Acknowledgements

The PIPA Committee would like to thank Esther Straghan, who wrote the course material. They would also like to thank the following members of the PIPA Training Working Party who were involved with the review, editing and uploading of this course:

  • Shirley-Ann van der Spuy, RedLine Pharmacovigilance
  • Sharon Braithwaite, PIPA Membership & Events Coordinator
  • Anne Turnbull, PIPA Operations Manager

Acronyms

  • ADR = Adverse Drug Reaction
  • ART = Article
  • CHMP = Committee for Medicinal Products for Human Use
  • CTD = Common Technical Document
  • DIR = Directive
  • EU = European Union
  • EEA = European Economic Area
  • FDA = Federal Drugs Agency
  • EMEA = European Medicines Agency
  • EVMPD = Eudravigilance Medicinal Product Dictionary
  • GVP = Good Pharmacovigilance Practice
  • HP = Health Professional
  • ICH = International Conference of Harmonization
  • ICSRs = Individual Case Safety Reports
  • MA = Marketing Authorisation
  • MAH = Marketing Authorisation Holders
  • NCEs = New Chemical Entities
  • PBRER = Periodic Benefit Risk Evaluation Report
  • PRAC = Pharmacovigilance Risk Assessment Committee
  • PSMF = Pharmacovigilance System Master File
  • PSUR = Periodic Safety Update Reports
  • PV = Pharmacovigilance
  • RMP = Risk Management Plan
  • SmPC/SPC = Summary of Product Characteristics

References

Guideline on Good Pharmacovigilance Practices (GVP)

Module V – Risk management systems (15 April 2014 – EMA/838713/2011 Rev 1*, Effective 28 April 2014) http://www.ema.europa.eu/docs/en_GB/document_library/…

Module V – Risk management systems (22 June 2012 -EMA/838713/2011, Effective 2Jul2012) http://www.ema.europa.eu/ema/index.jsp?curl=pages/…

RMP Template – Guidance on format of the risk management plan (RMP) in the EU – in integrated format http://www.ema.europa.eu/ema/index.jsp?…

Regulation (EU) No 1235/2010 – Of the European Parliament and of the Council of 15Dec2010

Directive 2010/84/EU – Of the European Parliament and of the Council of 15Dec2010

Commission Implementing Regulation (EU) No 520/2012 – on the Performance of Pharmacovigilance activities provided for in Regulation (EC) No 726/2004 and Directive 2001/83/EC

Common sections between RMP and PSUR

RMP: PSUR:
Part II, module SV – “Post-authorisation experience”, section “Regulatory and marketing authorisation holder action for safety reason” Section 3 – “Actions taken in the reporting interval for safety reasons”
Part II, module SV – “Post-authorisation experience”, section “Non-study post-authorisation exposure” Sub-section 5.2 – “Cumulative and interval patient exposure from marketing experience”
Part II, module SVII – “Identified and potential risks” Sub-section 16.4 – “Characterisation of risks”
Part II, module SVIII – “Summary of the safety concerns” (as included in the version of the RMP which was current at the beginning of the PSUR reporting interval) Sub-section 16.1 – “Summary of safety concerns”
Part V – “Risk minimisation measures”, section “Evaluation of the effectiveness of risk minimisation activities” Sub-section 16.5 – “Effectiveness of risk minimisation (if applicable)”

Relationship between the Risk Management Plan and the Periodic Safety Update Report

Some overlap, however objectives differ:

RMPs – pre-and post-authorisation risk-benefit management and planning.

PSURs – integrated, post-authorisation risk benefit assessment, set time periods, overall benefit risk profile of the medicinal product.

The two documents are complementary stand-alone documents, however contain common modules.

When RMP and PSUR submitted together:

– RMP should reflect the conclusions of the accompanying PSUR.

e.g. if new signal is discussed in PSUR and documented as an important identified or important potential risk, this risk should be included as a safety concern in the updated RMP submitted with the PSUR. The pharmacovigilance plan and the risk minimisation plan should be updated to reflect the MAH’s proposals to further investigate the safety concern and minimise the risk.

RMP part VII “Annexes to the Risk Management”

RMP should contain the 12 annexes listed:

RMP Annex 1: Interface between RMP and Eudravigilance/EPITT (electronic only).

RMP Annex 2: Current local SmPC and package leaflet. If multiple versions are included, show in which Member State(s) they are applicable. If available, a core SmPC should be provided with an overview of the changes applicable to the SmPC in each Member State.

RMP Annex 3: Worldwide marketing authorisation status by country (including EEA). Include – current licence status and dates.

RMP Annex 4: Synopsis of on-going and completed clinical trial programme.

RMP Annex 5: Synopsis of on-going and completed Pharmacoepidemiological study programme.

RMP Annex 6: Protocols for proposed and on-going studies in categories 1-3 of the section “Summary table of additional pharmacovigilance activities” in RMP part III.

RMP Annex 7: Specific adverse event follow-up forms.

RMP Annex 8: Protocols for proposed and on-going studies in RMP part IV.

RMP Annex 9: Synopsis of newly available study reports for RMP parts III-IV.

RMP Annex 10: Details of proposed additional risk minimisation activities (if applicable).

RMP Annex 11: Mock up examples of the material provided to healthcare professionals and patients as a requirement of Annex II of the Commission Decision or as a requirement of national authorisations including those using the mutual recognition or decentralised procedure, as applicable.

RMP Annex 12: Other supporting data (including referenced material).

RMP part VI “Summary of activities in the Risk Management Plan by Medicinal Product”

A summary of the RMP for each medicinal product will be made publically available – REG Art 23(3), Art 26(c), DIR Art 106(c) IR Art 31(2).

To be written by MAH, intended for the lay reader (not HCPs).

For each indication:

– Overview of disease epidemiology

– Summary of existing efficacy data i.e. treatment benefits

For the medicinal product

Summary of safety concerns:

– Important identified risks (what is known, and preventability)

– Important potential risks (what is known, why it is a potential risk)

– Important missing information (what is known)

Summary of risk minimisation activities by safety concern.

Planned post authorisation development plan (including any efficacy/safety studies).

Major changes to the RMP over time.