Faculdade de Farmácia da Universidade de Lisboa
Mestrado em Regulação e Avaliação do Medicamento e Produtos de Saúde
(University of Lisboa, Master in Evaluation and Regulation of Medicines and Health Products)
May 23 Seminar - Drug Risk Management in Regulatory Process & Risk Management Plans; workshop on real life case studies
Key note:
The recent regulatory environment leading to the benefit-risk management (BRM) process of a new medicine since the early phase of clinical
development till the registration and post commercialization must be considered by pharma, academia and regulators as an opportunity to partner with
health care professionals (HCP) and the society (consumers) to communicate in a complete balanced way the value of the drug and its best
management to minimize risk and optimize patient benefit. Al the stakeholders must be prepared to comply with the challenges of the new EU PV
legislation. Benefit-Risk assessment (BRA) and Risk-Management (RM) activities must be seen as dynamic and interconnected activities throughout
the life cycle of a drug. BRA and RM start with the approval of early clinical development trials to evaluate a new entity, especially with unknown
mechanism of action. In spite of all willingness to be transparent and make efficacy/safety documents public available, the rational behind BRA and
subsequent RM decisions is not easy to communicate neither readily understood by all HCP and consumers. Some advocate that both pharmaceutical
Industry (PI) and regulatory authorities (RA) should have a more quantitative approach to support the decisions, however, the more sophisticated
quantitative methods, assigning weights to benefits and risks to obtain a final score do not remove the unavoidable subjectivity neither add clarity or
transparency to the decisions. So, there are ongoing projects to ensure the accomplishment of the objectives of the legislation :

Ensure an effective benefit-risk communication to the different target audiences. The perception and acceptance of risk differ among age,
health status, culture and ultimately, every patient has to participate in the decision making on the personal BR balance. PI has to work with
regulators, payers and HCP on a framework to communicate the BRM in a non-paternalistic way to ensure that patients are adequately
informed to accept the risks that come with the benefit of a particular drug. For that purpose, is critical to keep public available updated,
interpreted and unbiased data. The biggest challenge is to overcome innumeracy of a large proportion of the population, finding representations
of numbers and probabilities that are intuitively comprehensible for them.

The exercise that determines if a drug benefit outweigh its risks is the basis of regulatory decisions to grant the initial market approval and in the
post-market review process as the new data gather from the real world drug exposure; the need to constantly evaluate the real-world benefit-
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Faculdade de Farmácia da Universidade de Lisboa
Mestrado em Regulação e Avaliação do Medicamento e Produtos de Saúde
(University of Lisboa, Master in Evaluation and Regulation of Medicines and Health Products)
balance of a drugs implies that risk management methodologies must capture real-world use of drugs, including use outside of the labelled
indication which requires processes adapted to a much more pro-active approach to risk management.

The development of core educational materials, PASS and PAES, such as registries and drug utilization studies and data capturing tools for
PhV data, must take into consideration the country specificities in the pattern of treatments, legal prescription control of medicines and
restrictions to the collection of health sensible data.

The implementation of measures to evaluate the effectiveness of RM activities and the corrective action plans following the evaluations,
without additional burden to the health institutions own control of prescription and dispense drugs to patients.

Whenever a new drug is approved with a Risk Management Plan (RMP) beyond the non-routine RM activities, is critical to develop feasible
RMP integrating measurable and meaningful outcomes to ensure the desired objectives of public health protection. At the European level,
the agency incorporate the perspectives of HCP and patients through multidisciplinary scientific committees composed by disease and
clinical pharmacology experts and consumers of medicines, who are currently involved in the development process of medicines at the
Scientific Advice Working Party (SAWP) and in the Pharmacovigilance Risk Assessment Committee (PRAC).

