Reinforced role for European Medicines Agency in crisis preparedness and management for medicinal products and medical devices

1.4.22: The European Medicines Agency (EMA) is today holding a workshop to inform stakeholders of the regulation reinforcing the EMA’s role in crisis preparedness and management for medicines and medical devices [REGULATION (EU) 2022/123 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL]. 

The new regulation was triggered largely in response to the COVID-19 pandemic ie a civil crisis to aim for better readiness to anticipate and respond to public health emergencies. It is clearly also relevant to shortages arising from conflicts such as related to Russia’s war against the Ukraine and the resulting mass migration.

This new Regulation [EU – 2020/123] of 25^th January 2022 was determined to be effective from the date of its publication in the Official Journal of the European Union – 31^st January 2022 and in practice applicable from 1^st March 2022 for the monitoring and mitigation of shortages of critical medicinal products. The EMA is already starting preparatory work with the aim of delivery the European Shortages Monitoring Platform in early 2025.

Success will depend on clear allocation of tasks and responsibilities. High level aims are improved, co-ordinated ways to identify shortages – including mapping surges in demand, streamline processes, remove barriers and enhance preparedness so that when issues arise the EMA and its partner agencies can react in the quickest way possible, within the spirit of the Charter of Fundamental Rights of the European Union that the Union is to “ensure a high level of human health protection in the definition and implementation of all Union policies and activities.”

The Regulation covers the following topics:

• Monitoring and mitigating shortages of medicines and devices
• Addressing public health emergencies through the Emergency Task Force (ETF)
• Coordinating expert panels on high-risk medical devices and in vitro diagnostics

The event provided an opportunity for the public and stakeholders to inform EMA of their needs, expectations and to discuss opportunities for further engagement with the agency.

Key milestones for the EMA include:

1^st March 2022 – start of development of systems re shortages of critical medicines including enhanced IT platforms

2^nd August 2022 – establishing a list of the main therapeutic groups for hospital care

2^nd September 2022 – registration of i-SPOCs (Single Points of Contact) from Marketing Authorisation Holders

2^nd February 2023 – development of systems re shortages of medical devices/in-vitro diagnostics

2^nd February 2025 – European Shortages Monitoring Platform “goes live”

The following are brief notes on the background and high level actions defined within the new Regulation.

 

The COVID-19 pandemic has highlighted the interconnectedness of human and animal ecosystems with regard to risks to health including two-thirds of new diseases and most pandemics from influenza to COVID-19. New risks include effects of changes in land use, new agricultural methods, wildlife trafficking and changes in food consumption.

“… as stated in Regulation (EU) 2021/522 of the European Parliament and of the Council (4), ‘human health is connected to animal health and to the environment and … actions to tackle threats to health must take into account those three dimensions’”.

Experience of the COVID-19 pandemic has highlighted lack of readiness  of the European Union and its Member States to addressing major public health emergencies. The EU has been “severely impeded by the absence of a clearly defined legal framework for managing its response to pandemics and by the limited mandates and resources of its health agencies, as well as by the limited degree of Union and Member States preparedness for public health emergencies that impact a majority of the Member States.”

“Shortages of medicinal products and medical devices have different and complex root causes which need to be further mapped, understood and analysed together with the different stakeholders in order to be comprehensively addressed. A better understanding of those shortages should include identification of vulnerabilities in the supply chain. In the specific case of the COVID-19 pandemic, the shortage of treatments for the disease had a variety of causes, ranging from production difficulties in third countries to logistical or production difficulties within the Union, where the shortage of vaccines was due to inadequate manufacturing capacity.”

Disruptions to supply chains for medicinal products and medical devices include “national export restrictions and bans, border closures impeding the free movement of such goods, uncertainty related to the supply for and demand of such goods in the context of the COVID-19 pandemic, and the lack of production in the Union of certain medicinal products or active substances…”.

Further challenges include “…increased risk of exposure to falsified medicinal products, medication errors, adverse effects resulting from the substitution of unavailable medicinal products with alternative ones, significant psychological distress for patients and increased costs for healthcare systems. … Member States competing with each other when they respond to the legitimate needs of their citizens, thereby contributing to uncoordinated actions at national level, such as national hoarding and stockpiling.”

