for their manufacturing in case of a future public health emergency.

The second line of action of the Alliance would address the diversification of global supply chains for critical medicines, including the identification of priority countries to be involved in strategic partnerships on the security of supply (see also below).

The third pillar should see the Alliance involved in the coordination and harmonisation of efforts to identify security of supply needs for critical medicines, on the basis of the above-mentioned identified vulnerabilities. Actions cited by the Communication, such as the Services of General Economic Interest (SGEI) coordinated at the EU level, should be compatible with the state aid framework. The Alliance may also represent the dedicated location where member states may better discuss the possibility of a new Important Project of Common European Interest (IPCEI) focusing on sustainable manufacturing of critical medicines (including off patent medicines).

Stockpiling, skills and financial support

EU stockpiling of critical medicines is another area of activity of the Critical Medicines Alliance. The goal is to overcome current limitations typical of national stockpile programmes; the development of a common strategic approach and a Joint Action on stockpiling has been announced for the first half of 2024, based on the previously mentioned vulnerability analysis and on the experience of the Union Civil Protection Mechanism (UCPM, that will continue to be part of the EU approach) and the rescEU stockpile.

The Alliance should also address the need for new and updated skills to work in the pharmaceutical sector, so to cope with the increasing impact of digitalisation, the evolution of the regulatory environment and the green transition. Pharmacists are cited in the Communication, as their curricula could be easily adjusted to accommodate education and training on new skills. Attention should be paid to increasing STEM (Science, Technology, Engineering and Mathematics) graduates. A Pact for Skills is the measure identified to actively involve key actors in educational and training activities aimed to fill industry skills gaps.

The Alliance would also play a significant role in better leverage and align EU and national funding: a goal deemed important in order to support improved long-term investment predictability for the private sector, and to avoid duplication of efforts. Among other tools cited by the Communication to reach it, the proposed Strategic Technologies for Europe Platform (STEP) is also inclusive of pharmaceuticals, biotechnologies and medical technologies. The creation of a Sovereignty Seal to promote synergies amongst existing programmes, and the Technical Support Instrument to enhance the administrative capacity of member states in managing shortages and producing critical medicines are among other proposed tools.

Diversification of supply chains

A second, fundamental line of action identified by the Commission addresses how to better diversify the complex, global pharmaceutical supply chain, also by means of new international partnerships with third countries. According to the Communication, the EU industry needs to have access to a broad range of essential inputs; to this regard, new strategic partnerships with third countries for production of critical medicines and active ingredients should be based on concrete actions of mutual interest.

The EU has 42 preferential trade agreements in place with 74 different trading partners, and a new one is under negotiation with India. The Commission also recalled the importance of bilateral meetings with China on issues affecting access to medicines supply chains, and of the dialogue with Latin America.

An improved regulatory convergence is another main objective of the planned actions at the international level, so to increase GMP compliance of medicinal products marketed in the EU and manufactured by extra-UE partners. To this instance, the Communication mentions the work of international bodies such as the ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) and ICMRA (International Coalition of Medicines Regulatory Authorities) for the harmonisation of standards for pharmaceuticals, and the WHO support to improved regulatory convergence. Many free trade and mutual recognition agreements (MRAs) signed by the EU also contain this type of obligation, and in some cases the sharing of non-sensitive market knowledge to anticipate possible problems too.

A new network of international partners should be created by the Commission within a year, in conformity with applicable state aid and antitrust rules. The network activities would focus on crisis preparedness and supply diversification. The Communication mentions also different international initiatives already in place, such as the Global Gateway to support local manufacturing of health products and announced another Team European Initiative in Africa on health security and pandemic preparedness and response. Another ongoing initiative is the EU-Latin America and Caribbean Partnership on manufacturing and access to vaccines, medicines and health technologies. The EU will also continue to support the provision of critical medicines in humanitarian contexts.


