Implementation of the new pharmacovigilance legislation

An agency of the European Union

Implementation of the new pharmacovigilance legislation: update on status

Patients/Consumers Working Party (PCWP) and Healthcare Professionals Working Group (HCPWG) Joint Meeting European Medicines Agency, London 24 September 2012

Presented by: Franck Diafouka, Project 00305 Manager, Pharmacovigilance and Risk Management Sector

1

• Major achievements

• Next steps

• Conclusion

Content

2

Implementation journey….

PSUR

PASS

PAES Article

57

PASS

RMP

Inspections

Pharmacovigilance audits Additional

monitoring

EURD list

Black symbol

Signal detection

Referrals PRAC

Pharmaco -vigilance systems

ADR reporting

Safety announ-cements

CHMP

Web forms

Renewal

Literature monitoring

Fees

EudraVigilance

Coordination Group

EC decision

Agendas

Minutes

EMCDDA

Implementing regulation

RoP

Lists

Public hearings

EU medicines web-portal

PRAC Mandate

Fees

Drug abuse

Medication errors

Public health

EMA

Member States

Signals

Lists PRAC advice

PRAC recommen

-dation

PHARMACOVIGILANCE

Good pharmacoVigilance practice (GVP)

3

Major achievements

• Input to EC Implementing Regulation (EU) No 520/2012 published on 19/06/2012.

• 11 Good pharmacoVigilance Practice (GVP) modules drafted:

– 7 adopted (first wave)

– 2 to be adopted (comments currently being addressed)

– 2 under public consultation (until 21st September).

• Other guidance documents (under preparation e.g. Q&A/referrals procedural guidance)

• Questions and Answers (Q&As) on transitional aspects (legal and practical) published on EMA website

4

Major achievements

• Input to EC Implementing Regulation (EU) No 520/2012 published on 19/06/2012.

• 11 Good pharmacoVigilance Practice (GVP) modules drafted:

– 7 adopted (first wave)

– 2 to be adopted (comments currently being addressed)

– 2 under public consultation (until 21st September).

• Other guidance documents (under preparation e.g. Q&A/referrals procedural guidance)

• Questions and Answers (Q&As) on transitional aspects (legal and practical) published on EMA website

5

Major achievements

• Input to EC Implementing Regulation (EU) No 520/2012 published on 19/06/2012.

• 11 Good pharmacoVigilance Practice (GVP) modules drafted:

– 7 adopted (first wave)

– 2 to be adopted (comments currently being addressed)

– 2 under public consultation (until 21st September).

• Other guidance documents (under preparation e.g. Q&A/referrals procedural guidance)

• Questions and Answers (Q&As) on transitional aspects (legal and practical) published on EMA website

6

Major achievements

• Input to EC Implementing Regulation (EU) No 520/2012 published on 19/06/2012.

• 11 Good pharmacoVigilance Practice (GVP) modules drafted:

– 7 adopted (first wave)

– 2 to be adopted (comments currently being addressed)

– 2 under public consultation (until 21st September).

• Other guidance documents (under preparation e.g. Q&A/referrals procedural guidance)

• Questions and Answers (Q&As) on transitional aspects (legal and practical) published on EMA website

7

Major achievements • Plan for prioritised implementation of the pharmacovigilance legislation by the European Medicines Agency.

• Format for electronic submission of product information (‘Article 57’):

– Electronic format (made available in June 2011)

– Publication of revised legal notice and detailed guidance and provision of specific ICT tools (made available in March 2012)

– Training.

• Gap analysis

8

Major achievements • Plan for prioritised implementation of the pharmacovigilance legislation by the European Medicines Agency.

• Format for electronic submission of product information (‘Article 57’):

– Electronic format (made available in June 2011)

– Publication of revised legal notice and detailed guidance and provision of specific ICT tools (made available in March 2012)

– Training.

• Gap analysis

9

Major achievements • Plan for prioritised implementation of the pharmacovigilance legislation by the European Medicines Agency.

• Format for electronic submission of product information (‘Article 57’):

– Electronic format (made available in June 2011)

– Publication of revised legal notice and detailed guidance and provision of specific ICT tools (made available in March 2012)

– Training.

