Road map to 2015

The European Medicines Agency’s contribution to science, medicines and health

Adopted by the Agency’s Management Board on 16 December 2010

An agency of the European Union The mission of the European Medicines Agency is to foster scientific excellence in the evaluation and supervision of medicines, for the benefit of public and animal health.

Legal role The European Medicines Agency is the • involves representatives of patients, European Union body responsible for healthcare professionals and other coordinating the existing scientific resources stakeholders in its work, to facilitate put at its disposal by Member States for dialogue on issues of common interest; the evaluation, supervision and • publishes impartial and comprehensible pharmacovigilance of medicinal products. information about medicines and their use; The Agency provides the Member States • develops best practice for medicines and the institutions of the EU the best- evaluation and supervision in Europe, and possible scientific advice on any question contributes alongside the Member States relating to the evaluation of the quality, and the European Commission to the safety and efficacy of medicinal products harmonisation of regulatory standards at for human or veterinary use referred to it the international level. in accordance with the provisions of EU legislation relating to medicinal products. Guiding principles

Principal activities • We are strongly committed to public and animal health. Working with the Member States and the • We make independent recommendations European Commission as partners in a based on scientific evidence, using state- European medicines network, the European of-the-art knowledge and expertise in our Medicines Agency: field.

• provides independent, science-based • We support research and innovation to recommendations on the quality, safety stimulate the development of better and efficacy of medicines, and on more medicines. general issues relevant to public and • We value the contribution of our partners animal health that involve medicines; and stakeholders to our work. • applies efficient and transparent • We assure continual improvement of our evaluation procedures to help bring new processes and procedures, in accordance medicines to the market by means of a with recognised quality standards. single, EU-wide marketing authorisation • We adhere to high standards of granted by the European Commission; professional and personal integrity. • implements measures for continuously • We communicate in an open, transparent supervising the quality, safety and efficacy manner with all of our partners, of authorised medicines to ensure that stakeholders and colleagues. their benefits outweigh their risks; • We promote the well-being, motivation • provides scientific advice and incentives and ongoing professional development to stimulate the development and improve of every member of the Agency. the availability of innovative new medicines; • recommends safe limits for residues of veterinary medicines used in food- producing animals, for the establishment of maximum residue limits by the European Commission;

Road map to 2015 2 The European Medicines Agency’s contribution to science, medicines and health Table of contents

1. Executive summary...... 4 2. Introduction...... 6 3. Setting the scene: the Agency and its environment...... 7 3.1. The European Medicines Agency as a public-health agency...... 7 3.2. Collaboration with the Agency's partners...... 7 3.2.1. Operating within the EU regulatory network...... 7 3.2.2. Positioning the Agency on the international scene...... 7 3.3. Interaction with the Agency's stakeholders...... 8 4. The Agency’s drivers for progress and change...... 9 4.1. Efficient operation of the Agency's core business...... 9 4.2. Addressing public-health needs...... 9 4.3. New and emerging science...... 9 4.4. The impact of increasing globalisation...... 10 4.5. The model for regulation of medicines...... 10 4.6. Ensuring patient/consumer and animal-health protection...... 11 4.7. Demands for greater transparency and openness...... 11 5. Addressing the drivers for progress and change...... 12 5.1. Current achievements...... 12 5.2. Objectives and priorities for the next five years...... 12 5.2.1. Performing the Agency's core tasks...... 12 5.2.2. The Agency's strategic areas 2011-2015...... 13 Strategic area 1: addressing public-health needs...... 15 Strategic area 2: facilitating access to medicines...... 18 Strategic area 3: optimising the safe and rational use of medicines..... 23 6. Implementing the Agency’s road map...... 26 7. Conclusion...... 27

Road map to 2015 3 The European Medicines Agency’s contribution to science, medicines and health 1. Executive summary

This road map sets out a strategic vision for the operation of the European Medicines Agency (hereinafter 'the Agency') over the five-year period from 2011 to 2015.

It has been drafted in consultation with the activities; challenges relating to the Agency’s European partner organis­ations movement of clinical research to and with the public, to ensure as broad a developing countries, to ethical consensus as possible on the best approach standards and to regulatory and to the Agency’s fulfilment of its public supervision arrangements in non-EU mandate to protect and promote public countries; the attendant need for closer health1 in the European Union (EU) over and more intense cooperation between the coming years. international partners;

After a brief overview of the main European • continue to review the model for and international factors that characterise regulation of medicines in the EU, the evolving operational environment of the particularly with regard to: the Agency, the document sets out in some development of medicines; the benefit/ detail the key drivers for progress and risk balance; the point of decision- change to which the Agency is subject, making for authorisation; post- namely the needs to: authorisation follow-up; the growing importance of health technology • ensure efficient operation of its core assessment bodies; specific consider­ business, which is of critical ations relating to herbal medicines; a importance to the continuing success possible reconsideration of the extent of the Agency in the face of the to which legislation governing veter­ increasing scope and complexity of its inary medicines is tailored to the responsibilities under EU legislation; specific requirements of this sector;

• address public-health needs, through • ensure patient/consumer and measures that include: promoting the animal-health protection, with availability of medicines for rare particular emphasis on: progressing diseases, unmet medical needs and the implementation of initiatives within paediatric use; promoting the rational the framework of the European Risk and better-targeted use of medicines Management Strategy and the to reduce morbidity and mortality; European Surveillance Strategy; investigating the impact on public implementing the new pharmaco­ health of decisions taken by regulators; vigilance legislation to address facilitating the availability of veterinary increased public demands for more medicines; promoting closer refined pharmacovigilance tools and coordination of activities in human and better communication on the benefits veterinary areas; and risks of medicines; supporting the European Commission’s development • further develop the regulatory of a legislative framework that is more framework for new and emerging appropriate to the needs of modern science, in particular with respect to veterinary medicine; benefit/risk evaluation, potential safety issues, and ethical and environmental • meet public demands for greater considerations; transparency and openness with respect to the Agency’s activities, its • address the impact of globalisation decision-making processes and the in the pharmaceuticals sector, ready availability of up-to-date characterised by: the increasingly information on medicinal products, global nature of research, development, adverse drug reactions and clinical manufacturing and clinical-trial trials.

1 Throughout this document, the term 'public health' is used to refer to both human and animal health, unless otherwise stated.

Road map to 2015 4 The European Medicines Agency’s contribution to science, medicines and health Executive summary

To address these drivers for progress and Specific indicators of the expected impact/ change, the Agency's first priority over the result of each of the activities in these next five years will continue to be the strategic areas are identified in the body successful delivery of its core business. In of this road map, while a separate ‘From addition, the Agency has identified three vision to reality’ document (to be published strategic areas within which it will focus its in the course of 2011) will set out detailed efforts in the years ahead: information on the Agency’s planned implementation of these activities. • Addressing public-health needs, by pursuing the following objectives: The success of the Agency in implementing the vision set out in this road map will be -- stimulate medicines development in contingent upon the availability of the areas of unmet medical needs, necessary resources, as well as upon the neglected diseases and rare dis­ continuing support and cooperation of the eases, and for all types of medi­cines Agency’s partners in the EU regulatory for veterinary use; network. -- facilitate new approaches to medicines development; -- apply a more proactive approach to public-health threats where medi­ cines are implicated. • Facilitating access to medicines, by pursuing the following objectives:

-- address the high attrition rate during the medicines-development process; -- reinforce the benefit/risk-balance assessment model; -- continue to improve the quality and the regulatory and scientific consistency of the outcome of the scientific review. • Optimising the safe and rational use of medicines, by pursuing the following objectives:

-- strengthen the evidence base in the post-authorisation phase to enable better regulatory decision-making; -- enhance patient safety by avoiding unnecessary risks to patients as a result of the use of medicines; -- become a reference point for infor­ mation on medicines evaluated by the Agency; -- improve the decision-making process by taking due account of patient experience, thus contributing to the rational use of medicines.

