WHO Technical Briefing Seminar07 November 2019

Pharmacovigilance in WHO

Regulation of Medicines and other Health Technologies

Shanthi Pal

Group Lead, Medicines Safety, Safety & Viglance

2

WHO Regulatory Activities: Focus on Access and Outcomes

• Increase knowledge of real life adverse events and coordinate actions taken against adverse events

• Mitigate risks and protect against substandard / falsified products

• Contain antimicrobial resistance

• Set global norms and standards (written & physical) and nomenclatures

• Increase common understanding on regulatory requirements by authority & manufacturer

• Standardize approach used by quality control labs

• Set effective and efficient regulatory systems in LMICs through collaborative & harmonized approaches with reliance principles

• Increase confidence in medical products produced in LMICs

• Assure safety, quality, appropriateness & efficacy of medical products used in LMICs: medicines, vaccines, medical devices, cold chain equipment, vector control products & in vitro diagnostics

• Increase competition to shape the market

Reduced mortality and morbidity

Decreasedregulatory burden

Decreased costof regulation

Reduced time for regulation

Increased regulatory capacity in LMIC

Technologies,

Standards and Norms

Regulatory Systems

Strengthening

Prequalification

TeamSafety & Vigilance

2

Ensuring normative and technical excellence drives impact at country level

Dr Shanthi Pal

Medicines Safety Group Lead

Dr Noha Iessa

Technical Officer

Mr Takahiro Goto

Technical Officer

Mrs Leticia Megias

Technical Officer

Mrs Ayako Fukushima

Technical Officer

Ms Eirini Neofytou

Secretary

Mrs Luz Caguioa

Secretary

Medicines Safety Group

The programme

Achievements to date

The future

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Outline

Page 4

WHO Programme for International Drug Monitoring

• World Health Assembly Resolution 16.36

• INVITES Member States to arrange for a systematic collection of information on serious adverse drug reactions observed during the development of a drug and, in particular, after its release for general use.

5

How it started

Thalidomide

1961

WHO Programme for International Drug Monitoring (PIDM) 1968

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Growth of WHO Programme for International Drug Monitoring

Page 6

1968

Agreement between WHO and Kingdom of Sweden

Global Database of adverse events: Vigibase in Uppsala

Training, tools, research, signal detection

1978: Birth of the WHO Collaborating Centre for International Drug Monitoring (UMC)

WHO ‘s Role: Policies, Strategies, Guidelines, PV in Public Health Programmes

Key SAV Priorities in 2014 - 2018

WHO Advisory Committees: Safety of Medicinal Products (ACSoMP

2003

Other WHO Collaborating Centres that support PV

• Oslo (1982)

ATC DDD, training in Drug Utilization studies

• Morocco (2010) ✓ Francophone/Arabic

countries ✓ PV for preventing ADRs:

rational use of medicines✓ Cross cutting service across

health interventions

• India (2015)➢Regulatory Aspects➢Region focus: SE Asia

166 Members of the WHO PIDM, 136 Full members and 30 associate members

2019

WHO Programme for International

Drug Monitoring (PIDM) members

PV Centre

Regulatory Decisions

Communication, Training etc

Point of CareAdverse Events

Reporting

Data AnalysisTherapeutic

Decision

Minimum Pharmacovigilance

Operations

Global Data

0

5

10

15

20

25

1967 1969 1971 1973 1975 1977 1979 1981 1983 1985 1987 1989 1991 1993 1995 1997 1999 2001 2003 2005 2007 2009 2011 2013 2015 2017 2019

Mill

ion

s

What have we learnt so far?

SOURCE:WHO global database of ICSRs (Vigibase)

MEDICINES

Number of reports on adverse events with medicines

0

3

2

1

20

00

201

6

200

42

006

201

02

012

20

17

201

4

200

2

200

8

+14% p.a.

Annual meetings hosted in rotation by regions

▪ There is a global increase in the number of medicines adverse events reported, up to +60%p.a. in South East Asia. Part of this increase is due to rise in awareness thanks to trainings held by WHO

▪ There is a positive correlation between the region focus trainings and the increase in number of adverse report overtime (e.g., 4 region specific trainings in Africa, leading to a significant increase of reports submitted of 14% p.a. since 2000). Regions where lowest number of specific trainings held are also the regions where the number of reports overtime increase is the lowest (Americas region +3%p.a., European region +12% p.a.)

4

20

06

20

04

1

0

20

14

20

10

20

00

3

20

16

20

17

5

6

2

20

12

20

08

20

02

+17% p.a.

20

14

20

16

50

20

00

20

10

20

17

20

08

20

20

06

20

12

20

04

0

20

02

40

30

10

+12% p.a.

20

12

140

20

20

17

20

14

120

100

80

20

16

60

0

40

20

10

20

08

20

02

20

04

20

00

20

06

+3% p.a.

8

4

2

0

10

6

20

00

20

08

20

04

20

16

20

12

20

14

20

02

20

10

20

17

20

06

+60% p.a.

25

35

30

201

4

0

201

02

012

200

4

15

200

6

20

10

200

2

200

8

20

17

20

00

5

201

6

+25% p.a.

