Guideline on good pharmacovigilance practices (GVP)

1 28 march 2017. EMA/838713/2011 Rev 2*. Guideline on good pharmacovigilance practices (GVP). Module V Risk management systems (Rev 2). Date for coming into effect of first version 2 July 2012. Date for coming into effect of Revision 1 28 April 2014. draft Revision 2* finalised by the Agency in collaboration with Member 16 February 2016. States draft Revision 2 agreed by the European Risk Management Facilitation 23 February 2016. Group (ERMS FG). draft Revision 2 adopted by Executive Director 24 February 2016. Release for public consultation 29 February 2016. End of consultation (deadline for comments) 31 May 2016. Revised draft Revision 2 finalised by the Agency in collaboration with 9 march 2017. Member States Revised draft Revision 2 agreed by the EU Network pharmacovigilance 23 march 2017. oversight Group (EU-POG). Revised draft Revision 2 adopted by Executive Director as final 28 march 2017.

2 Date for coming into effect of Revision 2* 31 march 2017. Note: RMPs submitted for initial marketing authorisation applications and D121 responses applying GVP Module V Rev 1 will be accepted for a further 6 months, and all other RMP submissions (including D91 responses for an initial application under accelerated assessment) will be accepted for one further year until 31 march 2018. * Note: Revision 2 is a major revision with modifications throughout and contains the following: further clarification of what RMPs should focus on in relation to an important identified or important potential risk and missing information;. removal of duplication within GVP Module V;. removal of duplication of information in other guidance documents;. See websites for contact details European Medicines Agency The European Medicines Agency is Heads of Medicines Agencies an agency of the European Union European Medicines Agency and Heads of Medicines Agencies, 2017.

3 Reproduction is authorised provided the source is acknowledged. further guidance on the expected changes in the RMP during the life cycle of the product;. updated requirements for different types of initial marketing authorisation applications, with the aim to create risk-proportionate RMPs. The guidance is updated in parallel to an amended RMP template for initial marketing authorisation application. Guideline on good pharmacovigilance practices (GVP) Module V (Rev 2). EMA/838713/2011 Rev 2. Page 2/36. Table of contents Introduction .. 5. Terminology .. 6. Structures and processes .. 7. Principles of risk management .. 7. Responsibilities for risk management .. 8. Overview of the format and content of the risk management plan (RMP) .. 8. RMP part I Product(s) overview .. 11. RMP part II Safety specification .. 12. General considerations for generic products and advanced therapy medicinal products.

4 12. Generics .. 12. Advanced therapy medicinal 12. RMP part II, module SI Epidemiology of the indication(s) and target population(s) .. 13. RMP part II, module SII Non-clinical part of the safety specification .. 13. RMP part II, module SIII Clinical trial exposure .. 14. RMP part II, module SIV Populations not studied in clinical trials .. 14. RMP part II, module SV Post-authorisation experience .. 15. RMP part II, module SVI Additional EU requirements for the safety specification 15. RMP part II, module SVII Identified and potential risks .. 15. RMP part II, module SVII section Identification of safety concerns in the initial RMP submission .. 17. RMP part II, module SVII sections Risk considered important for inclusion in the list of safety concerns and Risk not considered important for inclusion in the list of safety concerns .. 17. RMP part II, module SVII section New safety concerns and reclassification with a submission of an updated RMP.

5 17. RMP part II, module SVII section Details of important identified risks, important potential risks, and missing information .. 18. RMP part II, module SVIII Summary of the safety concerns .. 18. RMP part III pharmacovigilance plan (including post-authorisation safety studies) 19. RMP part III section Routine pharmacovigilance activities .. 19. Specific adverse reaction follow-up questionnaires .. 20. Other forms of routine pharmacovigilance activities .. 20. RMP part III section Additional pharmacovigilance activities .. 20. RMP part III section Summary table of additional pharmacovigilance activities .. 21. RMP part IV Plans for post-authorisation efficacy studies .. 22. RMP part V Risk minimisation measures (including evaluation of the effectiveness of risk minimisation activities) .. 22. RMP part V section Risk minimisation plan .. 25.