“In order to facilitate the prevention, monitoring and reporting of shortages of medicinal products, the Agency should set up an information technology (IT) platform, to be known as the European shortages monitoring platform (‘ESMP’), that is capable of processing information on the supply of and demand for critical medicinal products during public health emergencies or major events and, outside of those situations, to allow for reporting on shortages of medicinal products that are likely to lead to public health emergencies or major events.”

Medicine Shortages Steering Group – MSSG
This executive steering group is to be established within the Agency to ensure robust responses to major public health events and coordinate urgent actions within the Union.
The MSSG is to establish lists of critical medicinal products (CMPs), to ensure monitoring of CMPs and provide advice and recommendations on the actions to safeguard the quality, safety and efficacy and supply of CMPs.

Emergency Task Force – ETF
This new ETF is to provide advice on scientific questions related to the development of treatments and vaccines and on clinical trial protocols free of charge to entities involved in their development, such as marketing authorisation holders, clinical trial sponsors, public health bodies, and academia.

Medical Device Shortages Steering Group – MDSSG
This new Steering Group is to coordinate urgent actions within the Union in relation to the management of supply and demand issues of medical devices, and to establish a list of critical medical devices in the case of a public health emergency.

Robust transparency measures and standards are needed regarding the EMA’ Agency’s regulatory activities in relation to medicinal products and medical devices relevant to this Regulation.

European database on medical devices (Eudamed)
Rapid access to and exchanges of health data, including real world data will be needed and should be part of the interoperable European Health Data Space. Provision should be made for setting up and managing new IT infrastructures and their synergy with other existing IT systems and IT systems under development, including Eudamed and for enhanced protection of data infrastructure from possible cyber attacks.

Cooperation with European Centre for Disease Prevention and Control (‘ECDC’) During public health emergencies or major events, the Agency should ensure cooperation with the ECDC including the sharing of data, regular communication at an executive level e.g. re meetings of the ETF, the MSSG and the MDSSG.

Donald Singer
EACPT Delegate
EMA Healthcare Professionals Working Party

 

 

European Medicines Agency to hold a public update on COVID-19 vaccines on 11 December

EMA will organise a public meeting on 11 December 2020 to inform European citizens about the EU regulatory processes for the approval of COVID-19 vaccines and the Agency’s role in their development, evaluation, approval and safety monitoring.

The COVID-19 pandemic is an unprecedented global crisis, with devastating health, social and economic impact. Safe and effective vaccines for COVID-19 are urgently needed to respond to this crisis and reduce its effects.

Together with the European medicines regulatory network, EMA is supporting the development of COVID-19 vaccines and has taken steps to speed up the evaluation processes for these vaccines. The Agency and its partners are doing so while ensuring that the same high regulatory standards for quality, safety and efficacy are being applied to COVID-19 vaccines.

The public meeting will inform citizens about EMA’s role in the pandemic and of EU regulatory procedures. It will also give the opportunity to the public and stakeholder groups to speak and share their needs, expectations and any concerns, that will be considered by EMA and the European medicines regulatory network in the decision-making process.

The EMA will publish the list of speakers who will make an intervention in advance of the event.

The public meeting will be broadcast live and will be open to all citizens. In addition to the selected list of speakers, during the meeting there will be a mailbox open via EMA’s website for the public to make comments.

The agenda and all information related to the event are available on the EMA website event page.

Please check EMA’s dedicated webpage on COVID-19 for the latest updates.

Updates from the European Medicines Agency: from vaccines to repurposing medicines and pharmacovigilance

24th-25th September
The European  Medicines Agency has hosted its first meetings in Amsterdam  for its Healthcare Professional Working Party and Patient and Consumers Working Party since the move of the Agency from its former Canary Wharf headquarters in London. The sessions coincided with the launch of a further three year work programme agreed between the EMA and its working parties.

Papers from the meetings will be available on the EMA website. 

Key themes in the new work programme will include secure supply of medicines, digital media for health, public health strategy on antibiotic resistance, addressing vaccine hesitancy, early access to medicines, pharmacovigilance, and encouraging patient engagement.