The PI must organize teams with enough medical and regulatory expertise and ensure an early involvement and communication with
regulators at the country level. This is critical not only to develop educational materials adapted to the socio-cultural environment, but also
to contribute to the communication with HCP and patients about the rational and the individual responsibility on monitoring the efficiency of
the RMP.
This first part of the seminar starts with an overview presentation about BRA till the implementation of RMP
in the post-market real-life. The second
part will engage the audience in the discussion about the perspective of the society on the future approach to BRA&RM based on a real life example to
illustrate to main challenges and areas under discussion to improve benefit&risk management, assessment and communication.
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Faculdade de Farmácia da Universidade de Lisboa
Mestrado em Regulação e Avaliação do Medicamento e Produtos de Saúde
(University of Lisboa, Master in Evaluation and Regulation of Medicines and Health Products)
Agenda
09:00
Isabel Boaventura: Opening and welcome
Dave Gillen : Opening conference
09:15
From benefit-risk evaluation to benefit- risk management
during the life cycle of a medicine
10:15
Coffee-break
Maria Duarte: EU Risk Management Plan: Objective,
Structure and template. Risk minimization measures
10:45
Isabel Boaventura: Challenges to implement and conduct a
RMP at the country level
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12:00
Lunch
13:30
Risk Management Plans – workshop on real life case
studies
Presentation of the case study (disease background,
known risks, potential risks)
14:00
Group breakdown
15:30
Group presentation
16:00
The real case study – current status
16:30
End of sessions
Objective and structure of the seminar
Historical perspective on how and why the regulatory
science, tools, realities, and perceptions of medicines
benefit-risk have evolved, future trends, differences
across the regions, roles of different partners, the
meaning of transparency, examples of the BR
evaluation in early CT and at the registration phase.
Outline of the current European regulatory framework.
Interaction between sponsor and regulators before and
after EMA approval of a medicine; interactions with
national competent authorities and HCP. Practical
approaches to protecting patient safety (centralized vs
local responsibilities).
Engage students in dialogue on current opportunities
and challenges in managing product risk in the context
of benefit, considering the target population of the
medicine, medical needs and the characteristics of the
health care delivery system. A real case will be
presented to allow the students to propose a RMP, risk
minimization measures and the respective
effectiveness measurement tools. The seminar will
conclude with a presentation of the final European
regulatory decision and current impact and status at
international and national level.
Faculdade de Farmácia da Universidade de Lisboa
Mestrado em Regulação e Avaliação do Medicamento e Produtos de Saúde
(University of Lisboa, Master in Evaluation and Regulation of Medicines and Health Products)
At the conclusion of this seminar the participants should be able to:


