The European Medicines Agency (EMA) has published Revision 2 of its Guideline on Good Pharmacovigilance Practices (GVP) Module III – Pharmacovigilance Inspections, which came into effect on 10 September 2026. This revision incorporates significant new legal provisions, particularly regarding the inspection of subcontracted pharmacovigilance activities, as introduced by Commission Implementing Regulation (EU) 2025/1466. The updated module also strengthens the risk-based inspection cycle, clarifies remote inspection procedures, updates legal references, and aligns with revised Union procedures.
This article provides a comprehensive medical and regulatory analysis of the revised GVP Module III, examining its scope, key changes, inspection types, planning processes, scope of inspections, follow-up actions, regulatory sanctions, and the roles of various stakeholders within the EU pharmacovigilance network. The implications for marketing authorisation holders, applicants, and third-party subcontractors are discussed in detail, with practical guidance for achieving and maintaining compliance.
1. Introduction: The Evolving Landscape of Pharmacovigilance Inspections
Pharmacovigilance inspections are a critical component of the EU’s regulatory framework for ensuring that marketing authorisation holders (MAHs) comply with their legal obligations to monitor and report the safety of medicinal products. The European Medicines Agency’s Good Pharmacovigilance Practices (GVP) Module III provides comprehensive guidance on the planning, conduct, reporting, and follow-up of these inspections.
Revision 2 of GVP Module III, finalised on 4 September 2026 and effective from 10 September 2026, introduces important updates that reflect the evolving regulatory landscape. As noted in the EMA’s announcement, this version “addresses amendments to the Implementing Regulation, which provide for authorities to inspect marketing authorisation holder (MAH), but also organisations the MAH may subcontract tasks to and their subcontractors.”
2. Key Changes in Revision 2
Revision 2 of GVP Module III incorporates several significant updates, summarised in the following table:
| Change Category | Description |
| New legal provisions on subcontracting | Incorporation of Articles 6(3) and (4) and Article 13(1a) of Implementing Regulation (EU) No 520/2012, as amended by Commission Implementing Regulation (EU) 2025/1466, relating to subcontracting |
| Deletion of clinical trials reference | Removal of the mention of clinical trials, now governed by Regulation (EU) No 536/2014 |
| Updated legal references | Updates to Regulation (EU) 2024/568 in relation to fees |
| Updated web references | Revised references and information on web access to referenced documents |
| Alignment with Union procedures | Alignment with referenced Union procedures throughout the module |
| Clarifications on remote inspections | Enhanced guidance based on experience with remote inspections |
| Strengthened risk-based inspection cycle | Reinforcement of the risk-based approach to inspection planning and scheduling |
| Clarification on timing of document provision | Clarification regarding when documents should be provided to inspectors |
| Editorial improvements | Overall editorial improvements, specification of legal references, and alignment with other GVP modules |
Important Note: As the Implementing Regulation (EU) 2025/1466 was subject to public consultation in the EU, Revision 2 of GVP Module III was not itself subject to public consultation.
3. Legal Framework and Scope of Pharmacovigilance Inspections
3.1 Legal Basis
The legal basis for pharmacovigilance inspections in the EU is established through:
- Directive 2001/83/EC (referenced as ‘DIR’)
- Regulation (EC) No 726/2004 (referenced as ‘REG’)
- Commission Implementing Regulation (EU) No 520/2012 (referenced as ‘IR’), as amended by Commission Implementing Regulation (EU) 2025/1466
In this GVP Module, legal requirements are identified by the modal verb “shall” , while guidance for implementation is provided using “should.”