Central Amsterdam

Major topics discussed during the current Amsterdam meetings included initiatives to address vaccine hesitancy, updates on pharmacovigilance and initiatives on repurposing of medicines. In addition, the EMA provided updates from its major standing committees, including the Committee for Orphan Medicinal Products (COMP), Pharmacovigilance Risk Assessment Committee (PRAC), Committee for Advanced Therapies (CAT), Committee for Medicinal Products for Human Use (CHMP), Paediatric Committee (PDCO) and Committee on Herbal Medicinal Products (HMPC).

Isabel de la Mata, Principal Advisor on Public Health and Crisis Management at the European Commission discussed current initiatives to address vaccine hesitancy, an early priority of EU President-elect Ursula van der Leyer.

De la Mata noted that vaccine coverage is below 95% in many EU member states. A 2019 Eurobarometer on vaccine confidence had highlighted several key points of misinformation, for example with 48% of respondents thinking that vaccines often produce serious side effects, 38% that vaccines can cause the disease they prevent and 55% considering that vaccines overload and weaken the immune system.

A Global Vaccination Summit had been held on 12^th September with around 400 delegates political, technical, patients and other - and with WHO collaboration. This led to a 10 point document including new focus on reliable access to vaccines, safety and transparent, clear, independent information.

Actions by member states are to include developing national and regional plans, better access to vaccines, increased public health communications, more training of health professionals, accurate digital information on vaccination status and increased support for vaccine research and innovation.

European level actions are to include a new European Vaccination portal coordinated by ECDC (European Centre for Disease Control) with support from the EMA (EVIS - European Vaccine Information Sharing). Other work will consider dissemination of vaccine schedules, focus on the supply chain, including mitigating shortages and identifying and overcoming barriers to access.

A new coalition of healthcare workers for vaccination, launched on 5^th March in Brussels, aims to address and reverse reasons for outbreaks of measles and other vaccine-preventable infections in health workers as recently as 2017 and 2018, with transmission in the healthcare setting even in countries with high vaccination coverage.

John Kinsman, Expert in Social and Behavioural Change Communication at the ECDC, outlined Development of the European Vaccination information Portal. This is due to be piloted in December 2019 and launched in April 2020 during European Immunisation week.

The portal has a legal basis, arising from a 2016 European Commission call for the ECDC to work with EMA to develop the portal.  Issues include the reality that the majority of the public do not have a scientific background and making sure through content, language and accessibility that the portal is as widely available as possible.

The EMA is seeing an exponential increase in reporting by patients of suspected adverse drug reactions.  A pressing aim of the EMA is how best to learn from patient reporting of possible ADR. This will benefit from previous experience of patient reporting to national competent authorities  (e.g. US FDA and UK MHRA [patient reporting since September 2005]) and international agencies (e.g. the WHO Uppsala Monitoring Centre).

Plans for future meetings include proposals for further discussion of initiatives on vaccine uptake.

Updates on digital media and health at the European Medicines Agency

Safe and effective healthcare matters for society as a whole.

Digital media and health is the key theme of the latest joint meeting of the European Medicines Agency (EMA) Human Scientific Committees' Working Parties with Patients’ and Consumers’ Organisations (PCWP) and Healthcare Professionals’ Organisations (HCPWP) being held in London on 17^th and 18^th April 2018. Digital media and health topics are being discussed, including recent learning and trends with regard to mHealth, social media, real-word evidence and electronic product information.

Katja Neubauer from the European Commission opened the session with an update on EU initiatives with regard to digital health. She considered 3 priority areas on digitizing health and care: access of the citizen to his or her data for example in electronic medical records and electronic prescribing; access to big data to improve health policy and regulatory decisions; and using digital health make policy decisions more patient-centred.

She discussed clinical use studies, including development of European Reference rare diseases, applying digital health to anticipating epidemics and EU-wide infectious threats and applying Real World Data in medicines development.

An EC report on Digital Single Market strategy is due to be published on 25^th April.

Hans-Georg Eichler from the EMA went on to discuss the relevance of real world evidence to regulation of medicines, including understanding efficacy and monitoring for unexpected risk and for long-term risk. In particular, he considered use of real world evidence to match the speed of science progress with timely integration of innovations into clinical practice.

