GVP Module VI: An Overview

Pharmacovigilance is a foundation of patient safety, ensuring that medicinal products on the market maintain a positive benefit–risk balance throughout their lifecycle. Within the European Union (EU), pharmacovigilance activities are governed by Good Pharmacovigilance Practices (GVP), a comprehensive framework developed by the European Medicines Agency (EMA). Among all GVP modules, GVP Module VI is particularly important because it defines how suspected adverse reactions are collected, managed, and reported.

GVP Module VI focuses on the management and reporting of Individual Case Safety Reports (ICSRs). These reports form the backbone of signal detection, risk evaluation, and regulatory decision-making. A robust understanding of Module VI is therefore essential for Marketing Authorisation Holders (MAHs), sponsors, pharmacovigilance professionals, and regulatory affairs teams.

This article provides a detailed overview of GVP Module VI, its scope, key requirements, timelines, and its role in maintaining regulatory compliance and patient safety.

Understanding the Purpose of GVP Module VI

The primary objective of GVP Module VI is to ensure that all suspected adverse reactions related to medicinal products authorised in the EU are promptly collected, evaluated, and reported to the relevant authorities. These reports allow regulators to identify new safety signals, monitor known risks, and take appropriate regulatory actions when required.

Module VI applies to:

• Medicinal products authorised in the EU
• Suspected adverse reactions occurring both within and outside the EU
• Reports originating from healthcare professionals, patients, literature, non-interventional studies, and other sources

The module establishes harmonised standards to ensure data quality, consistency, and timeliness across the EU pharmacovigilance system.

What Is an Individual Case Safety Report (ICSR)?

An Individual Case Safety Report is a structured record of information describing a suspected adverse reaction experienced by a patient following the use of a medicinal product. For a report to qualify as a valid ICSR under GVP Module VI, four minimum criteria must be met:

• An identifiable patient
• An identifiable reporter
• At least one suspected adverse reaction
• At least one suspected medicinal product

If any of these elements are missing, the report is considered invalid and should not be submitted to EudraVigilance, although follow-up efforts must continue to obtain missing information.

Scope of Adverse Reactions Covered Under Module VI

GVP Module VI covers a broad range of safety information, ensuring comprehensive monitoring of medicinal products. This includes:

• Serious and non-serious adverse reactions
• Expected and unexpected adverse reactions
• Adverse reactions related to off-label use, medication errors, misuse, abuse, and occupational exposure
• Adverse reactions occurring due to product quality defects
• Reactions related to drug interactions, overdose, or lack of efficacy (where relevant for safety evaluation)

This wide scope reflects the EU’s proactive approach to capturing all safety-relevant data that may affect a product's benefit–risk profile.

Sources of ICSRs

Module VI recognises multiple sources from which ICSRs may originate. MAHs are required to have systems in place to capture safety data from all relevant channels, including:

• Spontaneous reports from healthcare professionals
• Direct reports from patients or caregivers
• Scientific and medical literature
• Reports from non-interventional studies and post-authorisation safety studies
• Digital media, including company-controlled websites and social media platforms
• Regulatory authorities and licensing partners

MAHs must continuously monitor these sources and ensure that safety information is processed without delay.

Reporting Timelines Under GVP Module VI

One of the most critical aspects of Module VI is its strict reporting timelines, which are designed to enable rapid regulatory assessment.

Serious Adverse Reactions

• Must be reported within 15 calendar days of initial receipt
• Applies to serious cases occurring both inside and outside the EU

Non-Serious Adverse Reactions

• Must be reported within 90 calendar days
• Applies only to cases occurring within the EU

The clock starts as soon as any MAH personnel becomes aware of the minimum information required for a valid ICSR. This underscores the importance of pharmacovigilance training across all company functions, including sales, marketing, and medical affairs.

Reporting to EudraVigilance

All ICSRs covered under GVP Module VI must be submitted electronically to EudraVigilance, the EU’s central database for managing suspected adverse reaction reports.