EC Communication (part 1): How to address critical medicines shortages

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by Giuliana Miglierini

As announced on 3 October in the speech given by Commissioner Stella Kyriakides at European Parliament Plenary Session, the EU Commission has published on 24 October its Communication on medicine shortages and strategic healthcare autonomy.

The planned actions are firstly targeted to prevent and mitigate on the short-term critical medicine shortages, thus avoiding the reoccurrence of situations such as those experienced in the 2022. Mid- and long-term actions have been also addressed to support the strategic autonomy of the European pharmaceutical supply chain. Among these is the creation of a Critical Medicines Alliance, to start operations in early 2024.

Improving the management of critical shortages of medicines and ensuring a steady security of supply for the EU has been our priority since day one. We need a single market for medicines in the EU and a new approach to better tackle shortages of critical medicines. Today we are putting forward collective actions to work closer with the industry and help Member States improve the security of supply for the coming winter and in the long-term.” said Stella Kyriakides, Commissioner for Health and Food Safety.

In this first post, we will examine actions in the field of medicines shortages, leaving the medium and long-term ones to a following article (part 2).

Prepared for future winters

The first goal of the EU Commission is to avoid situations of shortages of critical antibiotics such as those that occurred last year. To this instance, the Health Emergency Preparedness and Response Authority (HERA) and the European Medicines Agency (EMA) have already identified key antibiotics potentially at risk of critical shortages in the winter season, also in future years.

Immediately after the release of the Communication by the Commission, EMA published the details of the announced new European Voluntary Solidarity Mechanism for medicines, the MSSG Solidarity Mechanism.

The mechanism was developed by EMA’s Medicines Shortages Steering Group (MSSG), on the basis of the informal experience made during the pandemic. In case of critical shortages escalated to the MSSG for coordination at European level to request assistance, other member states may be of help through the rescEU stockpile mechanism to redistribute medicines from available stocks. The activation of the Union Civil Protection Mechanism (UCPM), via its 24/7 available European Response Coordination Centre (ERCC), aims to coordinate and logistically support the voluntary transfer of medicines, and it should represent the last resort, after the interested member state had exhausted all other possibilities.

The MSSG also developed a Toolkit including recommendations on how to tackle shortages of critical medicines. Among others are the monitoring of available stocks, supply and demand, interactions with marketing authorisation holders and manufacturers for increasing the manufacturing capacity and for the fair distribution of medicinal products, the implementation of regulatory flexibilities and actions aimed to improve communication to the public and international cooperation with other regulators to early identify critical shortages.

The other actions to tackle shortages

The first version of the Union list of critical medicines is expected to be released by the end of 2023. It will allow the development of further actions, on the basis of the analysis of the vulnerabilities of the supply chain of selected medicines to occur by April 2024.

In addition to the practical recommendations relative to demand forecasting at national level, the Commission is working on an EU Mechanism for Demand Signalling that should better support the collective EU public sector in its decisions. A new European Shortages Monitoring Platform for reporting information regarding available stocks and shortages of medicines is expected to start operating in 2025. Many future actions shall be supported using artificial intelligence to extract information about trends in demand and supply from existing data.

At the regulatory level, a new Joint Action has been announced for early 2024 to promote the effective use of flexibility as well as of measures applied at national level (i.e. magistral preparations of local pharmacies). Regulatory flexibilities may include, among others, the quick authorisation of alternatives, the approval of alternative suppliers of raw materials or finished products, or the temporary extension of shelf-life.

Another initiative announced for 2024 should see the issuing of an EU guidance on procurement of medicines, better detailing the already existing tools and practices supporting the security of supply. In the meantime, an EU joint procurement for antibiotics and treatments for respiratory viruses should be activated for the incoming winter.

The Communication contains some recommendations for member states and the pharmaceutical industry. The former are called to monitor and fully enforce the supply obligations of companies, to develop effective communication plans, and to consider how national procurement rules and criteria can increase security of supply. Industrial stakeholders should continuously monitor the evolution of demand and supply of critical medicines, assuring to the full the supply obligation under EU law. Early communication of critical situations to regulators should also occur, as well as the implementation of recommendations, both on regulatory flexibilities and on the elements of the pharmaceutical revision that could already be applied.