Road map to 2015 5 The European Medicines Agency’s contribution to science, medicines and health 2. Introduction

In 2005, the European Medicines Agency is dependent on the availability of the developed a longer-term strategy2 to guide necessary resources. Detailed information its proactive approach to the continuing on the implementation of the road map will evolution of the pharmaceutical arena in be provided in the document 'From vision the European Union (EU). This strategy to reality', to be published shortly. focused mainly on contributing to better promotion and protection of public health, Striving for as broad a consensus as possible improving the regulatory environment for on the best way forward, the Agency medicinal products, and helping to stimulate discussed the 'Road map to 2015' with its innovation, research and development in partners and stakeholders. Following public the EU. consultation in 2010, which included face- to-face discussions, and subsequent The Agency's 'Road map to 2015' is a consideration of the comments received, continuation of this longer-term strategy, this revised version of the road map was building on current achievements, but also adopted by the Agency's Management Board taking due account of the changing at its 16 December 2010 meeting, and environment in which the Agency will have subsequently made public. to operate over the next five years. In further developing its road map project, the Agency will ensure that its vision is consistent with and complementary to strategic directions provided by the European Commission3,4,5,6, the Council of the European Union7 and the Heads of Medicines Agencies8.

The 'Road map to 2015' sets out the Agency's vision, elaborates on the main drivers for progress and change that will impact on it, and explores the main initiatives to be undertaken to successfully meet the challenges it will face. This vision encompasses the Agency's strategy for both medicines for human and veterinary use, in line with the joint responsibility of the Agency9. It should be noted that the successful delivery of the Agency's vision

2 The European Medicines Agency Road Map to 2010: Preparing the Ground for the Future (EMEA/H/34163/03/Final). 3 European Commission’s Better Regulation strategy (see Better Regulation website). 4 Communication from the Commission to the European Parliament, the Council, the European Economic and Social Committee and the Com- mittee of the Regions – Safe, Innovative and Accessible Medicines: a Renewed Vision for the Pharmaceutical Sector (COM(2008) 666 final). 5 Future Challenges Paper: 2009-2014, Euro- pean Commission Health & Consumer Protection Directorate-General. 6 Communication from the Commission to the European Parliament and the Council: European agencies – The way forward (COM(2008) 135 final). 7 Draft Council Conclusions on Innovation and Solidarity in Pharmaceuticals (16586/1/10). 8 A Strategy for the Heads of Medicines Agencies, 2011-2015. 9 An explicit reference to either sector will only be made where necessary.

Road map to 2015 6 The European Medicines Agency’s contribution to science, medicines and health 3. Setting the scene: the Agency and its environment 3.1. The European Medicines When considering the Agency's environment, its partnership with other EU bodies (i.e. Agency as a public-health the European Commission and EU agencies) agency also needs to be taken into account, as does The mission of the Agency is to foster its collaboration with specific European scientific excellence in the evaluation and bodies involved in medicines regulation, supervision of medicines, for the benefit of such as the European Directorate for the public health. This is fully in line with the Quality of Medicines and HealthCare (EDQM) Agency's legal role and responsibilities to and the Official Medicines Control provide the EU institutions and Member Laboratories (OMCL) network. The Agency's States the best-possible scientific advice interaction with other EU public-health on any question relating to the evaluation agencies in particular, such as the European of the quality, safety and efficacy of Food Safety Agency (EFSA) and the medicinal products referred to it in European Centre for Disease Prevention accordance with the EU legal provisions. and Control (ECDC), has expanded over The Agency's sphere of responsibilities has time. Collaboration with the European gradually expanded over time, in line with Commission increasingly focuses on a new EU legislation, most recently in the deepening of the interaction in the fields of fields of paediatric and advanced-therapy research-related work and emerging medicinal products. Furthermore, new diseases. legislation is under way (e.g. in the fields of falsified medicines and pharmaco­ 3.2.2. Positioning the Agency vigilance) that will further increase the Agency's (coordinating) role in the pharma­ on the international scene ceutical arena. As a result, the Agency's International cooperation nowadays builds involvement in public health (within the on long-established interaction in fora such context of the authorisation and supervision as the International Conference on of medicinal products) has further increased Harmonisation ((V)ICH), the Codex and will continue to do so, thereby estab­ Alimentarius and the World Organisation lishing the Agency as an important guardian for Animal Health (OIE), as well as of public health in the EU. collaboration with the World Health Organization (WHO) and involvement in more recent projects such as the 3.2. Collaboration with the Transatlantic Administrative Simplification Agency's partners initiative. Other important international activities in the pharmaceutical sphere are 3.2.1. Operating within the the mutual-recognition agreements (MRAs) and similar agreements. Further and EU regulatory network important progress in the international field A critical factor for the Agency's success has been made through confidentiality has been the provision by the Member arrangements concluded with the U.S., States of high-quality scientific resources Japanese, Canadian and Australian health for the evaluation and supervision of authorities. New developments relate to medicinal products. This provision of the interaction with standards-development resources, coordinated by the Agency, is organisations in the framework of the one of the features of the EU regulatory development of international standards for network – a concept that is unique in the the definition of data structures, as well as world. Another feature of this network is the development of controlled and the platform provided by the Agency for internationally agreed terminologies the coordination of activities at EU level defining valid entries. (e.g. in the field of mutual recognition and decentralised medicines, and certain aspects The coming years will see intensified efforts relating to clinical trials). In its 'Road map to further expand international cooperation, to 2010', the Agency emphasised the need in line with the Agency's international to strengthen the partnership between all strategy. This strategy will elaborate on the EU regulatory authorities, leading to the creation of synergies through collaboration, establishment of a network of excellence cooperation and communication with at EU level. Further reinforcing this international regulatory partners, with a partnership will continue to be pivotal for view towards supporting in the long term the Agency. a global approach to the authorisation and supervision of medicines.

Road map to 2015 7 The European Medicines Agency’s contribution to science, medicines and health 3. Setting the scene: the Agency and its environment

3.3. Interaction with the Recognising the added value of patients and consumers in benefit/risk considerations Agency's stakeholders – in that they enrich regulatory decisions One of the key features of the Agency's by complementing them with the views interaction with stakeholders since its of those directly affected by regulatory establishment has been dialogue with the decisions – the debate currently focuses pharmaceutical industry. While this dialogue on how to achieve more structured involve­ initially focused on the innovative-medicines ment of patients in the Agency's work. industry, there has over recent years been Likewise, discussions are ongoing in both further diversification, with increasing the human and veterinary areas on how involvement of the generics and non- to better engage healthcare professionals prescription-medicines industries. in the Agency's activities. Another trend is the increasing contribution by academia An element of growing importance is the and learned societies to the Agency's involvement and participation of civil-society work, which supports the development of representatives (patients/consumers/users regulatory science10. of medicines and healthcare professionals) in the Agency's activities, either as experts Furthermore, as the scope of the Agency's in a particular (therapeutic) field or as role and responsibilities increases, the range individuals representing their respective of its stakeholders will extend to additional association. Their membership of the branches of the pharmaceutical sector, such Management Board and some scientific as the distribution chain and the field of committees, as well as their involvement medical devices and diagnostics. in other parts of the Agency's work, has led to the development of specific frameworks for interaction.

10 Regulatory science is defined as a range of sci- entific disciplines that are applied to the quality, safety and efficacy assessment of medicinal products and that inform regulatory decision- making throughout the lifecycle of a medicine. It encompasses basic and applied medicinal science and social sciences, and contributes to the development of regulatory standards and tools.

Road map to 2015 8 The European Medicines Agency’s contribution to science, medicines and health 4. The Agency’s drivers for progress and change