Key requirements include:

• Use of the ICH E2B(R3) format for electronic transmission
• Compliance with EMA-defined data standards and terminologies, such as MedDRA for adverse reaction coding
• Regular monitoring of EudraVigilance acknowledgements and error messages
• Timely correction and resubmission of rejected or invalid cases

Accurate and complete data entry is essential, as poor-quality reports can compromise signal detection and regulatory decision-making.

Follow-Up and Case Management Responsibilities

GVP Module VI emphasises follow-up activities. MAHs are expected to actively seek additional information to improve the completeness and medical value of ICSRs, particularly for serious or clinically significant cases.

Follow-up efforts may include:

• Requesting missing demographic or clinical data
• Obtaining outcomes, laboratory results, or medical history
• Clarifying product exposure details such as dose, duration, and indication

Each follow-up report must be submitted to EudraVigilance within the same timelines as initial reports, calculated from the date the new information is received.

Quality Management and Documentation

To ensure compliance with GVP Module VI, MAHs must maintain a robust pharmacovigilance system supported by clear documentation and quality controls. This includes:

• Standard Operating Procedures (SOPs) for case intake, processing, and reporting
• Training records demonstrating staff awareness of adverse event reporting obligations
• Quality checks to ensure accuracy, completeness, and consistency of ICSRs
• Audit trails documenting case versioning, follow-ups, and submissions

Module VI is closely linked to GVP Module I (Pharmacovigilance Systems and Quality Systems), underscoring the need for an integrated, well-governed PV framework.

Regulatory Impact and Inspections

Non-compliance with GVP Module VI can have serious regulatory consequences. During pharmacovigilance inspections, authorities often focus heavily on ICSR management due to its direct impact on patient safety.

Common inspection findings include:

• Late or missing ICSR submissions
• Inadequate follow-up of serious cases
• Poor documentation of case receipt dates
• Insufficient training of non-PV staff

Such deficiencies may lead to corrective and preventive actions (CAPAs), regulatory warnings, financial penalties, or, in severe cases, suspension or revocation of marketing authorisations.

Why GVP Module VI Matters

GVP Module VI is more than a regulatory obligation; it is a critical mechanism for protecting patients and maintaining public trust in medicinal products. High-quality adverse reaction reporting enables early identification of risks, supports evidence-based regulatory decisions, and contributes to safer use of medicines across diverse patient populations.

For pharmaceutical companies, effective implementation of Module VI also demonstrates regulatory maturity, operational excellence, and a strong commitment to patient safety.

Conclusion

GVP Module VI defines the EU’s expectations for the collection, management, and reporting of suspected adverse reactions through Individual Case Safety Reports. By establishing clear standards for validity, timelines, data quality, and follow-up, the module ensures that safety information is transformed into actionable regulatory insight.

For MAHs and pharmacovigilance professionals, mastering GVP Module VI is essential not only for compliance but also for fulfilling their ethical responsibility to safeguard patients throughout the product lifecycle. A well-structured ICSR process ultimately strengthens pharmacovigilance systems and supports the continuous evaluation of a medicine’s benefit–risk balance.

FAQs

1. What is GVP Module VI?

GVP Module VI outlines requirements for collecting and reporting suspected adverse reactions via Individual Case Safety Reports in the EU.

2. What is an ICSR in pharmacovigilance?

An ICSR is a structured report documenting a suspected adverse reaction linked to a medicinal product.

3. What are the reporting timelines under GVP Module VI?

Serious cases must be reported within 15 days, while non-serious EU cases must be reported within 90 days.

4. Where are ICSRs submitted in the EU?

ICSRs are submitted electronically to the EudraVigilance database.

5. Who must comply with GVP Module VI?

Marketing Authorisation Holders, sponsors, and organisations responsible for pharmacovigilance activities in the EU must comply.