Example: biology

Pharmacovigilance and Risk Management - Elsevier

CHAPTER13 Pharmacovigilance andRisk ManagementSuzanne Gagnon*, Peter Schueler**, James (Dachao) Fany*ICON Clinical Research, North Wales, Pennsylvania, USA**ICON Clinical Research, Langen, Hessen, GermanyyICON Clinical Research Pte Ltd/Asia Pacific, SingaporeCHAPTER OUTLINED efinition of Pharmacovigilance and RiskManagement 142 The Importance of Implementing aSystematic Pharmacovigilance Approachin Global Clinical Trials 142 Operational Overview ofPharmacovigilance 143 Components and Capabilities of aComplete PharmacovigilanceSystem 144 Pharmacovigilance Policies, Regulations,and Guidance Documents 145 Adverse Event Reporting 145 Standard Operating Procedures, Study-Specific Procedures, and SafetyPlans 147 Quality Management System 147 Organizational Structure of aPharmacovigilance Department 148 Departmental Organization 148 Collaboration and Teamwork on GlobalClinical Trials 148 Role of The Medical Monitor 149 Roles and Responsibilities of thePharmacovigilance Team 150 Head of Pharmacovigilance 150 Drug Safety Physician/Directors of DrugSafety 150 Qualified Person for Pharmacovigilance inEurope 150 Pharmacovigilance /Drug Safety

trial performed to evaluate a new oncology compound. The product was dosed cyclically, administered intravenously every 21 days. Review of aggregate data from the initial eight patients suggested that the product caused a transient hepatitis, particularly apparent after the first dose, as shown by the spiking ALT levels.

Tags:

  Management, Risks, Pharmacovigilance, Initial, Oncology, Pharmacovigilance and risk management

Information

Domain:

Source:

Link to this page:

Please notify us if you found a problem with this document:

Other abuse

Transcription of Pharmacovigilance and Risk Management - Elsevier

1 CHAPTER13 Pharmacovigilance andRisk ManagementSuzanne Gagnon*, Peter Schueler**, James (Dachao) Fany*ICON Clinical Research, North Wales, Pennsylvania, USA**ICON Clinical Research, Langen, Hessen, GermanyyICON Clinical Research Pte Ltd/Asia Pacific, SingaporeCHAPTER OUTLINED efinition of Pharmacovigilance and RiskManagement 142 The Importance of Implementing aSystematic Pharmacovigilance Approachin Global Clinical Trials 142 Operational Overview ofPharmacovigilance 143 Components and Capabilities of aComplete PharmacovigilanceSystem 144 Pharmacovigilance Policies, Regulations,and Guidance Documents 145 Adverse Event Reporting 145 Standard Operating Procedures, Study-Specific Procedures, and SafetyPlans 147 Quality Management System 147 Organizational Structure of aPharmacovigilance Department 148 Departmental Organization 148 Collaboration and Teamwork on GlobalClinical Trials 148 Role of The Medical Monitor 149 Roles and Responsibilities of thePharmacovigilance Team 150 Head of Pharmacovigilance 150 Drug Safety Physician/Directors of DrugSafety 150 Qualified Person for Pharmacovigilance inEurope 150 Pharmacovigilance /Drug Safety ProductManager 151 Drug Safety Associate 151 Medical Assistant 151 Safety Systems Specialists 151 Pharmacovigilance Trainer 152 Appropriate Facilities forPharmacovigilance 152 Safety Databases 152 Safety Case Processing andReview 152 Steps in Serious Adverse Event CaseProcessing 153 Global Safety

2 Reporting 153 Safety Data Review andAssessment 154 Individual Subject Data 154 Subject Profiles 154 Review of Aggregate Data 155 Signal Detection and Analysis 155 Managing Risk 157 Risk Management Plans and RiskEvaluation and MitigationStrategies 157 Outsourcing While BuildingPharmacovigilance Capacity 158 General Considerations andConclusions 158 References 159141 Global Clinical Trials Playbook. 2012 Elsevier Inc. All rights OF Pharmacovigilance AND RISK MANAGEMENTThe World Health Organization (WHO) defines Pharmacovigilance as the science and activ-ities relating to the detection, evaluation, understanding, and prevention of adverse reactionsto medicines or any other medicine-related problems. The definition and scope of pharma-covigilance have evolved to recognize the importance of a systems approach for monitoringand improving the safe use of simpler definition describes Pharmacovigilance as the processes and science of monitoringthe safety of medicines and taking action to reduce risk and increase ,the assessment of benefit versus risk must begin during the preclinical evaluation of a medic-inal product and must extend throughout its full life a result, there is now added focus on safety and risk assessment after a product has receivedregulatory approval.

3 When it is placed on the market and prescribed to large there is no international standard that dictates the components of an adequatepharmacovigilance system or the processes to be engaged in risk Management , there isconsensus among the major regulators that Pharmacovigilance is necessary and important inthe development and commercialization of medicinal it is essential in building capacity for clinical trials to understand the components,the functions, and the processes required for full and effective Pharmacovigilance and IMPORTANCE OF IMPLEMENTING A SYSTEMATICPHARMACOVIGILANCE APPROACH IN GLOBAL CLINICAL TRIALSThe amount and variety of safety-relevant data gathered from different patient populations inglobal clinical trials are enormous; therefore it is crucial that a concise and systematic approachto Pharmacovigilance be implemented.

