Updates on Union Procedures &

GVP Modules GPvP Symposium, 14 March 2014

Dr Anya Sookoo, Expert Inspector, GCP & GPvP

Content

A forward look at the new Union procedures for

pharmacovigilance inspections in the EU/EEA.

A look at the changes to GVP modules since

March 2013 and what is still to come.

Other changes on the horizon.

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What are Union procedures and why do

I need to know about them?

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How to be a good European…

Directive 2001/83/EC requires competent authorities to co-

operate with EMA to ensure that the legal requirements

governing medicines are complied with.

This co-operation consists in sharing information with

EMA on both inspections that are planned and that have

been conducted.

Where non-compliance is detected (critical or major

findings), competent authorities are required to inform

other Member States, the EMA and the Commission.

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GVP Module III - Inspections

The GVP module describes at high level how competent

authorities co-operate with EMA to meet the requirements of the

updated legislation and to promote a harmonised approach to

pharmacovigilance inspections in the EU.

The GVP module states, “Pharmacovigilance inspections should

be planned, coordinated, conducted, reported on, followed-up

and documented in accordance with inspection procedures

consistent with agreed Union pharmacovigilance inspection

procedures developed by the PhVIWG to support harmonisation

for the mutual recognition of pharmacovigilance inspections

within the EU.”

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Routine EU PhV inspection

programme

Some MAHs appear to be confused about how this works:

In accordance with EMEA/INS/PhV/105504/2008 (on EMA’s website) a four-year plan of routine PhV inspections of MAHs with centrally authorised products (CAPs) is produced by EMA and adopted by CHMP.

These inspections are conducted by the Supervisory Authority (Member State where the PSMF is located if a PSMF has been implemented) and may include sites within and outside the EU.

Most of these inspections are conducted as part of national inspection programmes in accordance with national SOPs.

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CHMP requested PhV inspections

However…

The CHMP may adopt a specific request for a Supervisory Authority inspection to be conducted of a MAH with CAPs e.g. often when a specific trigger is identified.

When CHMP makes a specific request, the inspection is co-ordinated by EMA and the Supervisory Authority follows EU SOPs for planning, conducting and reporting the inspection (not national SOPs).

Currently, the format of the inspection report is different from that used for national inspections, the report belongs to EMA and post-inspection activities are co-ordinated at EU level.

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National inspection programmes

In addition, each Member State has its own national PhV inspection programme.

The national inspection programme includes routine PhV inspections that are part of the EU programme and inspections of MAHs that only hold national authorisations.

National inspections are conducted in accordance with national SOPs, which vary between different Member States.

GVP Module III states national inspectorates should co-operate with each other and EMA to minimise duplication and maximise the use of available resources.

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Union procedures

New Union procedures for PhV inspections are to be adopted in March 2014 and will soon be published by EMA. The procedures will be appendices to Module III.

The Union procedures will replace the current EU procedures for CHMP requested PhV inspections.

The Union procedures contain guidance for all types of PhV inspections conducted by EU competent authorities i.e. for purely national inspections, for national inspections conducted to meet the requirements of the EU programme (for MAHs with CAPs) and for EU inspections adopted at the specific request of CHMP.

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Union procedures

Union procedures will not replace national PhV inspection procedures. However, national PhV inspection procedures will have to be reviewed and, where necessary, updated to ensure consistency with the content of Union procedures.

The aim is to promote a harmonised approach to PhV inspections. The procedures will also describe new processes for sharing information and interacting with PRAC. A new repository for Member States to share inspection reports/ summaries should go live after March 2014.

Consistency is promoted via discussions at quarterly EU PhV Inspector’s Working Group meetings; by inspectors participating in an annual EU training course and through joint inspections. Other initiatives (e.g. PIC/S) may assist.

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Union procedures

Union procedure on the coordination of EU Pharmacovigilance

Inspections.

Union procedure on the preparation, conduct and reporting of EU

pharmacovigilance inspections.

Union procedure on the sharing of information on EU

pharmacovigilance inspections.