3.2 Objectives of Pharmacovigilance Inspections
The objectives of pharmacovigilance inspections are to:
- Determine that the marketing authorisation holder has personnel, systems, and facilities in place to meet their pharmacovigilance obligations
- Identify, record, and address non-compliance
- Use inspection results as a basis for enforcement action, where considered necessary
3.3 Scope of Inspection Authority
Competent authorities of the Member States, in cooperation with the Agency, shall conduct pharmacovigilance inspections of marketing authorisation holders or third parties subcontracted for pharmacovigilance tasks. This includes:
- Third parties subcontracted directly by the marketing authorisation holder
- Third parties further subcontracted by such subcontracted third parties
Inspections are carried out by inspectors appointed by national competent authorities, who are empowered to inspect:
- Premises
- Records
- Documents
- Pharmacovigilance System Master File (PSMF)
3.4 The Pharmacovigilance System Master File (PSMF)
The PSMF is a critical document for inspection planning and conduct. Key requirements include:
| Requirement | Details |
| Location | Must be located either at the site in the EU where the main pharmacovigilance activities are performed or at the site where the QPPV operates |
| Availability | Must be permanently and immediately available to inspectors at the site where it is kept |
| Electronic form | If kept electronically, data must be directly available at the site |
| Purpose | Used for planning and conducting inspections |
4. Inspection Types
4.1 Pharmacovigilance System and Medicinal Product-Related Inspections
| Inspection Type | Focus | Description |
| Pharmacovigilance system inspections | Procedures, systems, personnel, and facilities | Determines compliance with regulatory pharmacovigilance obligations; may use product-specific examples |
| Medicinal product-related inspections | Product-specific activities and documentation | Primarily focused on product-related pharmacovigilance issues; some aspects of the general system may be examined |
4.2 Routine and For-Cause Inspections
| Inspection Type | Trigger | Focus |
| Routine inspections | Scheduled in advance as part of inspection programmes | No specific trigger; risk-based approach; usually system inspections with product examples |
| For-cause inspections | Specific trigger recognised | More likely to focus on specific processes or compliance issues; full system inspections may also be performed |
Triggers for For-Cause Inspections:
- Risk-benefit balance: Change in risk-benefit balance; delays in identifying or communicating a risk; communication to the public without prior notification to authorities; non-compliance or safety issues identified during monitoring; suspension or withdrawal without advance notice
- Reporting obligations: Delays or omissions in reporting; poor quality or incomplete reports; inconsistencies between reports and other sources
- Requests from competent authorities: Failure to provide requested information within deadlines; poor quality or inadequate data provision
- Fulfilment of commitments: Concerns about RMP commitments; delays or failure to carry out specific obligations; poor quality of reports requested as specific obligations
- Inspections: Delays or inappropriate implementation of corrective and preventive actions; information from other types of inspections (GCP, GMP, GLP, GDP); inspection information from other authorities
- Others: Concerns following PSMF review; non-inspection-related information from other authorities; other sources of information or complaints
4.3 Pre-Authorisation Inspections
Pre-authorisation inspections may be conducted to verify the accuracy and successful implementation of the pharmacovigilance system as described by the applicant. These are not mandatory but may be requested in specific circumstances.
Considerations for requesting pre-authorisation inspections:
- The applicant has not previously operated a pharmacovigilance system within the EU or is establishing a new system
- Previous information indicates a poor history or culture of compliance
- Medicinal product-specific safety concerns warrant examination of the applicant’s ability to implement risk minimisation measures, meet safety conditions, or manage routine pharmacovigilance
Possible outcomes of pre-authorisation inspections:
| Outcome | Recommendation |
| Concerns raised | Not granting the marketing authorisation |
| Re-inspection prior to marketing authorisation | |
| Granting with recommendation for early post-authorisation inspection | |
| Imposition of safety conditions |
4.4 Post-Authorisation Inspections
Post-authorisation inspections are performed after marketing authorisation has been granted and are intended to examine whether the MAH complies with its pharmacovigilance obligations.
4.5 Announced, Unannounced, and Remote Inspections
| Inspection Type | Description |
| Announced | Majority of inspections; notified in advance to ensure availability of relevant individuals |
| Unannounced | Conducted when announcement could compromise objectives or when urgent safety reasons exist |
| Remote | Performed by inspectors remote from the premises; may be used when key sites are outside the EU, third parties are unavailable, or logistical challenges exist (e.g., pandemic, travel restrictions) |
4.6 Re-Inspections
Re-inspections may be conducted on a routine basis or following significant non-compliance. Risk factors are assessed to prioritise re-inspections.
5. Inspection Planning: A Risk-Based Approach
Pharmacovigilance inspection planning is based on a systematic and risk-based approach to make the best use of surveillance and enforcement resources while maintaining a high level of public health protection.
5.1 Factors Considered in Inspection Planning
| Category | Factors |
| Inspection-related | Compliance history from previous inspections; re-inspection date recommended by inspectors or assessors |
| Medicinal product-related | Additional pharmacovigilance or risk-minimisation activities; marketing authorisation with safety conditions (e.g., PASS, additional monitoring); large sales volume; limited availability of alternative treatment |
| Marketing authorisation holder-related | Never inspected; markets many products in EU; resources available for PV obligations; no previous marketing authorisation in EU; negative information from authorities; changes in organisation (mergers, acquisitions) |
| Pharmacovigilance system-related | Extent and number of third parties involved in subcontracted activities; change of QPPV; changes to safety database(s); changes in contractual arrangements; delegation or transfer of PSMF management |
6. Sites to Be Inspected
6.1 Location of Sites
Sites to be inspected may be located:
- Within the EU (e.g., PSMF location or EU QPPV site)
- Outside the EU (where main pharmacovigilance centre, databases, and/or activities are located outside the EU)
Member States and the Agency shall cooperate in the coordination of inspections in third countries.