6 RMP part V section Summary of risk minimisation measures .. 25. RMP part VI Summary of the risk management plan .. 25. RMP part VII Annexes to the risk management plan .. 26. RMP annex 1 .. 26. Guideline on good pharmacovigilance practices (GVP) Module V (Rev 2). EMA/838713/2011 Rev 2. Page 3/36. RMP annex 2: Tabulated summary of planned, on-going, and completed pharmacovigilance study programme .. 27. RMP annex 3: Protocols for proposed, on-going, and completed studies in the pharmacovigilance plan .. 27. RMP annex 3 part A: Requested protocols of studies in the pharmacovigilance plan, submitted for regulatory review with this updated version of the 27. RMP annex 3 part B: Requested amendments of previously approved protocols of studies in the pharmacovigilance plan, submitted for regulatory review with this updated version of the RMP .. 27.

7 RMP annex 3 part C: Previously agreed protocols for on-going studies and final protocols not reviewed by the competent authority .. 27. RMP annex 4: Specific adverse event follow-up forms .. 28. RMP annex 5: Protocols for proposed and on-going studies in RMP part IV .. 28. RMP annex 6: Details of proposed additional risk minimisation activities .. 28. RMP annex 7: Other supporting data (including referenced material) .. 28. RMP annex 8: Summary of changes to the risk management plan over time .. 28. The relationship between the risk management plan and the periodic safety update report .. 29. Quality systems and record management .. 29. Operation of the EU network .. 29. Requirements for the applicant/marketing authorisation holder in the EU .. 29. Risk management plans with initial marketing authorisation applications .. 30. New applications under Article 10(1), generic.

8 31. New applications under Article 10c, informed consent .. 32. New applications under Article 10(3), hybrid .. 32. New applications under Article 10b, involving fixed combination medicinal products .. 32. New applications under Article 10a, well established medicinal use .. 32. New applications under Article 10(4), biosimilar products .. 33. New applications for homeopathic and herbal products not falling within the scope of the simplified registration .. 33. Risk management plans first submitted post-authorisation .. 33. New risk management plans at the request of a competent authority to address one or more safety concerns .. 33. Unsolicited risk management plan submission in post-authorisation phase .. 33. Submission of a risk management plan to competent authorities in the EU .. 33. Risk management plans updates .. 34. Assessment of the risk management plan within the EU regulatory network.

9 35. Transparency .. 36. Guideline on good pharmacovigilance practices (GVP) Module V (Rev 2). EMA/838713/2011 Rev 2. Page 4/36. Introduction A medicinal product is authorised on the basis that in the specified indication(s), at the time of authorisation, the risk-benefit balance is judged to be positive for the target population. Generally, a medicinal product will be associated with adverse reactions and these will vary in terms of severity, likelihood of occurrence, effect on individual patients and public health impact. However, not all adverse reactions and risks will have been identified at the time when an initial marketing authorisation is granted and some will only be discovered and characterised in the post-authorisation phase. The aim of a risk management plan (RMP) is to document the risk management system considered necessary to identify, characterise and minimise a medicinal product's important risks.

10 To this end, the RMP contains: 1. the identification or characterisation of the safety profile of the medicinal product, with emphasis on important identified and important potential risks and missing information, and also on which safety concerns need to be managed proactively or further studied (the safety specification');. 2. the planning of pharmacovigilance activities to characterise and quantify clinically relevant risks, and to identify new adverse reactions (the pharmacovigilance plan');. 3. the planning and implementation of risk minimisation measures, including the evaluation of the effectiveness of these activities (the risk minimisation plan'). As knowledge regarding a medicinal product's safety profile increases over time, so will the risk management plan change. Regulation (EC) No 726/2004, Directive 2001/83/EC and Commission Implementing Regulation (EU).