He considered case studies on accelerating drug development, contrasting findings from real world evidence with those from classical randomized clinical trials; applying real world evidence to monitoring potential long term adverse effects of medicines – for example from risks of insertional mutagenesis following gene therapy for thalassaemia which needs surveillance for decades; and applying real world evidence to understanding therapeutic complexity – for example deciphering combinatorial complexity in oncology treatment with regard to differences in therapeutic impact from treatment order, dose and washout duration between treatments.

He also discussed applying learning for health care from other sectors (aviation, automotive …), including data-driven innovation from rapid feedback loops.

Alison Cave from the EMA discussed key points from recent workshops hosted by the Agency. She stressed the need for a common data model for Europe. A key theme arising from discussion of EMA registries had been the need for common core data elements, checks on data quality (consistency, accuracy and completeness), long-term curation, availability and governance.

Jane Mosely discussed how real-world evidence and patient registries can be used to support early access to medicines, risk-benefit analysis and provide rapid replication within different populations of initial findings. She noted that there are currently limited requests for data from real-world evidence to support pre-authorisation decisions and post-authorisation questions about safety and efficacy. Some aspects which need to be considered include eligibility of participants, outcome definition, patient safety, and extrapolation of findings throughout the EU.

Alexios Skarlatos (EMA) and Dr. César Hernández García (Spanish Agency of Medicines and Medical Devices) discussed Electronic Product Information. Steps include consultation on revising Patient Leaflet content and adding agreed new content, including targeted messages for relevant subgroups of patients. There are already case studies from the Netherlands (Watchyourmeds), quick guides for patients in Norway and in Spain structured product information accessible e.g. by scanned quick response (QR) codes. International standards are needed and transition to a Digital first model.  There will be a European Commission-EMA-HMA multistakeholder workshop on the use of electronic Summary of medical Product Characteristics (SmPC)/Patient Leaflets (PL) on 28^th – 29^th November 2018.

Further speakers will discuss from health professional, regulator, patient, consumer perspectives Real World Evidence (Kieran Breen, Patient Representative on the EMA Committee for Advanced Therapies), mHealth (Kathi Apostolidis, European Cancer Patient Coalition) and Social Media (Caroline Morton, International Bureau for Epilepsy).

More about the meeting and the presentations can be found on the EMA website.

Developing a Common Health Data Model for Europe

The European Medicines Agency has been holding a 2 day international workshop in London [11th -12th December 2017] to define  opportunities and challenges for a common health data model in Europe. The expected outcome of the workshop was agreeing guiding principles for the development of such a Common Data Model (CDM) in Europe, including key criteria for validation in the context of regulatory decision-making.

See more about the workshop
 

A common data model could help harmonise healthcare data across multiple data sets and provide a mechanism to conduct pan-European studies in a timely manner to address regulatory questions. At the same time, applying a common model to European data has multiple challenges. The meeting brought together regulators with academia, data holders and the pharmaceutical industry.

Sessions included talks from experts from North America and the European region discussing lessons learned and current challenges in very large current clinical data resources, regulatory verification and related issues. Common data model case studies  included Sentinel – the Harvard-based FDA system for accessing patient data from health data partners across the USA and CNODES (the Canadian Network for Operational Drug Effect Studies) which can access data on 100 million patients – a similar scale to Sentinel.

The U.S. Food and Drug Administration's (FDA) Sentinel Initiative uses a common health data model to improve the FDA’s ability to identify safety issues for medical products. Sentinel actively surveys pre-existing electronic healthcare data from multiple sources.

Themes at the workshop included ensuring the relevance of CDMs to health policy, keeping timelines short, inter-operability, consent and related ethical issues, and careful internal and external validation of clinical definitions, data, software and analytical models.

From the perspective of health professionals, policy makers, regulators and the public, key future questions include whether clinical outcomes from common data models will be generalisable or only relevant to specific sub-populations based on geography, genetics, demographics and/or complex co-morbidity.  In the era of precision medicine there is the clear need is to avoid “right” answers from the wrong clinical populations and “wrong” answers from the right populations.
Further key points to consider include the cost of CDMs and who should pay; and whether updating existing databases will be sufficient or will new, more robust databases be needed.