• Gap analysis

• No strategic gaps identified – only operational

• Leads and timelines assigned for gap resolution

Gap analysis

Identification and traceability of biologics

Supply to existing Patients of withdrawn

medicines

Ongoing issues in EPiTT to be closed or

mapped to new processes

EMA support for NAPs

And transitional issues

For NAPs

Outputs of PRAC and Coordination Group

Collection of data to review the impact of the legislation over

time (10 yearly review)

International liaison in The context of the new

Pharmacovigilance legislation

Templates and formats

Agenda structure for

PRAC meetings Short-term workaround ICT solutions to

support business processes

Process to collect information to publish withdrawn products

Support from Working Parties to Committees

• No strategic gaps identified – only operational

• Leads and timelines assigned for gap resolution

Gap analysis – status September 12

Identification and traceability of biologics

Supply to existing Patients of withdrawn

medicines

Ongoing issues in EPiTT to be closed or

mapped to new processes

EMA support for NAPs

And transitional issues

For NAPs

Outputs of PRAC and Coordination Group

Collection of data to review the impact of the legislation over

time (10 yearly review)

International liaison in The context of the new

Pharmacovigilance legislation

Templates and formats

Agenda structure for

PRAC meetings Short-term workaround ICT solutions to

support business processes

Process to collect information to publish withdrawn products

Support from Working Parties to Committees

12

Major achievements

• Establishment of Training Coordination Group to coordinate pharmacovigilance training within the EU network, in liaison with joint Heads of Medicines Agencies (HMA)/EMA Office of Training Steering Group (OTSG)

• Detailed Business Process Maps to support:

– future revision of ICT Project Definition Documents

– on-going development of Standard Operating Procedures (SOPs), Working Instructions (WINs) and Templates.

• EMA website will serve as the EU Medicines Web-portal

13

Major achievements

• Establishment of Training Coordination Group to coordinate pharmacovigilance training within the EU network, in liaison with joint Heads of Medicines Agencies (HMA)/EMA Office of Training Steering Group (OTSG)

• Detailed Business Process Maps to support:

– future revision of ICT Project Definition Documents

– on-going development of Standard Operating Procedures (SOPs), Working Instructions (WINs) and Templates.

• EMA website will serve as the EU Medicines Web-portal

14

Major achievements

• Establishment of Training Coordination Group to coordinate pharmacovigilance training within the EU network, in liaison with joint Heads of Medicines Agencies (HMA)/EMA Office of Training Steering Group (OTSG)

• Detailed Business Process Maps to support:

– future revision of ICT Project Definition Documents

– on-going development of Standard Operating Procedures (SOPs), Working Instructions (WINs) and Templates.

• EMA website will serve as the EU Medicines Web-portal

15

Major achievements • Upgrade of EMA corporate website (e.g. publication of safety-related referrals through the PRAC, search tool, RSS feed for agendas and minutes, …)

• Establishment of Pharmacovigilance and Risk Assessment Committee

• Enhanced cooperation with European Monitoring Centre for Drugs and Drug Addiction (EMCDDA)

• Preparation of initial lists of European Union Reference Dates (EURD) for Periodic Safety Update Reports and Products under additional monitoring

16

Major achievements • Upgrade of EMA corporate website (e.g. publication of safety-related referrals through the PRAC, search tool, RSS feed for agendas and minutes)

• Establishment of Pharmacovigilance and Risk Assessment Committee (PRAC)

• Enhanced cooperation with European Monitoring Centre for Drugs and Drug Addiction (EMCDDA)

• Preparation of initial lists of European Union Reference Dates (EURD) for Periodic Safety Update Reports and Products under additional monitoring

Establishment of PRAC

• Nomination of PRAC members (except civil society representatives appointed by the EC).

• Meeting schedule for 2012:

• Inaugural meeting 19 and 20 July.

