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Risk
ManagementPlan24. April 2008
Helge Gydesen
Epidemiology
Novo Nordisk A/S
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Slide no 218/01/2014
Agenda
Regulatory environment2
What is a Risk Management Plan3
Implications for post marketing activities5
Who, When and How4
Conclusions6
Motivation: Examples of withdrawals1
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Slide no 418/01/2014
Regulatory guidance
Three guidelines from FDA
The ICH E2E Guideline
EU risk management Guideline
All can be found on International Society forPharmacoEpidemiology (ISPE) homepagewww.pharmacoepi.org under the left hand headingresources
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Risk management-Definition and purpose
A Risk Management system is a set of pharmacovigilanceactivities and interventions designed to proactively identify,characterise and prevent or minimise risks relating tomedicinal products, including risk communication and theassessment of the effectiveness of risk minimisation
interventions. The purpose of the Risk Management Plan (RMP) is:
to identify the risks associated with a medicinal product
develop methods to clarify further the safety profile of aproduct
plan ways to minimise risk to individual patients in clinical use.
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Slide no 1418/01/2014
Risk Management Plan Development
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Risk management- The role of Epidemiology
Author and maintain the epidemiological sections of a Risk Management Plan(RMP) as per guidelines from regulatory authorities and NN SOP on ongoingbasis. Support the updating of RMP periodically. Provide epidemiologicalexpertise in Risk management activities throughout the life cycle of NNproducts.
Provide timely epidemiology support to project teams to design and
implement epidemiological studies, to review study proposal from internaland external sources, to analyze adverse events reporting data, and tointerpret and report on data analysis results to other line functions.
Contribute in safety risk evaluation once a safety signal has been detectedand in communication of safety information and thereby propose andimplement risk minimization activities.
Provide epidemiology support in preparation of Periodic/ Annual SafetyReports (PSUR/ASR) if required by the regualatory authorities.
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Slide no 1918/01/2014
When to start the work with the RMP?
Approval
Pharmacovig i lance
Product
Life Cycle
Exposure
(Potential Denominator)FIM Phase I Phase II
Phase IIIPhase IV
Drug Discovery/Preclinical Clinical Development Post Marketing
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Slide no 2018/01/2014
RMP: A change in approach
Proactive in stead of reactive
Not a defensive approach, in stead: demonstrate safety
Focus on different type of epidemiological studies instead of normal pharmacovigilance
Pharmaco epidemiology in stead of standardpharmacovigilance
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Slide no 2118/01/2014
Risk management Plans examples ofidentified risks: EXUBERA
Smoking-induced alterations in Pharmacokinetics (druginteraction studies/passive smoking)
Changes in Pulmonary Function (Long term PASS,Special Asthma study, Paediatric studies)
Increased Insulin Antibody Levels (Long term PASS,Paediatric studies)
Rare Pulmonary Events (Epi Lung Cancer study)
11 studies running until 2019, covering more than 75000patients
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Any questions or comments?
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