 Future EACPT Congresses will be held in:
- 2019 Stockholm
- 2021 Athens
- 2023 Rotterdam

The EACPT was founded in 1993 - 24 years ago - and now includes as members all major national organisations for clinical pharmacology in Europe, as well as organisations from further afield internationally. The EACPT aims to provide educational and scientific support for the more than 4000 individual professionals interested in clinical pharmacology and therapeutics throughout the European region, with its congresses attended by a global audience. The EACPT also advises policy makers on how the specialty can contribute to human health and wealth.

Clinical Therapeutics, the Official Journal of EACPT

European Medicines Agency to move from London to Amsterdam

After a final round dead-heat vote by member states on Monday 20th November, following the drawing of lots, Amsterdam has been confirmed as the new home for the European Medicines Agency. On current plans, the EMA will be operating in Amsterdam from April 2019.

The EMA's Patients and Consumers Working Party annual meeting

Meantime the EMA's Patients and Consumers Working Party (PCWP) is holding its annual meeting with all EMA eligible patient/consumer consumer organisations to consider relocation preparedness, patient and consumer involvement in EMA activities, highlights from major EMA committees and updates on pharmacovigilance, information on medicines and future work programmes in 2018 and 2019 for the PCWP and the EMA's Healthcare Professionals Working Party.

The European Medicines Agency is concerned with regulation of medicines and other advanced therapies for humans and animals for 28 countries across the European Union.

The EMA has established mechanisms for involving patients in regulatory assessment: patients’ value perception and value systems. The EMA also has an increasing remit to engage with stakeholder organisations and to improve transparency in its activities for the ~510 million citizens of the European Union. Furthermore the EMA has a major role in educating patients, carers and health care professionals about medicines.  

There remain many decisions and actions for the coming months needed to ensure the smooth relocation of the EMA to Amsterdam and either to develop systems to retain UK expertise for the EMA or replace that expertise. For the EMA, these include:

• maximising staff retention
• maintaining capacity to continue the work of the EMA 
• continuing productive engagement with stakeholder groups: patients, carers, healthcare professionals ...
• maintaining the capacity of the EMA to engage with the public

For the UK, there are pressing questions regarding the future regulation of medicines in the UK post-Brexit, the impact of loss of international influence of UK regulators and other experts on medicines and the impact of loss of biotech and pharmaceutical companies from London to Amsterdam.

Global threat of antibiotic resistance

WHO estimates of impact on mortality from AMR

The European Medicines agency, in partnership with the ECDC (European Centre for Disease Prevention and Control), is holding a workshop on global challenges from antimicrobial resistance (AMR). 

There are 3 major current approaches to tackling AMR: 
1. reducing selection pressure on microbes to reduce the chance of their developing AMR. This needs strategies to reduce overuse of antimicrobial medicines. 
2. reducing human/human and animal/human transmission microbes. This needs effective infection control measures
3. increasing the availability of new antibiotics through more R & D combined with limiting their use within evidence-based guidelines - ie effective antibiotic stewardship.

There needs to be an integrated approach combining a pipeline of effective new antimicrobial and careful stewardship of existing antimicrobials through their effective use. However from a recent international survey, 20% of the public who took part were unaware that overuse of antibiotics leads to antimicrobial resistance to treatment. Furthermore 44% were unaware that antibiotics are ineffective against colds and 'flu'.

The WHO has estimated that, without major global action, by 2050 there may be ~400,000 preventable deaths annualy in the European region alone, as a result of lack of effective antiobiotics for serious infections.

Martial Plantady from the European Commission opened the day by discussing the EU Action plan launched in 2011 and running until 2016 against the threats from antimicrobial resistance. He noted that many solutions were described within the plan however there remain major challenges to effective implementation of the Plan, including:
- widespread and worldwide antibiotic use for growth promotion in livestock
- resulting need to push strategy to ban antibiotic use in livestock beyond the EU
- availability of animal and human data across member states
- effective surveillance on appropriate and prudent use of antimicrobials in humans
Some solutions include 
- effective dissemination of guidelines on prudent use of antibiotics in animals and humans
- Antibiotic Awareness Days
- more effective coordination of R & D across industry and academic sectors on new antimicrobials, alternatives, vaccines and rapid diagnostic tests
- engagement with key health professional and patient stakeholder organisations
The new EU Action Plan on antibiotic resistance was published in June 2017, with 3 pillars supported by strengthened measures for infection prevention and control:
- making the EU Region a best practice region on AMR
- improving research and innovation
- shaping the global agenda on AMR