Comments from the stakeholders

The interested pharmaceutical associations promptly reacted to the EU Commission’s Communication.

EFPIA particularly welcomed the structural measures to address the industrial dimension of medicines shortages in the medium and long term, as the Critical Medicines Alliance. The development of solutions targeting the specific root causes of shortages, and measures aimed at mitigating shortages in the short term should be “proportionate and provide efficient, workable solutions that serve public health needs”. EFPIA asks for the industry to be included in the design and implementation of new processes and highlighted the “missed opportunity” represented by sharing of the information stored in the European Medicines Verification System (EMVS).

In response to Member State and Parliament calls for a Critical Medicines Act, this communication is a positive first step for the security of supply of medicines. Medicines for Europe will partner with the EU to implement these important reforms”, said Medicines for Europe President, Elisabeth Stampa. The associations ask, among others, for a strategic EU reserve of essential medicines, and EU funds and State aid projects to incentivise investments in greener and more secure manufacturing processes for essential medicines and active pharmaceutical ingredients (APIs). Digitalisation of the regulatory system and harmonisation of pack sizes and presentations would be also helpful.

European community pharmacists also welcomed the Communication, as it may help to avoid new, severe medicine shortages like the one experienced last winter. “PGEU’s annual survey confirms that shortages exist in all EU countries across all types of medicines, causing detriment to patients’ health, waste of resources and frustration. Every day, we spend hours managing shortages and finding solutions to guarantee continuity of treatment for our patients”, commented PGEU President Koen Straetmans. As for the common strategic approach to stockpiling, according to PGEU it should be guaranteed that stocks will not be to such an extent as to jeopardize the general supply of medicines, nor they should generate unnecessary waste.

EuropaBio, representing the biotech industry, positively commented on the Communication and highlighted that EU actions should not be limited to essential medicines, but should target also the growing dependency on third countries for innovation medicines.


HERA reports on stockpiling of antimicrobials

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By Giuliana Miglierini

The European Health Emergency Preparedness and Response Authority (HERA) has published the two final reports, prepared by McKinsey Solutions for the European Commission, describing respectively the results obtained during the first and second phases of the antimicrobial resistance (AMR) feasibility study on stockpiling.

Antibiotic resistance represents a major threat for human health, as many active substances are losing efficacy towards many bacterial species. The first report (deliverables D1–D5) focuses on the mapping exercise run during the project and aimed to assessing the current situation, identifying vulnerabilities, and reviewing the stockpiling systems currently available in the EU and at the global level.

The second report (deliverables D6-D7) discusses the vulnerabilities identified in the previous phase and the potential tools and solutions to address them, including the assessment of available options for stockpiling of antimicrobials at EU level.

Mapping of the current situation

According to the first report, 32 classes of antibiotics were identified as critical with respect to the need to ensure continued access to patients in order to offer sufficient therapeutic and prophylactic options against systemic bacterial infections.

The analysis proceeded further to identify narrower sets of antibiotics most useful to treat infections due to common pathogens with acquired antibiotic resistance: a first subset of 20 substances was indicated as specially relevant as first- or last-line/reserve therapies against AMR pathogens, and from this a shorter sublist of 13 was identified as last-line/reserve therapies for severe and potentially lethal infections.

The report did not identified any critical market withdrawal of antibiotic substances from the EU market, even though some criticalities may occur in some member states. Alternatives with better efficacy and/or safety profiles are still available on the market for the six substances identified as fully withdrawn.

According to the report, stockpiling at the EU level might not have a direct impact on the mitigation of market-driven trends. Improved monitoring of potentially critical future withdrawals would be needed to enable early detection of shortages and establishment of counteractions.

