Glossary

1. Objectives of Pharmacovigilance

• Detect & Assess Adverse Drug Reactions (ADRs) – Identifies unexpected/expected or serious/non-serious and severe/moderate/mild side effects/adverse events/adverse drug reactions.
• Ensure Drug Safety & Benefit-Risk Balance – Evaluates if a drug remains safe for public use. The process attempts to balance the benefits and risks.
• Prevent Medication Errors & Public Health Risks – Reduces harm caused by improper use.
• Regulatory Compliance & Risk Management – Aligns with Good Pharmacovigilance Practices (GVP) and regulatory reporting obligations.

2. Key Components of Pharmacovigilance

Adverse Drug Reaction (ADR) Monitoring

• Collection of spontaneous reports from healthcare professionals, patients, and literature.
• Collection of safety reports from studies
• Classifies ADRs as serious, non-serious, expected, or unexpected.

Individual Case Safety Reports (ICSRs)

• Reports of specific patient cases experiencing ADRs. Reporting of one or several suspected adverse reactions to a medicinal product that occur in a single patient at a specific point of time.
• Submitted through EudraVigilance (EU) to EMA via gateway or web-based EVWEB tool, and to FAERS (U.S.).

Periodic Safety Update Reports (PSURs) 

• PSURs are pharmacovigilance documents intended to provide an evaluation of the risk-benefit balance of a medicinal product at defined time points after its authorisation.

• The objective of the PSUR is to present a comprehensive and critical analysis of the risk-benefit balance of the product, taking into account new or emerging safety information in the context of cumulative information on risk and benefits

• EMA and national competent authorities assess information in PSURs to determine if there are new risks identified for a medicine and/or if its risk-benefit balance has changed.

• Marketing authorisation holders (MAHs) are legally required to submit PSURs, in line with current legislation.

• According to the EURD list of the EMA, there are exceptions with regard to the PSUR submission. For example, generic marketing authorisations are often excluded from PSUR submission

Risk Management Plan (RMP)

• Strategic plan outlining risk minimization measures for new drugs, and is also to be renewed for these drugs.
• Includes monitoring protocols and risk communication strategies.

Signal Detection & Benefit-Risk Assessment

• Uses data analysis tools to identify potential safety concerns.

(A ‘signal’ in the context of signal detection refers to information that indicates a possible link between a medicinal product and an adverse event or reaction. However, this has not yet been conclusively proven or fully confirmed. It is therefore a suspicion or an assumption that the medicinal product could cause a certain reaction that is either new or unexpected.)

• Supports regulatory decision-making on drug restrictions or withdrawals.

3. Regulatory Framework for Pharmacovigilance
 

·  European Union (EU)

• Regulatory Authority: EMA – Pharmacovigilance Risk Assessment Committee (PRAC)
• Key Regulations:
  • Regulation (EU) No 1235/2010: This regulation outlines the responsibilities and requirements for pharmacovigilance, including the monitoring of the safety of medicinal products and the actions required in case of adverse drug reactions.
  • GVP Guidelines: Good Pharmacovigilance Practices (GVP) guidelines provide a framework for monitoring the safety of medicines on the market and ensure high standards for drug safety in the EU.

·  United States (U.S.)

• Regulatory Authority: FDA – Center for Drug Evaluation & Research (CDER)
• Key Regulations:
  • 21 CFR Part 312: Governs investigational new drug applications (IND), specifying the guidelines for clinical trials of new medications.
  • 21 CFR Part 314: Outlines the requirements for new drug applications (NDA), detailing how companies must submit applications and evidence to obtain approval for a new drug.
  • 21 CFR Part 600: Contains regulations specific to biological products, including standards for licensure, manufacturing, and post-marketing safety.

·  United Kingdom (UK)

• Regulatory Authority: MHRA – Medicines and Healthcare Products Regulatory Agency
• Key Regulations:
  • Human Medicines Regulations 2012: Comprehensive regulations that cover all aspects of the authorization, sale, and supply of medicines, integrating European directives and national legislation into a single framework.