• 3,4,5 September

• 1,2,3,4 October

• 29,30,31 October

• 26,27,28,29 November

17

Establishment of PRAC

• Principles of meeting schedule: PRAC to take place two-weeks before CHMP and Coordination Group

• To ensure high quality PRAC outputs

• To ensure robust scrutiny by CHMP and Coordination Group

• To facilitate communications

• Rules of Procedure

• Chair and Vice-Chair were elected: June Raine (United Kingdom) and Almath Spooner (Ireland)

• Principles of Rapporteur appointment and Transparency/Communication agreed 18

Establishment of PRAC

• Definition of PRAC outputs to be handled:

– with a formal decision-making phase

– without a formal decision-making phase

19

PRAC outputs with formal decision-making phase

21

PRAC outputs with formal decision-making phase

Referrals Art. 107 & 31

PSUR Single

assessment

PASS results

Activities

22

PRAC outputs with formal decision-making phase

Referrals Art. 107 & 31

PSUR Single

assessment

PASS results

PRAC

PRAC AR

PRAC recommenda

-tion

European Medicines Web-portal = EMA website

Activities

23

PRAC outputs with formal decision-making phase

One CAP at least?

Referrals Art. 107 & 31

PSUR Single

assessment

PASS results

PRAC

PRAC AR

PRAC recommenda

-tion

European Medicines Web-portal = EMA website

Activities

24

PRAC outputs with formal decision-making phase

One CAP at least?

Referrals Art. 107 & 31

PSUR Single

assessment

PASS results

PRAC

CHMP

PRAC AR

PRAC recommenda

-tion

Yes

European Medicines Web-portal = EMA website

Decision-making process

Activities

25

PRAC outputs with formal decision-making phase

One CAP at least?

Referrals Art. 107 & 31

PSUR Single

assessment

PASS results

PRAC

CHMP

CHMP in line with

PRAC?

PRAC AR

PRAC recommenda

-tion

CHMP disagree-

ment

CHMP opinion

European Medicines Web-portal = EMA website

Decision-making process

Activities

Yes

26

PRAC outputs with formal decision-making phase

One CAP at least?

Referrals Art. 107 & 31

PSUR Single

assessment

PASS results

PRAC

CHMP

CHMP in line with

PRAC?

EC

PRAC AR

PRAC recommenda

-tion

CHMP disagree-

ment

EC decision

CHMP opinion

European Medicines Web-portal = EMA website

Decision-making process

Activities

Yes

27

PRAC outputs with formal decision-making phase

One CAP at least?

Referrals Art. 107 & 31

PSUR Single

assessment

PASS results

PRAC

CHMP

CHMP in line with

PRAC?

EC

MAH

Member States

PRAC AR

PRAC recommenda

-tion

CHMP disagree-

ment

EC decision

CHMP opinion

European Medicines Web-portal = EMA website

Decision-making process

Activities

Yes

28

PRAC outputs with formal decision-making phase

One CAP at least?

Referrals Art. 107 & 31

PSUR Single

assessment

PASS results

PRAC

CHMP

CHMP in line with

PRAC?

EC

Coord. Group

MAH

Member States

PRAC AR

PRAC recommenda

-tion

CHMP disagree-

ment

EC decision

No

CHMP opinion

European Medicines Web-portal = EMA website

Decision-making process

Activities

Yes

29

PRAC outputs with formal decision-making phase

One CAP at least?

Referrals Art. 107 & 31

PSUR Single

assessment

PASS results

PRAC

CHMP

CHMP in line with

PRAC?

EC

Coord. Group

MAH

Member States

PRAC AR

PRAC recommenda

-tion

CHMP disagree-

ment

EC decision

No

CHMP opinion

European Medicines Web-portal = EMA website

Decision-making process

Activities

Consen-sus?

Yes

30

PRAC outputs with formal decision-making phase

One CAP at least?

Referrals Art. 107 & 31

PSUR Single

assessment

PASS results

PRAC

CHMP

CHMP in line with

PRAC?

EC

Coord. Group

MAH

Member States

Consen-sus?

PRAC AR

PRAC recommenda

-tion

CHMP disagree-

ment

CG disagree-

ment

EC decision

No

CHMP opinion

CG position + timetable

European Medicines Web-portal = EMA website

Decision-making process

Activities

No

Yes

31

PRAC outputs with formal decision-making phase

One CAP at least?

