PHARMACOVIGILANCE SYSTEM MASTER FILE

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Pharmacovigilance System Master File Karsten Lollike MD, PhD, E*MBA Corporate Vice President and QPPV Global Safety Novo Nordisk A/S

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Agenda • Requirement overview of the PMSF (incl. how to maintain it) • Transition from DDPS to PSMF (when and how to do it?) and their comparison • Request to DDPS from non-EEA countries • Audit and inspection findings in PMSF • Training requirements • Conclusions

Presentation title

Who is this? A. Henrik Møllgaard B. Lasse Svan Hansen C. Mikkel Hansen

Date

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Presentation title

Have you already transitioned to the PMSF? • Yes • No

Date

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Much good advice on what to do – organisations are different and therefore produce different solutions – this is my personal views based on my organisation

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Half full or half empty? What do you communicate?

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Transition to from DDPS to PMSF – when? • By July 2015 at the latest • At the time of submission of initial marketing authorisation application or at submission of renewal • Recommend to do it a.s.a.p. (at inspection you will be asked for data in the annex format)

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DDPS compared to PSMF Summary of PV system

DDPS

PMSF

PMSF Annexes

=must be submitted to authorities

Should reside in EU* together with QPPV

* Norway, Iceland or Lichtenstein also ok

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There is no PSMF template as such available. The structure and content of the PSMF as well as its maintenance is defined by the Commission Implementing Regulation and ESPECIALLY in the GVP Module II By using GVP Module II, you will more or less come up with: 1. Introduction and Scope (which products/linking) 2. Qualified Person Responsible for Pharmacovigilance 3. Organisational Structure 4. Sources of Safety Data 5. Computerised Systems and Databases 6. Pharmacovigilance Processes 7. Pharmacovigilance System Performance 8. Quality System 9. Business Continuity 10. List of Annexes 11. Known Gaps in the PSMF 12. List of Abbreviations

8.1. Quality Management System Overall 8.2. Quality Management Review 8.3. Document and Record Control 8.4. Procedural Documents 8.5. Training 8.6. Pharmacovigilance Audits 8.7. Corrective Actions and Preventive Actions and Deviations 8.8. Procedures Relevant for Chapter 8

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DDPS • Qualified Person Responsible for Pharmacovigilance • Organisation • Documented Procedures • Databases • Contractual Arrangements with Other Persons or Organisations Involved in the Fulfilment of Pharmacovigilance Obligations • Training • Documentation • Quality Management System • Supporting Documentation

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PMSF • Qualified Person Responsible for Pharmacovigilance • Organisational Structure • Overview of PV Agreements and Contracts • Contractual Arrangements with External Parties on Pharmacovigilance • Sources of Safety Data • Computerised Systems and Databases • Pharmacovigilance Processes • Pharmacovigilance System Performance • Quality System • Business Continuity • Annex A-I

Annexes A: The Qualified Person Responsible for Pharmacovigilance • QPPV documentation incl. delegation of tasks • Affiliate QP’s in EU

C: Sources of Safety Data • List of study sources, including any studies, registries, surveillance or support programmes

B: The Organisational Structure of the MAH • List of affiliates • List of PV agreements with affiliates and 3rd parties

D: Computerised Systems and Databases • List / detailed information on PV computer systems, e.g. validation status, back-up procedures, change control

Annexes E: Pharmacovigilance Process and Written Procedures • List of procedures

G: Quality System • Lists of planned audits and conducted audits and • Critical and major findings

F: Pharmacovigilance System Performance • Full list of PV KPI’s and actual measurements

H: Products • List of authorised products, incl. traceability to risk minimisation

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Maintenance Summary of PV system

PMSF

PMSF Annexes

With change of QPPV

When major changes to system

Dynamic

Annex I: Document and Record Control: • Change control, document logbook

Presentation title

What to provide outside of EU?

PMSF

• Requirement is often a (detailed) description of pharmacovigilance system • We provide special version of PMSF stating that annexes will not be available.

Date

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How to eat an elephant?

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From “current” to “future” practice…… December 2010 Regulation and Directive adopted by the European Parliament and European Council

New PV Legislation

April 2011 Internal NN workshop and initial gap analysis facilitated by WCI Consulting Group

January 2012 Project created with the aim of analysing and implementing new legislation

First NN workshop

(GS Newsletter April issue): How is Global Safety handling the new PV legislation?

May 2012 Stakeholder Group formed with members from other impacted NN areas

Pharma Package Project formed

Gap Analysis & Roadmap approved

(Communication to Global Safety HQ-staff & Affiliates): Where are we in Global Safety / Novo Nordisk?

NEW PHARMACOVIGILANCE LEGISLATION

June 2012 Initial gap analysis, impact assessment and roadmap approved by GSMan

(Global Safety Quarterly Mtg, Annual Conference & NovoNews): How to comply with new EU safety law?

August 2012 -> All roadmap activities completed for first wave GVP guidelines

Roadmap activities completed

(CR Quarterly Mtg & launch of info-video for NN Affiliates): What are the impact and new responsibilities?

