This document summarizes the major changes brought about by the new European Union pharmacovigilance legislation. It overviews the goals of improving safety monitoring and decision making. Key changes include new guidelines on pharmacovigilance systems and risk management, the establishment of the Pharmacovigilance Risk Assessment Committee, more stringent reporting rules, and increased transparency including public access to safety information. The legislation aims to modernize the EU pharmacovigilance system and better protect public health.

1. Dr. Vijay bhushanam

2. New legislation - Goals
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Reduce the burden of ADRs and optimise the use of medicines
Clarify roles and responsibilities
Science based, Risk based/proportionate approach
Increase proactiveness, Reduce redundancy
Integrate benefit and risk
Ensure robust and rapid EU decision-making
Strengthen the EU Network
Engage patients and healthcare professionals
Increase transparency, awareness and accountability
Provide better information on medicines

3. New legislation - Aims
 Improve the EU-PV system
 Simplify regulatory decision making
 Provide a legal basis for proactive Pharmacovigilance
 Involve patients more closely in the reporting of ADRs
 Overall Objective: “To
protect public health”

4. New legislation - Timeline
 2003: EC decision to undertake an assessment of PV system
 2005: Independent study completed
 2006- 2008: Research, consultation, policy development
 2010: New legislation adopted by the European Parliament
and European Council (Dec 2010)
 2012: First wave of requirements entered into force (2nd July)
 2012: GVP Guidelines (16 modules) finalized after public
consultation (February and December 2012)

5. Major/Key changes
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The new Good Vigilance Practice Guidelines (GVP)
The Pharmacovigilance Risk Assessment Committee (PRAC)
The Pharmacovigilance System Master File (PSMF)
Using a Periodic Benefit Risk Evaluation Report (PBRER)
More stringent ICSR submission rules
Publishing summaries of Risk Management Plans (RMP)
Requirement to perform Post-Approval Safety Studies (PASS)
Assignment of an Additional Monitoring Status
Commitment to openness and transparency
Eudravigilance policy to disclose postmarketing safety
information to the Public

6. Major/Key changes – GVP
 Good Pharmacovigilance Guidelines(GVP):
 Replaces Eudralex Volume 9A.
 Applies to all medicinal products, irrespective of the MA
granting procedure.
 Divided into 16 modules.
 Uses MedDRA terminology.

7. Major/Key changes – GVP
GVP - Table of Contents
Status
Introduction
Completed
Final GVP chapters
• Modules
Most of them Adopted
•Product or populationb specific considerations
Open for public consultation
Final GVP Annex I - Definitions
Adopted
Final GVP annex II - Templates
Adopted
Final GVP annex III - Other pharmacovigilance guidance
Most of them Adopted
Final GVP annex IV - ICH guidelines for pharmacovigilance
Adopted
Final GVP annex V - Abbreviations
Published
Draft GVP chapters and annexes for public consultation
Open for public consultation
Templates for submission of comments
Published
Privacy statement for public consultation
Published

8. Major/Key changes – GVP
Mod.
no.
Title
Status
Effective from
I
Pharmacovigilance systems and their quality systems
Adopted
2nd July 2012
II
Pharmacovigilance system master file
Adopted
12th April 2013
III
Pharmacovigilance inspections
Adopted
12th Dec 2012
IV
Pharmacovigilance audits
Adopted
12th Dec 2012
V
Risk management systems
Adopted
2nd July 2012
VI
Management and reporting of adverse reactions
Adopted
2nd July 2012
VII
Periodic safety update report
Adopted
2nd July 2012
VIII
Post-authorisation safety studies
Adopted
25th April 2013
Adopted
25th April 2013
Member States' requirements for transmission of
VIII
add-I information on non-interventional PASS

9. Major/Key changes – GVP
Title
Mod.
no.
Status
Effective from
IX
Signal management
Adopted
2nd July 2012
X
Additional monitoring
Adopted
25th April 2013
XI
Public participation in pharmacovigilance
Under Dev. Q3, 2013
XII
Continuous PV, ongoing benefit-risk evaluation,
regulatory action, planning of public communication
Under Dev. Q3, 2013
XIII
Incident management (to be included in module XII)
Under Dev. Q3, 2013
XIV
International cooperation
Under Dev. Q3, 2013
XV
Safety communication
Adopted
XVI
Risk-minimisation measures: selection of tools and
effectiveness indicators
Under Dev. Q2, 2013
23rd Jan 2013