At the 68th World Health Assembly in May 2015, the World Health Assembly endorsed a global action plan to tackle antimicrobial resistance, including antibiotic resistance, the most urgent drug resistance trend. Carmen Pessoa da Silva from the WHO underlined the key point that if AMR remains unresolved, the global threat would be enormous both for human health as well as for the world economy. She summarised 5 key elements of WHO strategy against AMR.
1. improved awareness and understanding (annual WHO awareness week)
2. strengthen knowledge through surveillance and research 9WHO Global AMR Surveillance System - GLASS - further report due in Jan 2018 - 47 countries are fully enrolled - 25% of member states)
3. reduce incidence of infection
4. optimise use of anti-microbial medicines
5. ensure sustainable investment for R & D

The Pharmaceutical Group of the European Union represents the ~400,000 community pharmacists who dispense medicines for the ~500 million population of the European Union. Around 46 million people visit a community pharmacist every day in Europe.
James Wilkinson discussed efforts of the PGEU to educate community pharmacists and the public in rational use of antimicrobial medicines.

Personalised Medicines and the European Medicines Agency

London, 14th - 15th March
The European Medicines Agency is hosting workshops for its Working Parties of  Patients', Consumers' and Health Professionals' organisations.

The 14th March workshop aims to create awareness among these organisations of how the work of the European Medicines Agency (EMA) relates to personalised medicines. 

The 15th March workshop provides updates on other EMA and relevant external acfivities including feedback on topic groups on Social Media and on Risk Minimisation from medicines, European Antibiotic Awareness, Action plans on Biosimilars, feedback from key EMA committees and synergies with other organisations.

Key aims
- understanding how European and global landscapes are shaping policy developments
- illustrating how activities of the European medicines regulatory network contribute to personalised medicine with existing legislation and regulatory tools
- discussing how clinical practice and public participation can support personalised medicine in the context of European Union (EU) regulatory activities
- identifying areas requiring attention from EU regulators, patients, healthcare professionals and civil society at large
- reflection by the working parties on priority areas for future contributions in broader multi-stakeholder discussions. 

Speakers include:  
- Sandra Kweder from the US Food and Drugs Administration, discussing  the US precision medicine initiative. She highlighted the need to personalise medicines with cancer a key driver - only 80% of patients estimated to respond better when individual genomic and proteomic information is available.

- briefings from EMA's Scientific Committees e.g.  PRAC chair June Raine discussing pharmacogenomics in pharmacovigilance e.g. preventing serious skin reactions to abacavir in HIV patients and limiting toxicity of anti-cancer agents e.g. 5-fluoro-uracil and capecitabine

- updates from research organizations e.g. Denis Lacombe from EORTC  (European Organisation for Research and Treatment of Cancer) on changing clinical research pathways, very expensive drugs and data-driven healthcare from "-omics" to "economics".
 
- developing diagnostics and treatments for rare diseases e.g. from Julian Isla on improving management of Dravet Syndrome - a rare, catastrophic, lifelong form of epilepsy that begins in the first year of life with frequent and/or prolonged seizures. 

- Ulrich Jäger from the European Haematology Association https://www.ehaweb.org/ on health professional perspectives on precision medicine, including practical challenges to applying precision medicine within a typical 7-12 minute consultation.    

- Dominique Monnet from the ECDC [European Centre for Disease Prevention and Control] reported on progress in developing European Antibiotic Awareness days, held annually on 18th November. The ECDC is mandated to monitor current and potential future risks to human health from communicable disease. Individual EU member states are responsible for risk management of established communicable disease.

The EMA will publish the presentations, videorecording and a workshop report.

The next EACPT Congress is in Prague from 24th - 27th June 2017

Prague EACPT Congress registration is now open

The EACPT was founded 24 years ago and now includes as members all national organisations for clinical pharmacology in Europe, as well as organisations from further afield internationally. The EACPT aims to provide educational and scientific support for the more than 4000 individual professionals interested in clinical pharmacology and therapeutics throughout the European region, with its congresses attended by a global audience. The EACPT also advises policy makers on how the specialty can contribute to human health and wealth.