CONFERENCIA Inovação

“Pharmaceutical Innovation:
A New R&D Strategy in the EU”
19-20 November 2007

Viseu, Portugal
Report of the Conference
Portuguese EU Presidency 2007

Pharmaceutical Innovation: A New R&D Strategy in the EU
EU2007.PT
Table of Contents
I - Executive Summary 5
II - Key issues arising from the Conference 7
III - Opening Session 9
IV - Opening Lecture 11
V - Round Table
– Promoting Pharmaceutical Research, Development and Innovation in the EU: a Common Goal 13
VI - Workshop 1
– Innovation and Development: constraints and opportunities 17
VII - Workshop 2
– SME and R&D Funding 20
VIII - Workshop 3
– Who will Pay for Innovation? 25
IX - Workshop 4
– Partnerships for Success 30
X - Round Table
– Brave New World: “Preparing the Future” 33
XI - Conclusions of Workshops and Future Perspectives 40
XII - Presentation on Initiative of the Incoming Slovenian EU Presidency 45
XIII - Closing Session 46
Annexes
XIV - Conference Programme 48
XV - List of participants 52

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I - Executive Summary
The National Authority of Medicines and Health Products, Infarmed, I.P. and the European Commission, organised
a Conference “Pharmaceutical Innovation: a new R&D Strategy in the EU”, on 19 and 20 November 2007, in Viseu,
Portugal, under the context of the Portuguese EU Presidency. The subject of this Conference was in line with the
18 months EU Presidencies programme (Germany, Portugal and Slovenia). The conference was supported finan-
cially by the European Commission.
The aim of the meeting was to discuss with relevant stakeholders at EU level the state-of-the-art of pharmaceutical
innovation in Europe, innovation supportive initiatives and structures, the regulatory framework of new therapies
and technologies, implementing strategies to boost competitiveness in the European pharmaceutical sector and
better promote public health.
Four workshops focused on relevant topics: 1) innovation constraints and opportunities; 2) Small and Medium En-
terprises and Research & Development funding; 3) funding of innovation; and 4) establishment of successful part-
nerships at global level. The discussion around these items led to relevant conclusions and recommendations.
Participants recognised the importance of promoting the discussion on pharmaceutical innovation under the
framework of the EU Presidency, namely for the momentum it brings to the sector.
Participants agreed that innovation is critical for the development and growth of the EU and that currently faces
constraints, but new expectations are emerging from the use of new technologies. However, to overcome the dif-
ficulties there is a need for all stakeholders to collaborate together in order to succeed in the innovative field.
The Innovative Medicines Initiatives (IMI) by the European Commission and EFPIA was discussed and recognised as a
major opportunity for Europe in the years ahead, to strengthen its science base and reduce the lag with other regions.
Its main innovations are the active collaboration of all stakeholders and the amount of funding available for research.
The words “partnership” and “collaboration” were probably the most repeated during the conference. The re-
search and development (R&D) cycle is a long and complex one and no single actor is able to carry that process
all along by itself. Therefore, there is a need for combined efforts and synergies to optimise and rationalise R&D
and funding processes. Some examples of successful partnerships on research and innovation were presented
and discussed.
It was stressed the need for a social contract between the industry and society to address real clinical needs and
to reward innovation. Small and Medium Enterprises (SMEs) were recognised as a key actor within the R&D cycle
and the discussion highlighted the growing need for education and training, especially a more professional attitude
in pursuing funding.
Overall, the regulatory framework on research and innovation (ex: advanced therapies) was also analysed. Despite
the need for minor improvements, there is a general perception that the legislation in place is adequate. Partici-
pants acknowledged that a balance of risks between regulatory requirements and specific characteristics of these
products and a risk/profit distribution business model are needed.

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Attendants considered important that regulators also become part of the R&D process and do their part in facili-
tating the evaluation process by reducing the bureaucratic burden and increasing transparency. Additionally, to
assist regulatory agencies in adopting a new attitude towards the pharmaceutical industry, some elements were
put forward, such as stimulating competence and scientific advice. Regulatory agencies and the industry should
become partners in the approval process and try to solve problems jointly.
The Conference promoted an important dialogue between national and European stakeholders and helped con-
solidating the idea that R&D is a rather global task and not only an European issue. A set of important conclusions
and recommendations was achieved, that can be subject to further discussion, improvement and action at the
national and Community levels.

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II - Key issues arising from the Conference
Characterization of the R&D environment: the challenges of pharmaceutical innovation are complex and
include high failure and attrition rates, soaring R&D costs, increasing regulatory hurdles for new products’
approval and prices negotiations for new products. Recent figures indicate that the number of new products
entering the market decreased while the level of resources invested dramatically increased, leading to high
prices of new medicines. In this context, the current R&D model needs some adaptation in order to be sus-
tainable.
Objectives: address R&D bottlenecks, select pre-competitive areas, select technologies with high potential,
create critical mass and consult key stakeholders.
Opportunities: new technologies and new delivery systems and their application bring new, positive expecta-
tions (however, it is important to assess risks/toxicology). Promising medicines discovered using “New Science”
are underway; new advanced therapies and emerging treatments are witnessing intense innovation; delivery
systems still require innovation; need to sharpen the tools for preclinical drug development, like validations of
new biomarkers and prediction based on modelling and simulation. Industry and academia should invest and
collaborate more in understanding the biology and molecular mechanisms of diseases. Better understanding of
diseases mechanisms, in vitro and in vivo models predictive of clinical safety, in silico simulation of disease pa-
thology, validate omics-base markers and simulate translational medicine. Need for public available toxicology
databases of well defined compounds to exploit the systems toxicologic potential of genomics, metabonomics
and proteomics profiling (European Centre of Drug Safety). The development and validation of alternative stud-
ies (non-animal tests) is an example of quality assurance in biomedical research.
Innovation concept: need for a clear support for innovation in all its forms.
Better access to new technologies: Health Technology Assessments should allow decision-makers to en-
sure efficient healthcare spending, identify and reward medicines that bring the highest benefit to patients.
Reward Innovation: focus should be on value and not on the cost. Pricing should reflect value. Benefits
of incremental innovation should be recognised. One of the keys to overcome the impasse is by rewarding
innovation which is based on the therapeutic value namely by EU funded R&D and innovation (7th Research
Framework Programme), through public and private partnerships.
EU innovation initiatives: the 6 th and 7th Framework Programmes and the EFPIA SRA contributed to the
new accelerated development of medicines. IMI key advantages are the active participation (“collaboration”)
of all stakeholders and the amount of 2 billion euros dedicated for R&D funding, and its major research areas
are: safety (pre and clinical); knowledge management; education and training; and efficacy (general, disease
specific). Need for a coordinated science-driven initiative between DG Enterprise and DG Research when
promoting pharmaceutical research.
Successful innovation examples: national and international mirror platforms for innovative medicines have
been developed. Examples of different countries with programmes to promote pharmaceutical research and
innovation were given (Spain, Italy, The Netherlands and USA).

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New R&D tools: knowledge management platforms, funding and support research infrastructures at EU level
and education and training on safety. Recent scientific advice figures indicate a decrease of negative opinions, par-
ticularly for orphan drugs. Continued education, early interaction in the R&D process and communication between
the different stakeholders is essential.
Clinical Trial development: a competitive edge for the EU. Growing need to develop a world class of clinical
pharmacology capabilities, good academic centres with translational biology/experimental medicine.
Education and training: human resources, researchers were recognised as a key element towards the success
of R&D projects. The development of “critical mass” in enterprises, research centres and regulatory agencies is
fundamental. Stakeholders should further invest in continued education and training programmes, particularly
SMEs.
Developing countries: it was recognised the need for the EU to further increase its support to the access of
essential medicines in developing countries. In this context, it has been highlighted the WHO initiative to boost
research on diseases that affect poor countries.

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III - Opening Session
Prof. Vasco Maria (Infarmed, Portugal) referred the positive breakthroughs of the pharmaceutical industry in the past
in the therapeutic areas like diabetes, cardiovascular, oncological and central nervous system diseases, as well as
the new biologic therapies. That the new medicines under research in the genetic, new technologies (omics) and
molecular biology fields will allow patients to have renewed hopes for pathologies yet without treatment, such as
degenerative diseases and cancer. In this context he briefly mentioned that innovation aims at: better, faster and
affordable medicines, satisfy unmet medical needs, sustainability of health systems, all based on a patient centred
approach.
He presented the Conference main objectives: 1) to promote a discussion on the current pharmaceutical research
and innovation framework; 2) discuss constraints and opportunities to the current R&D model; 3) discuss the
ongoing EU Innovation initiatives; 4) discuss ways towards the establishment of public-private partnerships and
networks; 5) and to present and discuss concrete innovative examples of successful partnerships.
As expected outcomes, he highlighted; 1) the characterization of the main constraints to innovation in the EU; 2)
definition of a platform and networks of common understanding involving relevant stakeholders; 3) and the discus-
sion of R&D incentives.
The Minister of Health (Portugal) stressed the importance of R&D of new technologies for health systems, being
this one of the main objectives of the European Health Strategy. He underlined the relevance of the European
pharmaceutical industry role towards EU citizens’ health and economic growth.
In the new global era pharmaceutical R&D is changing and new technologies and treatments are emerging, such
as regenerative medicine, personalised treatments and nanomedicine. These are already affecting industrial strat-
egies, the structure of the industry (SMEs), the conduction of clinical trials and the way medicines are dispensed.
The regulatory framework needs, thus, to adapt to this new environment and respond to it in the best possible
way, such as through effective regulatory and scientific advice. New stakeholders are also becoming involved in
the pharma sector, such as SMEs, patients and private financial entities.
The minister pointed out three major factors: 1) as of 2008, Portugal will dedicate to R&D 1% of its annual budget;
2) the establishment of a Centre of Competitiveness and Excellency in the north of Portugal in a partnership involv-
ing companies, universities and State laboratories; 3) and the recent call for proposals of the Ministry of Health
which resulted in 330 new projects in clinical research. Portugal is the sixth OECD country in terms of health ex-
penditure and the third on pharmaceuticals. According to Prof. Correia de Campos the Government’s goals is not
to spend less, but to spend better.
Dr. Octavi Quintana Trias (DG Research, European Commission) presented the European Commission’s research
programmes which have a major objective of fostering “collaboration”. These are mostly multinational consortia,
coordination of national funding programmes with the possibility of participation of researchers from any country.
The 7th Framework Programme is composed of various elements, namely, an annual budget gradually increased
(+75% by 2013), European Research Council proposals, collaborative research (Health Research Budget of 6,1
billion euros for 7 years), strengthen research infrastructures, SMEs, human potential and science careers. The EU

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currently manages about 5% of total public spending in R&D in the EU and invests 1,9% of the GDP in research.
Mr. Thomas Lönngren (EMEA) stressed the importance of pharmaceutical innovation and R&D under the EU strat-
egy. The focus should remain in getting new medicines for patients.
The EMEA Executive Director recognised European Commission’s initiatives: IMI from DG Research, and also
other initiatives from DG Enterprise, where legislative proposals are being put forward.
Mr. Lönngren pointed out that stimulating innovation is one of the top priorities for the EMEA as stated in the
Agency’s Road Map, its work programme and the EMEA Think Tank report. Also, legislation implemented by the
EMEA have contributed to innovation/orphan drugs, SMEs, scientific advice, paediatrics, and in the near future
the legislation on advanced therapies.
He also mentioned two EMEA initiatives: 1) a new scientific procedure for validation of biomarkers that is under
consideration; 2) a project related to the outcome of the assessment. In concluding, it was also recognised that
drug development is a global business and not only an European problem. There is a need to operate on a world
basis and to recognise the needs of developing countries.
Mr. Arthur Higgins (EFPIA) mentioned the importance of Europe as a powerhouse of pharmaceutical R&D. The
research-based pharmaceutical industry is by far the biggest investor in health research worldwide and the main
source of new, innovative life-saving drugs in all disease areas. In 2006 alone, it invested more than €22 billion in
R&D, corresponding to 18% of all industrial R&D in Europe; and employed about 640,000 people, 100,000 of
whom in R&D.
Unfortunately, the pharmaceutical sector’s centre of gravity is shifting from Europe to the US and emerging mar-
kets such as India and China. This for a variety of reasons: firstly, the lack of innovation-friendly conditions, as
pharmaceutical innovation is often perceived as a threat to European healthcare systems rather than a driver of
economic growth. Secondly, soaring R&D costs combined with a downward pressure on prices are making it
harder for many pharmaceutical companies to recoup their R&D expenditure before patents expire. In addition
to that, patients in Europe face increasing delays in access to new medicines, as regulatory procedures become
more complicated and the balance shifts more towards risk-avoidance than clinical benefit.
Key aspects considered to reverse these trends are: the need to rebuild the industry’s reputation and have the right
framework conditions to support pharmaceutical innovation. Some measures have been taken forward in recent
years to reinforce trust in stakeholders, such as the adoption of stringent codes of conduct for marketing practices
and interaction with patient organisations, increasing the transparency of clinical trial data, significant investments
in the R&D of new life-saving medicines and partnerships with key stakeholders to improve access to medicines
in the developing world.
Concerning the right framework conditions, Mr. Higgins pointed out the need for a swifter patient access to new
discoveries through a better risk-benefit balance; a fair reward for innovation, including incremental innovation;
strong intellectual property rights and healthcare policies focusing on the value rather than the cost of medicines.
In his conclusions, Mr. Higgins underlined the importance of the Innovative Medicines Initiative (IMI), a unique pub-
lic-private partnership designed jointly by the European Commission and EFPIA with the potential of challenging
the status quo of drug discovery and creating critical mass for European research and innovation, so that better
and safer medicines can be made available more quickly to patients
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IV - Opening Lecture: Current Status