Innovation in the field of new antibiotics is still largely insufficient, with only six substances currently in phase 3 clinical development. These might prove useful especially as the ultimate reserve line of therapy after exhaustion of the currently available therapeutic options. The report suggests that, upon reaching approval, these innovative substances could be considered for future stockpiling or incentives to facilitate launch in the EU.

The analysis of supply chain vulnerabilities aimed to identify higher priority antibiotics as possible candidates for stockpiling. The report highlights that the analysis was “significantly limited by a lack of outside-in transparency”. Potential single points of failure and/or past disruptions in most supply chains were identified for the 32 critical antimicrobial classes, but the lack of capacity data made the in-depth analysis particularly difficult.

Six representative sets of antibiotic substances were assessed, for five of which less than 25% of API manufacturing occurs in the EU. Similar trends have been also observed for the remaining 26 classes. The supply of critical intermediates (i.e., 6-APA and 7-ACA) appears particularly worrying and may potentially lead to a future shortage of that specific antibiotic/class in the case of a shock. HERA report warns against the possible risks related to potential vulnerability to trade disruptions and unforeseen geopolitical shocks, which may lead to a significant shortage in case of failure of just a single manufacturing site, independent of its location.

The feasibility study also mapped the already existing or planned stockpiling systems, so to use this information to better design the new, EU-level stockpiling system. Four different levels were identified, ranging from the EU’s and member states’ systems to multilateral and/or international NGO stockpiles, stockpiles/inventories in the commercial value chain, and extra-EU national stockpiles.

At the EU and EFTA national level, 13 countries reported a national stockpile that includes antimicrobials, even if greatly differing as for the chosen model. The rescEU system was identified at the EU level as the most relevant mechanism potentially useful to complement and/or integrate with a publicly managed physical stockpile of antibiotics.

The Stop TB Partnership’s Global Drug Facility (GDF) was identified as one of the international models of interest, together with the US Strategic National Stockpile (SNS). The GDF includes more than 2,000 partners and acts as the largest purchaser and supplier of medicines to treat tuberculosis in the public sector globally. The suggestion is for HERA and the European Commission to collaborate with the GDF in case of a TB-related demand spike. The SNS may represent a significant example of how to address many of the criticalities highlighted by the report.

How to better address stockpiling of antibiotics

The second report builds on the above-mentioned observations to go deeper in analysing from different perspectives and targets the possible approaches to the stockpiling of antibiotics. The indication is for HERA to consider using existing initiatives (e.g., rescEU, the EU’s Joint Procurement Agreement and the Emergency Response Coordination Centre) and to work closely with EU member states and other EU agencies (i.e., EMA and the ECDC).

An important warning was also made: stockpiling is just “a short-term mechanism. It does not alter the fundamental market environment. It can only represent one part of any answer to the challenges faced by health agencies including HERA, whether AMR-related or otherwise”.

A sudden and unpredictable surge in demand and an interruption to supply are the two archetypes analysed to better identify how to address stockpiling.

More than 30 potential demand scenarios were considered, leading to the identification of one high priority stockpiling candidate (higher demand for anti-mycobacterial medicines due to a surge of imported tuberculosis cases) and other three important, but not yet prioritised scenarios. These include stockpiling against the accidental or deliberate release of a bacterial pathogen, treating bacterial super-infections due to a viral pandemic, and the potential rapid spread of an AMR pathogen in the current European context.

Stockpiling for supply chain disruptions was also assessed, leading to the conclusion that alternative products are available as substitutes in the great majority of cases. A point of attention is represented by cross-class substitution, that might provoke different side effects for different groups of patients and could represent a potential factor for the promotion of AMR. More complex treatment procedures (e.g., i.m. vs oral administration), higher costs for healthcare systems and organisational issues for providers should also be considered.

Virtual stockpiling to be managed through the new European Shortages Monitoring Platform (ESMP) or the existing European Medicines Verification System (EMVS) would increase transparency of the system. A mandate or incentives to support private sector physical stockpiling was considered as the most feasible option available. Efforts should be made by the EU Commission to better characterise the relationships between the economic sustainability of limited generics productions (e.g. oral formulations for paediatric use of narrow-spectrum genericised penicillins) and the risk of shortages.