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
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Describe the differences between important identified risks and important potential risks
Understand the rational for the current risk management environment and regulatory framework
Understand the contribution of each stakeholder in the BR& management evaluation
Understand the impact of health literacy on risk communication and the effectiveness of risk minimization tools
Understand the impact of RMP and effectiveness tools in the Health Care System
Describe the different tools to risk minimization and the importance of real world data to assess the BR during the medicines life cycle.
Faculdade de Farmácia da Universidade de Lisboa
Mestrado em Regulação e Avaliação do Medicamento e Produtos de Saúde
(University of Lisboa, Master in Evaluation and Regulation of Medicines and Health Products)
Speakers Affiliations and CV
David Gillen (BSc MD FFPM)
David is the Head of Drug Safety and Risk Management for EMEA / APAC for Celgene Ltd. In addition David acts as the Deputy QPPV for Celgene’s
Pharmacovigilance System. David has been at Celgene since January 2012. Prior to this role he held the role of Head of International Medical Affairs
for Gilead Sciences. In this role he managed and led a group of Medical Directors across Europe and Asia – Pacific.
David qualified in Medicine from St Mary’s hospital in 1992. During his undergraduate medical training he completed a BSc in Physiology and Clinical
Pharmacology. He retained this interest in Pharmaceutical Medicine during his postgraduate training in Medicine and Cardiology and joined Pfizer
Global Research and Development in Sandwich in 1998. At Pfizer, David worked in Clinical Development and in Medical Affairs in the UK and also
spent time working at a global level in New York for 4 years. He rejoined Pfizer UK in April 2007 as UK Medical Director having spent 2 years at Wyeth
UK as Medical Director from 2005. Prior to leaving Pfizer David was Vice President for Medical Affairs in Pfizer’s Primary Care Business Unit covering
Europe, Canada, Australia and New Zealand where he established a Regional medical affairs group covering Pfizer’s primary care portfolio of
medicines.
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Faculdade de Farmácia da Universidade de Lisboa
Mestrado em Regulação e Avaliação do Medicamento e Produtos de Saúde
(University of Lisboa, Master in Evaluation and Regulation of Medicines and Health Products)
David has been active in the UK Clinical Research community for many years. He represented the Industry on the Academy of Medical Sciences
Rawlin’s review looking into UK Clinical Research competitiveness and improving its Governance. Beyond Clinical research, David has served on the
Innovation sub- committee of the ABPI (Initiating the ABPI Real – World data project), worked at NICE and the UKCRC and was a member of the RCP
working party looking at the relationship between Industry, Academic Medicine and the NHS. He is now a member of EFPIA’s Pharmacovigilance
Committee.
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Faculdade de Farmácia da Universidade de Lisboa
Mestrado em Regulação e Avaliação do Medicamento e Produtos de Saúde
(University of Lisboa, Master in Evaluation and Regulation of Medicines and Health Products)
Isabel Boaventura, MD
Summary
A specialist in Internal Medicine by training, has 20 years of experience in the pharmaceutical industry.
After 12 years of practice in the University Hospital of Lisboa, she started her career in the pharmaceutical industry as scientific advisor in Bayer Portugal,
moving one year later to Merck Sharp Dohme, where she developed the units of pharmacovigilance, medical information and clinical operations. Later on, as
medical director, she supervised medical, regulatory affairs, reimbursement& access and clinical operations. Medical Director at Celgene since 2007.
Experience
Medical Director at Celgene Portugal (2007 – Present)
Associate Medical Director, Arthritis and Respiratory Dep.Merck, USA, NJ (2000).
Medical Director at Merck Sharp Dohme, Portugal (2002 – 2007).
Education
University of Lisboa, Faculdade de Medicina de Lisboa (1981-1991).
Royal Post Graduate Medical School Hammersmith Hospital, London (1988)
Competency in Pharmaceutical Medicine (1997).
Post-Graduate Course in Informed Consent, Faculdade de Direito de Coimbra, Centro de Direito Biomédico (2006).
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Faculdade de Farmácia da Universidade de Lisboa
Mestrado em Regulação e Avaliação do Medicamento e Produtos de Saúde
(University of Lisboa, Master in Evaluation and Regulation of Medicines and Health Products)
Research activity
Hypertension (Sodium Balance and 24 h- ABPM) sponsored by a grant of INIC/Centro de Cardiologia da Universidade de Lisboa (1989-90).
Publications and oral communications
Nine papers and abstracts related to her practice and research activity (1984-94).
Regular communications at scientific and post-graduate courses related to drug research and development, GCP and risk management (2005-Present).
Co-author in 3 publications related to risk-management and cost-sharing (2010).
Academic activity
Lecturer in Clinical Pharmacology and Therapeutics, Faculdade de Medicina de Lisboa (2007-Present)
Guest Lecturer of Faculdade de Farmácia de Lisboa (2008-Present), Universidade de Aveiro (Training Programme in Pharmaceutical Medicine, 2010-Present)
and Faculdade de Ciências Médicas (2013-present).
Affiliations to scientific and professional associations
Soc. Portuguesa de Medicina Interna, Soc. Portuguesa de Cardiologia, Soc. Portuguesa de Hipertensão. Assoc. Portuguesa de Farmacologia Clínica.
Assoc. Portuguesa de Médicos da Indústria Farmacêutica
Member of the Medical Association Board for the Competency in Pharmaceutical Medicine (2009-Present).
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Faculdade de Farmácia da Universidade de Lisboa
Mestrado em Regulação e Avaliação do Medicamento e Produtos de Saúde
(University of Lisboa, Master in Evaluation and Regulation of Medicines and Health Products)
Maria Duarte, Pharma D
Drug Safety & Risk Management at Celgene
Summary
A pharmacist by training Dr. Maria Duarte has a Master in Regulation and Evaluation of Medicines and Health Products by the University of Lisbon.
While attending the master course she has developed a research on spontaneous reporting and risk management plans in community pharmacies, in
collaboration with the South Pharmacovigilance Center.
Since 2014, she has become responsible for management of the case processing and local RMP plans at Celgene Portugal.
Experience
Drug Safety & Risk Management at Celgene Portugal (2014 – Present)
Pharmacovigilance Technician at Unidade de Farmacovigilância do Sul (2013-2014)
Community Pharmacist at Farmácia Parque das Nações (2010-2013)
Education
University of Lisbon, Faculty of Pharmacy (2011-2014) – Master in Regulation and Evaluation of Medicines and Health Products
University of Lisbon, Faculty of Medicine and UFLVT (2013) – Intensive Pharmacovigilance Course
University of Lisbon, Faculty of Pharmacy (2005-2010) - Master in Pharmaceutical Sciences
Interests
Pharmacovigilance, risk management, public health, pharmaco-epidemiology
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