of Pharmaceutical Innovation in the EU
Conclusions
• Activation of all stakeholders in a proper organisation of framework;
• Flourishing academic and clinical research;
• Establishment of pre-competitive collaboration among industry;
• Research programme for translational medicine, efficacy, safety and knowledge management;
• Clinical methodology research improvement;
• Existence of proactive regulatory authorities;
• Availability of skilled and highly trained workforce provided by pan European curricula and courses;
• Ample funding for both big science and little science to promote the process related pharmaceutical
sciences.
Prof. Ole J. Bjerrum (University of Copenhagen, Denmark) argued that the current process of developing medicinal
products is characterized by patented profit driven innovation and an intensive and science based regulation for be-
ing able to deliver innovative, safe and effective medicines. Currently it results in useful but not affordable drugs for the
citizens of Europe. The reasons behind this have roots in inefficient R&D and regulatory processes. The positive side is
that this gives room for process innovation. In this connection it is important to note that the so much needed innovation
cannot take place without heavy interventions from both political and authority side.
In fact, Europe is lagging behind in its ability to generate, organise and sustain innovation processes. Prof. Bjerrum de-
fined innovation, presented some R&D investment figures (NME’s and biotech products) comparing Europe and the US
in recent years and stressed that the treatments with new biological orphan drugs have unaffordable prices. In recent
years, the number of new products decreased and the overall level of resources invested dramatically increased, leading
to unaffordable prices for new medicines. The current European drug development process is, thus, not sustainable.
A vision for an EU environment hosting a flourishing pharmaceutical innovation is much needed - a patent protected
free market for successful product innovation; universities and hospitals hosting pharmaceutical research; availability of
skilled workforce; strong regulatory agencies providing guidance; governmental funding; venture funding and societal
attitudes of risk-taking.
Many biological drugs for unmet medical needs are coming to the market, new targets have been identified with very
little knowledge about the biology and, for this reason, industry and academia should invest and collaborate more in
understanding the biology and molecular mechanisms of diseases.
Prof. Bjerrum referred that new advanced therapies and emerging treatments, such as personalised medicines, cell
therapies, gene silencing therapies and nanotechnology are areas with high innovation intensity.
The 2005 Strategic Research Agenda (SRA) forms a solid basis for innovation improvement in the EU on the basis of
public and private partnerships. Its key objectives are: define R&D bottlenecks, select pre-competitive areas, select
technologies with high potential and need to create critical mass, build on European strengths and consult and work
with key stakeholders. The SRA focuses on a number of efficacy issues such as the development of better understand-
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ing of disease mechanisms, of in vitro and in vivo models predictive of clinical efficacy, of in silico simulation of disease
pathology, validate omics-based biomarkers and simulate translational medicine. It also envisages creating a disease-
specific European Imaging Networks, developing a framework for partnership with the regulators for innovative clinical
trial designs and analysis and coordinate with national patient networks.
On the safety side, there is a critical need for public available toxicology databases of well defined compounds to exploit the
systems toxicologic potential of genomics, metabonomics and proteomics profiling. In this area, the SRA aims at creating
a European Centre of Drug safety, establish a framework for biomarkers development which will evaluate human relevance
and regulatory utility, develop in silico methods, study rodent non-genotoxic carcinogens, develop databases and tools for
data analysis in pharmacovigilance and provide healthcare training in detection of adverse drug reactions.
Prof. Bjerrum also underlined the need to establish knowledge management platforms, funding and support research
infrastructures (bioinformatics, structural biology infrastructures, functional genomics in animals, biobanks, clinical trials
network) at EU level and also education and training on safety, biostatistics, translational oriented physicians and clinical
investigators.
According to Professor Ole J. Bjerrum clinical trial development represents a competitive edge for the EU. There is an
urgent need to develop a world class of clinical pharmacology capabilities, good academic centres with translational
biology/experimental medicine. There is also a need for new clinical study designs where several approaches wait
proper validation (seamless phase II/ phase III trials, electronic data capture and management, flexible designs, learn
and confirm trials and new statistical approaches, e.g. Bayesian statistics). Also as important elements are the micro-
dosing concept and deliverables and the Process Analytical Techniques (PAT) which allow for an increase of quality in
development and manufacturing and reducing time and production costs.
In modern times, regulators’ goals are: make safe and efficacious medicines available to patients without unnecessary
delays and at the same time they should consider guidelines, remain exigent on the authorisation of innovative products
and increase demands for post marketing clinical trials.
Simultaneously, new medicines are being developed but regulated under the traditional paradigm; there is an need to
adapt scientific requirements into the regulatory framework and assess real innovations.
Advantages of research joint collaborations are: academic-industrial partnerships reduce costs and integrate scientific
know-how; further funding is necessary to set free all types of innovation; current trend goes for large consortia which
are important for solving complex and expensive research; and funding for “little science” is equally important to get
smaller innovative research groups.
Prof. Bjerrum referred DG Research recent programmes supporting innovation, namely the 6th and 7th Framework Pro-
grammes, the EFPIA Strategic Research Agenda under which many financial resources have contributed to the “new
accelerated development of medicines”. However, he noted a need for a coordinated science-driven initiative between
the DG Enterprise and DG Research in promoting pharmaceutical innovation.
Prof. Bjerrum pointed out that one of the main advantages of the Innovative Medicines Initiative (IMI) is the active partici-
pation of all stakeholders: research community public and private; the pharmaceutical industry including SMEs; public
authorities (regulators, policy makers, technology providers); and users (hospitals, patient associations, ethical com-
mittees). National mirror platforms for innovative medicines have also spread across Europe (Spain, The Netherlands,
France, Italy, Ireland, Denmark, Sweden) and learned societies in drug development and regulation involving research-
ers and scientists of various disciplines (transferring promising science related activities) are also developing represent-
ing an independent “third force”.
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V - Promoting Pharmaceutical Research,

Development and Innovation in the EU:
a Common Goal
Innovative Medicines Initiative

Dr. Octavi Quintana Trias (DG Research, European Commission) presented the Innovative Medicines Initiative
(IMI). IMI is a new research funding instrument characterized by a private/public partnership by European Commis-
sion and EFPIA (the European Federation of Pharmaceutical Industries and Association). It will have a total budget
of 2 billion €. The European Commission shall contribute with 1 billion € from the Seventh Framework Programme of
the European Community for research, technological development and demonstration activities (2007-2013) and
EFPIA will contribute also with 1 billion €. IMI is a Joint Undertaking and according with the EU Council decision it
will last until 31 December 2017.
IMI long-term objective will be to re-invigorate the European bio-pharmaceutical sector and foster Europe as
the most attractive place for pharmaceutical R&D; thereby, on the long term, enhancing access to innovative
medicines for patients. This will be achieved by removing the major bottlenecks in drug development. IMI major
research areas, based on the Strategic Research Agenda recommendations, are: safety (pre-clinical and clinical);
knowledge management; education and training; and efficacy.
One of the key works for this initiative is “collaboration”. It will provide “neutral ground” for the necessary collabora-
tion between all stakeholders and structure the strongly fragmented European research base, a task that cannot
be done by one single stakeholders’ group.
Dr. Quintana Trias also presented some of the expected benefits from IMI: increased inward private research in-
vestment; better collaboration with all relevant stakeholders; early interaction with regulators (EMEA) and smoother
approvals; fewer post-marketing withdrawals; fewer patients needed in pivotal trials; faster interpretation of safety
findings through sharing pre-competitive toxicology data; lower development risk for SMEs and increased access
to Venture Capital for SMEs; increased mobility between private and public sector; enhanced access to better
medicines for patients; and better co-ordination internationally of biomedical research.
Regulatory Agencies and Innovation

On the topic “Regulatory Agencies and Innovation”, Dr. Karl Broich (BfArM, Germany) stressed that pharmaceuti-
cal innovation is a challenge for the Community, for the National Competent Authorities and for the Pharmaceutical
Industry in the EU and globally. Increasing the rate of pharmaceutical innovation is needed to better protect public
health and improve pharmacological treatment options of EU citizens; moreover, such innovations should be faster
available to the Community. This represents new scientific, ethical, technical and legislative challenges to the EU
pharmaceutical framework of the 21st century.

Further Information on IMI:
http://ec.europa.eu/research/health/imi/index_en.html
http://www.imi-europe.org
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Regulatory bodies must be proactive in this process on the national and the European level, as innovation strives
in various areas such as paediatrics, advanced therapies (gene and cell therapy, tissue engineering), geriatrics and
improvement for “specific needs” (pharmacogenomics/pharmacogenetics – personalised medicines). Personnel
of the regulatory bodies must keep up with advances in legislation, health sciences and technology (developing
update guidance documents reflecting the scientific state-of-the-art and increasing the European harmonisation
on scientific advice, quality, efficacy and safety and in integrating the knowledge on new technologies).
Dr. Broich highlighted the EMEA Think Tank Group on Innovative Drug Development group which has been set up
to foster research and innovation in the pharmaceutical industry, consisting of EMEA staff and members of sci-
entific committees and Working Parties to identify bottlenecks in the development of innovative medicines. In this
regard, he also mentioned the CHMP specific tools on innovative drug development such as the approval under
exceptional circumstances, conditional approval, accelerated assessment and compassionate use programmes.
In this context, he concluded that continuing education, early interaction and communication between the different
stakeholders and close cooperation between national competent authorities among each other and the EMEA is
essential. The pharmaceutical industry is encouraged to present their pipeline in portfolio meetings, and scientific
advice should be applied for early in the development and throughout the lifecycle of their products. Pharmaceuti-
cal innovation is a global task.
The Role of Scientific Advice

Prof. Beatriz Lima (University of Lisbon, Portugal) presented an overview on the historical progress of scientific
advice since 1995, its definition and key goals, thought to be a tool aiming at optimising drug development pro-
grammes and facilitating the evaluation of medicines. Figures on the evolution of scientific advice and protocol
assistance indicate a significant increase from 1999 to 2004.
Prof. Lima presented the framework of scientific advice and protocol assistance, namely the Scientific Advice
Working Party (SAWP) and its scope. She underlined that scientific advice is still optional and product related,
especially for products under the centralised procedure (e.g. new emerging therapies, safety aspects, condi-
tional marketing authorisation, etc). Contribution to the Paediatrics Investigation Plans is also foreseen.
She briefly presented the procedure and its various steps, starting with the appointment of coordinators/experts
and followed by a pre-submission meeting (optional) in order to receive early feedback and increase quality of
request, before the start of the procedure. The pre-submission meeting is mainly recommended for first time
users of scientific advice, for requests on specific types of medicinal products and therapies and broad and
more general advice.
It was also presented the framework of scientific advice and protocol assistance in the context of innovation.
Protocol assistance generally corresponds to scientific advice for companies developing Orphan Medicinal
Products (OMP). In the case of paediatrics, scientific advice is free when applying for paediatrics only and is di-
rected only to scientific/medical aspects of the planned development, e.g. clinical study design, quality aspects
of new paediatric formulation. Figures on the evolution of scientific advices in recent years (2003-2006) show an
increase for chemical and also for biotechnology medicinal products.
It was considered to be highly relevant the encouragement of the discussion on innovation and non-clinical is-
sues, such as the increase of mechanisms of action related to safety aspects, the impact of innovative formula-
tions on Paediatrics and safety of known substances (e.g. nanopharmaceuticals, inhalation route), the relevance
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of animal species, animal models such as the use of transgenics and the use of homologous proteins, and
non-clinical program designs. New questions related with clinical efficacy are emerging such as endpoints, the
formal validation vs. face validity of biomarkers and mechanism of action.
Another conclusion has been that the use of scientific advice shows a decrease on negative opinions, par-
ticularly on orphan medicines. In concluding, Prof. Lima stressed that current trends point towards a positive
impact of scientific advice with the increase of the number of requests, clearly showing recognition of its value
by sponsors.
Views from the Industry

Mr. Brian Ager (EFPIA) highlighted important breakthroughs by the industry in the recent decades contributing
to the increase of life expectancy and reduction of mortality (AIDS, cancer and cardiovascular diseases) and
significant progress in quality of life (asthma, diabetes). But many challenges are still lying ahead (Alzheimer’s,
multiple sclerosis, orphan diseases).
R&D investment in Europe is growing however it is still behind the US and there is increasing competition from Asia.
Some of the reasons pointed out were: the under-investment in research, education and training; lack of a single
market; and the perception of innovation largely as a cost. Market access delays in Europe are also generally high.
Investment in R&D is still an unpredictable process as it starts with companies investing in research during 12 to
15 years without any certainty of success. At the end of this period it may happen that only 3 to 5 substances
reach the market. The excessive control of prices by European Governments was also considered as an ob-
stacle.
As main priorities, Mr. Ager referred the need for improvements in the regulatory framework, mantaining high
standards of Intellectual Property Protection, strengthen Europe’s science base and market access.
The Innovative Medicines Initiative Joint Undertaking (EC-EFPIA) was considered to be an extremely important
tool for the future in improving Europe’s science base.
EU Initiatives and Harmonization - EMEA – ICH

Dr. Spiros Vamvakas (EMEA) briefly presented some aspects of the International Conference of Harmoniza-
tion (ICH) history. Harmonisation of regulatory requirements was pioneered by the European Community in
the 1980s with the movement towards the development of a single market for pharmaceuticals. The success
achieved in Europe demonstrated that harmonisation was feasible. At the same time there were bilateral discus-
sions between Europe, Japan and the US on possibilities for harmonisation. The birth of the ICH took place at
a meeting in April 1990, hosted by EFPIA in Brussels. The six parties to ICH represent the regulatory bodies and
research-based industry associations in the three regions, Europe, Japan and the USA.
The ICH process has achieved success with the development and implementation of more than 50 guidelines
in quality, safety, efficacy and multidisciplinary areas because it is based on scientific consensus developed
between industry and regulatory experts and because of the commitment of the regulatory parties to implement
the ICH tripartite, harmonised guidelines and recommendations.