Referrals Art. 107 & 31

PSUR Single

assessment

PASS results

PRAC

CHMP

CHMP in line with

PRAC?

EC

Coord. Group

MAH

Member States

Consen-sus?

PRAC AR

PRAC recommenda

-tion

CHMP disagree-

ment

CG disagree-

ment

EC decision

Yes

No

CHMP opinion

CG position + timetable

European Medicines Web-portal = EMA website

Decision-making process

Activities

No

Yes

PRAC outputs without formal decision-making phase

33

PRAC outputs without formal decision-making phase

Risk Management

Plan

Renewal

Type II safety

variation

Activities

Pharmacovigi-lance audits

Pharmacovigi-lance

inspections

Annual reassessment

Coordination of safety announce

-ments

34

PRAC outputs without formal decision-making phase

Risk Management

Plan

Renewal

Type II safety

variation

Activities

Pharmacovigi-lance audits

Pharmacovigi-lance

inspections

PRAC Advice

Annual reassessment

Coordination of safety announce

-ments

35

PRAC outputs without formal decision-making phase

Risk Management

Plan

Renewal

Type II safety

variation

Activities

Pharmacovigi-lance audits

Pharmacovigi-lance

inspections

PRAC Advice

Annual reassessment

Coordination of safety announce

-ments

Functionalities of EV and PSUR

repository

Activities

Black symbol for additional

monitoring

Literature monitoring

36

PRAC outputs without formal decision-making phase

Risk Management

Plan

Renewal

Type II safety

variation

Activities

Pharmacovigi-lance audits

Pharmacovigi-lance

inspections

PRAC Advice

Annual reassessment

Coordination of safety announce

-ments

Functionalities of EV and PSUR

repository

Activities

Black symbol for additional

monitoring

Literature monitoring

37

PRAC outputs without formal decision-making phase

Risk Management

Plan

Renewal

Type II safety

variation

Activities

Pharmacovigi-lance audits

Pharmacovigi-lance

inspections

PRAC Advice

PASS Protocol

Activities

Annual reassessment

Coordination of safety announce

-ments

Functionalities of EV and PSUR

repository

Activities

Black symbol for additional

monitoring

Literature monitoring

38

PRAC outputs without formal decision-making phase

Risk Management

Plan

Renewal

Type II safety

variation

Activities

Pharmacovigi-lance audits

Pharmacovigi-lance

inspections

PRAC Advice

PASS Protocol

Activities

PRAC output directly

applicable

Annual reassessment

Coordination of safety announce

-ments

Functionalities of EV and PSUR

repository

Activities

Black symbol for additional

monitoring

Literature monitoring

39

PRAC outputs without formal decision-making phase

Risk Management

Plan

Renewal

Type II safety

variation

Activities

Pharmacovigi-lance audits

Pharmacovigi-lance

inspections

PRAC Advice

PASS Protocol

Activities

PRAC output directly

applicable

Annual reassessment

Coordination of safety announce

-ments

Signal detection

Activities

Functionalities of EV and PSUR

repository

Activities

Black symbol for additional

monitoring

Literature monitoring

40

PRAC outputs without formal decision-making phase

Risk Management

Plan

Renewal

Type II safety

variation

Activities

Pharmacovigi-lance audits

Pharmacovigi-lance

inspections

PRAC Advice

PASS Protocol

Activities

PRAC output directly

applicable

Annual reassessment

Coordination of safety announce

-ments

Signal detection

Activities

PRAC Recommenda

-tion Functionalities of EV and PSUR

repository

Activities

Black symbol for additional

monitoring

Literature monitoring

41

PRAC outputs without formal decision-making phase

Risk Management

Plan

Renewal

Type II safety

variation

Activities

Pharmacovigi-lance audits

Pharmacovigi-lance

inspections

PRAC Advice

PASS Protocol

Activities

PRAC output directly

applicable

Annual reassessment

Coordination of safety announce

-ments

Signal detection

Activities

PRAC Recommenda

-tion Functionalities of EV and PSUR

repository

Activities

Black symbol for additional

monitoring

Literature monitoring

EURD list (PSUR)