Five lines of possible action

The second report identifies five possible lines for future action aimed to strengthen the antibiotic supply chain and improve the stockpiling feasibility. At first instance, it would be important to improve transparency and reporting, so to better enable the availability of targeted preparedness and response measures.

This might include the harmonisation and extension of mandatory reporting of medicine shortages across the EU, the possibility for HERA to access regulatory data from agencies and information from marketing authorisation holders on supply chain setup and inventories in the case of a healthcare emergency situation, the implementation of an opt-out mechanism from stockpiling obligations at final product level, and the introduction of a general extension of reporting requirements for the supply chain of antibiotic products sold in the EU.

The second line of possible action addresses how to lower wastage in existing private and public inventories and stockpiles. Available options include regulatory measures and limited financial support for drug stability studies or for packaging options able to maintain product quality over longer periods of time.

Facilitation and regulatory support for mutual recognition of national level approvals for antibiotics might help to improve the flexibility of existing inventories and stockpiles, so as to better mitigate the shortages occurring in some member states.

Other two complementary approaches have been identified as potentially useful to improve the supply chain resilience of the EU antibiotics market. On one hand, diversified and in-market antibiotic manufacturing capacities and capabilities could be supported by targeted incentives and investments. On the other, the maintenance of reserve/convertible manufacturing capacity for hard-to-make substances might be also supported, so to better face the need to rapidly compensate the increased requests from patients should disruptions occur.


EMA’s Industry stakeholders group (ISG)

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by Giuliana Miglierini

The Industrial Stakeholder Group (ISG) is a new initiative recently launched by the European Medicines Agency (EMA) in order to favour the dialogue with the industrial stakeholders. The first meeting of the ISG, the 21 June 2022, focused on the mandate of the Group and on the three priority topics to be addressed during the pilot phase: the Emergency Task Force (ETF), the issue of shortages of medicines and medical devices and the medical device expert panels.

The initiative is part of the activities planned by EMA for the implementation of its extended mandated, as for Regulation (EU) 2022/123.

The mandate of the ISG

The main scope of the ISG is to provide a dedicate forum to capture the industrial point of view and proactively inform on open issues during the implementation of EMA’s extended mandate. The ISG will focus on human medicines and will complement other existing tools, such as industry platform meetings, bilateral meetings, topic or project related meetings. The outcomes obtained from the pilot phase will form the basis of an analysis to evaluate if to extend the scope to other initiatives.

The Chair of the ISG is nominated by the Agency’s Executive Director; the group is composed by one member and one alternate from selected EU industry organisations relevant to the subject of discussion, on the basis of a call for expression of interest. Additional representatives of selected organisations and observers may also participate to specific meetings, according to the topics on the agenda. Observers include the European Commission, EMA’s committees (e.g. CHMP, ETF, CMDh, SPOC WP, SMMG), the EU Network, Notified bodies; ad-hoc observers may be also invited from member states and stakeholder groups.

Appointed members will be responsible to liaise with the respective industrial rganisations, so to contribute the discussion with their point of view and to keep them updated on the outcomes of the ISG meetings. The current schedule includes four quarterly meetings per year; the next two are fixed for the 26 September and 22 November 2022. The summary report of each meeting will be available in EMA’s website.

The Emergency Task Force

The new Emergency Task Force (ETF) builds upon the experience gathered during the pandemic and acts within EMA to advise and support on medicines for public health emergencies and preparedness.

The ETF is in charge of coordinating all efforts following the declaration of a public health emergency by health authorities, in strict coordination with all other relevant bodies including the European Health Emergency preparedness and Response Authority (DG HERA), the European Centre for Disease Prevention and Control (ECDC), the WHO and the European Commission.

The new ETF started operating on the new mandate on 22 April. Its composition is based on expertise, and it includes representatives of EMA’s Scientific Committees and Working Parties as well as selected patients and healthcare professionals and clinical trials experts from various member states.