2007: Introduction of annual PVFrancophone course

2007: Introduction of active surveillance (malaria)

2008: Network of PV consultants for Africa

2016: Tools and training to improve quality of reports

2015: Regional meeting on Strengthening Pharmaco-vigilance systems

WHO PV Regional Networks 2010: PV training course for ASEAN countries started

2015: PV workshop (active monitoring) in Indonesia

2015: PV inspection course in China

2015: PV inspection course in Malaysia

2017/18: Joint Assessments

2010: Active surveillance of HIV medicines

2012: WHO guideline on Patient Reporting

2008: Affordable PV data management system developed for LMICs

2010: WHO-Global Fund decision to include Min PV in GF grants;

2011: WHO ISoP PV Curriculum Developed

Other systems that had an

impact on global reporting

Other systems that had an impact

on global reporting

South-East Asian regionEastern Mediterranean region European region American regionAfrican region Western pacific region

Average # ICSRs submitted to WHO / 100,000 population of reporting countries

Key regional training activities to strengthen reporting (excluding annual meetings)

Unravelling the growth factors

Factors that contributed to increasing reporting rates……. tailored efforts

• Dialogue with Global Fund: PV in programmes where large vols of medicines are used (HIV, malaria, TB, through Global Fund)

• If we complement Spontaneous Reporting with Active Surveillance

• If we used appropriate technology (Vigiflow, e-reporting, Apps)

• If we had the relevant legal framework (patient reporting, ME)

• Then we would have >>> impact

>>c16

PHARMACOVIGILANCE LANDSCAPE IN LMICS

Main Strengths▪Most LMICs with established

national PV center for data collection and upload to WHO Safety Database

▪Strong willingness to improve PV systems

Challenges▪ Low local capacity / capability to

analyze data collected

▪ Low NRA capacity / capability to take action from alert signals received: Only a small fraction (3 in 55 according to 2010 survey by WHO) of the NRAs regularly take specific actions from signals

17

What are the PV ‘asks’ in LMIC

• Lack of political support

• Lack of resources

• Lack of stakeholder

engagement /competence

• Lack of Regulatory systems

or inadequate function

• Lack of communication and information exchange

%

Implemente

d out of the

total

countries in

the region

%

Implemente

d (of those

with data

available)

Number of

Countries

with Indicator

Implemented

Number of

Countries

with data

available

Number

of

Countrie

s

Group of

countries

9494454848A. Industrialized

133851339B. Upper middle

income

92951757C1.Lower middle

income

41221749C2.Low income

Capacity to detect significant vaccine safety issue

WHO survey of PV systems in 55 countries

Smart Safety Surveillance: Risk-based prioritization of PV activities

3S Core Approach (1)

• Risk-based prioritization

Choosing a few priority Products: Exclusive to your region/country; little product-experience worldwide; large volume of expected use etc

• Making holistic plans: from legal framework to data collection, analysis and action, to manage risks

• Choosing appropriate tools and methods• Registers? Active/solicited monitoring? Studies?

• E reporting? Apps?

• Leveraging available resources:

• Vigibase, Vigiflow

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• Reliance: • RMP plus Annex?

• Sentinel sites for studies: Others in the region better placed to investigate signals?

• Work sharing: joint assessments; regional safety review committees

• Identifying what cannot be delegated: • point of care, case management,

• oversight of RMP

• National data management, causality assessment, signal detection

• B/R decisions for your populations

• Communication strategy

3S Core Approach (2)

Sustaining PVMaking 3S/PV part of a bigger story

Page 22

23

SDG 3 – Target 3.8

Achieve universal health coverage, including

financial risk protection, access to quality essential

health-care services and access to safe,

effective, quality and affordable essential

medicines and vaccines for all.

24

To continue to support Member States upon their request in the area of regulatory system strengthening, including, as

appropriate, by continuing to:

Evaluate national regulatory systems

Apply WHO evaluation tools

Generate and analyze evidence of regulatory system performance

Facilitate the formulation and implementation of institutional development plans

Provide technical support to national regulatory authorities and governments

WHA Resolution 67.20 What WHO should do

WHO Five-Step Process for Strengthening Regulatory Systems

PRE MARKETING

Pre-clinical ClinicalProducti

on&

Quality Control

Marketing and sales

Post-Marketi

ng

Non Common Regulatory

Function (vaccine)

WHO RECOMMENDED REGULATORY FUNCTIONS FOR MEDICINES AND VACCINES BASED ON PRODUCT LIFECYCLE

Common Regulatory

Functions for medicines &

vaccines

Medical devices and IVDs, blood & blood

pdts (2020)

POST MARKETING PRODUCT LIFECYLCE

National Regulatory System (RS)

Regulatory Inspection (RI)

Laboratory Access and Testing (LA)

Clinical Trials Oversight (CT)

Vigilance (PV)

Licensing premises (LI)

Registration & marketing authorization (MA)

Market surveillance and Control (MS)

NRA Lot release (LR)

Integrating PV and 3S principles into the Institutional Development Plan (IDP)

27

NRA

Benchmarking

Include 3S PV in the IDP as

part of end to end Regulatory

System Strengthening

NRA

Re-Assessment

Assessed

gaps

Institutional

Development Plan &

Implementation

Stepwise and

measurable

progress

PV as part of NRA

Benchmarking

PV as part

of NRA Re

assessment

28

Key Themes of WHO’s 13th Draft General Programme of Work 2019-

2023

Mission Promote Health - Keep the World Safe - Serve the Vulnerable

Strategic Priorities

Health Coverage: 1 billion more people with health coverageHealth Emergencies: 1 billion more people made saferHealth Priorities: 1 billion lives improved

Strategic Shifts

Set up global

leadership

Focus

global

public

goods

on

impact

Drive impact in every country

Policy dialogue

Strategic support

Technical assistance

Service delivery

Fragile health

system

Mature health system

Strategic

Strategic shift in how we support countries

Short term Medium term Long term

Low

reso

urc

e N

RA

sM

ed

ium

re

sou

rce

NR

As

Hig

h

re

sou

rce

NR

As

Min PVReliance

Infrastructure and Capacity

Core Competence (self development)Collaboration& Cooperation

Targeted investigations

Technical support to other NRAs Sentinel sites

Host multi-country platforms

< 2 y < 5 y > 5 y

Selective Tiered Approach & Linked with the WHO GBT, GRP Principles