(adopted by CHMP and CG)

‘Additional monitoring’

list

Activities

42

PRAC outputs without formal decision-making phase

Risk Management

Plan

Renewal

Type II safety

variation

Activities

Pharmacovigi-lance audits

Pharmacovigi-lance

inspections

PRAC Advice

PASS Protocol

Activities

PRAC output directly

applicable

Annual reassessment

Coordination of safety announce

-ments

Signal detection

Activities

PRAC Recommenda

-tion Functionalities of EV and PSUR

repository

Activities

Black symbol for additional

monitoring

Literature monitoring

EURD list (PSUR)

(adopted by CHMP and CG)

‘Additional monitoring’

list

Activities

Lists published on EMA website

43

Major achievements • Upgrade of EMA corporate website (e.g. publication of safety-related referrals through the PRAC, search tool, RSS feed for agendas and minutes)

• Establishment of Pharmacovigilance and Risk Assessment Committee (PRAC)

• Enhanced cooperation with European Monitoring Centre for Drugs and Drug Addiction (EMCDDA)

• Preparation of initial lists of European Union Reference Dates (EURD) for Periodic Safety Update Reports and Products under additional monitoring

44

• Article 28c(2): ‘The Agency and the EMCDDA shall exchange information that they receive on the abuse of medicinal products including information related to illicit drugs’.

• Working arrangement (first signed in 2010) amended by EMA and EMCDDA Directors to strengthen information-exchange practices.

• More timely response to potential public health threats

Enhanced cooperation with EMCDDA

45

Major achievements • Upgrade of EMA corporate website (e.g. publication of safety-related referrals through the PRAC, search tool, RSS feed for agendas and minutes)

• Establishment of Pharmacovigilance and Risk Assessment Committee (PRAC)

• Enhanced cooperation with European Monitoring Centre for Drugs and Drug Addiction (EMCDDA)

• Preparation of initial lists of European Union Reference Dates (EURD) for Periodic Safety Update Reports and Products under additional monitoring

46

List of European Union Reference Dates • Adopted by PRAC in September before presentation to CHMP and Coordination Group for agreement.

• Initial list (3,364 substances) to be published on 30th September – becomes binding as of April 2013.

• List will be updated monthly (maintenance process to be finalised).

47

Major achievements

• Development of proposal for black symbol

• Five Stakeholders meetings held (3 in 2011 and 2 in 2012)

• Enriched governance structure (maintained until end 2012 – to be reviewed)

48

Major achievements

• Development of proposal for black symbol

• Five Stakeholders meetings held (3 in 2011 and 2 in 2012)

• Enriched governance structure (maintained until end 2012 – to be reviewed)

49

Major achievements

• Development of proposal for black symbol

• Five Stakeholders meetings held (3 in 2011 and 2 in 2012)

• Enriched governance structure (maintained until end 2012 – to be reviewed)

50

Project Oversight Committee (ERMS-FG)

Project Coordination

Group

12 Subproject Teams and EMA Task-Force

EMA/MSs Project Team 1

- Audits / Inspections

EMA/MSs Project Team 2

- PSURs

EMA/MSs Project Team 3

- ADR Reporting / Additional reporting / Signals

EMA/MSs Project Team 4

- RMP/PASS/ PAES/ Effectiveness of risk minimisation

EMA/MSs Project Team 5

- Committees / Referrals

EMA/MSs Project Team 6

- Communica-tion / Transparency

Enriched governance structure

51

Project Oversight Committee (ERMS-FG)

+ ICT added

Project Coordination

Group + ICT added

12 Subproject Teams and senior management EMA Task-Force

EMA/MSs Project Team 1

- Audits / Inspections

EMA/MSs Project Team 2

- PSURs

EMA/MSs Project Team 3

- ADR Reporting / Additional reporting / Signals

EMA/MSs Project Team 4

- RMP/PASS/ PAES/ Effectiveness of risk minimisation

EMA/MSs Project Team 5

- Committees / Referrals

EMA/MSs Project Team 6

- Communica-tion / Transparency

Enriched governance structure - EMA Management Board

- Heads of Medicines Agency

- ICT Directors and various groups

52

Next steps • Lessons learnt exercise and gap analysis to be finalised

• Practical aspects of public hearings to be finalised

• SOPs/WINs/Templates being finalised

• Update of fees regulation and pharmacovigilance legislation led by the European Commission