The following business drivers are shaping which will heavily impact on existing the future tasks of the Agency and the healthcare systems. An aspect that will environment in which it operates. remain high on the public-health agenda relates to the availability of medicines for rare diseases and other current unmet 4.1. Efficient operation of medical needs, such as medicines for the the Agency's core business paediatric population. Rational and better- targeted use of medicines has been The main focus for the Agency over the identified years ago as an important factor coming years will continue to be the in reducing morbidity and mortality. Another operation of its core business11, in line with aspect that requires careful consideration the tasks described in current and upcoming is the need to investigate the impact on EU legislation. The Agency's roles and public health of decisions taken by regulatory responsibilities have further expanded since authorities, and to subsequently introduce the drafting of the 'Road map to 2010', and the necessary remedial actions. now cover a wide range of activities. The European Commission's impact assessments In the area of animal health, the European of new legislative provisions in the areas of Commission will be implementing during falsified medicines and pharmacovigilance the period covered by this road map the have indicated that the consequences will revised Community Animal Health Strategy be very important for the EU regulatory (CAHS)13. The Agency is a key partner in network – and for the Agency in particular, terms of facilitating the availability of given its coordinating role. medicines for veterinary use that will be needed to deliver parts of this strategy. Efficiency will, therefore, be even more key to the successful operation of the Agency's The Agency's contribution to the CAHS core business. An important consequence needs to be seen within the 'One World, of the growing area of responsibilities is One Health' concept14, whereby promotion that the Agency's tasks have become much of health in animals promotes health in more complex. The Agency currently humans. Being an Agency with responsibility comprises six scientific committees and for medicines for both man and animals, it some 35 working parties and other is well placed to promote closer coordination (scientific) fora, to which it provides between activities in the human and scientific support. A particular challenge in veterinary areas, bringing together relevant this area relates to the interactions and expertise to pursue shared objectives. interdependencies that exist at various levels between these fora. 4.3. New and emerging 4.2. Addressing public-health science needs While new and emerging science (such as personalised medicine, nanotechnologies, As highlighted in the European Commission's novel-novel drug development, regenerative 12 white paper , there are several challenges medicine and synthetic biology15, as well to public health that require a new strategic as advances to streamline non-clinical and approach. These cover demographic clinical development) is becoming changes (including population ageing), increasingly established as part of the new emerging public-health threats, wave of medicines development, providing antimicrobial resistance, climate change new ways to address current unmet medical (particularly in view of the emergence of needs, there are still aspects of this field new diseases) and the rapid development that require careful consideration, primarily of new technologies (including e-health),

13 Animal Health Strategy for the EU (2007-2013): ‘Prevention is Better than Cure’ (ISBN 978-92- 11 Core business is defined as the Agency’s involve- 79-06722-8). ment in the authorisation and supervision of medicinal products for human and veterinary 14 ‘One World, One Health’ website. use, in accordance with EU legislative provisions, 15 Synthetic biology refers to two main activities: including the processes supporting these tasks. the design and construction of new biologically 12 White Paper – Together for Health: A Strategic based parts, novel devices and systems, and the Approach for the EU 2008-2013 (COM(2007) 630 redesign of existing, natural biological systems final). for useful purposes.

Road map to 2015 9 The European Medicines Agency’s contribution to science, medicines and health 4. The Agency’s drivers for progress and change

the appropriateness of the current legal/ particularly Codex Alimentarius, in setting regulatory framework, in particular with acceptable limits for residues of veterinary respect to the benefit/risk evaluation and medicines in animal foodstuffs, and in risk- the development of tools for the anticipation assessment methodologies. An increased of potential safety issues. There is thus a focus on international cooperation need for debate on how best to support and recognises the fact that EU consumers are translate the new science into regulatory only really protected from risks related to requirements. Further thought will also have products of animal origin when the same to be given to aspects such as ethical and standards are applied, irrespective of environmental considerations. Such whether animals are reared in the EU or important scientific progress will require elsewhere. regulators to be attuned to the new technologies in both human and veterinary fields, and to learn from research and 4.5. The model for regulation experience in other industry sectors. of medicines

In addition, the Agency is likely to be The model for regulation of medicines is a confronted within the next few years with complex concept, encompassing elements challenges stemming from a reappraisal of such as the requirements for medicines the device legislation in the EU and, in development, the benefit/risk balance, the particular, activities focusing on the point of decision-making for granting a interaction between medical devices/ marketing authorisation, and post- diagnostics and medicinal products. authorisation follow-up. Added complexity Interaction between the sectors of medicinal comes from a split of activities undertaken products, medical devices and diagnostics at national level (clinical-trial responsibility, should be facilitated to nurture a synergistic scientific-advice handling, etc.) and at EU approach. level (equally scientific-advice handling, assessment of paediatric investigation plans, etc.). Over the past few years, there 4.4. The impact of increasing have been several developments in each of globalisation the areas cited above that de facto mean that the current model for medicines The importance of globalisation has regulation is being reviewed. A recent increased over time and will continue to do development in the pharmaceutical arena so. One of the main drivers is the global is the growing importance of health nature of medicines development and technology assessment (HTA) bodies on the research. Manufacturing and clinical-trial access to market of novel medicines, due activities will continue to see an increased largely to increased pressure on healthcare international focus over the coming years. budgets. Of particular note in this respect The movement of clinical research to is the work already undertaken within the developing countries presents particular framework of the European Network for challenges, such as safeguarding the HTA Joint Action (EUnetHTA JA) on the integrity of the data, ensuring equivalent relative effectiveness of pharmaceuticals. ethical standards are met, the threat of double standards, and the need to have More specific considerations relate to the confidence in local regulatory and field of herbal medicinal products, where it supervision arrangements. Another field of needs to be acknowledged that the growing concern relates to the increasing innovative concept of list entries and manufacture of active pharmaceutical monographs has not really been followed ingredients (APIs) outside the EU, and in up in terms of subsequent marketing- particular the potential for substandard authorisation applications, and that remedial material to enter the supply chain. action is therefore necessary. Furthermore, aspects related to borderline issues with In the area of regulation of medicines for nutritional supplements still require veterinary use, the impact of globalisation resolution. will also become increasingly noticeable in terms of closer and more intense cooperation The past thirty years have seen a gradual with international partners. During the next convergence of the legislation governing five years, particular efforts will be needed medicines for human and veterinary use, to develop, with the OIE, an appropriate leading to an improvement in the quality approach to extending the influence and of veterinary medicines but also to an uptake of VICH guidelines beyond the overall increase in regulatory requirements existing member and observer countries. and in their complexity. In 2009, the Also, in light of the recently revised EU European Commission recognised the need legislation governing maximum residue for a review, and launched an impact limits (MRLs), closer cooperation will be assessment of the veterinary medicines required with international partners, legislation that covered, among other

Road map to 2015 10 The European Medicines Agency’s contribution to science, medicines and health 4. The Agency’s drivers for progress and change

issues, whether or not there is a need to mation available (e.g. information on the reconsider the extent to which the legislation opinion/decision-making process for the governing veterinary medicines should, in evaluation and supervision of medicinal future, be tailored to the specific products, on adverse drug reactions and requirements of this market sector. on clinical trials).

Efforts will have to be strengthened to make 4.6. Ensuring patient/ up-to-date medicinal product information consumer and animal-health readily available. Providing greater protection transparency will entail specific challenges, such as finding the right balance between For several years, the focus within the EU making more information and documents has been directed towards a more proactive available more quickly and protecting approach in ensuring patient safety, while commercially confidential information, while continuing efforts to further improve the also complying with personal-data spontaneous reporting scheme. This legislation. More openness of operation and resulted, in 2005, in a number of legislative increased transparency should go hand in changes for medicines for human use, hand with efficient and targeted introducing new tools such as the novel communication. This becomes even more concept of risk-management plans. In important in situations that require a addition, strategic initiatives were launched coordinated approach, such as emerging in the EU within the framework of the public-health threats. European Risk Management Strategy (medicines for human use) and the European Surveillance Strategy (medicines for veterinary use). In both cases, the aim is to achieve high standards of human and animal-health protection with respect to the use of medicines. Work is under way16 to further progress the implementation of the various initiatives. It needs to be recognised, however, that public opinion over time has become much more risk- averse, resulting in increased demands for more refined pharmacovigilance tools for medicines for human use, as well as better communication on the benefits and risks of medicines. The new pharmacovigilance legislation will provide an appropriate framework to address these demands. Likewise, the European Commission's review of the veterinary medicines legislation provides an opportunity to develop a framework more appropriate to the needs of modern veterinary medicine.

4.7. Demands for greater transparency and openness For any public body in the field of medicines regulation, transparency and openness are important factors in its ability to gain, maintain and strengthen the trust of its stakeholders. Demand for information and openness on the Agency's activities will increase over the coming years, so action is needed both in terms of the tools available (for accessing documents and public data­ base information) and the content of infor­

16 Implementation of the Action Plan to Further Progress the European Risk Management Strategy: Rolling Two-Year Work Programme (EMEA/280089/2007).