International Conference of Harmonisation of the Technical Requirements for the Registration of Pharmaceuticals for Human Use.
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EMEA/CHMP experts are key players in the development and maintenance of guidelines. Currently more than 15
ICH topics are being developed / maintained and the EMEA is participating in all these activities.
Alternative Methods and Innovation

Dr. Laura Gribaldo (Joint Research Centre Ispra-ECVAM, European Commission) presented the European Centre
for the Validation of Alternative Methods (ECVAM) which is part of the European Commission’s Joint Research
Centre (JRC) and was established in response to Article 23 of Directive 86/609/EEC on the protection of labora-
tory animals.
ECVAM coordinates and funds validation studies on non-animal test methods; furthermore, it conducts research
in several areas of toxicology relevant to the safety testing.
The cost of drug development has increased sharply in recent years, while approval of innovative drugs has
declined. This “productivity gap” represents a major challenge for the pharmaceutical industry in Europe and
throughout the world. One of the main reasons for the lack of new, innovative drugs is the high attrition rate during
drug development. Three factors are major contributors and represent 66% of the causes for termination of drug
development projects: toxicity in animals (20%), non-acceptable unwanted effects in humans (11%) and lack of
therapeutic efficacy (25%). Both lack of efficacy and unpredicted toxicity is due to the paucity of mechanism based
and predictive preclinical toxicity testing approaches.
European pharmaceutical research suffers from considerable fragmentation due to a rigid compartmentalisation
of the stakeholders in different countries and sectors of activity (academia, established industry, bio-tech Small
and Medium Enterprises, clinicians, regulators, patients). To harness the scientific know-how and expertise that
exists across the European Union in the pharmaceutical sector, action at community level has been called for by
the G10 high level group on innovation and provision of medicines. Moreover, there is a trend toward stronger
recognition of alternatives, due to increasingly evident shortcomings of current approaches. Amendments of the
European Parliament into the JRC 7th Framework Programme have added the obligation to address alternative
methods in this field.
ECVAM is mainly focused on coaching of the development of alternative approaches; (pre) validating in interna-
tional collaborative studies international harmonisation; and in providing support for regulatory acceptance.
Validation of alternative tests is one of the rare examples of quality assurance in biomedical research.
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VI - Workshop 1
- Innovation and Development:
Constraints and Opportunities
Pharma R&D: Level of Development

Dr. Manuel Gonçalves (GlaxoSmithKline, Portugal) mentioned that innovation is a fundamental part for the contract
with society, since new medicines and vaccines would improve healthcare for individual citizens and the health
care system by reducing mortality and morbidity, preventing disease or mitigating the complication of a disease,
improving quality of life and reducing the over all healthcare spending. Some examples were given of current and
future medicines/vaccines that are being developed by GSK.
It was pointed that one of the most significant factors in the average cost of drug development is the cost of failure
that must be taken into account. The challenge was considered to be the affordability to R&D.
Some aspects were considered negative: slow access to markets, short-term and cost-fixed policies and little at-
tempt to differentiate between highly innovative products and so-called “me-toos”.
Disease priorities should be identified, screening and prevention systems put in place and healthcare interventions
optimised. A strategic agenda for health and the development of new medicines should be set with industry to
ensure that unmet needs are addressed, disease prioritisation is clear and patients get access to the medicines
that will really improve their lives.
Focus should shift to value not cost and pricing should reflect value. The benefits of incremental innovation should
also be recognised.
The human and economic value of medical innovation

Dr. José Almeida Bastos (Merck, Sharp and Dohme, Portugal) considered innovation as a driver of health gains, eco-
nomic growth and development and identified the need to find a balance between health innovation and access.
The speaker mentioned the Lisbon Agenda objective of transforming Europe into the world’s most competitive
knowledge based economy by 2010, highlighted the role of the business sector and of R&D for economic growth,
job creation and product innovation.
Positive effects of biopharmaceutical innovation were identified, namely the reduction of mortality and the increase
in quality of life. Subsequently, it was argued that the economic value of innovation allows the reduction of health
care costs and improves productivity. The pharmaceutical R&D expenditure in Europe, USA and Japan between
1990 and 2006 was presented. Since the year 2000 the USA are spending more in R&D than Europe. He also
concluded that high tech clusters in Europe are smaller and less dynamic than those in the United States.
He identified a paradox of the system: on the one side the investments in innovation and on the other side the
questioning of the value of innovation when time comes to disseminate it. To solve this paradox Dr. Bastos identi-
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fied the need of a pact for innovation and research. Furthermore, counterfeiting was identified as a public health
problem, which according to the WHO represents 8% to 10% of the global medicine supply chain and is estimated
to grow 13% annually through 2010. This growth is higher than the rate of legitimate pharmaceuticals.
The speaker concluded that the health sector is an important source of innovation and that innovation is essential to
economic growth. A better balance between innovation, equitable access and affordable costs must be found.
Independent Research
Dr. António Addis (Italian Medicines Agency, AIFA) presented the strategy that was adopted by AIFA, consider-
ing innovation and development, the limits of the current regulatory scenario and the increasing pharmaceutical
expenditure. This strategy involves a model for ranking therapeutic innovation, an active pharmacovigilance pro-
gramme, a risk sharing approach and an independent research programme. It was identified the need of involving
industry as a partner.
Independent research is focused on 3 areas: (1) orphan drugs for rare diseases and drugs for non-responders;
(2) comparison among drugs and therapeutic strategies and (3) strategies to improve the appropriateness of drug
use and pharmacoepidemiology studies.
It was emphasised that management of drug registration procedures and governance of drug expenditure should
be balanced and the need for more careful reconsideration of the EU regulatory system. The gap between patient’s
needs and regulatory policy should be filled.
The Spanish Experience

Dr. Cristina Avendaño (Agemed, Spain) underlined the importance of the support to innovation strategies by regu-
latory agencies through commitment with relevant projects established by the European Commission such as
the Joint Technology Initiative on Innovative Medicines and the European Technology Platform on Global Animal
Health.
Furthermore, she identified some of the Agencies responsibilities on this matter:

• facilitate the appearance of innovative products in terms of their success in covering previously unmet thera-
peutic needs;
• right balance between facilitating access of patients to new and efficacious medicines and the need to en-
sure that new medicines arrive to the patient as safely as possible.
In Spain a reward is given to incremental innovation: 5 years “protection” from the reference prices system in case
of galenic innovation with therapeutic gain. This therapeutic gain is evaluated by the medicines agency.
It is important to reach a balance between rapid access of patients to new efficacious medicines and the need to
ensure that they arrive to patients as safely as possible.
Dr. Avendaño identified possible immediate improvements of the system: the improvement of harmonisation pro-
cedures, the sharing of scientific assessments between authorities and the telematic submission. Another impor-
tant point focused was the fact that the public health and National Health Systems agenda is not covered by the
research agenda of the pharmaceutical industry.
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Finally, advanced therapy medicinal products’ opportunities and constraints were identified, such as new treat-
ment opportunities, common rules in the EU to facilitate innovation and clinical use.
Biotecnol - Antibody therapies as innovative medicines and value

generators in an increasing global world
Dr. Pedro Pissara (Biotecnol, Portugal) argued that the major force acting to slow market growth over the period
2006-2012 was generic competition against patent-expired products.
Innovation was identified to be possibly the only way to counter such erosion. New products towards unmet needs
and previously untreated diseases are emerging from the efforts of the genomic and proteomic era, as well as from
the better understanding of mechanisms of diseases.
It was also mentioned that monoclonal antibodies were therapeutic products that due to their high-efficacy, high-
specificity and high-safety profiles represent an increasingly growing market and are shaping the way medicine is
practiced today.
Biotecnol was presented as being a biopharmaceutical company that has a special focus on the development of
antibody-based therapies to treat life-threatening diseases such as cancer. Companies should invest in innovation
if they want to succeed in an increasingly competitive world.
Bial’s experience
Dr. Luís Portela (Bial, Portugal) focused on the positive influence of medicines on health, as well as a comparison
of the R&D investment as percentage of sales in 2005 in several economic sectors to conclude that the highest
investments were made in the pharmaceutical sector.
Also focused, were the high numbers of R&D sites that closed down in Europe, not compensated by new ones,
a tendency that did not occur in the USA or in Asia. The reducing competitiveness of European pharmaceutical
companies was another problem mentioned.
Hurdles of the pharmaceutical industry were identified: long list of patent expirations, increasing R&D costs, pricing
pressures in developed countries, degree of public outcry over drug safety standards and the increase in regula-
tory requirements.
Several suggestions to restimulate pharmaceutical R&D were made such as the shortening of the R&D cycle, the
investment in therapeutic “niches” and the decentralization of R&D.
Bial’s experience was described, specifically focusing on R&D activities.
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VII - Workshop 2
– SME and R&D Funding
European R&D Funding for SME

Dr. Bernd Reichert (DG Research, European Commission) pointed the European solutions and support initiatives
to the SME under the 7th Framework Programme of the European Commission DG Research.
The first and most important step to provide SME with a quality support service is their classification in order to
organize the wide and spread universe of European SME. The Cooperation Programme encourages SME to par-
ticipate in collaborative research projects and its final target is to reach 15% of the SME with a distribution of €5
billion until 2013, giving as an example financial benefits without bank guarantees.
Partnerships between industry and academia are also envisaged in the 7th Framework Programme through the
People Programme with staff training and temporary hosting of experienced researchers.
Specifically for R&D performing SME, the Eurostars Programme focus on the guidance to a market oriented tech-
nology research, facilitates access to funding and align national programmes. It has €400 million to address (€100
million from EC) over 6 years and, at this time, 22 Member States and 5 associated countries are committed to
this Joint Programme.
The Joint Technologies Initiatives which includes the efforts of the European Commission, Member States and
industry enforce the creation of European pools of investment in strategic research programmes. Through the In-
novative Medicines Initiative a faster development of new knowledge, tools and methods for safer medicines can
be possible with a budget of €2 billion for 7 years. The Community contribution (€1 billion) will be entirely directed
to SME and academia for research, including pharmaceutical area. On the other hand, the same amount will be
given by industry and will also involve SME and academia.
Biomedical research at the University – Industry Interface

The role and success factors of University/Industry R&D Interfaces in the field of Biomedicine were highlighted by
Prof. Manuel Carrondo (IBET, Portugal), the CEO of IBET, a successful Portuguese Interface.
The drivers from the side of industry focus mainly on the trained resources and the efficient use of the know-how
and new technologies combination. These represent the added value for innovation.
On the side of universities the perspective for professional careers and the academic revenues are determinant
factors to assure the viability for the relationship with industry. These drivers allow enhancing the main success
factor: knowledge transfer between different sources of expertise is much more beneficial than technology trans-
ference.
The University/Industry Interface outcomes involve research project contracts and collaboration in the use of as-
sets. This involvement shows that start-up and spin-off companies have a management performance four times
more successful.
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Following the drivers for industry and universities, the outcomes are a value added for both sides taking into con-
sideration the companies’ dynamics, where is essential to follow trends to include in the proposals to the industry,
as a fundamental key factor for success in the R&D university/industry partnerships.
Several conditions to build an interface should be granted, such as defining expectations, managing perceptions,
creating trust, promoting excellence and requiring mature partners to strengthen the partnership. To reinforce the
Interface, governments and European institutions should participate more widely in the financial support. Partner-
ships face growing constraints which difficult their development, namely the bureausclerosis, the organizational
differences between R&D institutions and industry. These factors are driving companies to drop the projects and
contributing to the despair of researchers.
IBET’s example was shown, explaining how the largest biotechnology research organization in Portugal brings
together, partners and collaborators, public institutions and private companies.
Its mission is to foster the competitiveness of its customers and partners, by creating wealth out of knowledge of
Chemistry, Biochemistry and Biology and its target economic areas are the Pharmaceuticals/Health Care, Agro-
forestry/Agroindustry and Environment.
The main IBET’s activity areas are consultancy for biotechnological industry processes, support to build new
companies, start-ups and spin-offs, collaborations or contracts to support third parties innovation and support
technology transfer and processes consultancy.
Biotech Funding, Neuropharma: A Case Study

Dr. Belén Sopesén (Neuropharma) presented a case study for a biotech company funding, Neuropharma.
Generally, three keys for success in the biotech field were highlighted. A clear and structured business plan
focusing the R&D strategy is mandatory, putting in evidence competitive advantages and opportunities, tech-
nological platforms and therapeutic targets and the market description. A key point for new pharmaceutical
R&D companies is the definition of a selected therapeutic area to focus on. The company strategy should also
include the potential alternative to pharmaceutical outsourcing for the need to acquire a particular skill not avail-
able in-house.
To perform the right strategy the right people is needed. Through the R&D process about 75 different disciplines
are part of the role, from molecular bioscientists to regulatory affairs team and strategic marketing team. Once
more, outsourcing is an elementary instrument for R&D development.
The third key for success is the potential sources of funding. The biotech market environment involves long term
development (final product reaches the market in 10/12 years), high capital requirements and investors willing-
ness to shorter term profitability. The EU public funding is oriented to early stages of development. Funding
alternatives are private funding, through entrepreneurs, business and private investors, as it is in Neuropharma’s
case, venture capital and capital markets. Public grants and tax incentives can not be excluded as important
funding incentives.
Neuropharma is a practical case study of successful funding to date. The company is a small R&D biotech com-
pany established in 2000 with the aim of researching, developing and commercializing innovative, effective and
safe compounds to treat diseases of the nervous system with a special focus on neurodegenerative diseases
and in particular Alzheimer’s disease.
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The 3 key factors model describes how Neuropharma has taken it into consideration when setting up a R&D
company and searching for funding, namely the Business Plan, R&D strategy and the management of human
resources.
Are SMEs equipped to use all the aid available for them?
Mr. Johan Vanhemelrijck (EuropaBio) presented the current SME perspective on the question raised above.
EuropaBio, the European Association for Bioindustries, represents life science industry across different sec-
tors (health, agri-food, industrial biotech), start-ups, established biotechs and multinationals.
For EuropaBio, SME are not equipped to use the available aid due to their specificities: too small (1/3 has
under 20 people), too young and work overloaded. Therefore, it is necessary constant guidance and support
from other actors, such as consultants, Chambers of Commerce, cluster managers, bio-regions, regulatory
agencies, and risk managers. Most of the companies meet the Young Innovative Enterprises (YIE) definitions
without their own knowledge.
At different levels, SME can count on regional aid, through initial investments, training and human resources
cluster support, incubators, entrepreneurs training and tech transfer; national aid programmes, as “The 8
State Aid”, and European aid, such as the EMEA SME office. “The State Aid” wide scope involves 8 different
areas more likely to need support and advice: R&D projects, technical feasibility studies, industrial property
right costs for SME, young innovative enterprises, process and organizational innovation in services, in-
novation advisory services and innovation support services, loan of highly qualified personnel for SME and
innovation clusters.
Furthermore, on the aid project submission SME expect support decisions in short notice and a quick im-
plementation and payment reaction without bureaucratic burden. Information is always required to proceed
with the process or to improve it. Expectations disappointments will lead SME to drop their projects due to
slow processes and decision contradictions, such as the difference between European rules and national
implementation. When comparing with the US SME development, the EU environment is unfavorable to
growth and SME are less likely to survive after the first year. European companies that follow their path need
to keep investment standards attractive. In order to access US finance markets, European companies use
management instruments to achieve their goal: mergers and acquisitions, relocation of operations or head-
quarters and attracting US investors.
SME and R&D Funding

The Portuguese official SME aid office, InovCapital, dependent of the Ministry of Innovation and Economy,
represented by Mr. João Fernandes, has as mission to support and reinforce the availability of appropriate
financing solutions throughout SME development life-cycle. This goal requires the active participation of the
entire entrepreneurial infrastructure, including the business owners and managers, the financial services
industry, government policy makers, academia and the media.
From the SME side, new and growing SME have to earn investors’ interest and commitment by the attractiveness
of business profile compared to other available investment opportunities. The SME internal capabilities to attract
investors should be improved and reinforced to supply sufficient, timely and accurate information to financial
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providers in order to get appropriate financial resources and other related services at competitive conditions.
From the government’s side, policy makers should ensure that entrepreneurial environments, in which young
firms are created, developed and traded are favourable to entrepreneurs and investors, avoiding inappropri-
ate and costly legislative, fiscal or regulatory systems and actively strive to remove existing barriers.
The general attitude to finance SME should accept the need for public risk sharing schemes whenever needed,
assure the existence of public loan guarantee schemes and related initiatives to securitize SME debt, encourage
private investment into market failure areas, recognize the valuable role of banks, strengthen the links between
business groups and investors, emphasize the practical relevance of venture capital as an investment to create a
new company, or expand a smaller company that has undeveloped or developing revenues.
Figures show that a large number of companies do not fulfill all criteria necessary to be financed, otherwise the
total amount of investment would have been allocated.
To apply to the venture capital of InovCapital various criteria were mentioned: potential to growth, persistent
and competent promoters and managers, well supported business plans, innovative products and processes,
predisposition to create wealth in a partnership and capacity to forecast a “realistic and interesting” exit strategy.
On the other side, InovCapital is able to offer growth potential, proactive financial capacity, specialized funds,
expertise in very small operations, innovation and technology and expansion and internationalization areas and
an experienced team.
AdI Support Measures to Entrepreneurial R&D – Innovation