10. Major/Key changes - PRAC
 Pharmacovigilance Risk Assessment Advisory Committee
(PRAC):
 A new EMA committee
 Meets monthly from September 2012
 Replaces the Pharmacovigilance Working Party
 Advises to
 CHMP and CMDh
 Members include (appointed by MS and EC)
 Experts from the EU Member States
 Representatives from Patient organisations
 Representatives from Healthcare professionals

11. Major/Key changes - PRAC
 Due regard to
 Risk Management Systems
 Therapeutic effect of the products
 Periodic Safety Update Reports
 Signal detection
 Additional Monitoring Status
 Urgent procedures
 Design and evaluation of PASS
 Pharmacovigilance inspections

12. Major/Key changes - PRAC

13. Major/Key changes - PSMF
 Pharmacovigilance System Master File (PSMF) replaces DDPS.
 MA applicants and MAHs are required to maintain PSMF.
 To be provided within 7 days upon request by the EMA.
 The Pharmacovigilance System Summary comprises of:
 a signed statement
 the location of PSMF
 the name and contact details of the QPPV
 the Member States in which the QPPV resides and operates
 proof that the applicant has a QPPV

14. Major/Key changes - PBRER
 Periodic Benefit Risk Evaluation Report (PBRER)
 Replaces Periodic Safety Update Report (PSUR)
 Scope changed from interval safety analysis to benefit-risk
evaluation
 Includes a Benefit versus Risk statement
 New evaluation sections, including a section to give an
overview on signals (tabulated as new, ongoing or closed)
 Interval listings no longer required
 Deletion of the chapter “Analysis of individual case
histories”

15. Major/Key changes - PBRER
 Not required for generic products, well-established use products,
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homoeopathic products and traditional herbal products
Six-monthly reports, summary bridging reports, or addendum
reports will not be accepted.
Time interval between data-lock point and submission –
expanded.
New assessment procedure involving PRAC.
Assessment will lead to automatic regulatory action (i.e,
variation, suspension or revocation).
Assessment reports of PSURs will be published on a European
medicines web portal.

16. Major/Key changes - ICSR
 Individual Case Safety Report (ICSR) Submission Rules
 Requirement to submit non-serious ICSRs is extended to cases
reported from Post-authorization solicited settings such as:
 Post-Authorisation Safety Studies (PASS)
 Post-Authorisation Efficacy Studies (PAES)
 Non-Interventional Studies (NIS)
 Patient Support Program (PSP)
 Market Research Studies (MRS)
 Non-serious ICSRs shall be submitted within 90 days to
EudraVigilance

17. Major/Key changes - RMP
 Risk Management Plan (RMP) is divided into several parts.
 The RMP will include
 a summary of the efficacy of the product.
 an evaluation of the effectiveness of risk minimisation measures.
 PRAC will have regulatory oversight of RMPs.
 PRAC will appoint a rapporteur for an individual RMP, who will
work with the (co-) rapporteur appointed by CHMP.
 Summaries of RMPs shall be made publicly available via web
portals.

18. Major/Key changes - RMP
 Educational materials for health professionals and patients are
required in RMP for a new product.
 UK version must be submitted to the MHRA prior to issue.
 MA application (after 21 July 2012) are required to submit a
RMP.
 Includes generic MA applications also.
 Should be submitted in template for the EU-RMP.
 For MAs granted before 21 July 2012 without an existing RMP -
no obligation to submit a RMP (unless concerns arise).