Road map to 2015 11 The European Medicines Agency’s contribution to science, medicines and health 5. Addressing the drivers for progress and change 5.1. Current achievements 5.2. Objectives and priorities The 'Road map to 2010' clearly states that for the next five years its ultimate objective is to ensure that the Agency adequately prepares the ground for 5.2.1. Performing the further success in the future, building on Agency's core tasks the achievements of its first 10 years. At regular intervals17,18, the Agency has To address the aforementioned business reported on progress made with the drivers, the Agency's first priority over the implementation of its 'Road map to 2010'. next five years will continue to be on the Overall, the Agency largely succeeded in successful delivery of its core business in delivering the planned activities and accordance with current and new EU initiatives and in meeting its 2010 priority legislation. While the Agency's tasks have objectives of top-quality scientific further expanded over the past years in the assessment, timely access to safe and field of innovative medicines, access to the effective medicines, continuous monitoring centralised procedure for both generic/ of medicinal products, access to information, biosimilar and non-prescription medicines and specific needs for veterinary medicines. has now also become a reality, and in fact Although it can be concluded that the constitutes an important part of the Agency has now successfully prepared the Agency's core business activities and thus ground for the future, further progress on its workload. It also needs to be the 2010 road-map objectives is still acknowledged that the scope of the work needed19. Where further work remains to to be undertaken in other areas did not be done to complete these objectives, this significantly increase. This is for instance has been incorporated in the objectives and the case in the field of herbal medicinal priorities for the next five years, as outlined products, although the past years have in Section 5.2. indicated the need for remedial action to address aspects such as adjusting the In addition, the Agency has been at the priority list of herbal substances, forefront in other fields, for instance the preparations and combinations thereof to development of scientific guidelines for the needs of the market operators, and to biosimilar and advanced-therapy medicinal undertake initiatives to facilitate the uptake products, thus paving the way for access of the traditional-use registration scheme20. by EU citizens to these new types of medicines. Scientific excellence (as a result Since 2005, additional challenges have had of EU-wide pooling of expertise and data) to be addressed as a result of new legislation has been a key strength. In this respect, it in the fields of paediatric and advanced- should be stressed once again that such therapy medicinal products. This resulted excellent progress has been highly in a marked increase in workload. From dependent on close collaboration between 2011 onwards, the Agency will be faced the Agency and the national competent with the implementation of two new pieces authorities within the context of the EU of EU legislation in the fields of regulatory network, and in particular on the pharmacovigilance and falsified medicines, valuable input of high-quality specialist which will require careful planning, in expertise provided by the Member States. collaboration with the Agency's partners Another important enabler has been the and stakeholders, because of the important Agency's continuing review of the operation impact these new provisions will have on of its core business, which has identified the regulatory environment. efficiency gains and allowed process improvements to be introduced. Taking into account concerns voiced with respect to the current regulatory framework for medicines for veterinary use, the Agency will work with the European Commission and other partners in the EU regulatory network to analyse the outcome of the Commission's impact assessment and 17 Status Report on the Implementation of the Road develop firm proposals designed to simplify Map (EMEA/171321/2006). 18 Second Status Report on the Implementation of the Road Map (EMEA/359050/2007). 19 A third and final status report on the implementa- tion of the ‘Road map to 2010’ will be prepared 20 Action Plan for Herbal Medicines 2010-2011 and published in 2011. (EMA/831327/2009).

Road map to 2015 12 The European Medicines Agency’s contribution to science, medicines and health 5. Addressing the drivers for progress and change

the framework for veterinary medicines and authorities, pharmaceutical industry, ensure it is tailored to the specific academia and patients/consumers/users of requirements of this sector. medicines will be more systematically used, thereby strengthening the role of the Efforts to strengthen the Agency's efficiency Agency in promoting discussions with all of will continue in line with the European its stakeholders on important regulatory Commission's Better Regulation strategy, and scientific challenges. thereby further reducing the administrative burden. Taking into account the need to strive for the most cost-efficient way of 5.2.2. The Agency's strategic operating, the Agency will continue to work areas 2011-2015 on re-engineering and improving the processes supporting its core business. More To address the business drivers listed in detailed information on the measures to be Section 4, the Agency has identified three taken is provided in the 'From vision to strategic areas for the future: reality' document. • addressing public-health needs; Successful delivery of the Agency's facilitating access to medicines; objectives and priorities also requires that • operational and organisational aspects be • optimising the safe and rational use of carefully reviewed to verify their adequacy medicines. for the years to come. Following the publication of the European Commission's Objectives in the area of addressing public- 21 report on its evaluation of the Agency , a health needs will include stimulating the conference was held at the Agency on 30 development of medicines for unmet June 2010 to discuss the findings and medical needs (particularly novel anti­ recommendations made. Several biotics), medicines for rare and neg­lected recommendations relate to the complexity diseases, and all types of veterinary of interactions within the Agency's scientific medicines. Tackling challenges posed by fora and to the Agency's architectural the steady integration of new and emerging capacity to deal with an ever-increasing science into modern medicine will be a workload. Recommendations not requiring further focus of activities in this strategic legislative changes are addressed in the area, as will the need to learn from recent 'From vision to reality' document. public-health threats and further improve preparedness mechanisms for future threats Acknowledging the Agency's achievements or crises. so far, the focus for the next period will also be directed more towards the quality of the The Agency's focus in the area of facilitating outcome of the Agency's work, and in access to medicines will be on activities particular on how to increase this quality. designed to reduce the productivity gap It should also be recognised that there will that currently exists in the development of be other developments and challenges in medicines. Activities in this area will include the fields of science, medicines and health investigating the underlying reasons for the that the Agency will have to face, and to productivity gap, encouraging the use of which it believes it can provide an important scientific advice during the development contribution. Pivotal in achieving this aim process, and promoting early interaction will be to further strengthen the close between regulators and sponsors. The collaboration and cooperation with the Agency will also explore how regulatory Agency's partners in the context of the EU pathways can best align market access of regulatory network, building on the excellent new medicines with the growing knowledge progress made over the past years. In over time of benefits and risks. addition, in some areas the scientific and technical developments may be so important In the area of optimising the safe and that they require coordinated consideration rational use of medicines, the Agency's and debate by the wider (scientific) focus will be on minimising the risks to community, where relevant at international public health that are inherent in the 'real- level, to find the best-possible answers to world' use of medicines. Extrapolating the challenging questions on regulation and positive benefit/risk balance identified in a science. In these situations, the existing clinical-trial setting for a medicine in a given concept of putting in place dedicated therapeutic indication for a well-defined discussion fora involving regulatory target population to the real-life use of the medicine should be further explored. Consideration must also be given here to off-label use of medicines, which can result in adverse events that trigger (important) 21 European Commission – Evaluation of the Euro- pean Medicines Agency – January 2010 – Final regulatory remedial action. It needs to be Report. acknowledged that the Agency is limited in

Road map to 2015 13 The European Medicines Agency’s contribution to science, medicines and health 5. Addressing the drivers for progress and change

its contribution to addressing this issue, but For each of the three strategic areas it has a role to play in raising better identified, the Agency has set specific awareness at the level of the wider objectives that it will target through its community on the rationale for its opinion/ activities over the course of the period of decision-making. Other activities such as this road map, together with impact/result improved risk-minimisation tools, post- indicators by which the Agency can measure authorisation follow-up and outcomes its success in achieving those objectives, research will complete the Agency's as described in detail in the following initiatives in this area. sections.

Road map to 2015 14 The European Medicines Agency’s contribution to science, medicines and health 5. Addressing the drivers for progress and change

Strategic area 1: addressing public-health needs

Objectives22 Impact/result indicators

Stimulate medicines development in • Increase in the number of areas of unmet medical needs, scientific-advice requests for neglected diseases and rare diseases, medicines for unmet medical and for all types of medicines for needs, neglected diseases and rare veterinary use. diseases, and for all types of medicines for veterinary use. • Increase in the use of specific procedures such as Article 58 procedures (under Regulation (EC) No 726/2004).

Facilitate new approaches to medicines • Existing model for medicines development. regulation is adapted to enable integration of new and emerging science.

Apply a more proactive approach to • Effective preparedness mechanisms public-health threats where medicines that take due account of learnings are implicated. from previous public-health threats/crisis situations are available. • The ‘One World, One Health’ concept is applied to link the protection and improvement of animal health with the protection and improvement of human health. • The Committee for Medicinal Products for Veterinary Use (CVMP) Strategy on Antimicrobials 2011- 201523 is successfully completed.