Mr. Carlos Lajas (Agência de Inovação, Portugal) presented a Portuguese innovation support structure by
the national Innovation Agency (AdI). AdI is a private company, showing how the promoters wish to have a
flexible organization to pursue its objectives. The capital is held by FCT – Science and Technology Foun-
dation from the Ministry of Science Technology and Higher Education-, by IAPMEI – Institute of Small and
Medium Size Enterprises and Innovation - and PME Investimento, both from the Ministry of Economy and
Innovation
AdI’s mission is the promotion of entrepreneurial innovation, namely of technological nature, and the eco-
nomic valorization of results from research and technological development carried out in Portugal.
The vision of this company aims to be a privileged partner of all innovative organizations.
For that reason, AdI strategic objectives are the promotion and economic valorization of R&D activities,
the support and promotion of technology based innovation, the promotion and support of recruitment by
enterprises of highly qualified human resources and the support of technology transfer activities.
In order to achieve its goals, the instruments used to support SMEs involve different key areas.
In the human resource training area, AdI purpose is the achievement of advanced qualification of Portu-
guese young professionals (at least 1 year and maximum 2 years) in international well known R&D organiza-
tions – CERN, ESA and ESO - in strategic technological areas where they have the possibility to contribute
to increase the competitiveness of Portuguese companies.
The support for PhD courses in Enterprises –”BDE” – is a joint initiative of the Portuguese Innovation Agency,
for the promotion within the entrepreneurial environment, and the Science and Technology Foundation, for the
evaluation and management of grants. This partnership aims to promote advanced training in an entrepreneur-
ial environment, through the cooperation between enterprises and universities. And both sides are rewarded:
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enterprises develop new projects and students are allowed to attain the PhD degree granted by the University.
Financial support of R&D projects co-promotion aims to bring together enterprises and R&D performers to
develop technologies which allow for the conception of new products, processes and services, and to pro-
mote results and technological transfer to the productive sectors and entrepreneurial technological innovation.
Other important area is the fiscal incentives support to entrepreneurial R&D activities. In this case, eligible ex-
penses in R&D activities and operational expenses are considered.
The last instrument of SME support is the interface between demand and supply of technology through the par-
ticipation in Networks of International Cooperation: Innovation Relay Centre (71 IRC in 27 European countries,
Iceland, Israel, Norway, Switzerland, Turkey and Chile), Eureka (35 European countries) and Iberoeka (21 Ibero-
american countries).
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VIII - Workshop 3
– Who will Pay for Innovation?
What can the Commission do?

Mr. Thomas Heynisch (DG of Enterprise and Industry, European Commission) gave an overview of the current
sate of play for innovation, from a regulator’s view taking into account the instruments at hand to implement
an adequate strategy that can aid in the fulfilment of the Lisbon agenda.
He stressed that there can be no doubt that Europe is an attractive location for research and development.
There seems to be a consensus on the need for urgent action to get Europe’s economy moving. Consequent-
ly the European Commission has placed growth and creating new jobs at the top of its political agenda.
Health in particular is one of the sectors where the Commission can generate growth. Pharmaceuticals,
medical technologies and healthcare services in general are the markets of the future. Ageing societies in the
industrialised world and increasingly in developing countries, will make this area one of the sectors where
Europe has to regain and keep a competitive edge. The Commission is committed to the aim of creating an
environment conducive to innovation and business.
In this way a clearer definition of what kind of innovation should be supported and developed is lacking. For
the Commission, the current definition is that “Innovation is anything that brings novelty to the market”. A con-
sequent R&D policy can only be one but very important facet in the efforts to create a favourable environment
for new technologies and growth in general.
To achieve the strategic goals set by the Lisbon Agenda, the Commission has been working intensely and
has set up several Commission Initiatives for Innovation such as the Innovative Medicines Initiative and the
Pharmaceutical Forum and Innovation. Whilst the IMI initiative has recently been put into operation, the Fo-
rum has a long history of accomplishments and is designed to provide a broad political mandate to discuss
and agree ways forward on key non-legislative issues that have an impact on European competitiveness and
health policies.
In pursuit of its objectives, the Forum established three working groups that cover the following topics: infor-
mation to patients, pricing and reimbursement and relative effectiveness. The Commission is aware of the fact
that these are particularly sensitive issues. There are no obvious solutions but a key to finding a way forward
will be to change the common perspective on medicinal prices. Short-term investment in medicines can de-
liver long-term reductions in health care costs – reduction in hospital stays etc. While not ignoring the costs
of medicines, the Commission must not underestimate the value of medicines.
In short, effective ways of establishing good practices on impact of cost containment policies on healthcare
costs, patients’ access and reward for innovation must be sought and implemented in Europe.
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Public Health, Innovation and Sustainable Financing

Mr. Kees de Joncheere (World Health Organisation) focused on the outcome of the InterGovernmental Working
Group on Public Health, Innovation and Intellectual Property (IGWG) and on the possibilities yet to explore of the
so called “push and pull” mechanisms in terms of increased public funding and price differentiation.
The World Health Assembly Resolution WHA 59.24 established the IGWG in order to create a framework for a
medium term global strategy and plan of action to boost research into medicines and other health products for
diseases that disproportionately affect the poor, and also analyse the relationship between intellectual property
and public health. Within this working group, negotiations take place on various innovation proposals put forward
during the consultation process WHO is facilitating together with Member States and stakeholders. These negotia-
tions will continue in 2008.
The second IGWG discussed eight main elements: prioritizing R&D needs; promoting R&D; transfer of technol-
ogy; building innovative capacity; management of intellectual property; improving delivery and access; ensuring
sustainable financing mechanisms; and establishing monitoring and reporting systems.
In 2004 WHO conducted the Priority Medicines for Europe and the World study for the Netherlands EU presidency
that proposed a public health focused pharmaceutical R&D agenda based on pharmaceutical treatment gaps. The
study also identified regulatory barriers for innovation. Apart from “push” mechanisms as increased public fund-
ing for basic health research, the study also explored the use of alternative “pull” mechanisms for pharmaceutical
innovation that would reward important therapeutic innovation by granting higher prices, and by linking prices of
medicines to per capita income of countries. Several countries already provide selective incentives for therapeutic
innovation through their reference price systems and through differential reimbursement rates. Advanced market
commitments may provide alternative financing mechanisms for innovation.
Worldwide too many people still lack access to essential medicines: More than 1/3 of world’s population lack regu-
lar access and in Africa less than 50% of the population has regular access to essential medicines.
Any draft plan of action to tackle this issue would have to include a prioritization of R&D needs, the promotion of
R&D, building and improving innovative capacity, the capability of technology transfer, adequate management of
intellectual property, improvement of delivery and access, sustainable financing mechanisms and the establish-
ment of monitoring and reporting systems.
Rewarding innovation is a key aspect of pricing i.e. real innovation should be rewarded. However, pricing should
reflect ability to pay possibly measured as Gross National Income (GNI) per capita. Pharmaco-economics already
provides the methods for reactive price setting and could be used proactively.
Paying for Innovation or Paying for Health Care

Under the general topic of innovation versus its financing on public health, Prof. Miguel Gouveia (Universidade Católica
Portuguesa, Portugal) presented several questions for discussion: the value of innovation in health care, how is inno-
vation paid for, the relationship between innovation and health related industries in Europe, the direct public support
for research and finally the financing of health systems and paying for innovation have to be carefully considered.
The payment of innovation in health care is made either upstream through public direct funding research, or ven-
ture capital (or other equity/private based financing) for biotech starters; and also through applied R&D at estab-
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lished corporations and publicly financed centres, or downstream through public and private funding of the health
care system’s demand for innovative products and services.
Many arguments for better treatment rest on the idea that European indicators measuring industry innova-
tion such as patents, revenues, citations, research employment, etc. have been lagging behind those for the
US, and that this loss of competitiveness has been worsening. This happens both for health care related and
non-health care related industries.
The industry in Europe is characterized by lower labour productivity ( 53,5%), lower market shares, lower
growth than in the US, comparatively absent venture capital for starters, lower patent productivity (numbers
and citation intensity) and brain drain from Europe to the US.
Something what policymakers could do to help the development of the innovative health related indus-
try could be to dedicate more funding (examples: higher levels of direct socialization/subsidization of
research expenses, credit guarantees, more funding downstream: providing the health systems with
more financing to pay for health innovations). This would help creating a truly European market for in-
novations.
If paying for innovation happens mostly at the health system level, there is still the question of whether the
payment for innovative treatments is only done by the health system or if there is some substantial cost shar-
ing by the consumer. Given the large potential for moral hazard in the adoption of expensive technologies,
some cost-sharing is warranted, i.e. ultimately the answer to the question of who should pay for innovation
must include “the consumers” of health care, not just the taxpayers.
Innovative Therapies will require innovative Financing

Dr. Fernando Royo (Genzyme, Europe) referred the existence of several possible answers to the question
“Who will pay for innovation?”.
Innovation cannot be regarded as a product, but rather as a process, hence not something to be acquired,
but to participate at. According to OECD, Innovation means “new products, business processes and organic
changes that create wealth or social welfare”. Under this perspective, the EU, as the largest economy in the
world, simply cannot afford to lag behind in innovation. Along the same reasoning path, the EU cannot afford
denying its citizens the best and most advanced medical therapies. And this includes every citizen, namely
those with rare or currently untreatable diseases. However, healthcare universality, excellence and financial
sustainability are, admittedly, difficult to reconcile.
The largest saving opportunity is by reducing real or perceived risks, through predictable regulatory require-
ments, market access, pricing & reimbursement, liabilities, etc. or, better yet by sharing with the establish-
ment of partnership initiatives such as the innovative medicines initiative. Risk, not just in medical but in statis-
tical terms (success vs. failure odds), is a key parameter for the rising R&D costs of new, innovative therapies,
almost all of which must be funded via increasingly volatile and sensitive financial markets.
Hence, the solutions to some of today’s hurdles will require figuring out, and applying, innovative financing
schemes, in which the risks are more fairly -and timely- shared between the various stakeholders. These will
certainly require abandoning long established, even cherished, paradigms; but such brave approaches are
also an essential element of innovation.
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In conclusion, all involved parties should have a more patient-centric approach and strive towards industry &
payers benchmarking commonalities (e.g. capitation, or disease management costs). Timelines in biomedical
R&D are forcefully longer than in most other sectors. But this should simply prompt us into urgent action
Affordable Innovation Meeting Public Health Needs

For Ms. Rita Kessler (Association Internationale de la Mutualité) innovation is a central issue for all those who are
concerned with pharmaceutical therapy: patients and citizens, health professionals, the pharmaceutical industry,
health policy makers and regulatory authorities - as well as the organisations paying for medicines. For all new
products, it is essential to identify the “therapeutic advance” in comparison to the alternative treatments. Accord-
ing to the US FDA, only one out of four new drugs produces some kind of therapeutic progress. The added thera-
peutic value can only be demonstrated through comparative analysis. AIM strongly calls for the consistent use of
comparative trials and of post-marketing studies.
However research is the basis for innovation. Costs of medicines’ development have increased tremendously
(bringing a new medicine to market can cost up to $1bn) and at the same time the output of innovative medicines
is low. Financial input to R&D could be boosted by limiting investment in marketing (promotion, advertising) so that
the money could be better invested in R&D. In our market economy, R&D does not focus on ‘public health’-defined
priorities but on promising and lucrative markets.
Even the best new medicine is of no use if unaffordable. Thanks to the Portuguese Presidency the European Par-
liament agreed last October on the ratification of an amendment to WTO intellectual property rules (TRIPS) aimed
at easing poor countries’ access to essential medicines. This amendment set out the conditions for compulsory
licences for the production and export of cheap generic copies of patent medicines to poor countries unable to
manufacture them.
Even in Europe, medicines are not always affordable. For AIM a fair negotiated price is the decisive principle. AIM
has declared that improving the transparency of the components underlying the final price is of utmost importance
for economic optimisation between supplier, payer and patient across Europe. A fair price should reflect a balance
between: supplier-investment (requiring ethical profit), the therapeutic benefit (clinical necessity) for the patient, and
the capacity of third-party payers to pay for the product. We need a price based on benefit: ‘value for money’.
The pharmaceutical industry in Europe and worldwide is one of the most profitable in general, which suggests to
us that pharmaceutical companies can too often take advantage of a monopolistic market situation which is not
justified by underlying intellectual property rights. New ideas for means of rewarding innovation are a priority.
Who Will Pay for Innovation: patients perspective

Ms. Mary Geraldine Baker (European Federation of Neurological Associations) patients’ contribution to innovation
is done by actively interacting with their carers in the management of their respective illnesses. For this some basic
principles have to be abided by to be referred to a doctor with a real interest in their illness; a better telling of the
diagnosis, an early, rather than late, referral to the multidisciplinary team, continuity of care, participation in the
management of their illness.
Patients have expressed a desire for greater access to treatments. To meet this desire it will require innovation and
change.
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Voluntary organisations can help build bridges to the power bases of central government and medical and social
services. They cannot exist within a vacuum; they need to be flexible and responsive to outside influences. Moreo-
ver, they need to combine the knowledge and clinical observations of the doctors with the experiences of those
living with, and impacted by, chronic illnesses on a daily basis. Only then will it be possible to achieve an integrated
picture of the challenges of managing chronic conditions.
For the providers of service to deliver appropriate and cost effective care they need to listen to the voices of the
voluntary organisations and recognise the necessity for changing attitudes. Service delivery has to be appropriate
to meet the needs. Societies can no longer afford the wastage of time and resources.
The only way to move forward is to work in the establishment of solid partnerships.
Generic competition, healthcare sustainability

and head room for innovation
Mr. Greg Perry (European Generic Medicines Association) stressed out that generic medicines play a critical role
in ensuring equitable access to medicinal care in Europe and in stimulating innovation and this role will increase
as population ages and demands increase on healthcare systems. Generics have been pointed out as highly
important in reducing costs and creating headroom to help pay for new innovative products. On the other hand,
biosimilars offer new opportunities both for the growth of the generic industry and for the control of national health
expenditure.
For the generics industry, three cornerstones are indispensable to access affordable medicines: 1) an efficient reg-
ulatory system; 2) adequate prescribing and dispensing practices; 3) and a balanced patent system. Even though
the new pharmaceutical legislation introduced a better regulatory environment for generic medicines, patent link-
age, linking the marketing approval or any other procedure related to price, reimbursement and substitution of the
generic to the patent status of the reference product, is pointed as a threat for agencies and generic medicines.
Nevertheless, despite increased Intellectual property Rights the rate of “innovation is declining”.
Therefore, in the EGA’s view, a new focus for pharmaceutical innovation would encompass creating an EU equiva-
lent to USA National Institutes of Health, establishing better links between science and business, building Europe’s
scientific base, implementing substantial changes in the business model of R&D companies, promoting a proper
application of inventive step in patent approval, supporting added value innovation through the pricing systems to
bring added clinical value to patients and ensuring immediate and strong competition from generic medicines to
original products once patents have expired.
The introduction of a coherent generic medicines policy, which includes incentives for physicians to prescribe
generic medicines, removing disincentives for pharmacists to dispense generic medicines, and providing informa-
tion and incentives to patients to ask for generic medicines and granting automatic pricing and reimbursement
approvals and substitution status for generic medicines once they have obtained market authorisation (MA) would
be major steps forward.
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IX - Workshop 4
– Partnership for Success
Key factors for optimising of R&D investment in Europe