6.2 Inspection of Subcontractors
A critical update in Revision 2 is the explicit provision for inspecting third parties subcontracted to conduct pharmacovigilance tasks. Key points include:
| Provision | Details |
| Inspection authority | Any third party subcontracted to conduct pharmacovigilance tasks may be inspected |
| Purpose | To confirm their capability to support the MAH’s compliance with pharmacovigilance obligations |
| Obligation to agree | The third party has the obligation to agree to be inspected in the subcontract |
| Further subcontracting | This applies to third parties that further subcontract tasks |
| Documentation | Inspection arrangements should be clearly documented when tasks are further subcontracted |
6.3 Selection of Sites
The type and number of sites to be inspected should be selected appropriately to ensure that key objectives within the inspection scope are met.
7. Inspection Scope
7.1 Elements Considered in Preparing Inspection Scope
| Element | Description |
| PSMF information | Information supplied in the Pharmacovigilance System Master File |
| Pharmacovigilance system functioning | Compliance data from the Agency (e.g., EudraVigilance reporting, data quality audits) |
| Specific triggers | Triggers identified for for-cause inspections |
| Additional data | May be requested in advance to select appropriate sites or clarify aspects of the pharmacovigilance system |
7.2 Scope of Routine Pharmacovigilance Inspections
| Area | Elements to Examine |
| Individual Case Safety Reports (ICSRs) | Collecting, receiving, exchanging from all sources; assessment (reporter assessments, event terms, seriousness, expectedness, causality); follow-up and outcome recording; reporting requirements and timeliness; record keeping and archiving |
| Periodic Safety Update Reports (PSURs) | Completeness and accuracy of data; addressing safety topics; formatting; timeliness; ongoing safety evaluation (signal detection, methods, investigations, RMP implementation, data provision, safety communications) |
| Non-interventional studies | Reporting of ICSRs; submission of study results and safety information; selection of reference safety information; inclusion in ongoing safety evaluation |
| Pharmacovigilance system | QPPV roles and responsibilities; MAH roles and responsibilities; PSMF accuracy, completeness, maintenance; training, qualifications, experience of staff; quality system coverage and adherence; fitness for purpose of computerised systems; contracts and agreements |
7.3 Scope of For-Cause Inspections
The scope depends on the specific trigger(s). Elements may include:
- QPPV involvement and awareness of medicinal product-specific issues
- In-depth examination of processes, decision-making, communications, and actions relating to a specific trigger and/or product
7.4 Scope of Re-Inspections
For re-inspections, the scope should consider:
- Review of the status of the pharmacovigilance system and/or corrective and preventive action plan(s)
- Review of significant changes made since the last inspection
- Review of process and/or product-specific issues identified from assessment of information provided by the MAH
8. Inspection Process and Follow-Up
8.1 Inspection Process
Pharmacovigilance inspections should be planned, coordinated, conducted, reported on, followed-up, shared, and documented in accordance with the agreed Union Procedures for Pharmacovigilance Inspections. This supports harmonisation for the mutual recognition of pharmacovigilance inspections within the EU.
8.2 Inspection Follow-Up
When non-compliance is identified, follow-up is required until a corrective and preventive action plan is completed. Follow-up actions may include:
| Follow-Up Action | Description |
| Review of corrective and preventive action plan | Assessment of the MAH’s proposed actions |
| Review of periodic progress reports | When deemed necessary |
| Re-inspection | To assess appropriate implementation of the action plan |
| Requests for data | Submission of previously un-submitted data |
| Requests for variations | E.g., to amend product information |
| Requests for impact analyses | Following review of data not previously considered |
| Requests for safety communications | Including amendments of marketing and/or advertising information |
| Meeting with MAH | To discuss deficiencies, impact, and action plans |
| Communication to other authorities | Including those outside the EU |
| Other product-related actions | Depending on impact, may include recalls or actions relating to marketing authorisations or clinical trial authorisations |
9. Regulatory Actions and Sanctions
When non-compliance with pharmacovigilance obligations is detected, the necessary action is judged on a case-by-case basis. The potential negative public health impact of the non-compliance determines what action is taken.