Gaps in medicines To address these findings, research should development not only focus on the development of new An important public-health challenge medicines, but equally target known currently faced is the lack of medicines for substances (looking for new therapeutic unmet medical needs, neglected diseases areas or improved ways of administration), and rare diseases. One of the most critical thereby benefiting from a well-known safety areas concerns the limited availability of profile as a result of wide population novel antibiotics for human use, often exposure. caused by unfavourable conditions for The Agency plans to take the following developing new effective antibiotic agents, actions: and of strategies to limit the development of antimicrobial resistance. In addition to • Investigate and analyse, in close infectious diseases, other fields of concern collaboration with the pharmaceutical with regard to gaps in medicines develop­ companies concerned, the reasons for ment are rare and neglected diseases, discontinuing the development of leading in particular to challenges for medicines for human use, starting with developing countries. selected designated orphan medicines, and propose remedial action. Any solution should favour a holistic approach, including the use of novel endpoints, different study designs and 22 Only longer-term objectives, with corresponding a more appropriate use of the impact or result indicators, are described in this accelerated assessment scheme for document. Further information will be provided medicines intended for unmet medical in the document ‘From vision to reality’ and the Agency’s annual work programmes. needs, rare diseases and neglected diseases in the EU and beyond. 23 CVMP Strategy on Antimicrobials 2011-2015 (EMA/CVMP/287420/2010).

Road map to 2015 15 The European Medicines Agency’s contribution to science, medicines and health 5. Addressing the drivers for progress and change

• Assume a more proactive role in consideration will be given in the advising the European institutions on veterinary field to clarifying the any gaps in medicines development, prospects for developing novel taking into account the Agency's antimicrobials for animals, taking into knowledge-base on medicines under account the need to retain the efficacy development, and on better incentives of critically important antimicrobials in to stimulate medicines development. human medicine. This should result in the establishment of a list of prioritised unmet needs, on • Support the European Commission in which the public would be consulted implementing the revised CAHS before sending it to the responsible 'Prevention is Better than Cure', by European Commission services. This continuing its efforts within the EU approach could also be taken for regulatory network to promote the neglected diseases in developing availability of medicines for veterinary countries, to complement existing use that will be needed to deliver the initiatives such as Article 58 opinions strategy, and those indicated for minor (under Regulation (EC) No 726/2004). use and minor species in particular. In Recent experience with the supply this context, the Agency will pursue shortage of radiopharmaceuticals24 has approaches to facilitate authorisation indicated that it would be appropriate of vaccines against epizootic diseases to also carefully consider the need for and assist where possible with bringing the development of new imaging novel tools for disease control to agents. market (i.e. those diseases identified as priorities within the European • Explore how best to contribute towards Technology Platform for Global Animal tackling challenges stemming from Health's DISCONTOOLS project). demographic changes, in particular population ageing. Taking into account current achievements in this field, the New and emerging science Agency will make additional efforts to Scientific progress over the next five years ensure that the needs of elderly people will be an important driver for change. are considered in the development and Building on current experience with evaluation of new medicines and in the advanced therapies (cell therapy, gene post-authorisation follow-up of already therapy and tissue engineering), the Agency approved medicines. will have to address new challenges on the horizon relating to nanotechnologies, novel- • Launch initiatives to address the lack novel drug development, synthetic biology, of development of antibiotics and the and regenerative and personalised medicine. potential threat of antimicrobial The concept of personalised medicine is resistance arising from the (mis)use steadily evolving from a theoretical concept of antimicrobials in human and into an integral part of modern medicine. veterinary medicine. Reference is in The Agency has already been confronted this respect made to the work with this concept, primarily in the oncology performed within the context of the field. Some centrally authorised products Trans Atlantic Task Force on already have personalised (pharmaco­ Antimicrobial Resistance (TATFAR), to genomics) indications in the approved which the Agency will contribute, as product information. Many different well as to activities jointly undertaken applications of novel nanotechnologies to by the Agency and other EU agencies medicines development are also a reality, such as ECDC and EFSA25,26. Initiatives but experience is still very limited. In already launched outside the EU (e.g. addition, the field of nanotechnology is very in the field of tuberculosis) should also diverse. Likewise, only a small number of be taken into account. Specific applications may be seen over the next years for regenerative medicine. For these novel scientific approaches, the scientific/ technical and regulatory challenges will be 24 Workshop Outcome and Recommendations very significant. – Current Use and Future Needs of Radio­ pharmaceuticals Labelled with Radionuclides The Agency plans the following actions to Produced in Reactors and Possible Alternatives address these challenges: (EMA/150127/2010). 25 ECDC/EMEA Joint Technical Report: The bacterial • To advise in the field of human challenge: time to react. A call to narrow the gap medicines, through pooling of specialist between multidrug-resistant bacteria in the EU and development of new antibacterial agents. expertise, on the necessary adaptation 26 ECDC/EFSA/EMEA/SCENHIR Joint Report on of the regulatory framework to the new Antimicrobial Resistance (AMR) Focused on technologies. This will complement Zoonotic Infections.

Road map to 2015 16 The European Medicines Agency’s contribution to science, medicines and health 5. Addressing the drivers for progress and change

existing initiatives such as the setting- ceuticals have demonstrated the need for up of a dedicated biomarker- preparedness if regulatory authorities are qualification procedure and the to be able to cope adequately with public- provision of regulatory and scientific health threats/crises. This requires the support to the Innovative Medicines availability of dedicated processes and Initiative (IMI). systems, as well as efficient coordination not only across the EU regulatory network, • To explore, within the forthcoming but also with non-EU regulators and with review of the legislation governing the pharmaceutical industry. Although each veterinary medicines, to what extent of these emerging situations has its own the requirements of evolving science characteristics, they often have three (stem-cell technology, growth factors elements in common: the complexity of the and other biologically active molecules, problem (including communication aspects), and tissue engineering) can be met the global dimension and the need to find within the existing legal framework and a solution quickly. to what extent new legislation would be required. While recognising that it Another area of major concern is the is impractical to develop a framework growing threat of substandard active as comprehensive as in the field of substances and falsified medicines. While advanced therapies for human use, a the development of specific EU legislation lack of legislation should not be allowed is under way in these fields, the issue will to be an impediment to the development remain high on the political agenda until of novel veterinary medicines, implementation of the new legislative particularly as there is currently great proposals. interest in adapting advanced therapies for human use to veterinary applica­ Several public-health threats require the tions. The methodology for assessing application of the 'One World, One Health' the safety to consumers of these new concept to be effectively addressed, technologies and substances when whereby promoting health in man is linked administered to food-producing species with promoting health in animals. will require particular attention. Antimicrobial resistance is one such threat that requires a coordinated approach, in terms of minimising the potential for Public-health threats resistance to arise from the use of antimicrobial agents in both man and The H1N1 influenza pandemic in 2009 animals. From the veterinary perspective, underlined the importance of prompt action this approach is recognised within the CAHS in response to emerging public-health and the CVMP Strategy on Antimicrobials. threats. Putting in place the necessary preparedness mechanisms has proven to Planned actions: be a very complex exercise that involves many aspects, including the availability of • Acknowledging that it will never be a dedicated legal/regulatory framework for possible to have a 'one size fits all' the authorisation and supervision of response, the Agency will investigate medicines, rapid scientific-assessment – on the basis of accumulated processes, and a targeted and coordinated experience, and in close collaboration communication strategy. In addition, it with its partners and stakeholders – requires the Agency to expand its interaction whether its preparedness mechanisms beyond the EU regulatory network in which should be revised. it operates. Excellent collaboration between all parties in the wider EU public-health • The Agency will conduct, in collaboration environment has been and will continue to with its partners and relevant be pivotal in addressing this challenge. stakeholders, a 'lessons learned' While experience in this field is growing, exercise after each major event, to with lessons being learned from previous further improve existing preparedness pandemic-like situations and bioterrorism mechanisms. strategies being taken into account, there is also a need to prepare for new communi­ • The Agency will foster the implementation cable-disease patterns caused by climate of the actions proposed within both change and increased, unrestricted travel. the CVMP Strategy on Anti­microbials and the CAHS, in terms of continuing Recent experience with public-health threats and enhancing its interactions with all such as the H1N1 pandemic, the contami­ relevant stakeholders,­ as well as with nation of rotavirus vaccines, the emergence the European Commission, the Codex of bluetongue, the contamination of medici­ Alimentarius and OIE, to promote nal products containing or derived from prudent use of veterinary antimicrobials. heparin and the shortage of radiopharma­

Road map to 2015 17 The European Medicines Agency’s contribution to science, medicines and health 5. Addressing the drivers for progress and change

Strategic area 2: facilitating access to medicines

Objectives Impact/result indicators

Address the high attrition rate during • Increase in the percentage of the medicines-development process. successful marketing-authorisation applications for new medicinal products by encouraging that scientific advice is sought and adhered to. • Scientific information on failed medicines-development processes is made available to the scientific community.