Mr. Brian Ager (EFPIA) pointed out the organisation’s perception on the current challenges posed to research
and innovation: a need for more R&D versus the need to tackle major societal issue as the environment,
bioterrorism, antibiotic resistance, neglected diseases; the need for more efficient R&D versus the increasing
cost of innovation; the increasing investment in R&D without corresponding to an increase in NCEs on the
market versus pressure on prices.
On the other hand, opportunities lye ahead to face these challenges: new technologies (genomics and other
new technologies - proteomics, lipidomics, imaging and finding the right molecules for the right targets and
bringing them to the right patients); new ways of working (collaboration between pharmaceutical companies,
with other stakeholders (academia, SMEs, patients organisations) and with public authorities.
The Innovative Medicines Initiative (IMI) was presented as a major achievement for improving Europe’s science
base in addressing causes of delay or bottlenecks in the R&D process and in accelerating the discovery and
development of more effective innovative medicines with fewer side-effects. IMI is a public-private partnership
founded by the European Federation of Pharmaceutical Industries and Associations and the European Com-
mission aiming at pre-competitive collaboration.
Benefits from IMI were highlighted aiming at getting more funding for research, more cost efficient R&D, a bet-
ter investment environment and more innovative solutions in line with the Lisbon Agenda objectives. Among
other aspects, some of IMI’s first year expected topics were also refereed: 5 in Safety; 1 in pharmacovigi-
lance; 3 in diabetes; 3 in brain disorders; 3 in COPD & asthma; and 6 in Education & Training. Dr. Ager also
gave an overview on the structure of IMI, its evaluation process, the description of the topics, the description
and presentation of proposals, peer review and the eligible funds.
Successful collaboration between industry partners and the critical

path institute: qualification of safety biomarkers for regulatory
decision making by the predictive safety testing consortium
Dr. Jacky Vonderscher (Novartis, Switzerland) presented the Critical Path Initiative (C-Path), which is a third
party, partner, and project catalyst. In response to the FDA Critical Path Initiative, Industry partners formed
a consortium in early 2006 with the goal of testing a process by which biomarkers for safety could be quali-
fied for use in regulatory decision-making.
In parallel, the Predictive Safety Testing Consortium (PSTC), a collaboration project involving academia
and industry, works with regulatory authorities to qualify new biomarkers in 5 areas (nephrotoxicity, hepa-
totoxicity, vascular injury, carcinogenicity and muscular injury) for both drug development and regulatory
decision-making.
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The outcome of this collaboration has been extremely positive. In June 2007, the PSTC Nephrotoxicity Working
Group submitted a Voluntary eXploratory Data Submission (VXDS) to FDA and EMEA which contained data in
support of the qualification of 7 new safety biomarkers of drug-induced kidney injury for use in specifically defined
preclinical settings and, for certain markers, in selected early clinical settings.
At present, the qualification of these markers is under review by both the FDA and EMEA and a decision is awaited.
From academia to biotech: US and Portuguese examples

Dr. Tiago Outeiro (Instituto de Medicina Molecular, Portugal) pointed out that one of the industry’s limitations is that
there are too few innovative treatments reaching the market. All stakeholders are aware that new approaches to
healthcare delivery systems are needed throughout the world.
Dynamic business/university partnerships as a new driver in drug discovery and healthcare academia is increas-
ingly becoming the source of new concepts for tackling disease. Close associations between the different stake-
holders can ensure successful partnerships and lead to the creation of start up companies, essential drivers for
innovation. Scientists can bring a new rational approach to drug discovery and research-intensive universities, with
their broad bases of expertise and collaborative networks.
Technology transfer by which university or biotech generated intellectual property (IP) reaches the market via in-
dustrial partners has proven to be good process. However, the means by which universities and industry can work
together in dynamic collaborations to generate IP is much less well understood.
There is a growing realisation that academia is a critical part of the pharma innovation network but there are few
opportunities to evaluate how this relationship can be made to work effectively. The EU, and Portugal in particular,
have a lot to learn from examples of success in the US. In his presentation Dr. Outeiro presented some personal
experiences and examples of successful partnerships.
Partnership for Success – The Strategy of a Modern Agency

Prof. Jan Liliemark (Medicinal Products Agency, Sweden) presented some elements which characterize the new
paradigm in regulatory agencies. From scrutinizing and error-seeking agency to a partner for the applicant with
an aim to facilitate the drug development process, during the pre- and post-approval phases, for the benefit of
patients and pharmaceutical industry.
There are certain areas where a modern agency needs to focus. Scientific advice is one such area because im-
proved quality and easy access to advice will optimize the development process and facilitate the approval process.
Another focus area is the approval process itself. The recently created peer-review function within the centralized
approval process is an important initiative which, however, may need further improvement and strengthening.
The contribution from peer-reviewers should have a particular emphasis on list of questions and the risk manage-
ment program. To be a successful partner a national agency has to maintain a high level of scientific and regulatory
quality. The creation of a positive assessors’ working atmosphere with demanding work tasks and a strong quality
assurance strategy are important tools in this respect.
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TI Pharma: Jointly Shaping the Future of Medicines

Dr. Jorg Janssen (TI Pharma, The Netherlands) presented the Top Institute Pharma (TI Pharma), which bundles
leadership in research and education in areas critical for the international competitiveness of the pharmaceutical
industry in the Netherlands.
The Institute conducts groundbreaking, cross-disciplinary research and offers advanced training programs fo-
cused on improving the efficiency of the entire drug discovery and development process. This will reduce the
‘time- & cost-to-patient’ of new medicines and contribute to the well-being of the society. TI Pharma devotes
special attention to the Priority Medicines project of the WHO.
The foundation of TI Pharma enables the Dutch knowledge infrastructure to meet the industrial demands to short-
en/reduce time- & cost-to-patient by increasing the total research capacity on important themes and by improving
the efficiency and effectiveness of the conducted research.
The collaboration model of TI Pharma and an overview of research topics was addressed.
Partnerships for R&D and business development

Dr. Pedro Cruz (ECBIO, Portugal) presented the company’s experience in establishing partnerships for R&D and
business development.
Since the beginning of its research activities in 2003, ECBio has been collaborating with several European universi-
ties and hospitals as well as biotech and big pharma companies in the development of new technologies. When
engaging in R&D partnerships, the major motivations include accessing technical know-how, gaining access to
specialized equipment / technology and elevating company profile as a technology leader. The identified success
factors in this case are the complementary expertise/strengths, the collaborative experience and past collabora-
tion partners, the existence of high quality staff and the definition of an IPR agreement upfront
As the projects move from basic research to clinical trials, ultimately envisaging the commercialization, business
development partnerships assume increased relevance as they allow accessing specific business know-how,
foster product / technology commercialization and sharing costs, risks and profits. For the success of these part-
nerships it is necessary to have a common strategic vision compatibility of culture / mode of operation, comple-
mentary aims and a royalty agreement upfront.
It is clear that strategic partnerships are critical to success. Partnerships offer SMEs valuable assistance for prod-
uct development (R&D partnerships) and commercialization (business development partnerships).
Overall, the best strategy for an SME involved in R&D and clinical trials in the field of advanced therapies will most
probably involve a risk/profit distribution business development model.
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X - Round Table
Brave New World: “Preparing the Future”
Immunobiologics and advanced therapy medicinal products
Conclusions
• Current system needs optimisation.
• The regulatory system has to be filled with diverse specialised experts. Regulators have to adapt the
standards from large products to individually prepared products.
Dr. Klaus Cichutek (Paul-Ehrlich-Institut, Germany) presented the three types of Advanced Therapy Medicinal Products
(ATMPs): 1) gene therapy products, 2) somatic cells therapy products (viable, substantially maniplated cells combined
or not with supportive materials intended to exert a pharmacological, immunological or metabolic action); and 3) tissue
engineered products, engineered cells administered to repair, regenerate or replace human tissue, in some cases as-
sociated with structural materials.
With regard to gene therapy products, the most common approach is to transfer genes through the use of viral delivery
vectors either in vivo or ex vivo on cells then administered to patients. Adoptive immunotherapy was presented as a
somatic cell therapy product example. In immuno- cell therapy of cancer, autologous dendritic cells are loaded with
tumor protein or tumor cell extracts and re-administered with the intention to trigger or potentiate a cytotoxic immune
response against the tumor cells. Tissue engineered products, were illustrated by the use of autologus chondrocyte
progenitor cells administered during surgery to regenerate or repair cartilage in the knee. Stem cells from various
sources and targeting different tissues are being highly researched with a view to develop human somatic cell therapy
or tissue engineered products.
This new therapeutic field based on advanced therapies is under construction. Annex 1 to Directive 2001/83/EC is
being revised. The current definitions of somatic cell therapy and gene therapy medicinal products and the data require-
ments for marketing authorisation applications for ATMPs via the centralized procedure will be updated. Dr. Cichutek
mentioned as an example on the need to revise definitions that the gene therapy medicinal product definition should at
least include products mediating homologous repair of a non-functional gene (ex: for the treatment of inherited immune
dysfunctions based on non functional genes through DNA repair in vitro/ex vivo).
The regulation on ATMPs will enter into application in December 2008. From then onwards all ATMPs will require mar-
keting authorisation via the centralised procedure. The donation, procurement, storage, testing and manipulation of cells
as starting material for cell-containing products of human origin must also be in compliance with Directive 2004/23/EC.
Guidelines are being finalised or revised for cell-based products prepared by the Cell Based Products Working Party
and for gene transfer/therapy medicinal products by the Gene Therapy Working Party, with quality aspects being added
or reviewed by the Biologics Working Party (BWP). Guidelines for gene therapy also address issues in related to the en-
vironmental risk assessment as some gene therapy medicinal products contain genetically modified organisms. There
is also the need for long-term monitoring after completion of a clinical trial and after licensing.
Currently there is no licensed product for gene therapy on the EU market, but applications have been made.
The Committee for Advanced Therapies (CAT) will be a new committee at the EMEA drafting the opinion on the EU-wide
marketing authorisation application of ATMPs through the centralised procedure. A single application will have to be
formally accepted, validated and evaluated. For national authorities this has the advantage to pool EU expertise in the
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CAT with some additional expertise. The CAT membership will be composed of one representative per Member State
and co-opted members; it will also need gene therapy, cell therapy, tissue engineered and special medical expertise.
Some tissue engineered products have already been marketed in EU Member States via national procedures. Per-
spectives among SMEs diverge as some argue that they are too small to cope with a centralised marketing authori-
sation, others argue that some products are only needed regionally. At the EMEA level, product -specific working
parties have been established to respond to the special needs of ATMPs. These Working Parties work together with
large pharmaceutical companies, but also with small biotech companies as well as groups of academics maintain-
ing regular contacts with stakeholders and training of assessors and provide advice to the CHMP and the European
Commission, upon request. A discussion group on gene therapy products has also been set up at ICH level also
bringing in Chinese experts with a view to harmonise thinking and scientific standards to bring new products to the
market, as very often these products travel to the EU from the US for clinical trials and licensing.
Important aspects to support the development process were pointed out: national scientific advice by the regulatory
authorities in Member States; scientific advice at EMEA level; and in between, there is an informal briefing meeting by
the CHMP Gene Therapy Working Party and the CHMP Working Party on Cell-based Products where scientific discus-
sions take place which is an important occasion for the exchange of information between the industry and regulators.
Giving early scientific advice for a good early study which may be able for licensing is an essential element during the
preparation of the dossier.
Regulators need therefore to focus on training the assessors. Clinical assessors should also have expertise on these
specific products and there is a need to involve medical specialists, as these are very specific treatments.
Cell-based advanced therapies