There are three distinct area of activities for the Task Force. Scientific advice and support to clinical trials for the development of medicines to be used during the emergency will be directly managed and assessed by the ETF, free of charge and flowing a fast-track procedure. The new streamlined procedure should lead to the outcome in 20 days; deceleration criteria are also considered, i.e. premature evidence to address the medical need, high workload or lack of urgency. Expected benefits include the reduction of the use of medicines with insufficient evidence of efficacy and the increase of safe and harmonised use across the EU of new products from the pipelines ahead of authorisation. Activities of the ETF will cover all stages of development, from pre-authorisation (e.g. rolling applications or paediatric plans) to post-authorisation (e.g. major changes), investigational products and compassionate use.

The systematic assessment of the available evidence on medicines will be the focus of the scientific reviews, while recommendations will target medicines not yet authorised or topics of particular scientific or public interest. These may include, for example, the monitoring of new outbreaks and epidemics and the information on potential radiological, chemical or bioterrorism agents.

All lists of medicines under assessment to address a declared emergency will be made public to increase transparency, as well as the CHMP opinions on the use of medicines not yet authorised, Product Information, EPARs end Risk Management Plans.

Two dedicated mailboxes are also available, the first for sponsors of clinical trials to request EMA/ETF support for facilitating CTA and approval and sponsors agreement to conduct larger multinational trials ([email protected]), the second for manufacturers to discuss with EMA/ETF their development programs or plans for scientific advice prior to any kind of formal submission ([email protected]).

Shortages of medicines

EMA’s extended mandate in this area include the monitoring and mitigation of shortages of critical medicines and medical devices, and the setting up, maintenance and management of the European Shortages Monitoring Platform (ESMP). The action also includes the establishment of the Medicines Shortages Steering Group (MSSG), which will be supported by the Working Party of singles points of contacts in the members states (the EU SPOC Network) and a network of contact points from pharmaceutical companies (the i-SPOC system). A corresponding Executive Steering Group on Shortages of Medical Devices (MDSSG), to be created by February 2023, will be in charge of adopting the list of categories of critical medical devices and to monitor their supply and demand.

According to Regulation (EU) 2022/123, pharmaceutical companies are required to identify a i-SPOC to act as the reference contact for EMA should the Marketing Authorisation Holder (MAH) have medicinal products be included in the lists of critical medicines. All information has to be provided through the IRIS platform; the registration process opened on 28 June 2022 and is comprehensive of two steps (the IAM preliminary requirement for the creation of the account and the following IRIS submission).

Scheduled milestones will see the establishment of a list of the main therapeutic groups for hospital care (due by 2 August 2022), the registration of i-SPOCs from MAHs (by 2 September 2022), and the definition of shortages of medical devices and in vitro diagnostics (by 2 February 2023). The ESMP platform is expected to go live by 2 February 2025, and will represent a single reference point to make information available on shortages, supply and demand of medical products, including the marketing status and cessation.

Expert panels on medical devices

Regulation (EU) 2022/123 establishes the hangover of expert panels on medical devices from the Joint Research Centre (JRC) to EMA, thus adding a completing new type of activity for the Agency.

The new Secretariat is coordinating the activities of the Screening panel composed by 70 experts in charge of the decision whether to provide a scientific opinion, eleven thematic expert panels and expert panels sub-groups (for a total of approx. 130 experts), and a Coordination Committee inclusive of the Chair and vice-Chair of all the expert panels.

The main task of the expert panels is to provide opinion to the notified bodies for certain high-risk medical devices and in-vitro diagnostic, for the assessment of their clinical and/or performance evaluation. EMA is specifically involved in the coordination of the Clinical Evaluation Consultation Procedure (CECP) for medical devices and Performance Evaluation Consultation Procedure (PECP) for in-vitro diagnostics. Further details on the procedures and their interfaces with the ETF is available here.


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”.