Reinforce the benefit/risk-balance • Increased inclusion of quantitative assessment model. elements, alongside an improved elaboration of the rationale for the decision/opinion in the benefit/risk considerations, for subsequent publication in the European public assessment reports (EPARs) (medicines for human use). • The concept and practice of benefit/risk assessment are embedded as part of the scientific- review process and subsequently communicated in EPARs as part of the methodology used for assessment (medicines for veterinary use).

Continue to improve the quality and the • Structured external surveys regulatory and scientific consistency of performed by the Agency’s the outcome of the scientific review. stakeholders on the outcome of the scientific reviews demonstrate an increase in the quality and the consistency.

Medicines-development process, early assessment • Although the concept of preparing and continuing dialogue guidelines on medicines development in the fields of both human and Despite the increase in research efforts in veterinary medicines has been in place previous years, the pharmaceutical sector for several years, it would seem timely is confronted with the widely recognised to strengthen the involvement of phenomenon of the medicines-development stakeholders (and in particular pharma­ productivity gap. Feedback has indicated ceutical industry, academia/learned that both the suboptimal management of societies and patients' organisations) the medicines-development process by in this process, for instance by sponsors in some instances and new organising workshops at a very early requirements for medicines development stage of guideline development, so that have been identified as important stakeholders can actively contribute contributing factors. In order to address towards developing guidelines of the the high attrition rate during the medicines- highest quality in medical, regulatory development process and the increasing and scientific thinking. This would be productivity gap, the Agency is of the view beneficial both in areas that require that a number of initiatives could be further guideline development and in undertaken to improve the situation: fields where existing guidance should be adapted to take account of evolving science.

Road map to 2015 18 The European Medicines Agency’s contribution to science, medicines and health 5. Addressing the drivers for progress and change

• Furthermore, although the Agency is animal or clinical studies, avoidance of already collaborating with the European the use of inappropriate parameters, Commission, and in particular etc.), the Agency is of the view that it Directorate-General Research, on would seem appropriate to explore, in research-related aspects, its involve­ collaboration with the pharmaceutical ment has so far been rather fragmented. industry, what incentives could be The Agency would therefore like to offered to make this otherwise lost create a platform for dialogue with the information available to the scientific Commission, to improve its input into community. the EU research agenda for medicines. This would complement current • The Agency will continue to strengthen initiatives on fostering innovation in its engagement with the pharmaceutical the context of IMI and the European industry, the European Commission, Technology Platform for Global Animal EDQM and the European Centre for Health, to which the Agency already Validation of Alternative Methods provides an important contribution, (ECVAM) to promote the '3Rs' concept and where efforts over the next years (replacement, refinement and reduc­ will have to continue. tion) in the development of medicines, replacing wherever possible the use of • Acknowledging that the scientific advice animals by validated alternatives. provided by the Agency if adhered to by the sponsor increases the success • With respect to the veterinary sector, rate of marketing-authorisation measures will be explored to increase applications, the Agency will continue both the uptake and the perceived its efforts to optimise the scientific- usefulness of the scientific-advice advice process. procedure, through discussions with the pharmaceutical industry, taking • Current experience with engagement into account experience gained in the of regulatory authorities in early-phase field of medicines for human use, while development plans of the pharmaceu­ recognising the particular requirements tical industry has indicated that it is of the veterinary sector. Pending the advantageous to establish early development of proposals for amending dialogue with sponsors and to provide the current legislative framework to regulators with considerable knowledge cope better with the requirements of of the data at an early stage, which in products and approaches entirely new turn facilitates the scientific-review to veterinary medicines, the Agency process. While it is recognised that will promote early dialogue with further improvements can be intro­ applicants, to understand the regulatory duced, there is also a need to explore and scientific challenges that they face whether the concept of early dialogue in bringing these medicinal products in the framework of medicines to market. development could be widened, while maintaining it as a voluntary process. • Another aspect that needs careful The concept of scientific advice could consideration is the area of clinical trials be expanded to provide continuous of medicines for human use, and two scientific support during the develop­ major initiatives need to be highlighted. ment of a medicine, combined with The Conference on the Operation of earlier appointment and involvement the Clinical Trials Directive, held on 3 of (co‑)rapporteurs, which would October 2007, provided a number of augment the interaction between recommendations for further regulators and sponsors during the improvement. In addition, in 2009, the development of both human and European Commission began an impact veterinary medicines. This would assessment in view of the introduction require clear roles and responsibilities of changes to the clinical-trials to be defined for all parties involved. legislation. An aspect that will require particular attention is the regulatory • It needs to be recognised that even a oversight of medicines development, failed medicine-development process which should be further improved. The will generate useful information and development of new medicinal products scientific knowledge that, in most and of the underlying basic and instances, is currently lost, either translational research required to bring because of aspects relating to propri­ these medicines to patients are key etary information or because of the elements of a European Research lack of access to these data by reg­ Policy, which is of great importance in ulators. Taking into account the added view of the development of Europe as value of such data (in terms of a key location for biomedical research avoidance of repetitive and redundant and pharmaceutical development. A

Road map to 2015 19 The European Medicines Agency’s contribution to science, medicines and health 5. Addressing the drivers for progress and change

coherent regulatory process that can inspection coverage, but will also assist the development of medicines ensure, through existing platforms from their inception, through scientific where possible, a coordinated advice, first-in-human trials, and full approach to improving interactions clinical development is an important with developing regulatory element in enhancing the European authorities and capacity-building to research environment. There is a need facilitate better implementation of to introduce a clear, risk-based good manufacturing practice (GMP) approach so that trials of well- and supervision for manufacturers, characterised products are simpler and with respect to both medicines for quicker to initiate, and require lesser human and veterinary use. degrees of regulatory supervision, while trials of new, less well-known Benefit/risk assessment and products can be given the resources they require and merit. Simplifying and communication streamlining the current processes are To address the regulators' dilemma of essential to these objectives. balancing access to market vis-à-vis the need for as complete a data package as • The impact of the increasing possible prior to licensing, several factors globalisation of clinical research and need to be considered. Pivotal in this respect manufacturing and its movement to are benefit/risk assessment and developing countries (which may be communication. Work on improving the confronted with limited experience and benefit/risk-balance model concentrates on resources, and a less developed three major aspects: ensuring a consistent regulatory framework) needs careful approach, providing a better rationale for consideration. In order to address this the outcome of the benefit/risk review and challenge, the Agency will undertake improving the communication with the a number of initiatives, including the various stakeholders. This work goes hand- following: in-hand with the Agency's objective to focus -- In the area of clinical research, on further improving the quality of the further developing and subsequently outcome of the scientific review. The implementing the Agency's strategy27 following activities are envisaged: for acceptance of clinical trials • Optimising the benefit/risk-assessment conducted in third countries, process for medicines for human use including the development of advice can be undertaken through a variety and guidance on ethical standards of initiatives. Building on current and data-quality requirements for achievements, work should now focus, clinical trials submitted in the EU. in terms of the methodology used, on Furthermore, the Agency, in close the introduction of more quantitative collaboration with the Member State elements. The robustness of the national competent authorities and scientific review should be further its international partners, will invest strengthened through better use of in supporting capacity-building and expertise in the areas of statistics, local awareness with the regulatory decision-making and communication. authorities, research communities Furthermore, patient empowerment and pharmaceutical industry of those and patients' participation in healthcare countries. decisions will further stimulate the -- In the field of the manufacture of ongoing debate on the level of patients' APIs and of finished products, the involvement in the scientific-review Agency will develop with the Member process. This should lead to patients' States the necessary framework for utilities being taken into account in a implementing the new anti- more systematic way for the benefit/ falsification legislation. The Agency risk assessment. Likewise, it would will also build on existing collabora­ seem an opportunity to debate the level tion with its international regulatory of involvement of relevant practising partners. This will not only include healthcare professionals and academia/ exchange of information (on learned societies in the scientific- inspection planning and outcomes) assessment process throughout a and pooling of resources to increase product's lifecycle. Work will be undertaken to align the benefit/risk- assessment methodology with activities performed by other non-EU regulatory 27 EMEA Strategy Paper: Acceptance of Clinical authorities in this area. Trials conducted in Third Countries, for Evalu- ation in Marketing Authorisation Applications (EMEA/228067/2008).