19. Major/Key changes – PASS/PAES
 Performing a PASS/PAES may be required at first
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authorisation as well as post-authorisation.
The Competent Authority may impose an obligation on
the MAH to conduct such a study.
If the same safety concern applies to more than one
product a joined PASS may be advised.
New information detected during such studies shall be
communicated to the competent authority.
Proposed format and content of study protocols/reports.
(outlined in GVP module VIII)

20. Major/Key changes –
Additional monitoring list
 The Additional Monitoring Status Can be assigned at any time
of the product life cycle
 Subjected to more intense scrutiny (same as UK’s ‘Black
Triangle’ list).
 Published on
 MHRA site www.mhra.gov.uk/blacktriangle.
 Also available on the EMA website.
 EU-wide list (published by EMA) will replace the Black Triangle
list previously published by the MHRA.
 MAHs can remove Black Triangle status without contacting the
MHRA. (for products that are not listed on additional monitoring list)

21. Major/Key changes –
Openness and transparency
 Provides the public with information about
 The safety of marketed medicines.
 How to report suspected ADRs.
 If MAHs want to make a public announcement, they shall
inform the NCA, the EMA and the EC.
 Two important changes
 EU public hearings.
 Creation of medicines web portals.

22. Major/Key changes –
Openness and transparency
 The UK web portal is required to host
 SPCs and PILs
 UKPARs (now a legal requirement)
 Summaries of RMPs for medicines authorised
 Products subject to additional monitoring
 The MA conditions with deadlines for fulfilment
 Setup of interconnected web-portals:
 European medicines web-portal (www.ema.europa.eu)
maintained by the EMA
 Will be linked to national web-portals
 Alternative reporting media remains available

23. Major/Key changes –
EudraVigilance Access Policy
 ICSRs are expected to be submitted by MAHs directly to
EudraVigilance rather than via National Health Authorities
 Formerly, only Member State HA, the EMA and the European
Commission had access to EudraVigilance.
 The EudraVigilance access policy is changed to allow HCPs,
patients and consumers, as well as MAH and research
organisations accessing the information

24. Major/Key changes –
ADR reporting/Signal management
 New Definition of Adverse Reaction*:
 A response to a medicinal product which is noxious and
unintended.
 Also covers
 Medicinal errors
 Uses outside the terms of the MA
 off-label use
 misuse
 abuse
*Article 1, 11-D

25. Major/Key changes –
ADR reporting/Signal management
 Centralised reporting
 By industry to the Eudravigilance database at EMA.
 Will come into effect 6 months after the Eudravigilance
functionality is approved.
 Likely to be sometime in 2015.
 Until then transitional measures will apply.
 Inclusion of reports from patients as valid, reportable ADRs.
 Only medication errors that result in a serious ADR should be
submitted.
 Non-serious cases should not be reported to EudraVigilance
during the transitional period.
 Sending non-UK serious consumer reports by the company is
not mandatory.

26. Major/Key changes –
ADR reporting/Signal management
OLD
NEW

27. Major/Key changes –
ADR reporting/Signal management
 MAHs should report cases from the literature.
 Avoid duplication by monitoring the MHRA website.
 MAHs should review sites under their control for valid cases.
 No need to review internet sites not under the MAH’s control
(blogs, chatrooms and social media pages).
 MAHs will also be required to monitor the Eudravigilance
database according to their level of access.
 Signals should follow a process of validation, prioritisation and
assessment.

28. Major/Key changes –
Audit/Inspection
 PSMF should be made available to the NCA upon request.
 Changes to PSMF will not be automatically notifiable to the
Competent Authorities.
 Transitional period for introduction of PSMF ends in July 2015.
 Quality Systems:
 MAHs, NCAs and the EMA will be required to have a quality
system in place.
 Particularly for resource management, staff training, procedural
documentation, quality control, monitoring, and improvement.

29. Major/Key changes –
Audit/Inspection
 Inspections:
 Harmonisation of inspection activities in the EU.
 Legal basis for the conduct of pre-authorisation inspections.
 Adequate pharmacovigilance system as a condition of MA.
 MA applicants should be aware that the PSMF may be requested.
 For centrally authorised products, the Supervisory Authority
will be determined by the PSMF location.
 MHRA will continue to operate a risk-based inspection
programme.

30. Conclusion
 New legislation:
 Provides strong legal basis for use of MedDRA through all
steps of the pharmacovigilance process
 Major change project that will take a few years to fully
implement
 Provides an opportunity to greatly improve the European
system for the benefit of public health

31. THANK YOU