• Sixth Stakeholders forum (8th November)

• Publication of initial lists (e.g. EURD list)

• Finalise prioritised implementation for 2012

53

Next steps • Lessons learnt exercise and gap analysis to be finalised

• Practical aspects of public hearings to be finalised

• SOPs/WINs/Templates being finalised

• Update of fees regulation and pharmacovigilance legislation led by the European Commission

• Sixth Stakeholders forum (8th November)

• Publication of initial lists (e.g. EURD list)

• Finalise prioritised implementation for 2012

54

Next steps • Lessons learnt exercise and gap analysis to be finalised

• Practical aspects of public hearings to be finalised

• SOPs/WINs/Templates being finalised

• Update of fees regulation and pharmacovigilance legislation led by the European Commission

• Sixth Stakeholders forum (8th November)

• Publication of initial lists (e.g. EURD list)

• Finalise prioritised implementation for 2012

55

Next steps • Lessons learnt exercise and gap analysis to be finalised

• Practical aspects of public hearings to be finalised

• SOPs/WINs/Templates being finalised

• Update of fees regulation and pharmacovigilance legislation led by the European Commission

• Sixth Stakeholders forum (8th November)

• Publication of initial lists (e.g. EURD list)

• Finalise prioritised implementation for 2012

56

Next steps • Lessons learnt exercise and gap analysis to be finalised

• Practical aspects of public hearings to be finalised

• SOPs/WINs/Templates being finalised

• Update of fees regulation and pharmacovigilance legislation led by the European Commission

• Sixth Stakeholders forum (8th November)

• Publication of initial lists (e.g. EURD list)

• Finalise prioritised implementation for 2012

57

Next steps • Lessons learnt exercise and gap analysis to be finalised

• Practical aspects of public hearings to be finalised

• SOPs/WINs/Templates being finalised

• Update of fees regulation and pharmacovigilance legislation led by the European Commission

• Sixth Stakeholders forum (8th November)

• Publication of initial lists (e.g. EURD list)

• Finalise prioritised implementation for 2012

58

Next steps • Lessons learnt exercise and gap analysis to be finalised

• Practical aspects of public hearings to be finalised

• SOPs/WINs/Templates being finalised

• Update of fees regulation and pharmacovigilance legislation led by the European Commission

• Sixth Stakeholders forum (8th November)

• Publication of initial lists (e.g. EURD list)

• Finalise prioritised implementation for 2012

59

Conclusion • Biggest change to the EU regulatory framework since 1995

• Funding (and staffing) remains the key risk to system sustainability

• Journey is not over yet but we have a direction of travel: focus on promotion and protection of public health!

60

Conclusion • Biggest change to the EU regulatory framework since 1995

• Funding (and staffing) remains the key risk to system sustainability

• Journey is not over yet but we have a direction of travel: focus on promotion and protection of public health!

61

Conclusion • Biggest change to the EU regulatory framework since 1995

• Funding (and staffing) remains the key risk to system sustainability

• Journey is not over yet but we have a direction of travel: focus on promotion and protection of public health!

62

Thank you

PSUR

PASS

PAES Article

57

PASS

RMP

Inspections

Pharmacovigilance audits Additional

monitoring

EURD list

Black symbol

Signal detection

Referrals PRAC

Pharmaco -vigilance systems

ADR reporting

Safety announ-cements

CHMP

Web forms

Renewal

Literature monitoring

Fees

EudraVigilance

Coordination Group

EC decision

Agendas

Minutes

EMCDDA

Implementing regulation

RoP

Lists

Public hearings

EU medicines web-portal

PRAC Mandate

Fees

Drug abuse

Medication errors

Public health

EMA

Member States

Signals

Lists PRAC advice

PRAC recommen

-dation

PHARMACOVIGILANCE

Good pharmacoVigilance practice (GVP)