4 Systematic safety monitoring is needed to identifypreviously recognized and unrecognized adverse drug reactions and to evaluate the safety andefficacy of medicinal products during clinical trials and in the postmarketing is important that Pharmacovigilance not be perceived as a burden put upon the pharma-ceutical product development industry by the regulating bodies. Ongoing pharmacovigilanceshould be understood as essential to the only appropriate way to develop safe medicines,introduce them into the market, and have them survive in the market once approved. Not onlydoes the failure to perform ongoing safety assessment activities increase the chances of placingsubjects at risk unnecessarily, it also increases a company s risk of investing in the developmentof the wrong following example illustrates the value of ongoing systematic aggregate alanine aminotransferase (ALT) data reported during a clinicaltrial performed to evaluate a new oncology compound.

5 The product was dosed cyclically,administered intravenously every 21 days. Review of aggregate data from the initial eightpatients suggested that the product caused a transient hepatitis, particularly apparent after thefirst dose, as shown by the spiking ALT levels. It was thus advisable to re-evaluate the initialdosing and the dosing intervals, and closely monitor liver function in all patients to avoidunacceptable toxicity and to better assess the benefit/risk value and the appropriate populationfor the drug. Because the review was part of ongoing Pharmacovigilance during the clinicaltrial, the safety issue was identified and addressed early in clinical development. Such labo-ratory trend analysis yields maximum benefit when part of a systematic approach to building for Pharmacovigilance and medicine safety should address all processes fordeveloping individual and system capacity and enable achievement of sustainable ability to142 SECTION 4 How to Build and Enhance Pharmacovigilance and Risk Management Capacity and Capabilitymanage effectively the safety of patients and health systematic phar-macovigilance requires a full understanding of the scope of Pharmacovigilance , whichincludes both active safety reporting and postmarketing surveillance.

6 It involves the ongoingprocesses of risk identification, risk assessment, and risk mitigation. All of these processes areequally important to the pharmaceutical company, the regulatory authorities, the investigator,and the are many ways of building Pharmacovigilance capability, and many differences in howpharmacovigilance systems are created. Historically, companies created pharmacovigilancefunctionality as the need arose to assess their products under development. Since there arevariations in the required sample size of studies, geographical site distribution, adjuvant orcomparator products used, and in the definition of standard treatment in different countries,differences naturally evolved. Global Pharmacovigilance is an ongoing process of harmoni-zation. Currently, there are many national, cultural, and regulatory differences among coun-tries in how Pharmacovigilance is implemented.

7 The goal is always the accurate assessment ofthe benefit versus the risk of a product in the populations who receive it, and mature phar-macovigilance systems are able reach accurate conclusions despite different types of OVERVIEW OF PHARMACOVIGILANCEAn operational overview of Pharmacovigilance begins with safety information coming froma variety of sources, including clinical trials data, safety call centers, spontaneous reports, andliterature searches, each of which has the potential to create an individual case. Within thepharmacovigilance department each case is processed, assessed as to its relationship(causality) to the investigational product, and reported to the regulatory authorities and otherstakeholders, either as an expedited report or as part of an aggregate report, based uponpharmacovigilance policies, regulations, and guidance documents.

8 In addition, each casebecomes part of the total safety dataset for that medicinal data are systematically analyzed for safety issues and assessed for benefit versus risk,and periodic safety update reports (PSURs) are submitted to the regulatory authorities asadditional safety information is collected. This continues throughout the product s life findings are addressed in order to mitigate risk. This may include modification toa clinical trial design, changes in proposed labeling, implementation of a risk mitigation plan,FIGURE surveillance and trend analysis of liver function tests showing potentially liver-toxic effects in a cyclic : IMRAeICON Medical Review Application.(Please refer to color plate section)CHAPTER 13 Pharmacovigilance and Risk Management143or discontinuation of development or use of a marketed product.

9 A flow diagram summarizingthe major activities associated with Pharmacovigilance is shown inFigure AND CAPABILITIES OF A COMPLETEPHARMACOVIGILANCE SYSTEMB ased upon the intent and scope of Pharmacovigilance , there are certain components andcapabilities that are essential to a fully functioning Pharmacovigilance system, regardless ofhow a company s safety department is constructed (Figure ). These include:la qualified person for Pharmacovigilance (QPPV) (Europe)lsafety systems (database) case processing and reviewlmedical writing and aggregate reportingla sound quality Management system including standard operating procedures (SOPs),quality standards, metrics, and traininglsignal detection and risk analysislglobal safety reportingFIGURE of the major activities associated with Pharmacovigilance .

10 SAE: serious adverse event; QC: quality control.(Please refer to color plate section)FIGURE and capabilities of a fully functional Pharmacovigilance system. QPPV: qualified person for Pharmacovigilance ;EU: European Union; SOP: standard operating 4 How to Build and Enhance Pharmacovigilance and Risk Management Capacity and Capability144In some companies some activities may be performed by different departments, for example,safety regulatory reporting may be part of regulatory affairs, or aggregate report writing may bedone within a company s medical writing department. Some activities may be outsourced tocontract research organizations (CROs) or safety niche providers, while others are kept in-house, but all must be covered for complete Pharmacovigilance POLICIES, REGULATIONS, AND GUIDANCEDOCUMENTSIn the major regions of the world where medicinal products are developed, pharmacovigi-lance is highly regulated.


Related search queries