Pharmacovigilance Practices Summary

Risk Management Plan (RMP) Overview

• The RMP documents the necessary risk management system to identify, characterize, and minimize a medicinal product's important risks.
• Identified risks: undesirable clinical outcomes with sufficient evidence linking them to a product.
• Potential risks: undesirable outcomes with suspicion of causation but insufficient evidence to confirm.
• Important identified risks can impact a product’s risk-benefit balance, requiring further evaluation.
• Important potential risks may become significant if further confirmed.
• Missing Information refers to gaps in knowledge about the safety profile due to insufficient data for specific usages or populations.

Principles of Risk Management

• A key objective is to ensure the benefits of a medicinal product far outweigh its risks.
• RMPs are dynamic and must be updated throughout the product's life cycle.
• Risk management systems should be proportional to identified and potential risks, as well as the need for post-authorization safety data.

Responsibilities for Risk Management

• Main parties involved: applicants/marketing authorization holders and competent authorities.
• Applicants are responsible for having an effective risk management system and reviewing safety knowledge critically.
• Significant reviews of safety concerns are advised at 5 years and during PSUR submissions around 8-9 years post-authorization.

RMP Structure and Content

• The RMP consists of seven parts, following a standardized template as per regulatory guidelines.

Part I: Product Overview

• Contains administrative details and a current product overview, including active substance information, indications, and monitoring requirements.

Part II: Safety Specification

• Describes the product's safety profile, focusing on important identified risks, potential risks, and any missing information.
• Identifies populations at risk and outstanding safety questions needing investigation.
• Comprises eight RMP modules aligning with ICH-E2E guidelines.

Part III: Pharmacovigilance Plan

• Outlines how to further understand and characterize safety concerns.
• Includes investigating potential risks, and strategies for information gathering, and measuring effectiveness of risk minimization measures.

Part IV: Post-Authorization Efficacy Studies

• Lists any efficacy studies required as conditions for marketing authorization or under specific obligations.
• If no studies are required, this section can be left blank.

Part V: Risk Minimization Measures

• Details measures to minimize risks related to safety concerns, which includes routine activities applicable to all products such as labeling and package details.

Part VI: Summary of the Risk Management Plan

• A publicly available summary that includes key RMP elements and is updated with significant RMP changes.
• Must be written in clear, plain language for diverse audiences.

Part VII: Annexes to the RMP

• Should include relevant annexes applicable to multiple medicinal products.

Relationship Between RMP and PSUR

• RMP and PSUR are complementary documents; the PSUR provides retrospective assessments while the RMP focuses on prospective risk management.

Quality Systems and Record Management

• Final responsibility for RMP integrity lies with the marketing authorization holder, who must ensure updates reflect new information and maintain records of changes.

EU Network Operations

• Full RMP submission is required for initial marketing authorizations, but content may vary proportionally based on identified risks.
• RMPs must be submitted electronically as part of the initial marketing authorization process or through post-authorization procedures.

Assessment of RMP in EU

• RMP oversight is conducted by the Pharmacovigilance Risk Assessment Committee (PRAC), which appoints rapporteurs for coordinated assessment with other relevant committees.