Conclusions
• There is an active product development ongoing in the cell-based therapies’ field.
• We need to find a balance between risks, regulatory requirements and specific limitations of the cell-
based products.
• The benefit/risk ratio has to be positive for cell based medicinal products as for any medicinal prod-
ucts.
• Need to set up a network of experts and collaborate at earlier stages with the pharmaceutical industry
namely through scientific advice trying to assist small companies to succeed.
Dr. Paula Salmikangas (National Agency for Medicines, Finland) gave an overview of the status of activities in the
field of cell therapies in the EU.
Cell therapy products have been regulated as medicinal products in EU since directive 2001/83/EC, but the entry
of tissue engineered products into EU markets has been dependent on national regulations of each Member State.
The new advanced therapy regulation will classify both product classes as biological medicinal products and it will
create new practices for development and authorisation of the ATMP.
The Cell based Products Working Party is composed of 5 core members, representatives of the Efficacy, Safety
and Biologicals Working Parties and 10 to 15 additional experts from Member States selected base of their ex-
pertise in this field. The CPWP is to assist all parts involved, e.g. European Commission, EMEA, CHMP and other
Working Parties and provide guidance to industry and assessors.
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According to the definition, the primary mode of action for cell therapy products is pharmacological, immunological or
metabolic, whereas tissue engineered products aim to restore or regenerate physiological functions. Both types of Cell-
Based Medicinal Products (CBMP) contain viable cells, but they may include also medical devices, matrices, scaffolds,
biomolecules etc. and the cells may be engineered or genetically modified. Thus, these products may include prepara-
tions from simple cell suspensions up to very complex combination products, combining several research areas such
as biotechnology, cell biology, molecular biology and genetics, biomaterial technology, devices, bio-chemistry.
When looking at the database of Clinical Trails in the EU, we witness a strong development ongoing in the cell therapy
sector from 13 to 112 clinical trials in the past two years. New treatments are being developed for cardiovascular dis-
eases, cancer, neurological dysfunctions and structural/functional repair of various organs. In the near future, all of
these products already in national markets will be regulated according to the new ATMP regulation and their entry to EU
markets will be via centralised procedure.
It may take 10 years for a cell product to come into the market. There is already one submission of a tissue engineering
product at the EMEA under evaluation. The first cell therapy product type seen in the market was Apligraft/Organogen-
esis (1988) for the treatment of venous ulcers and diabetic foot ulcers. This type of products is also being developed in
the EU (ex: Intercytex, to develop two kinds of skin replacement products for acute and chronic wounds). In terms of ar-
ticular chondrocyte implantation, Carticel was the first product introduced in the US in 1995, produced from autologous
chondrocytes (ex: implanted to create new cartilage. ChondroCelect was the first of its kind in Europe. There is now a
second generation of these products where chondrocytes are implanted in scaffolds or matrices to get more support
for cells growth. Development is also ongoing on bone grafts, as Biotissue technologies are creating an autologous
bone graft for building bone in the jaw region.
In a recent workshop organised by the CPWP, EMEA and Infarmed new products going under development and ready
for Clinical Trials were presented. Companies are creating beads and fibres that contain cells (possibly genetic modi-
fied cells) and are covered by semi permeable membranes allowing the cells to produce the protein needed for the
treatment but does not allow the human body to attack the cells inside these beads or fibres. A product from a Danish
company intended to be introduced in the brain through a special device is already under phase I clinical trial and brings
positive prospects for highly debilitating diseases.
Tissue engineered also allows the development of products for the cosmetic field. Intercytex (UK) is developing a product
to be implanted to create new hair from human dermal cells grown from a small biopsy. Research groups from Italy are cre-
ating products for corneal regeneration. They use amniotic membranes as a support to grow corneal cells from patients.
An article of 1998 shows the developments underway for the next 10 years from now. One example presented to the
CPWP was provided by a US company producing artificial bladders, and different sizes of bladders could be provided
to all types of patients.
Regulators now face difficult times as these are completely different products from previous ones. These products face
various limitations such as limited sample size, short shelf-life, unique manufacturing process, applicability of conven-
tional test methods and the lack of availability of suitable animal models. On the other hand, they are high risk products:
microbiological purity lays on the aseptic processing and on the quality of raw materials, the risk of gene integration
and tumourigenicity, consistency of production and immunogenicity problems for all biologicals could be anticipated in
these products.
Currently, companies criticise the complex regulatory framework for these products, as there are 3 gene / cell
therapy directives, 2 medical devices directives, 17 EMEA guidelines, 5 monographs, 7 ICH guidelines, WHO ac-
tivities, 2 main ISO standards and other instruments are all applicable to these products.
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The major obstacles for the industry at the moment are short shelf-lives and how to meet the requirements
of release testing (potency, purity, sterility); specially for autologous products; extensive testing increases
the price of the product (one batch – one patient); GMP requirements for the clinical trial materials; process
of validation and consistency of production; suitable potency testing and correlation to clinical efficacy;
import of CBMP from third countries to EU (additional batch release in the EU?); EU legislation requires new
marketing authorisations when master cell bank is changed; difficulties to find relevant animal models for
pre-clinical testing; need to specific guidance on clinical trial design for cell based medicinal products.
The way we currently regulate cell based products is based on widely different rules (biologicals regula-
tions, device regulations and tissue engineered rules) and companies need to comply with all of these
rules. The EMEA CPWP tries to adopt a risk-based approach for regulation of the cell based as well as for
all ATMP. There is a need to find a network of experts on the device and biological sectors to overcome
difficulties.
Omics technologies
Conclusions
• Away from the post-war economic boom we are in the era of science and communication: integrated
knowledge management and education is essential.
• Mature markets and changing environment demand change both in pharmaceuticals regulatory frame-
work and in public health strategies.
• The current science-based regulatory system to be further developed in the lifecycle of the products to
bridge the current gap between approval and patient access to innovative medicines.
• Omics and molecular medicine offer tools for efficient science-based drug development and may also
help in public health choices, complementing current Health Technology Assessment (HTA) methods
Dr. Marisa Papaluca Amati (EMEA) started answering the question “why omics” today. Firstly, because the
pharmaceutical industry worldwide is an inefficient industrial sector, and we need to improve the way industry
works. Secondly, in terms of public health objectives it strives to keep up with the costs, not only the costs of
medicines but also of the side effects of medicines and of the consequences of the lack of efficacy of some
medicines. A final reason is the existence of unmet medical needs. It is therefore urgently needed a patient
centred approach, to support the EU based pharmaceutical innovation and contribute to the vitality of both
industry and health systems.
CHMP recently adopted a definition for pharmacogenomics and a guideline and a Pharmacogenetics Work-
ing Party was established.
What is omics and the difference between the various omics: pharmacogenomics; transcriptomics; proteom-
ics; metabonomics. The most important is that they are associated with very different volume of information
which is generated for their interpretation. The information element is what makes this new technology so
intertwined among each other and difficult to absorb in the regulatory system.
What is in fact new in terms of omics technologies with impact in drug development since June 2007. New
techniques using the Genomic Wide Analysis (which helped finding the genome wide map for the crohn dis-
ease) allowed us to also have the map of the diseases in the genome (Genemaps). Also important is the use
of bio-chips and lab-on-chip and the new methods for molecular definition like the terahertz radiation and
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spectroscopy are a few months old. In this context of omics technologies, bioinformatics is a fundamental
science and on the regulatory side we need to know what the limitations of the technology which is used and
how this can be compensated in the final benefit-risk assessment.
It has also been proven that our knowledge on diseases is changing, namely on the confirmed genetic contribu-
tors on common diseases. In April 2007, we had results of new studies on prostate cancer, type 2 diabetes,
crohn’s disease and age related macular degeneration. Since then until September 2007 much information was
published on these diseases.
In terms of pharmacogenomics based opportunities to improve the benefit risk for example with dose adjustments. In
this field, there is a huge number of products in the market which suffer of the lack of adjustment of their dosing. The
case of Venlafaxine raised many questions and missed opportunities in using innovation for the benefit of the patient.
On a different angle, it should also be considered the level of sophistication omics is introducing in our scientific knowl-
edge and the level of position using genomics and proteomics in understanding the mechanism of the viral replication,
the base of the disease and how we have been able to identify drugs which can work at the molecular level.
The use of genomics (for example with CCR5 antagonist) can also be used not only on humans but also to
explore the characteristics of virus and bacteria.
Are doctors educated enough to keep up with this knowledge? Fact: A large majority of physicians do not have
enough education to manage all these information for the benefit of the patients. With this in mid, the most im-
portant elements are knowledge management, algorithms and education.
Herceptin HER2 case study: biomarker used to identify a subset of patients with breast cancer who are likely
to respond to Herceptin (Trastuzumab). The effect of biomarkers results in the identification of target population
at the molecular level. This case was taken by regulators in a very restrict manner that it could be only used
in patients with multiple copies of the HER2 gene. This case led to an important issue: what do we do with
companion diagnostics in the EU? So far we have distinguished areas of responsibility, and it is known from the
cell and gene therapy that this responsibility has to be combined and the same applies for genomics and for
personalised medicines.
What does the EMEA to support innovation? A think-tank was set up two and half years ago with a view to
ensure that we have a science based regulatory environment and strengthen the regulatory process and exper-
tise. The Agency also tries to discuss issues with stakeholders to anticipate the impact on current practices and
policies and to support international efforts to develop harmonised global standards.
The Pharmacogenomics Working Party involves regulators and academia, omics labs and other institutions in
Europe sitting together to discuss with the sponsors of omics. Since 2003 there were 30 case studies and in 2007
(until November) 10 briefing meetings were held. An omics repository was also established identifying the models,
genes and approaches. The EMEA also works closely with the FDA to create the basis for a global approach to
biomarkers qualification, and thanks to the C-Path industry scientists this approach is now on a pilot phase and is
also preparing new Scientific Advice Working Party processes to evaluate new R&D methods within and beyond
biomarkers qualification process.
The Agency is revising its procedures to provide space for scientific advice on new methods for R&D in the lifecy-
cle of products. Omics technologies provide a reliable and credible set of tools to efficiently develop therapeutics
adapted to current and future health and industrial needs.
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New delivery systems: from controlled release to nanomedicine

and moving into the market
Conclusions
• Away from the post-war economic boom we are in the era of science and communication: integrated
knowledge management and education is essential.
• Mature markets and changing environment demand change both in pharmaceuticals regulatory frame-
work and in public health strategies.
• The current science-based regulatory system to be further developed in the lifecycle of the products to
bridge the current gap between approval and patient access to innovative medicines.
• Omics and molecular medicine offer tools for efficient science-based drug development and may also
help in public health choices, complementing current Health Technology Assessment (HTA) methods.
Prof. Rogério Gaspar (University of Lisbon, Portugal) initiated his presentation saying that nanomedicine medici-
nal products are on the market for 18 years and were firstly used in humans more that 25 years ago.
Nanomedicine means the biomedical applications of nanotechnology centred on the patient, specifically looking
for the pathology (unmet medical needs). The tools of nanotechnology and biomedical applications are comple-
mentary to other areas such as bio-nanotechnology.
Two important reports at EU level issued in 2005 gave room to a number of work-packages and definitions of
nanomedicine.
“Nanopharmaceuticals can be developed either as a drug delivery system or biologically active drug products”.
Nanomedicines concentrate mainly on cancer and neurodegenerative diseases. Cancer is really a success case
for a number of products that are on the market and a high hope for products on the pipeline.
The first example of nanomedicines entering the market was in the 1980 with liposome (ambisome) and since
then, a number of products very different in their construction, such as liposomes, nano particles, assembled
macro molecular bio conjugates and more recently a nano particles system approved by the FDA and the EU
(abraxane). Products on the pipeline are assembled macro molecular complexes, some related to cancer and
other therapeutic applications (examples in EU UCB for Crohn’s diseases and Xyotax for breast carcinoma in
the US).
What are the main objectives of these so different systems, called nanopharmaceuticals: reducing toxicity to
normal cells; increasing uptake by malignant cells; site-specific systems (antibody guidance); stealth avoidance,
increasing circulation in blood and reducing uptake by phagocytic cells.
A number of compounds have been developed in order to avoid the multi drug resistance in tumour cells such
as Doxorubicin and looking at a better accumulation of the cytostatic drug inside the cell through an endocytic
and intra cellular uptake.
On the regulatory field at EU level, experts on nanomedicine stress that there is no need for a new regulation
on medicinal products for nanomedicine as we currently know how to deal with liposomes and nano particles.
However, the biggest problem for the near future are the dendrimers or some of the non biodegradable systems,
the potential use of carbon nanotubes and eventually quantum dots for therapeutic and diagnostics purposes.
These new products pose new challenges in terms of toxicity of the materials.
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Some of the products on the market have been tried for a number of years with great success. One of the driving
forces has been the change in pharmacokinetics of the systems.
Caelyx has been centrally approved in the EU by the EMEA 12 years ago and Myocet is also centrally authorised.
The example of Abraxane was also given. Abraxane is a success case from a small company having a partnership
with a large company and is composed of albumin nano particles containing paclitaxel.
Overall, the conventional approach in 1970’s and 1980’s was mostly dealing with changes in pharmacokinetics of
drugs or proteins and in the 1990’s more specific subsets of macro molecular compounds like the polygutamate-
campothecin, polygutamate-paclitaxel or the HPMA copolymers which have a higher retention effect on those
vascularised solid tumours and showed an increasing efficacy in specific sets of populations in cancer.
Mylotarg was approved in the US and Xiotax is concluding phase III clinical trials. Some of the results presented
publicly show that one of the links is a double amino acid link which is specific for Catapcin-B and Catapcin-B ap-
parently is over expressed in women with breast carcinoma.
A new concept was recently developed. It consists on a mycell approach based on the copolymer, which was able
to identify, using omics technology, the specificity in terms of toxicity and efficacy of some of those polymers.
In the near future we will face the nano-“smart”-systems or nano-carrier driven systems. In this case, we are look-
ing for molecular recognition at the membranes cells and for some receptors, and a number of approaches have
already been tried in terms of immuno-liposomes, immuno-polymers and immuno-nano particles.
In Valencia, a group from the Prince Filipe Institute recently presented one of the roads for the future in macromo-
lecular complexation. It took some of nanomedicines which are macro molecular constructs in order to achieve
cancer targets with two different drugs in the same polymer construct, avoiding resistance from the tumour in the
specific subset (currently in pre-clinical development).
A work carried out at the Pharmacy Faculty of the Universidade de Coimbra in Portugal proved the concept of
liposomes with Doxorubicin to specific lung cancer patients. It was done in a clinical setting in-vitro and in-vivo.
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XI - Conclusions of the Workshops