Road map to 2015 20 The European Medicines Agency’s contribution to science, medicines and health 5. Addressing the drivers for progress and change

• Further work is also needed on expertise during the assessment phase, improving the transparency of the and consultation will continue with outcome of the scientific review, stakeholders, to identify the key including the justification for the parameters for measuring performance opinion/decision taken. This is even of the marketing-authorisation process more important in situations where the and to put in place systems to monitor Agency's views are not in line with the them. outcome of the review by non-EU regulatory authorities. Subsequently • An in-depth reflection is also needed communicating the outcome of the on how to further improve the use of benefit/risk assessment in the most the legal tools for the granting of a appropriate way represents a particular marketing authorisation. The Agency challenge. The Agency will, therefore, will ensure that the criteria for a prepare a strategy on benefit/risk- conditional marketing authorisation for assessment communication, liaising medicines for human use are better with all stakeholders to identify their adhered to, since it needs to be specific needs. recognised that this concept has not really been applied as initially foreseen. • In the veterinary sector, fundamental Likewise, consideration should be given differences exist in the approach to to whether, and in what form, the benefit/risk assessment, where the concept of conditional marketing direct risk is to the recipient animal authorisation might be introduced for whereas the perceptions of benefit veterinary medicines. derive from the owner, the keeper or the healthcare professional. The • In addition, a key issue for regulators databases and infrastructure required will be whether a more 'staggered' for quantitative approaches to benefit/ approval (or progressive licensing) risk assessment do not exist in the concept should be envisaged for veterinary sector and are unlikely to situations not covered by conditional be cost-effective to develop. Current marketing authorisations or marketing emphasis, therefore, is on the authorisations under exceptional development and documentation of a circumstances, for instance systematic methodology for benefit/ characterised by a better-defined or risk assessment, as well as on the more restricted population of good provision of training within the EU responders, followed by a broadening regulatory network. Therefore, work of the population post-authorisation over the coming years will focus first when more 'real-life' data are available. on more clearly embedding the benefit/ The Agency would like to launch a risk methodology in the assessment debate with all stakeholders on the procedure, adapting it to different appropriateness of introducing such a types of authorisation and medicinal concept, including a consideration of products (e.g. antimicrobials), and on appropriate incentives to support new better communication to the Agency's medicines development. It should be stakeholders about the methodology emphasised that progressive licensing used. Other challenges will be to should not lead to a reduced level of demonstrate within the EU regulatory evidence for first-time marketing network that a consistent approach to authorisation. benefit/risk assessment is applied irrespective of the licensing route, and • Strategies on the best way to increase that the methodology can bring benefits the knowledge of a medicine in the in terms of availability when applied to post-authorisation phase need to be medicines for emergency diseases and set up at the moment of licensing, and limited markets. subsequently reviewed when new information emerges. Although risk- • Further improving the quality and the management plans in the human regulatory and scientific consistency medicines field meet this aim and have of the outcome of the scientific-review been a real step forward, due account processes will be a key objective for needs to be taken of provisions in the the Agency. Activities will concentrate new pharmacovigilance legislation that on improving the benefit/risk-balance relate to such risk-management plans, model as outlined above. In addition, which will allow remaining uncertainties efforts will be directed to regular on efficacy and safety at the moment external surveys with stakeholders, to of licensing to be better addressed. monitor the outcome of scientific- Therefore, risk-management plans will review processes for medicines for be an important tool in supporting human use. For veterinary medicines, continuous benefit/risk assessment better use will be made of specialised throughout a medicine's lifecycle.

Road map to 2015 21 The European Medicines Agency’s contribution to science, medicines and health 5. Addressing the drivers for progress and change

Another tool for maximising the value process as summarised in the EPARs, of information generated in the post- including the rationale for the decision/ authorisation phase – especially for opinion, whereby more emphasis will orphan medicines – is the establishment also be put on the quantitative aspects and maintenance of patient registries. of the benefit/risk assessment, as Furthermore, work also needs to be already elaborated upon. Furthermore, undertaken to improve the formulation, the Agency will attempt to ensure that implementation and monitoring of post- the product-lifecycle concept is better authorisation commitments for integrated in the EPAR, so that the marketing authorisations not benefiting EPAR better meets the criteria of a from the conditional marketing 'living' document, providing up-to-date authorisation concept, with a view to and detailed information on the benefit/ increasing the efficiency of the system. risk profile of a medicinal product Particular attention will be paid to throughout the marketing phase. ensuring that compliance with these post-authorisation commitments is • The Agency will engage with HTA bodies adhered to. in the early stages of development of a medicine (to avoid as far as possible the appearance of two different Facilitation of the relative- medicine-development programmes) effectiveness assessment of and throughout the medicinal product's medicines for human use lifecycle, in terms of alignment of regulators' and HTA bodies' evidence A number of differences have been pointed requirements, through initiatives such out when comparing the licensing process as joint approaches to scientific advice, with relative-effectiveness and cost/benefit- mutual input on clinical guidelines and assessment processes, in terms of the debating evidence requirements choice of clinical endpoints, efficacy versus (including relative efficacy aspects). In effectiveness, and relative efficacy versus view of the vast amount of data placebo-controlled studies. This leads to a obtained through post-authorisation situation whereby regulators and HTA collection, maintaining the dialogue bodies, although both aiming for the with HTA bodies throughout a medicinal availability of medicines that make a product's lifecycle is very important, contribution to public health, are currently as this facilitates greater alignment of applying different approaches. Calls have such data collection. been made for closer interaction and collaboration between both parties of the healthcare system, while fully respecting their distinct roles and responsibilities. The High Level Pharmaceutical Forum agreed in October 2008 on a set of recommend­ ations28, including that Member States, with the involvement of the Agency, should continue their efforts to consider how EPARs can further contribute to relative- effectiveness assessments. The Agency aims to make progress in this field, albeit in a stepwise manner, while continuing to ensure that cost/benefit assessment remains distinct and separate from the licensing process. The Agency's work, therefore, will continue to be characterised by the exclusion of any economic consider­ ations.

Two major initiatives are envisaged:

• The Agency will improve as an information provider. HTA bodies rely heavily on EPARs, and the Agency will increase its level of transparency on the outcome of the scientific-review

28 High Level Pharmaceutical Forum 2005-2008, Final conclusions and Recommendations.

Road map to 2015 22 The European Medicines Agency’s contribution to science, medicines and health 5. Addressing the drivers for progress and change

Strategic area 3: optimising the safe and rational use of medicines

Objectives Impact/result indicators

Strengthen the evidence base in the • A regulatory model that facilitates the post-authorisation phase to enable better post-authorisation collection of data regulatory decision-making. on benefits and risks of medicinal products is put at the disposal of the regulatory system. • A pharmacovigilance framework appropriate to the needs and priorities of the veterinary sector is developed as an outcome of the European Commission's impact assessment of the legislation for veterinary medicines.

Enhance patient safety by avoiding • A revised risk-management concept unnecessary risks to patients as a result of that targets both novel the use of medicines. pharmacovigilance methodologies and a risk-minimisation toolbox better adapted to reduce harm is available.

Become a reference point for information • A high-quality, informative and on medicines evaluated by the Agency. targeted set of information on medicines falling within the sphere of the Agency's responsibilities is proactively put at the disposal of the EU regulatory network at the moment of licensing/updating of the marketing authorisation.

Improve the decision-making process by • Conclusions from outcomes-research taking due account of patient experience, projects analysing the impact of thus contributing to the rational use of regulatory decisions on public health medicines. are used to provide input into future regulatory policy decision-making.