Union procedure on the management of pharmacovigilance

inspection findings which may impact the robustness of the

benefit/risk profile of the concerned medicinal products.

Union guidance on document retention and record keeping for

pharmacovigilance inspections.

Union recommendations on the training and experience of inspectors

performing pharmacovigilance inspections.

More are to follow later on…

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Who knows what will happen if our own

Union is dissolved?

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GVP Developments

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GVP changes since March 2013

Module II (PSMF) – minor corrections and clarifications implemented in April 2013 e.g. for homeopathic products registered via the simplified registration procedure, the requirements to operate a pharmacovigilance system and produce a PSMF do not apply (these requirements do apply for traditional herbal medicinal products registrations).

Module VII (PSURs) – updates and clarifications were implemented in December 2013 to reflect the adopted PBRER guidance in ICH-E2C(R2) to aid international harmonisation. In addition, practical guidance was included on maintaining the EURD list. EURD list has been updated.

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GVP changes since March 2013

Module VIII (PASS) – minor clarifications implemented in April 2013 e.g. systematic literature review or a meta-analysis may be considered as PASS if their aims fulfil the criteria in the PASS definition; details of PASS conducted outside the EU should also be included in the EU PAS Register. National requirements for submission of PASS protocols, protocol amendments and study reports were also updated in an addendum to the module.

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New GVPs since March 2013

GVP Module X (Additional Monitoring) was published in April

2013. Holders of authorisations granted before 1 September

2013 which concern products subject to additional monitoring

should have included the black symbol ▼ and text in the SmPC

and PIL by 31 December 2013 (unless a delay was agreed).

The first product-specific GVP was published in December

2013, “Vaccines for prophylaxis against infectious diseases”. It

contains excellent guidance on pharmacovigilance processes

and issues that are relevant to vaccines.

A list of abbreviations that appear in the GVPs was published in

April 2013 and the list of definitions was updated.

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Proposed changes to GVP Module VI

(Management & reporting of adverse

reactions)

Proposals for amendments were released for consultation in June 2013

(the updated version has not yet been adopted and published) and include:

For non-interventional studies with data collection directly from HCPs

or consumers, non-academic sponsors should specify in the protocol

any adverse events to be actively sought and reported during the

study. Death and fatal outcomes are events which need to be actively

collected unless there is good justification for not doing this e.g. death

is a study outcome, patients included in the study have a disease with

high mortality.

Actively sought valid adverse reactions should be reported in

accordance with solicited reporting requirements. Serious and non-

serious reports of adverse events, which are not actively sought

should only be summarised in the interim or final study report.

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Still to come…

GVP Module XVI - “Risk minimisation measures: selection of tools

and effectiveness indicators”, initial version released for consultation

in June 2013. A final version has not yet been published.

GVP Module XI - Public participation in pharmacovigilance: due to

be released for consultation in second quarter 2014.

GVP Module XII - Continuous pharmacovigilance, ongoing benefit-

risk evaluation, regulatory action and planning of public communication:

due to be released for consultation in second quarter 2014.

GVP Module XIV - International cooperation: due to be released for

consultation in second quarter 2014.

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Advantages of the modular approach

Individual modules can be updated more easily and

frequently than the chapters in previous Volume 9A

guidance.

Topic-specific modules can be added as the need arises.

Stakeholder feedback and requests for clarification can

more easily be addressed in updates to modules.

Therefore, stakeholders are encouraged to submit requests

for clarification on significant points to EMA.

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What is still to be done?

Eudravigilance - as a single source for expedited reporting... 2016?

PSURs – single assessment for national authorisations & EMA PSUR repository.

XEVMPD – quality check and ability of MAHs to update data.

Public hearings – introduction in the context of the Urgent Union Procedure.

Literature searching – EMA to outsource.

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Perhaps after 2016 we will all feel like

this?

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Questions

For further information on MHRA Pharmacovigilance

Inspections and Good Pharmacovigilance Practice please visit:

http://www.mhra.gov.uk/Howweregulate/Medicines/Inspectiona

ndstandards/GoodPharmacovigilancePractice/index.htm

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