Introduction

2. Direct Healthcare Professional Communications

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NEXES
Glossary
Abbreviations
Other EU Guidelines and Relevant Terminology
ICH Guidelines
Templates

6. Distribution Requirements and Address Lists for Data Submission

 DETAILED TABLE OF CONTENTS

INTRODUCTION_________________________________________________________14

1. Legal Basis and Structure of Volume 9A (Human Pharmacovigilance)__________14

2. Legal Framework for Pharmacovigilance___________________________________15
3. The Roles of the Various Parties__________________________________________16
3.1 The Marketing Authorisation Holder________________________________________16
3.2 The Competent Authorities________________________________________________16
3.2.1 The Competent Authorities of the Member States______________________________16
3.2.2 The European Commission________________________________________________16
3.3 The EU Pharmacovigilance System_________________________________________16
3.3.1 The Role of Competent Authorities of the Member States for Products Authorised Through National
Procedures_____________________________________________________16
3.3.2 The Role of the Competent Authority of the Reference Member State for Products Authorised Through the
Mutual Recognition or Decentralised Procedure____________16
3.3.3 The Role of the Rapporteur for Products Authorised Through the Centralised Procedure17

3.3.4 The Role of the Agency___________________________________________________17

3.3.5 The Role of the CHMP Pharmacovigilance Working Party_______________________17

PART I: GUIDELINES FOR MARKETING AUTHORISATION HOLDERS_____________18
1. General Principles______________________________________________________19
1.1 Legal Basis of the Marketing Authorisation Holder’s Obligations for Pharmacovigilance19
1.2 Roles and Responsibilities of the Marketing Authorisation Holder and the Qualified Person Responsible for
Pharmacovigilance_________________________________________19
1.2.1 The Role and Responsibilities of the Qualified Person Responsible for
Pharmacovigilance_____________________________________________________________________
_20

1.2.2 Responsibilities of the Marketing Authorisation Holder in Relation to the Qualified Person Responsible for
Pharmacovigilance_________________________________________21
1.3 Contractual Arrangements_________________________________________________21
2. Requirements for Pharmacovigilance Systems, Monitoring of Compliance and Pharmacovigilance
Inspections___________________________________________22
2.1 Introduction____________________________________________________________22
2.1.1 Roles of the Marketing Authorisation Holder__________________________________22
2.1.2 Roles of the Agency_____________________________________________________22
2.1.3 Roles of the Competent Authorities in Member States___________________________22
2.1.4 Pharmacovigilance Inspections_____________________________________________23
2.1.5 Detailed Description of the Pharmacovigilance System to Be Included in the Marketing Authorisation
Application_________________________________________________23
2.1.6 Proof of the Services of a QPPV and of the Necessary Means to Notify Adverse Reactions, to be Included in
the Marketing Authorisation Application_______________________23
2.2 Detailed Description of the Pharmacovigilance System__________________________23
2.2.1 Location in the Marketing Authorisation Application and Update of the Detailed
Description____________________________________________________________23
2.2.2 Statement of the Marketing Authorisation Holder and the QPPV Regarding their Availability and the Means for
the Notification of Adverse Reactions______________23
2.2.3 Elements of the Detailed Description of the Pharmacovigilance System_____________24
2.2.3.a) Qualified Person Responsible for Pharmacovigilance (QPPV)____________________24
2.2.3.b) Organisation___________________________________________________________24
2.2.3.c) Documented Procedures__________________________________________________24
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2.2.3.d) Databases______________________________________________________________26
2.2.3.e) Contractual Arrangements with Other Persons or Organisations Involved in the Fulfilment of
Pharmacovigilance Obligations__________________________________________26
2.2.3.f) Training_______________________________________________________________26
2.2.3.g) Documentation_________________________________________________________26
2.2.3.h) Quality Management System______________________________________________26
2.2.3.i) Supporting Documentation________________________________________________27
2.3 Monitoring of Compliance by the Competent Authorities________________________27
2.3.1 Qualified Person Responsible for Pharmacovigilance___________________________27
2.3.2 Availability of Pharmacovigilance Data______________________________________27
2.3.3 Change in the Evaluation of the Risk-Benefit Balance of a Product_________________28
2.3.4 Expedited Adverse Reaction Reporting______________________________________28
2.3.5 Periodic Safety Update Reports____________________________________________28
2.3.6 Information Requested by Competent Authorities______________________________29
2.3.7 Submission of Safety Variations____________________________________________29
2.3.8 CHMP Commitments in Respect of Centrally Authorised Products________________29
2.3.9 Post-Authorisation Safety Studies___________________________________________30
2.3.10 Provision of Additional Data on Studies______________________________________30
2.4 Pharmacovigilance Inspections_____________________________________________30
2.4.1 Conduct of Inspections___________________________________________________30
2.4.2 Routine Inspections______________________________________________________31
2.4.3 Targeted Inspections_____________________________________________________31
2.4.4 Pharmacovigilance System Inspections______________________________________32
2.4.5 Product-Specific Inspections_______________________________________________32
2.4.6 Requesting and Reporting of Inspections_____________________________________32
2.4.7 Inspections of Contractors and Licensing Partners______________________________33
2.4.8 Inspections in European Economic Area_____________________________________33
2.4.9 Inspections in Third Countries_____________________________________________33
2.4.10 Fees for Inspections Requested by the CHMP_________________________________33
2.4.11 Procedures for Coordination of Pharmacovigilance Inspection for Centrally Authorised
Products_______________________________________________________________33
2.4.12 Procedures for Pharmacovigilance Inspections_________________________________33
2.4.13 Unannounced Inspections_________________________________________________34
2.4.14 Inspection Reports_______________________________________________________34
2.4.15 Follow-up of Inspection Findings___________________________________________34

2.4.16 Sharing of inspection information___________________________________________34

2.5 Regulatory Action_______________________________________________________34
3. Requirements for Risk Management Systems_______________________________36
3.1 Introduction____________________________________________________________36
3.2 Description of the Risk Management System__________________________________38
3.3 EU Risk Management Plan (EU-RMP)_______________________________________38
3.4 Situations Requiring an EU-RMP___________________________________________39
3.4.1 Marketing Authorisations via the Centralised Procedure_________________________39
3.4.2 Marketing Authorisations via the Mutual Recognition or Decentralised Procedures____40
3.5 Location in the Application________________________________________________40
3.6 Safety Specification______________________________________________________40