Patient safety (led by the Food and Drug Administration) initiatives. Pharmacovigilance and safety of medicines will continue to be a top priority for the The Agency's initiatives in this field for Agency, with a strong focus on ensuring medicines for human use will, in addition that both risks and benefits are monitored to preparing for the implementation of the throughout a medicinal product's lifecycle. new pharmacovigilance legislation, include Avoiding unnecessary risks to patients is the following: becoming an increasingly important factor in strategies on the protection of public • A revision of the risk-minimisation- health, e.g. in the context of antibiotic use. measures toolbox, in the framework of Efforts are undertaken at EU level and the current review and learning project internationally to enhance patient safety. on risk-management plans for human In the EU, the focus is on strengthening use, the aim being to further reduce research in this field and on launching new harm caused by the use of medicines. legislative proposals aimed at rationalising This should preferably be undertaken and strengthening the EU framework on using predefined criteria for analysis safety-monitoring of medicines for human drafted in collaboration with the use. In addition, international collaboration Agency's partners and stakeholders. on medicine safety as a result of globalisation Taking into account the impact of and the need for best use of resources will certain risk-minimisation measures on result in finding synergies between the the EU's health workforce (doctors, European Network of Centres for Pharmaco­ pharmacists, nurses, etc.) and the epidemiology and Pharmacovigilance pivotal role of healthcare professionals (ENCePP, led by the Agency) and Sentinel versus patients as regards the use of medicines, particular attention will be

Road map to 2015 23 The European Medicines Agency’s contribution to science, medicines and health 5. Addressing the drivers for progress and change

paid to how the risk-minimisation authorisation studies, thus meeting the measures impact on the work of needs of both regulators and HTA healthcare professionals throughout bodies. the EU. It should be recognised that this impact may vary according to the • Taking into account increasing public healthcare policies and systems in concern over potential effects on the place. environment of the use of medicines, and building on extensive experience • Progressing the European Risk already gained with veterinary Management Strategy, thereby medicines, initiatives should be taken complementing the new legislation on to look into the longer-term impact of pharmacovigilance, targeting aspects medicines for human use on the such as capacity-building for post- environment. Particular attention will authorisation monitoring; preparing have to be paid to the environmental for the introduction of international risks of nanomedicines. standards and controlled and inter­ nationally agreed terminologies in pre- • In the field of veterinary medicines, and post-authorisation phases; the European Commission's impact involvement in research-related assessment of the veterinary medicines activities on pharmacovigilance metho­ legislation will provide an opportunity dologies, in particular within the to develop a post-authorisation context of the IMI framework, to framework that is particularly suited investigate novel and better ways to to the needs and resources of the monitor the safety and benefit/risk animal-health sector. The Agency will balance of medicines. Another good consult with all involved stakeholders example of investment in regulatory on how best to develop an appropriate science relates to further initiatives to risk-management framework, and on be undertaken within the context of the extent to which it is possible to ENCePP to support decision-making on licence medicines for veterinary use at the benefits and risks of medicines. an earlier stage of development, based on the requirement to provide the necessary post-authorisation data. Post-authorisation follow-up • With a view to contributing to a more In order to optimise the safe and rational rational use of medicines for human use of medicines, more information has to use, the Agency will focus its efforts be obtained in 'real-life' situations: on raising better awareness among healthcare professionals of the rationale • As a starting point, and taking into for its opinion/decision-making. The account the provisions on post- existing forum with healthcare authorisation studies in the new professionals' organisations will be pharmacovigilance legislation, the used to debate how this can best be focus should be on the marketing- achieved. authorisation holder's post- authorisation development plan, and should include an exploration of the Authoritative source of kind of incentives that could be provided to pharmaceutical companies information to encourage them to voluntarily The Agency is meeting the demand for include such plans in the Agency's greater transparency and openness through current scientific-advice framework. initiatives such as the development of Secondly, recent developments in the policies on access to documents29, on access field of human medicines, such as a to information in the EudraVigilance firm new legal basis to require post- databases30, and on transparency31. In authorisation studies, will augment the addition, the Agency holds the following initial knowledge on a medicinal views: product's benefits and risks. This should ultimately lead to an integrated assessment of benefits and risks under real-life conditions. ENCePP is an important tool that will support the 29 European Medicines Agency Policy on Access to Documents (related to medicinal products for development of methods for post- human and veterinary use) (EMA/110196/2006). authorisation data collection, the 30 Draft EudraVigilance Access Policy for Medicines establishment of an inventory of for Human Use (EMEA/187439/2008) and Draft pharmacovigilance and pharmaco­ Eudra­Vigilance Access Policy for Medicines for epidemiology research centres, and Veterinary Use. the creation of a register of post- 31 EMEA Transparency Policy – Draft for Public Consultation (EMEA/232037/2009 – rev*).

Road map to 2015 24 The European Medicines Agency’s contribution to science, medicines and health 5. Addressing the drivers for progress and change

• Irrespective of the ongoing political munity. This will be done through debate on the best way forward for surveys with the various stakeholders providing information on medicines to in the veterinary sector to understand patients, the Agency should strive to better the types of information they become the authoritative source of would find most useful and how best information on all medicines it they can be presented. evaluates, both human and veterinary, for syndication to the EU regulatory network. This should also promote Outcomes research public recognition of the Agency as a The Agency has identified analysing the leading authority in the field of impact of regulatory decisions on public evaluation and supervision of medicinal health as an important activity for the years products. Initiatives should be directed ahead. Outcomes research in this field has towards the preparation by the Agency begun, in line with the Agency's internal of timely, targeted and high-quality control standards, which require it to information on the medicines it evaluate its activities. Efforts in this field evaluates. In this way, the Agency can will continue over the coming years, and concentrate on the quality and will include the following: consistency of the information provided, and other parties can focus on ensuring • Building on current initiatives (with maximum penetration of this emphasis initially on the benefit/risk- information among the target assessment and communication audiences, and in particular patients/ model), the Agency will further engage consumers/users of medicines and in monitoring the use of medicines for healthcare professionals, thereby fully human use, in close collaboration with respecting the characteristics of the EU its stakeholders. To gain maximum regulatory network in this field. understanding of the implications of Strengthening the interaction with the regulatory decisions, the focus for the NCAs and with organisations coming years should be on outcomes representing patients/consumers and research that looks at the actual versus healthcare professionals to build up a intended use of medicines, the network of excellence at EU level will effectiveness of risk-minimisation be an important target. Furthermore, measures, including aspects of joint reflection with the Member States feasibility in healthcare, and investi­ and other interested parties on how gates whether the current regulatory best to address technical developments model contributes to better therapy in the field of provision of information outcomes. The findings of this research on medicines – in particular the link should also be used to provide input with e-health – is also needed. to future regulatory policy decision- making. • Work should be undertaken to put more emphasis on balanced benefit/risk • Different priorities and data sources communication, to contribute to the apply to regulatory decisions in the implementation of the empowered- veterinary-medicines sector. Where patient concept. Aspects that will possible, opportunities will be taken to require particular consideration include conduct specific outcomes-research how best to address the complexity of projects in the veterinary field, focusing the data, as this requires careful particularly on collecting data at EU interpretation, and determining the level on the sale of antimicrobials in most appropriate time point for the Member States. communication on benefits and risks when new information emerges. It will be equally important to clearly communicate to healthcare profes­ sionals and patients, using the most appropriate communication tools, the reason why the medicinal product is not indicated for use outside the approved indication.

• For veterinary medicines, the objectives in terms of transparency and commun­ ication should be the same as for medicines for human use, although it will be necessary to tailor the messages and the way in which they are delivered to the needs of the veterinary com­

Road map to 2015 25 The European Medicines Agency’s contribution to science, medicines and health 6. Implementing the Agency’s road map

The Agency will implement its vision in line In addition, to optimise the implementation with the document 'From vision to reality'. of the road map, the Agency will complement This document will provide information on its planning process by applying a multi- the prerequisites to be fulfilled and the annual programming approach, which will enablers (including operational and equally cover a five-year timeframe. This organisational aspects) needed to allow the multi-annual programming will address Agency to successfully contribute over the aspects such as workload and (human) next five years in the fields of science, resources forecasts, budget planning, medicines and health. accommodation needs, etc., and will benefit the Agency by allowing decisions to be made in a more effective and predictable way, thus helping to ensure the Agency can gradually implement its vision over the next five years. Following endorsement by the Management Board, the multi-annual planning will feed into the Agency's annual work programmes.

Road map to 2015 26 The European Medicines Agency’s contribution to science, medicines and health 7. Conclusion

It is the Agency's view that the vision The Agency is looking forward to engaging outlined in this 'Road map to 2015', together with its partners and stakeholders to with the proposed solutions for addressing successfully implement its vision for the the challenges identified, will allow the next five years. Agency to increase its contribution to science, medicines and health, and thus to the protection of the human and animal populations of the European Union.

An important prerequisite for the successful delivery of the road map will be the further development and reinforcement of the EU regulatory network, which has already proven to be of fundamental importance to the EU's pharmaceutical sector.

Road map to 2015 27 The European Medicines Agency’s contribution to science, medicines and health European Medicines Agency

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Road map to 2015 The European Medicines Agency’s contribution to science, medicines and health