and Future Perspectives
Conclusions Workshop 1
Innovation and Development: Constraints and Opportunities
Conclusions
• Funding of research related to comparative efficacy, safety and access, including “old drugs”, needs
further improvement to be more effective.
• Some national experiences show that further EU support is needed, particularly in the context of involv-
ing the industry as a partner.
• These experiences highlight the need for more careful consideration of the EU regulatory system in
terms of the separation of marketing approval and access decision-making.
• Roles and responsibilities of the different stakeholders should be clarified in order to establish an “in-
novation friendly environment”.
• B to B models of small and big pharma look promising, are more flexible and could fuel other pharma
innovation models.
Recommendations
• Need for a new “social contract” between industry and society expressing and addressing real clinical
needs and rewarding real innovation.
• Pharmaceutical innovation needs “risk-sharing” (balance between access to innovation and data gath-
ering by the industry). We need creative and validated models.
• Incremental innovation should be rewarded through real incentives in pricing and reimbursement poli-
cies.
• Harmonisation of procedures, work sharing and other regulatory improvements are needed.
• Investigation-sponsored/independent research should be fully compliant with GCP and other clinical/
legislative requirements.
• Convergence of different areas (e.g. pharma, devices, food) provides a challenging opportunity for in-
novation in terms of learning from the diversity in technology, regulation and market features.
• Beyond all models and systems, teaching and education programmes are fundamental for success.
There is a need for real champions, individuals who are capable to make a difference.
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Workshop 2
SME and R&D Funding
Conclusions
• Various EU initiatives are underway to promote innovation. Funding is available. A more professional
approach in fund seeking is needed by stakeholders.
• A national case study of a platform between Industry and Academia stressed that organization of work,
networking and continuity on information sharing are key for success.
• Example presented of an SME emerging from a holding: business plan with specific needs for the clini-
cal development and how public incentives (tax relief) can be mixed with venture capital.
• SME’s face difficulties to reach information/communication.
• A large amount of venture capital and public funds is unused. Venture capital company says only 5% of
the funds available are applied. Very low number of companies funded due to lack of applications.
• National agency for innovation promotes entrepreneurial innovation, especially in the technological area.
Identifies the urgent need to participate in International Cooperation Networks (as Eureka, Iberoeka,
Innovation Relay Centers).
Recommendations
• Better education and training:
– to enable SMEs to apply for EU funding
– to communicate the added value they offer.
• Need for services (offered by institutions or available for outsourcing) be able to intermediate between
SMEs and Funds suppliers.
• European SMEs need to be more professional in the way to pursue funding. This implies a change in
mind set and a pluridisciplinary team that goes beyond “pure scientists”.
• SMEs should think “European” and look where the resources are independently of the country.
Workshop 3
Who will Pay for Innovation?
Conclusions
• Three drivers are key in establishing good practices on impact of cost containment policies: healthcare
costs, patients’ access and reward for innovation.
• Innovation should be paid by “the consumers” of health care and not just the taxpayers.
• Innovative Therapies require Innovative Financing, in which the risks are more fairly shared between the
various stakeholders are needed.
• Innovation cannot be regarded simply as a product, but rather as a process, hence not something to
be acquired, but to participate at.
• A new focus for pharmaceutical innovation for generic medicines comprises strong competition from
generics to original products once patents expire along with inventive step on patent approval and pric-
ing systems supporting innovation.
• Need for a more patient-centric approach and strive towards industry & payers benchmarking com-
monalities.
• Use of “Push and Pull” mechanisms for increased public funding.
• A new drug should be really innovative and cost effective: value for money
• The only way forward is to work in partnerships.
41
EU2007.PT
Recommendations
• The concept of Innovation needs harmonization.
• The criteria for which innovation will be funded needs discussion e.g. related to outcomes (as is hap-
pening for basic research).
• Partnerships for Research Funding to be established. Involvement of “targets” for the innovation should
be defined.
• More efficient strategies to promote innovation related to diseases affecting
poor regions need to be settled in an international context.
Workshop 4
Partnerships for Success
Conclusions
• Key factors for optimising R&D: regulation framework, Intellectual Property Rights, Scientific based
Knowledge.
• Innovative Medicines Initiative (IMI): Need for larger investment in R&D. New R&D Omics Technologies
and new ways of working. IMI benefits all stakeholders: Academia, SMEs, Pharmaceutical Industry.
• IMI First Year Expected Topics: 5 in Safety; 1 in Pharmacovigilance; 3 in Diabetes; 3 in Brain Disorders;
3 in COPD & Asthma; 6 in Education & Training.
• C-Path: Innovative consortium between Industry and the Critical Path Institute (US): funding partners
FDA, SRI International and University of Arizona. FDA and EMEA scientists serve as advisors. The main
target is the identification and qualification of safety biomarkers for clinical trials. 1st submission to the
EMEA/FDA of predictive safety testing nephrotoxicicity.
• Changing role of Regulatory Agencies: partner with the pharmaceutical industry; importance of new
instruments as scientific advice and quality management systems to improve processes and perform-
ances.
• National partnerships involving academia and industry in support of R&D:
• Use of an yeast model in neurodegenerative diseases;
• Molecular Diagnostics;
• Cell based assays and cell therapy protocols.
• Public-Private partnerships should focus specific therapeutic areas. New funding model involves
industry, academia and Government.
Recommendations
• Successful and innovative partnerships at international level. Strong commitment is needed by all
stakeholders.
• New R&D programmes should focus on specific therapeutic priorities.
• Funding partnerships should involve multiple actors.
• The results of national and international partnerships currently underway should be considered as a
positive indicator for future research programmes and projects.
42
EU2007.PT
Future Perspectives
Dr. Eric Abadie (EMEA Committee for Medicinal Products for Human Use, CHMP) presented the main conclusions
and recommendations of the EMEA/CHMP Think Tank group on innovative drug development envisaging estab-
lishing a critical view on the current and future scientific development of medicinal products and related regulatory
standards in Europe. Its main objectives were: top-quality scientific assessment; timely access to safe and effec-
tive medicinal products; continuous, reinforced monitoring of products safety and better informed patients.
The implementation plan laid out specifies concrete actions the EMEA will undertake in the coming years. Follow-
up to this action plan will be provided regularly through a yearly review and refinement of the agreed initiatives, in
line with and, where appropriate, as follow up to the EMEA Road Map.
As discussed, there are major areas the stakeholders have identified as opportunities for the regulators to support
and enhance pharmaceutical industry’s ability to efficiently develop new medicines according to the advances of
science and in line with patients’ needs.
The most significant and important recommendations for action during 2008/09 include opportunities for improv-
ing the EU operation in the following areas:
1. Communication and interaction with regulators during the lifecycle of the products (briefing meetings to be
further developed, faster scientific advice – new procedure for minor advice/clarifications, scientific advice
peer review). These are informal meetings with stakeholders including academia and companies on innovative
products. These meetings provide a more informal environment for discussions and in 2008 will be established
particularly for orphan medicinal products, advanced therapy medicinal products and SMEs.
2. Global harmonisation (routine discussions with other regulatory bodies (FDA) on biomarkers, setting up a new
procedure of qualification of biomarkers alongside US, parallel scientific advice).
3. Emerging science for clinical development and regulatory approval
a) translational development: involvement in the US Critical path Initiative and support to IMI, workshop and
training on new statistical methodologies and early development of biomarkers, harmonised EU-position on
requirements for early clinical trials;
b) advanced therapies: contribution to the EC implementation plans, informal dialogue opportunities, rolling
scientific evaluation and certification of quality and non-clinical data for SMEs).
4. Pharmacovigilance
Update risk management system-guideline, encourage scientific advice on risk management plans, analyse
and develop principles for acceptable standards in risk minimization activities, facilitate access to Eudravigi-
lance data/signal detection tools, establish a European network of centres for pharmacoepidemiology and
pharmacovigilance.
5. Guidelines
CHMP will provide the European Commission with a protocol of the proper assessment on benefit-risk bal-
ance. Quicker questions and answer documents, more reflection papers, prioritisation and early consultation
of experts and stakeholders.
43
EU2007.PT
6. Antimicrobials
Gap analysis on current medical needs for antimicrobials, priority list of pathogens: joint CHMP/PDCO WG with
ECDC to define and supervise its progress, technical report by the end of 2008.
This was considered an ambitious working plan on Innovation, adopted in November 2007 at the CHMP and it
will start being implemented in 2008. A major difficulty will be the resources needed and priorities and procedures
to be set up. To achieve these objectives the EMEA will pursue needed careful consideration, co-operation and
synergy within the EU network and the more global scientific and regulatory environment.
44
EU2007.PT
XII - Presentation on the initiative of the incoming

Slovenian EU Presidency
Dr. Martina Cvelbar (Agency for Medicinal Products and Medical Devices, Slovenia) presented the main initiatives
of the Slovenian Presidency in the field of medicinal products and health products, in particular the Conference:
Networking Meeting of the Competent Authorities for Pricing and Reimbursement of Pharmaceuticals, to be held
in Brdo, Slovenia, on 28-29 April 2008.
It seeks to preserve and build on the results of the recent P&R initiatives in the EU, and to build on the willingness
of the authorities to share the outcomes of their work and to consider best practices. Its strategic objectives will
be: to recognize the specific needs for cooperation in the pricing and reimbursement field and the ways to address
them; to preserve and build on the results of the recent pricing and reimbursement initiatives in the EU; to build
on the willingness of the authorities to share the outcomes of their work and to consider best practices; and to
establish and sustain a network capable of contributing to the EU cooperation among stakeholders for the benefit
of EU citizens.
As expected outcomes the meeting is expected to have a synergistic effect on overall impact of the work of the
authorities; it should provide an environment for the evaluation of the results of the Pharmaceutical Forum; net-
working process should in terms of timeline be viewed as a multi-presidency project.
The Conference envisages gathering representatives from pricing and reimbursement of the 27 Member States
and representatives from the European Commission.
45
EU2007.PT
XIII - Closing Session
Prof. Vasco Maria (Infarmed, Portugal) underlined the successful discussions held in Viseu during the two days
on innovation strategies. The debate on the current status on innovation at EU level was enriched by the active
participation of experts and stakeholders in discussing various issues and presenting different perspectives.
The main constraints and opportunities posed to innovation were identified such as the need to support SME,
strengthening the role of scientific advice at early R&D stages, the need to finance innovative R&D projects and
how to recognize and reward “real” innovation. It is essential that in the future Governments will find transparent
and robust measures in a way to allow the pharmaceutical industry to re-direct its R&D efforts.
Our goals remain unchanged: ensure the efficacy and safety of medicines at affordable prices, ensuring the sus-
tainability of health systems and to focus at the patients’ needs.
Currently, we witness an increase of public and private investment in research in Europe and Biomedicine is bring-
ing new expectations towards a new generation of medicinal products. However, it is important to better coordi-
nate investment efforts in Europe, to shorten the periods of R&D timelines, remove innovation obstacles and make
European a more attractive space and also reduce the number of market withdrawals through the processes of
risk minimisation. This last, Prof. Maria recognised to be an area into which Governments and regulators should
spend more resources on.
All these elements and initiatives show a strong European will to become a competitive economy in the pharma-
ceutical field in line with the Lisbon Strategy, in which research and innovation are two fundamental pillars.
Prof. Vasco Maria concluded saying that the main objectives of the Conference were achieved in a relevant set
of conclusions and recommendations which will be compiled in a report of the Conference. Prof. Vasco Maria
thanked all speakers, co-chairs and participants for their active participation to this Conference. A special thanking
was also given to the European Commission, to the Secretary of State for Health, Mr. Francisco Ramos and to the
organisers from Infarmed for their strong commitment to the initiative.
Mr. João Almeida Lopes (APIFARMA, Portugal) congratulated Infarmed for the organisation of the Conference,
which had successful results for its excellent and comprehensive programme. He highlighted some conclusions:
1) the raising costs of innovation and the decrease of innovative medicinal products; 2) the increasing complexity
of the regulatory framework is contributing to the increase of costs for innovation; 3) the need for combined solu-
tions among all partners, namely by deepening risk-sharing models during the whole life-cycle of medicines. Mr.
Almeida Lopes showed himself somehow surprised with the number of research centres that has closed down in
recent years in Europe.
In Europe, he concluded, when the results of innovation are normally ready to enter the market there is great dif-
ficulty to quantify “real” innovation and to define the “value for money”. Currently, innovation has a more complex
framework than in the US. To succeed in the 21st century we need to overcome this paradox, he pointed out.
Mr. Francisco Ramos (Secretary of State for Health, Portugal) congratulated Infarmed for organising this Confer-
ence. The Portuguese Presidency encompassed topics like the social inclusion of migrants and its repercussions
46
EU2007.PT
in Health up to pharmaceutical innovation. It brought to the European Health Agenda a set of uncommon and
comprehensive themes envisaging a compromise with our objectives for Europe, e.g. make from Europe a more
competitive and developed area and at the same time strengthening social cohesion.
He reiterated that we all have two main objectives: to protect citizens’ health and to reinforce the competitiveness
of European companies. To that end it is of key importance to improve access to national and international mar-
kets and to ensure efficient competition rules. Innovation supporting policies are fundamental to improve the R&D
framework, specifically involving key stakeholders.
As a key words or ideas for this conference, Mr. Ramos highlighted the need to define “real” innovation, the con-
cept of partnership in the regulatory, innovative and financing processes; and the existing trust among stakehold-
ers is a key element for making progresses.
In concluding, Mr. Ramos said that today we are more aware of the difficulties and constraints to innovation and
also more confident in the future as partners are adopting positive attitudes and endeavouring for challenging
areas in identifying new solutions such as reducing costs and bureaucracy and increasing transparency towards
better medicines for all.
47
EU2007.PT
Annexes
XIV - Programme
19 November 2007
08:45 Opening Session

A. Correia de Campos, Minister of Health, Portugal
Octavi Quintana Trias, DG Research, European Commission
Thomas Lönngren, EMEA
Arthur Higgins, EFPIA
9:30 Opening Lecture
Chair: Vasco Maria, INFARMED
“Current Status of Pharmaceutical Innovation in the EU”

Ole J. Bjerrum, Danish University of Pharmaceutical Science, Denmark
10:15 Coffee Break

10:45 Round Table
“Promoting Pharmaceutical Research, Development and Innovation in the EU: a
Common Goal”
Co-chairs: Alasdair Breckenridge, MHRA, United Kingdom

José Morais, INFARMED, Portugal
“Innovative Medicines Initiative”

Octavi Quintana Trias, DG Research, European Commission
“Regulatory Agencies and Innovation”

Karl Broich, BfArM, Germany
“The Role of Scientific Advice”

Beatriz Lima, University of Lisbon, Portugal
“Views from the Industry”

Brian Ager, EFPIA
“EU Initiatives and Harmonization - EMEA – ICH”

Spiros Vamvakas, EMEA
“Alternative Methods and Innovation”

Laura Gribaldo, European Commission, Joint Research Centre Ispra-ECVAM
12:45 Lunch
48
EU2007.PT
Programme
19 November 2007
14:15 Workshop 1 – Innovation and Development: Constraints and Opportunities
Co-chairs: João Lavinha, INSA, Portugal

Hubert Leufkens, MEB, Netherlands
1. “Pharma R&D: Level of Development?”

Manuel Gonçalves, GlaxoSmithKline, Portugal
2. “The Human and Economic Value of Medical Innovation”

José Almeida Bastos, Merck Sharp & Dohme, Portugal
3. “Independent Research”
Antonio Addis, Italian Medicines Agency, AIFA, Italy
4. “The Spanish Experience”

Cristina Avendaño, Spanish Medicines Agency, Spain
5. “Biotecnol”
Pedro Pissarra, Biotecnol, Portugal
6. “Bial’s Experience”
Luís Portela, Bial, Portugal
14:15 Workshop 2 – SME and R&D Funding
Co-chairs: Cristina Sampaio, University of Lisbon, Portugal

Rannveig Gunnarsdottir, Icelandic Medicines Agency, Iceland
1. “European R&D Funding for SME – 7th R&D EU Framework Programme and Related
Programmes”
Bernd Reichert, DG Research, European Commission
2. “Biomedical Research at the University - Industry Interface”

Manuel Carrondo, IBET, Portugal
3. “Biotech Funding, Neuropharma: A Case Study”

Belén Sopesén, Neuropharma
4. “Are SMEs equipped to use all the aid available for them?”
Johan Vanhemelrijck, EuropaBio
5. “SME and R&D Funding”

João Fernandes, InovCapital, Portugal
6. “AdI Support Measures to Entrepreneurial R&D – Innovation”

Carlos Lajas, Agência de Inovação, Portugal
49
EU2007.PT
Programme
19 November 2007
14:15 Workshop 3 – Who will Pay for Innovation?
Co-chairs: Jorge Gonçalves, University of Porto, Portugal

Beatriz Lima, University of Lisbon
1. “What can the Commission do?”

