This document provides an overview and approach to reviewing PV Systems. The goals are to quickly understand the overall safety system, develop hypotheses on risk areas, and prioritize deeper reviews. The approach establishes governance, reviews the organization, safety system including decision authority, performance metrics, and key safety issues. It recommends establishing a project team including safety, medical, R&D, and legal stakeholders. The review would include surveys, staff backgrounds, organizational structure, governance processes, roles and responsibilities, safety procedures, geographic footprint, communication processes, applications, performance monitoring, and addressing product safety issues. The next steps are to synthesize findings, recommend improvements, and implement and measure success over time through iteration.

1. Check up on PV systemGregory Fiore, MDConfidential – forInternal use only

2. Goals and ApproachGoalsQuickly gain understanding of the overall safety systemDevelop early hypothesis on possible risk areas Prioritize areas for deeper divesApproachEstablish governance for projectReview OrganizationReview Safety System, including decision authorityReview Performance, including metrics, etc.Review Safety Issues, for key products

3. Establish project governanceShould be L+2 for safety head (if possible)Should include key stakeholders (CMO, Medical Affairs, R&D, ?Legal, Compliance, Regulatory Affairs)Determine frequency of touching baseDetermine format for interactionEstablish framework including what is and is not in scope

4. Approach - OrganizationPerform 360 with internal stakeholders (key external stakeholders if agreed) to determine value and effectiveness of current systemClient to provide names, executives ensure accessDevelop structured surveyReview backgrounds of key PV staff, including training records (if feasible)Goal to ensure any gaps are identified and addressedReview organizational structure and geographyReview all governance processes overseeing safetyReview documents describing roles/responsibilities as well as Job DescriptionsReview SPS or DDPSReview written proceduresUnderstand geographic footprint, including competencies such as “centers of excellence”

5. Approach – Safety SystemReview DDPS and all written proceduresReview internal and external communication processesProcess mapIncluding all geographies Including all sources (internal, external, etc.)Including all “customers” of informationIncluding all variations (case type, etc.)Including all partnershipCatalog and understand all technical applicationsEnsure proper documentation, deep dive if requested

6. Approach – PerformanceReview system in place to monitor performanceIndividualSiteBy product, etc.Escalation processQualityInternal metricsFeedback from customersAudits/inspections

7. Approach – Safety IssuesReview product safety issuesEntire portfolio vs. targeted (size dependant?)Status (ongoing, closed, active, urgent)Response system

8. Next stepsSynthesizeFormulate high level recommendationsDesign implementation strategy, including change management approach if necessaryImplementMeasure degree of successIterate

9. Components of PV SystemQPPV and the back-up procedure to apply in their absence.Organization of the pharmacovigilance system describing the names, location and internal connections of the departments involved in pharmacovigilance activities within the company. A charter of the organizational structure should also illustrate the cooperation with external partners.Databases, listing of the data bases used for pharmacovigilance services, registration with the Eudravigilance system and description of processes used for (electronic) reporting.Contractual arrangements with other persons or organizations involved in the fulfillment of pharmacovigilance obligations.Training, recording regular education and further training of the staff involved in pharmacovigilance activities.Documentation, description of the locations of the different types of pharmacovigilance source documents, including archiving arrangements/retention process.Quality Management System.Supporting DocumentationLabeling process (IB updates, frequency and process, labels, CCDS, etc.)