9.1 Possible Regulatory Options
| Category | Options |
| Education and facilitation | Communication with MAH representatives to summarise non-compliances, clarify legal requirements, and review corrective actions |
| Information sharing | Provision of information to other competent authorities, the Agency, or third-country authorities |
| Inspection | Inspection to determine extent of non-compliance; re-inspection to ensure compliance |
| Warning letter / non-compliance statement / infringement notice | Non-statutory or statutory instruments stating the legislation breached and specifying steps and timeframes for rectification |
| Public listing | Making public a list of MAHs found to be seriously or persistently non-compliant |
| Actions against marketing authorisation(s) | Urgent safety restriction; variation; suspension or revocation; delays in granting new applications; safety conditions |
| Product recalls | Where important safety warnings have been omitted from product information |
| Action relating to marketing/advertising | Amendments or suspension |
| Clinical trials | Amendments or suspension due to product-specific safety issues |
| Administrative penalties | Fixed fines, fines based on company profits, or daily fines |
| Criminal prosecution | With possibility of imprisonment in accordance with national legislation |
10. Roles of Stakeholders in the EU Network
10.1 Role of the European Medicines Agency (EMA)
The Agency’s roles include:
- Coordination of monitoring of medicinal products authorised in the EU
- Coordination of verification of compliance with pharmacovigilance obligations
- Establishment and maintenance of processes through the Pharmacovigilance Inspectors’ Working Group (PhViWG)
- Coordination and implementation of a risk-based programme for routine inspections of MAHs with centrally authorised products
- Coordination of for-cause inspections requested by the CHMP
- Coordination of third country inspections
- Communication and follow-up of inspections across the Agency, PRAC, CHMP, CMDh, and third-country authorities
10.2 Role of the Pharmacovigilance Risk Assessment Committee (PRAC)
The PRAC may:
- Make recommendations on the need and scope of for-cause inspections related to medicinal products of EU interest
- Review the outcome of pharmacovigilance inspections and assess corrective and preventive action plans
- Provide input in the preparation of and agree on the risk-based programme for routine inspections
10.3 Role of the Committee for Medicinal Products for Human Use (CHMP)
The CHMP is responsible for:
- Requesting pharmacovigilance inspections in the context of the centralised authorisation procedure
- Endorsing PRAC recommendations on inspection outcomes and follow-up
- Adopting the risk-based programme for routine inspections
10.4 Role of the European Commission
For medicinal products authorised under Regulation (EC) No 726/2004, the European Commission may request the Agency to coordinate a pharmacovigilance inspection if public health information so mandates.
10.5 Role of the Member States
Member States should:
- Establish the legal and administrative framework for pharmacovigilance inspections
- Provide sufficient resources and appoint adequately qualified inspectors
- Plan, coordinate, conduct, report, follow-up, share, and document inspections in accordance with Union Procedures
- Prepare inspection programmes based on a systematic and risk-based approach
- Verify inspection status of MAHs planned for inspection by considering information shared under programmes in other Member States
- Use a common repository accessible to all Member States, the Agency, and the European Commission
10.6 Role of Marketing Authorisation Holders and Applicants
MAHs and applicants have the following responsibilities:
| Responsibility | Details |
| Always be “inspection-ready” | Inspections may be unannounced |
| Maintain and make available the PSMF | Permanently and immediately available at the site where it is kept |
| Ensure sites agree to be inspected | Including third parties subcontracted by the MAH or further subcontracted third parties |
| Provide information and documentation | Within given deadlines |
| Ensure relevant staff are present | For interviews or clarification during inspection |
| Ensure pharmacovigilance data is accessible | At a single point within the EU |
| Implement corrective and preventive action plans | Appropriate and timely, with prioritisation of critical and/or major findings |
11. Inspection Programmes and Cycles
11.1 Risk-Based Inspection Cycle
A programme for routine inspections for centrally authorised products is determined by the Agency in conjunction with supervisory authorities, PhViWG, PRAC, and CHMP. As a general approach:
- An inspection should be conducted within 4 years after the date of marketing authorisation of the first medicinal product
- Thereafter, a 4-year inspection cycle should be used
- The cycle may be shortened or lengthened based on ongoing risk assessment
11.2 Applicability of Inspection Results
If the same pharmacovigilance system is used for various authorisation types (centralised, national, mutual recognition, decentralised), the results of a supervisory authority inspection may be applicable for all products covered by that system.
