1. Check up on PV system Gregory Fiore, MD Confidential – for Internal use only

2. Goals and Approach Goals Quickly gain understanding of the overall safety system Develop early hypothesis on possible risk areas Prioritize areas for deeper dives Approach Establish governance for project Review Organization Review Safety System, including decision authority Review Performance, including metrics, etc. Review Safety Issues, for key products

3. Establish project governance Should 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 base Determine format for interaction Establish framework including what is and is not in scope

4. Approach - Organization Perform 360 with internal stakeholders (key external stakeholders if agreed) to determine value and effectiveness of current system Client to provide names, executives ensure access Develop structured survey Review backgrounds of key PV staff, including training records (if feasible) Goal to ensure any gaps are identified and addressed Review organizational structure and geography Review all governance processes overseeing safety Review documents describing roles/responsibilities as well as Job Descriptions Review SPS or DDPS Review written procedures Understand geographic footprint, including competencies such as “centers of excellence”

5. Approach – Safety System Review DDPS and all written procedures Review internal and external communication processes Process map Including all geographies Including all sources (internal, external, etc.) Including all “customers” of information Including all variations (case type, etc.) Including all partnership Catalog and understand all technical applications Ensure proper documentation, deep dive if requested

6. Approach – Performance Review system in place to monitor performance Individual Site By product, etc. Escalation process Quality Internal metrics Feedback from customers Audits/inspections

7. Approach – Safety Issues Review product safety issues Entire portfolio vs. targeted (size dependant?) Status (ongoing, closed, active, urgent) Response system

8. Next steps Synthesize Formulate high level recommendations Design implementation strategy, including change management approach if necessary Implement Measure degree of success Iterate

9. Components of PV System QPPV 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 Documentation Labeling process (IB updates, frequency and process, labels, CCDS, etc.)