·  World Health Organization (WHO)

• Regulatory Authority: Uppsala Monitoring Centre (UMC)
• Key Regulations:
  • WHO Programme for International Drug Monitoring: A global network that collects and analyzes data on adverse drug reactions, aiming to improve patient safety and foster worldwide pharmacovigilance.

4. Pharmacovigilance Reporting Systems

EudraVigilance (EU) 

• Gateway/ EVWEB:
  • electronic exchange of individual case safety reports (ICSRs) between EMA, national competent authorities (NCAs), marketing authorisation holders (MAHs) and sponsors of clinical trials in the EEA;
  • early detection and evaluation of possible safety signals;
• XEVMP:
  • (The database is designed to support the collection, reporting, coding and evaluation of data on medicines in a standardised and structured way.
• EVCT:
  • Electronic exchange of events occurring during clinical trials
      FAERS (U.S.) – FDA’s Adverse Event Reporting System.
      VigiBase (WHO) – WHO’s global pharmacovigilance database.
      Yellow Card Scheme (UK) – MHRA’s system for reporting suspected ADRs.
     

5. Pharmacovigilance in Clinical Trials vs. Post-Marketing

Clinical Trials (Pre-Marketing)

• Purpose of PV Activities:

  • Identify early safety signals & assess drug tolerability: This stage focuses on detecting any potential adverse effects of the drug early in its development, which helps in evaluating its safety for human use.
     

• Regulatory Reporting:

  • Development Safety Update Reports (DSURs): These reports are required annually and summarize all relevant safety information collected during the clinical trial period, helping regulatory bodies monitor the drug’s safety profile as it progresses through trials.

  • Expedited reporting: This involves the immediate reporting of serious and unexpected adverse reactions to ensure that regulatory authorities are aware of any potential safety issues that could impact patient health.

Post-Marketing Surveillance

• Purpose of PV Activities:

  • Monitor real-world safety & effectiveness: After a drug is marketed, ongoing surveillance is conducted to continue monitoring its safety and effectiveness in the general population. This helps in identifying any issues that may not have been apparent during the controlled clinical trial environments.

• Regulatory Reporting:

  • Periodic Safety Update Reports (PSURs): These reports are compiled at specified intervals and provide an overview of the global safety information for the drug, as gathered from various sources, including clinical studies and spontaneous reports.

  • Individual Case Safety Reports (ICSRs): These involve the collection and reporting of individual cases of adverse reactions, which are critical for ongoing safety monitoring.

  • Risk Management Plans (RMPs): These plans are designed to detail the strategies for identifying, characterizing, preventing, or minimizing risks associated with the drug.

6. Risk Management & Safety Signal Detection

Risk Mitigation Strategies:

• Black box warnings
• Restricted distribution programs
• Prescriber & patient education
• Educational materials
• Direct healthcare professional communications (DHPC)

Signal Detection Techniques:

• Data mining & AI algorithms
• Medical literature analysis
• Spontaneous ADR reports
   

7. Careers in Pharmacovigilance

• Pharmacovigilance Officer (PV Associate) – Handles ADR case processing & ICSRs.
• Drug Safety Specialist – Analyzes clinical trial safety data.
• PV Risk Manager – Develops Risk Management Plans (RMPs).
• Regulatory PV Scientist – Ensures compliance with FDA, EMA, and WHO standards
• QPPV Qualified person for pharmacovigilance
   

8. Common Challenges in Pharmacovigilance & How to Overcome Them

• Underreporting of ADRs – Improve patient & healthcare professional education.
• Data Overload from Global Reporting Systems – Implement AI-driven signal detection.
• Regulatory Variations Across Countries – Develop harmonized reporting strategies.

Why Pharmacovigilance is Critical to Drug Safety

• Prevents Serious Drug-Related Adverse Events.
• Ensures Compliance with Global Regulatory Authorities.
• Improves Patient Safety & Public Health Outcomes.