From “current” to “future” practice…… Steering Committee

Global Safety Management

Stakeholder Group

Other Novo Nordisk areas

Prj Coordination Group

Subgroup leads, Dep.QPPV, PM

SG I

SG II

SG V

SG VI

SG VII

SG VIII

SG IX

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Gap Analysis & Roadmap for Implementation 7

12

7

27

32

29

23

39

23

58 15

83 29 96 40

Identified gaps (total: 347)

Roadmap activities (total: 144)

Implementation – high level Roadmap cluster Module I – Pharmacovigilance Systems and their Quality Training Project Quality Control KPIs Business Continuity (part of PSMF) Make agreement with recruitment agencies (linked 3.2.2) Module II – Pharmacovigilance Systems Master Fileto (PSMF) Summary of System Master File System Master File – main document System Master File – annexes (1st version) System Master File – annexes (2nd version) Module V – Risk Management Plans RMP SOP RMP template Procedure discussions Training Evaluate publishing tools Module VI – Individual Case Safety Reports (ICSRs) Submission of non-serious cases ARGUS Safety System enhancements Regulatory reporting Update of SOPs Update of ARGUS User Manuals Test system pilot region Module VII –on Periodic Safety Update Reports (PSURs) Update of implementation plan SOP critical decisions Tools and internal discussions SOP update Training roadshow Module VIII – Post-Authorisation Safety Study (PASS) Consolidated list of affected SOPs Update of SOPs related to Non-Interventional Studies Update of SOPs related to Clinical Trials Update of SOPs related to Epidemiological studies/IIS Update of SOPs related to Global Safety Module IX – Signal Management QBIC documents novoDOCS/GlobeShare repositories Signal Mapping All modules Miscellaneous roadmap activities Definitions: – No delays expected – Minor delay expected (2 weeks)

2012 Aug

Sep

Oct

Nov

Dec

2013 Jan

Feb

Mar

Apr

Total:

Open / Closed / Total 0 1 1 1 1 2 1 1 0 Open / Closed / Total 0 2 2 0 6 6 0 10 10 5 0 5 Open / Closed / Total 1 0 1 1 0 1 7 1 8 2 0 2 1 0 1 Open / Closed / Total 0 1 1 9 0 9 4 0 4 7 2 9 6 2 8 Open / Closed / Total 2 0 2 11 1 12 13 0 13 1 0 1 1 0 1 Open / Closed / Total 0 2 2 3 0 3 5 0 5 3 0 3 4 0 4 Open / Closed / Total 2 0 2 2 0 2 1 0 1 Open / Closed / Total 17 5 22 110 34 144

Status Complete Status Complete Complete Complete Status

Status Complete

Status

Status Complete

Status

Status

PSMF - Outlining new expectations, challenges and 14-NOV-2012 You are now in orbit with the process and can approaches start working more on-going with performance

Discussion points: - Use data prior to cut-off? - Which gaps will we not cover immediately but put into a collection / improvement process - Learning curve: How can meaningful performance KPIs be set across organisation

Create and roll-out SOPs to govern future data collection. Communicate !

Get all the data you can from your partners and write the rest. You are now ready to launch v1. Migrate all data you have, e.g. the DDPS. Use data from last audit / inspection etc. to fill in lists in Annexes. Do an internal review Write an outline structure of the PSMF with all sections and note where you think the source/group for it is Identify major areas where you have partners inside/outside PV.

Our approach to writing the PSMF

Role of QPPV – psychological change From “know it all” to details left to experts

Date

Role of the QPPV – very much the same as with Vol. 9A • Establishing and maintaining / managing the MAH’s pharmacovigilance system • Having an overview of the safety profiles and any emerging safety concern in relation to the medicinal products for which the MAH holds authorisations • Acting as a single contact point for the Competent Authorities on a 24-hour basis

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Role of the QPPV • Important role • Extensive tasks • QPPV may delegate specific tasks to qualified and trained individuals but such delegation should be documented • QPPV maintains system oversight and overview of the safety profiles of all products and remains legal responsible • Should be heavily involved in change management of system and communication hereof

Date

Critical and Major PV Audit and Inspection findings – throughout the organisation and from partners - will be presented in the PSMF (annexes) Critical and major audit findings will be put into the PSMF (including audit findings from partners) Overview of inspection findings that affects overall PV system (in connection with renewal) Will only be removed once corrective actions are accepted (change log) Will be looked at by inspectors. Failure to follow the action plan may constitute a breach of legislation GCP audit findings will not be included (company decision – benchmarked) In relation to renewals you need to evaluate whether you have had inspection findings that affects the PV system

Presentation title

Date

Slide no 25

Training requirements are increasing

Training in Standard Operating Procedures are not enough, training in legislation must also take place. Training effectiveness should also be considered (e.g. tests, sign off etc.)

EU Countries

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Safety Responsible

2

TC Responsible

3

Safety Manager

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General Manager

PSMF

EU Legislation

Local Legislation

Learning’s from Inspection – October 2012 by Danish authorities and March 2013 by Belgian authorities • Don’t panic – the authorities are also getting used to the system • Be open and honest – tell what you have done and what you have not yet done, but when you will do it • Show implementation plans • Focus • • • • •

Data privacy Contracts Patient Support Programmes Market Research Programmes Training

• Overall fair process

Presentation title

CHRISTIAN WOLFFBRANDT Senior Training & QC Associate Global Safety

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Conclusions  Transition to PMSF a.s.a.p.  Transition is a major change management project that will demand extensive and repetitive communication via many different channels  Establish company wide process for how to include audit findings in PMSF