11.3 National Inspection Programmes
Member States are responsible for planning and coordinating pharmacovigilance inspections within their territory for products authorised nationally or via mutual recognition or decentralised procedures. They should prioritise inspections based on information from other inspections and use this information to prepare appropriate scopes.
12. Qualification and Training of Inspectors
Inspectors involved in pharmacovigilance inspections should be officials of, or appointed by, the Member State in accordance with national regulation. A sufficient number of competent and appropriately qualified and trained inspectors should be available.
Training requirements include:
- Training to ensure competence in preparing, conducting, and reporting inspections
- Training in pharmacovigilance processes and requirements
- Documented processes to ensure inspection competencies are maintained
- Keeping inspectors updated with current pharmacovigilance legislation and guidance
- Individual documentation and evaluation of training and experience
13. Quality Management of the Inspection Process
Quality of the pharmacovigilance inspection process is managed by national competent authorities and covered by their pharmacovigilance systems and associated quality systems. The process is also subject to audit. Quality and consistency of inspections is facilitated by the Union Procedures for Pharmacovigilance Inspections.
14. Inspection Fees and Transparency
14.1 Inspection Fees
For inspections requested by the CHMP, inspection fees and inspectors’ expenses are charged in accordance with Regulation (EU) 2024/568. For inspections performed in the context of national, mutual recognition, and decentralised procedures, similar fees may or may not apply depending on the legal requirements of the Member State carrying out the inspection.
14.2 Transparency
Information on the conduct and outcome of pharmacovigilance inspections and their follow-up may be made publicly available.
15. Practical Implications for Stakeholders
15.1 For Marketing Authorisation Holders
| Implication | Action |
| Subcontractor oversight | Ensure all third parties subcontracted for pharmacovigilance tasks (including further subcontractors) agree to be inspected and that arrangements are documented |
| PSMF maintenance | Maintain the PSMF permanently and immediately available; ensure electronic form is accessible |
| Inspection readiness | Be prepared for unannounced inspections at all times |
| Corrective actions | Implement corrective and preventive action plans promptly, prioritising critical and major findings |
| Risk-based compliance | Understand the risk factors considered for inspection planning and address any vulnerabilities |
15.2 For Third-Party Subcontractors
| Implication | Action |
| Agree to inspection | Include obligation to be inspected in subcontracts |
| Documentation | Clearly document inspection arrangements when further subcontracting |
| Compliance | Maintain compliance with pharmacovigilance obligations to support MAH compliance |
| Readiness | Be prepared for inspection by competent authorities |
15.3 For Regulatory Authorities
| Implication | Action |
| Risk-based planning | Implement systematic and risk-based inspection programmes |
| Information sharing | Use common repositories and share information on planned and conducted inspections |
| Harmonisation | Follow Union Procedures to ensure consistency and mutual recognition |
| Training | Ensure inspectors are adequately qualified and trained |
Conclusion
Revision 2 of GVP Module III represents a significant update to the EU’s pharmacovigilance inspection framework. The incorporation of new legal provisions on subcontracting, the strengthening of the risk-based inspection cycle, and the clarifications on remote inspections reflect the evolving nature of pharmacovigilance oversight in an increasingly complex global regulatory environment.
Key takeaways from this revision include:
- Expanded inspection authority: Competent authorities can now inspect not only MAHs but also third parties subcontracted for pharmacovigilance tasks, including further subcontractors. This closes a critical gap in the oversight of outsourced pharmacovigilance activities.
- Strengthened risk-based approach: The 4-year inspection cycle, subject to ongoing risk assessment, ensures that inspection resources are targeted where they are most needed.
- Clarified remote inspection procedures: The module provides updated guidance on remote inspections, reflecting lessons learned during the COVID-19 pandemic and other exceptional circumstances.
- Updated legal framework: References to Regulation (EU) 2024/568 on fees and alignment with other GVP modules ensure consistency across the regulatory framework.
- Clear responsibilities for all stakeholders: The module clearly delineates the roles of the EMA, PRAC, CHMP, Member States, and MAHs, facilitating a coordinated approach to pharmacovigilance inspections.
For MAHs and applicants, the message is clear: be inspection-ready at all times, maintain robust oversight of subcontracted activities, and implement corrective actions promptly when non-compliance is identified. For regulatory authorities, the revision provides a strengthened framework to protect public health through effective, risk-based pharmacovigilance inspections.