Thomas Heynisch, DG Enterprise and Industry, European Commission
2. “Public Health, Innovation and Sustainable Financing”

Kees de Joncheere, World Health Organisation
3. “Paying for Innovation or Paying for Health Care”

Miguel Gouveia, Portuguese Catholic University, Portugal
4. “Innovate Therapies will Require Innovative Financing”

Fernando Royo, Genzyme, Europe
5. “Affordable Innovation meeting Public Health Needs”

Rita Kessler, Association Internationale de la Mutualité
6. “Who Will Pay for Innovation”

Mary Geraldine Baker, European Federation of Neurological Associations
7. “Generic Competition, Healthcare Sustainability and Head Room for Innovation”

Greg Perry, European Generics Association
14:15 Workshop 4 – Partnerships for Success
Co-chairs: A. Vaz Carneiro, University of Lisbon, Portugal

Rannveig Gunnarsdottir, Icelandic Medicines Agency, Iceland
1. “Key Factors for Optimisation of R&D Investment in Europe”

Brian Ager, EFPIA
2. “Successful Collaboration between Industry Partners and the Critical Path Institute:
Qualification of Safety Biomarkers for Regulatory Decision Making by the Predictive Safety
Testing Consortium”
Jacky Vonderscher, Novartis, Switzerland
3. “From Academia to Biotech: US and Portuguese Examples”

Tiago Outeiro, Institute of Molecular Medicine, Portugal
4. “Partnership for Success – The Strategy of a Modern Agency”

Jan Liliemark, Medicinal Products Agency, Sweden
5. “TI Pharma: Jointly Shaping the Future of Medicines”

Jorg Janssen, TI Pharma, Netherlands
6. “Partnerships for R&D and Business Development”

Pedro Cruz, ECBIO, Portugal
17:30 End of day 1

19:00 Official dinner
50
EU2007.PT
Programme
19 November 2007
9:00 Round Table

“Brave New World: Preparing the Future”
Co-chairs: Cristina Sampaio, University of Lisbon, Portugal

Andrea Rappagliosi, EuropaBio
“Immunobiologics and Advanced Therapy Medicinal Products”

Klaus Cichutek, Paul-Ehrlich-Institut, Germany
“Cell-based Advanced Therapies”

Paula Salmikangas, National Agency for Medicines, Finland
“Cell-based Advanced Therapies”

Paula Salmikangas, National Agency for Medicines, Finland
“New Delivery Systems: From Controlled Release to Nanomedicine and Moving into the
Market”
Rogério Gaspar, University of Lisbon, Portugal
10:30 Coffee break

11:00 Conclusions of the Workshops
Co-chairs: Helder Mota Filipe, INFARMED, Portugal

Philippe Lechat, AFSSAPS, France
Presentation of Workshops
Rapporteurs
Future Perspectives
Eric Abadie, CHMP, EMEA
12:30 Presentation on initiative of the incoming Slovenian EU Presidency

Martina Cvelbar, Slovenian Medicines Agency, Slovenia
12:45 Closing Session

Francisco Ramos, Secretary of State for Health, Portugal
João Almeida Lopes, APIFARMA, Portugal
Vasco Maria, INFARMED, Portugal
13:15 Lunch
51
EU2007.PT
XV - List of Participants
Name Organisation
Adélia Noronha INFARMED, I.P.
Alasdair Breckenridge Medicines and Healthcare Products Regulatory Agency of UK
Alberto Aguiar AstraZeneca
Alberto José dos Santos Inez Genzyme Portugal, S.A.
Alexandra Heumber MSF
Alexandra Marques 3B´S Research Group – Universidade do Minho
Ana Maria Corrêa Nunes INFARMED, I.P.
Ana Maria Dias Bial – Portela e Cª, S.A.
Ana Maria Quintas Plataforma Saúde em Diálogo
Ana Paula Martins Merck Sharp & Dohme, Lda.
Andrea Rappagliosi EuropaBio
Andreia Filipa Limpo Mestre Instituto Superior de Ciências da Saúde Egas Moniz
António Addis AIFA – Agenzia Italiana del Farmaco
António Chaves Costa Tecnifar
António Correia de Campos Ministério da Saúde
António Lourenço Comissão de Ética para a Investigação Clínica – INFARMED, I.P.
António Manuel Núncio Faria Vaz Comissão de Ética para a Investigação Clínica – INFARMED, I.P.
António Vaz Carneiro Faculdade de Medicina da Universidade de Lisboa
Arthur Higgins EFPIA
Bart Wijnberg Ministry of Health, Welfare and Sport of Netherlands
Beatrice Oberle-Rolle Novartis Pharma AG
Beatriz Lima Faculdade de Farmácia da Universidade de Lisboa
Belén Sopesen Neuropharma
Bernd Reichert European Commission - DG Research
Brian Ager EFPIA
Carla Cristina Fernandes Gomes Ferraz Lynce, S.A.
Carla Machado INFARMED, I.P.
Carlos Andrade Miranda Comissão Parlamentar de Saúde – Assembleia da República
Carlos Lajas Agência da Inovação
Carlos Pires INFARMED, I.P.
Charles Bouchard Merck Sharp & Dohme, Co.
Cristina Avendaño Spanish Medicines Agency
Cristina de Mello Sampayo Faculdade de Farmácia da Universidade de Lisboa
Cristina Lopes APIFARMA
Cristina Sampaio Faculdade de Medicina da Universidade de Lisboa
52
EU2007.PT
Name Organisation
David Laurie Novartis Pharma AG
Denise Rennmann Bayer Schering Pharma AG
Elke Grooten European Generic Medicines Association
Eric Abadie EMEA
Evaldas Navickas Ministry Of Health of Lithuania
Fabian Waechter AGES PharmMed - The Austrian Medicines Agency
Fernando Leal da Costa Comissão de Avaliação de Medicamentos – INFARMED, I.P.
Fernando Royo Genzyme
Francisco Batel Marques Faculdade de Farmácia da Universidade de Coimbra
Francisco Ramos Minstério da Saúde
Gabriel Olim Instituto Português do Sangue
Gernot Spanninger Federal Ministry of Health, Family and Youth of Austria
Giusy Chiovato Rambaldo Bayer Schering Pharma AG
Greet Musch Federal Agency for Medicines and Health Products of Belgium
Greg Perry European Generic Medicines Association
Heitor Manuel de Jesus Venda Ribeiro Costa Medinfar
Helder Mota Filipe INFARMED, I.P.
Helena Paula Correia Beaumont INFARMED, I.P.
Helena Paula da Sousa Sepúlveda Azevedo 3B´S Research Group – Universidade do Minho
Henrique Luz Rodrigues Faculdade de Medicina da Universidade de Lisboa
Hubert Leukfens Medicines Evaluation Board - Netherlands
Hugo Hurts Ministry of Health of Netherlands
Inês Pedroso da Costa Eurotrials
Iolanda Agostinho INFARMED, I.P.
Isabel Abreu INFARMED, I.P.
Isabel Saraiva APIFARMA
Isabel Vieira INFARMED, I.P.
Isaura Vieira INFARMED, I.P.
Ivar Vollset Norwegian Medicines Agency
Jacky Vonderscher Novartis Pharma AG
Jan Liliemark Medicinal Product Agency of Sweden
Jean Pruneau Health Canada
João Almeida Lopes APIFARMA
João Barroca Bayer Portugal
João Cristóvão Martins Faculdade de Farmácia da Universidade de Lisboa
João Fernandes InovCapital
João Gomes Esteves APIFARMA
João Lara Everard Korangi – Produtos Farmacêuticos, S.A.
João Lavinha Instituto Nacional de Saúde Dr. Ricardo Jorge
João Lobo Antunes Instituto de Medicina Molecular da Universidade de Lisboa
João Norte Merck Sharp & Dohme, Lda.
Johan Van Hemelrijck EuropaBio
53
EU2007.PT
Name Organisation
Jorg Janssen TI Pharma
Jorge Gonçalves Faculdade de Farmácia da Universidade do Porto
Jorge Torgal Instituto de Higiene e Medicina Tropical
José A. Damas Móra Comissão da Farmacopeia Portuguesa - INFARMED, I.P.
José Almeida Bastos Merck Sharp & Dohme, Lda.
José Cunha-Vaz AIBILI
José Morais INFARMED, I.P.
José Pereira Miguel Instituto Nacional de Saúde Dr. Ricardo Jorge
Karl Broich BfArM – Federal Institute for Drugs and Medical Devices
Katrin Kiisk Estonian State Agency of Medicines
Kees de Joncheere World Health Organization
Kim Stratton Novartis Pharma, AG
Klaus Cichutek Paul-Ehrlich-Institut
Laura Duarte INFARMED, I.P.
Laura Gribaldo ECVAM
Luís Filipe de Sampaio dos Reis Medirex Pharma
Luís Guerra Romero Instituto de Salud Carlos III
Luís Monteiro Rodrigues Universidade Lusófona
Luís Portela BIAL – Portela & C.ª, S.A.
Manuel Carrondo IBET
Manuel Gonçalves Glaxo Smith Kline
Manuel Pizarro Comissão Parlamentar de Saúde – Assembleia da República
Manuela Machado Amgen Biofarmacêutica, Lda.
Margarida Menezes Ferreira INFARMED, I.P.
Maria Alice Palma Romeiro Bristol-Myers Squibb Farmacêutica Portuguesa, S.A.
Maria Amélia Gil Palma Neto INFARMED, I.P.
Maria Antónia Moreno Areias de Almeida Santos Comissão Parlamentar de Saúde – Assembleia da República
Maria Armanda Miranda Autoridade para os Serviços de Sangue e da Transplantação
Maria Cecília Martinho AIBILI
Maria do Céu Costa INFARMED, I.P.
Maria Emília Monteiro Universidade Nova de Lisboa
Maria Inês Dias Direcção Geral de Veterinária
Maria Irene Silveira Ordem dos Farmacêuticos
Maria Irene Veiga Vicente Domingues Plataforma Saúde em Diálogo
Maria João Morais INFARMED, I.P.
Maria João Portela INFARMED, I.P.
Maria João Teixeira de Queiroz Eurotrials
Maria José Parreira dos Santos Hospital Garcia de Orta
Maria Manuela Arteaga AICEP
Maria Teresa Ferreira Herdeiro Universidade de Aveiro – Secção Autónoma de Ciências da Saúde
Mariana Isabel Vaz Afonso Pires Madureira INFARMED, I.P.
Mário Amorim INFARMED, I.P.
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EU2007.PT
Name Organisation
Marisa Papaluca Amati EMEA
Martina Cvelbar Slovenian Medicines Agency
Mary Geraldine Baker European Federation of Neurological Associations
Mercedes Rodriguez Neuropharma
Miguel Antunes INFARMED, I.P.
Miguel Gouveia Universidade Católica Portuguesa
Miguel Vigeant Gomes Janssen-Cilag Farmacêutica
Nuno Simões INFARMED, I.P.
Octavi Quintana Trias European Commission – DG Research
Ole J. Bjerrum Danish University of Pharmaceutical Science
Óscar Carvalho INFARMED, I.P.
Parvin Danesh INFARMED, I.P.
Paula Costa Bial – Portela e C.ª, S.A.
Paula Salmikangas National Agency for Medicines of Finland
Pedro Amores da Silva Escola Superior de Saúde Ribeiro Sanches
Pedro Barosa Ordem dos Farmacêuticos
Pedro Cruz ECBIO
Pedro Faleiro INFARMED, I.P.
Pedro Pissara Biotecnol
Peter Villax Hovione
Philippe Lechat Agence Française de Securité Sanitaire des Produits de Santé
Piedad Ferré Ministry of Health of Spain
Rafael Fernandez Amgen Biofarmacêutica, Lda.
Rannveig Gunnarsdottir Iceland Medicine Control Agency (IMCA)
Rita Kessler Association International de la Mutualité
Rogério Gaspar Faculdade de Farmácia da Universidade de Lisboa
Rui Amandi de Sousa 3B´S Research Group – Universidade do Minho
Rui Fernando Jesus Santos Laboratórios Delta, Lda.
Rui Fragoso INFARMED, I.P.
Shelagh Kerr PhRMA
Spiros Vamvakas EMEA
Susana Bule Eurotrials
Teotónio Frederico Figueiredo Carmo Albuquerque Bristol-Myers Squibb Farmacêutica Portuguesa, SA
Thomas Heynisch European Commission –DG Research
Thomas Lonngren EMEA
Tiago Fleming Outeiro Instituto de Medicina Molecular da Universidade de Lisboa
Tomas Alonderis Ministry of Health of Lithuania
Vaidas Skyrius State Medicines Control Agency of Lithuania
Vasco de Jesus Maria INFARMED, I.P.
Walter Osswald INFARMED, I.P.
55
INFARMED
Autoridade Nacional do Medicamento e Produtos de Saúde, I.P.
Parque de Saúde de Lisboa
Av. do Brasil 53
Lisboa
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“Pharmaceutical Innovation:

A New R&D Strategy in the EU”

19-20 November 2007

Report of the Conference

Portuguese EU Presidency 2007

II - Key issues arising from the Conference

III - Opening Session

IV - Opening Lecture: Current Status

V - Promoting Pharmaceutical Research,

Innovative Medicines Initiative

Regulatory Agencies and Innovation

The Role of Scientific Advice

Views from the Industry

EU Initiatives and Harmonization - EMEA – ICH

Alternative Methods and Innovation

Pharma R&D: Level of Development

The human and economic value of medical innovation

The Spanish Experience

Furthermore, she identified some of the Agencies responsibilities on this matter:

Biotecnol - Antibody therapies as innovative medicines and value

Bial’s experience was described, specifically focusing on R&D activities.

European R&D Funding for SME

Biomedical research at the University – Industry Interface

Biotech Funding, Neuropharma: A Case Study

SME and R&D Funding

AdI Support Measures to Entrepreneurial R&D – Innovation

What can the Commission do?

Public Health, Innovation and Sustainable Financing

Paying for Innovation or Paying for Health Care

Innovative Therapies will require innovative Financing

Affordable Innovation Meeting Public Health Needs

Who Will Pay for Innovation: patients perspective

Generic competition, healthcare sustainability

Key factors for optimising of R&D investment in Europe

Successful collaboration between industry partners and the critical

From academia to biotech: US and Portuguese examples

Partnership for Success – The Strategy of a Modern Agency

TI Pharma: Jointly Shaping the Future of Medicines

Partnerships for R&D and business development

Cell-based advanced therapies

New delivery systems: from controlled release to nanomedicine

XI - Conclusions of the Workshops

3. Emerging science for clinical development and regulatory approval

XII - Presentation on the initiative of the incoming

XIII - Closing Session

08:45 Opening Session

9:30 Opening Lecture

Chair: Vasco Maria, INFARMED

“Current Status of Pharmaceutical Innovation in the EU”

10:15 Coffee Break

Co-chairs: Alasdair Breckenridge, MHRA, United Kingdom

“Innovative Medicines Initiative”

“Regulatory Agencies and Innovation”

“The Role of Scientific Advice”

“Views from the Industry”

“EU Initiatives and Harmonization - EMEA – ICH”

“Alternative Methods and Innovation”

14:15 Workshop 1 – Innovation and Development: Constraints and Opportunities

Co-chairs: João Lavinha, INSA, Portugal