Regulatory Capacity Regulatory Capacity Regulatory Capacity Regulatory Capacity

Strengthening and Strengthening and Strengthening and Strengthening and

Institutional Institutional Institutional Institutional

Development Plans: Development Plans: Development Plans: Development Plans:

Relevance to Relevance to Relevance to Relevance to

Influenza Vaccines Influenza Vaccines Influenza Vaccines Influenza Vaccines

Regulatory Capacity Regulatory Capacity Regulatory Capacity Regulatory Capacity

Strengthening and Strengthening and Strengthening and Strengthening and

Institutional Institutional Institutional Institutional

Development Plans: Development Plans: Development Plans: Development Plans:

Relevance to Relevance to Relevance to Relevance to

Influenza Vaccines Influenza Vaccines Influenza Vaccines Influenza Vaccines

Author: Mr. Lahouari Belgharbi, WHO Geneva Author: Mr. Lahouari Belgharbi, WHO Geneva Author: Mr. Lahouari Belgharbi, WHO Geneva Author: Mr. Lahouari Belgharbi, WHO Geneva

Presenter: Dr. Claudia P Alfonso, Scientist, WHO GenevaPresenter: Dr. Claudia P Alfonso, Scientist, WHO GenevaPresenter: Dr. Claudia P Alfonso, Scientist, WHO GenevaPresenter: Dr. Claudia P Alfonso, Scientist, WHO Geneva

5555thththth International Partners Meeting Influenza Vaccines, International Partners Meeting Influenza Vaccines, International Partners Meeting Influenza Vaccines, International Partners Meeting Influenza Vaccines, 27272727----28 28 28 28 March March March March 2012201220122012, Belgrade, Serbia, Belgrade, Serbia, Belgrade, Serbia, Belgrade, Serbia

Global challenges• Increased vaccine demand due to

global initiatives and coalitions

•Public awareness of vaccine safety, quality and efficacy increased through media, internet, social networks

•New vaccine QSS promoted by WHO and its expert committees

•Need to anticipate regulatory requirements to ease vaccine introduction

Global challenges• In-country QC systems need

increased sustained investment to meet demand for new vaccine testing

•Developing country production not consistent in volume, quality and cGMP

•Shift in vaccine market and increased segmentation: EPI vaccines production in developing countries; new vaccines production in developed countries

Global Initiatives/Coalitions to Promote

Immunization

WHO Expert Committee on Biological Standardization (ECBS)

Smallpox

Eradication

Polio Eradication

Measles Elimination

Global Action Plan (GAP) to Increase Influenza Vaccine Supply

Decade of vaccines (DoV)

Global Alliance for Vaccine & Immunization (GAVI)

Global Immunization Vaccine Strategy

UN Millennium Development Goals

(MDGs)

WHO Reform

WHO

Vaccine Prequalification (PQ)

Universal Child Immunization (UCI)

1947

1967 1977

19881987

1990

2000

2000

2006

2006

20102011

2020

2012

2015

Vaccine producing1990: 63 countries2010: 44 countries

Vaccine Demand Increased While Producing

Countries Decreased

1960 1980 2000

// //Diphtheria

Pertussis

Tetanus

YF Influenza

Polio

Measles

JERubella

HepB

Hib (conj)

Typhoid

CholeraPneumo (conj)

Rotavirus

HPV

Mening (conj)Dengue

MalariaTB

HIV/AIDS

Traditional

EPI

Underutilized

Vaccines

Future

The Vaccine Pipeline

Laboratory

access

Regulatory

inspections

Regulatory

inspections

Authorization clinical trials (Ethical review process, compliance against GLP,GMP,GCP)

Authorization clinical trials (Ethical review process, compliance against GLP,GMP,GCP)

Pre-marketing phase(licensing, registration, evaluation

process)

Post Marketing phase

Post marketing

AEFI

surveillance

Lot release

Market distribution

QualityQuality

SafetySafety

EfficacyEfficacy

Product

Evaluation

Product

Evaluation

Licensing

facility

ApplicationApplication

Applicants

Dossier (manufacturer or

distributor)

Applicants

Dossier (manufacturer or

distributor)

Marketing Authorization

(M.A.)

Marketing Authorization

(M.A.)

Vaccine Regulatory ProcessVaccine Regulatory Process

Inspections

testing

testing

monitoring

World Health Organization/Immunization, Vaccines and Biologicals (IVB), as of May

2011

WHO NRA Strengthening Program: the

5-Step Capacity Building Model

111 222 333 444 555 Su

sta

ina

ble

fu

nc

tio

na

l N

RA

indicators

Vaccine SourceUN agencyUN agency ProcureProcure ProduceProduce

PRIORITIES FOR IMPLEMENTATION

to ensure that all EPI vaccines are

of assured quality

�

�

�

�

�

�

�

�

�

�

�

�

�

�

�

� �

CTs : Clinical trls, UN: United Nations, AEFI: Adverse Events Following Immunization

Marketing Autorization & Licensing activities

Laboratory access

Regulatory inspections

Lot release

Authorization & monitoring of CTs

Postmarketing; AEFI

Regulatory system

for countries that conduct clinical trials

FunctionsundertakenBy producing countries with functional NRA

60 Member States with Functional NRA and IDP

(Oct 2011)

4/4/2012 10

2887 staff trained from countries

238 training sites

31 types of training courses

World Health Organization/Immunization, Vaccines and Biologicals (IVB), as of May 2011

NRA STATUS & INCOME GROUPS

VACCINE PRODUCING COUNTRIES, AS OF 2011

22

13

1

8

0% 20% 40% 60% 80% 100%

1.High income

2.All Middle & Low income

countries

Functional Not functional

NRA Status and Income Level

Vaccine Producing Countries (2011)

Vaccine Supply

OPV

35%

DTP

14%TT

10%

BCG

10%

Measles

6%

HepB

5%

Td

4%

MMR

4%

Influenza

4%

YF

2%Other

6%

Influenza

18%

Pneumo

16%

MMR

13%OPV

12%

DTP

10%

DTP-

HepB-Hib

8%

Varicella

6%

HepB

5%

DTP-

HepB-IPV

4%

Other

3%Meningoc

occal

5%

Vaccine Types

(Relative % of Doses)

Vaccine Types

(Relative % in US$)

5.5 Bn doses of vaccines

(2003-2004)

13.6 Bn US$ of vaccines

(2003-2004)For 158 WHO Member States (excl. China)

Vaccine Source

India

30%

Belgium

16%France

12%

Brazil

7%

Indonesia

7%

Italy

4%

USA

4%

Mexico

2%

Other

18%

Belgium

16%

France

14%

Mexico

8%

India

7%

Brazil

4%

Italy

2%

Korea

Rep.

2%

Other

11%

USA

36%

Vaccine Sources

(Relative % of Doses)

Vaccine Sources

(Relative % in US$)

5.5 Bn doses of vaccines

(2003-2004)

13.6 Bn US$ of vaccines

(2003-2004)For 158 WHO Member States (excl. China)

Vaccine Source

India

27%

France

18%

Japan

1%Korea Rep.

2%

Indonesia

2%Italy

3%

Denmark

1% Others

3%

Viet Nam

5%

Belgium

38% Brazil

29%

India

13%

France

11%

Thailand

10%

Belgium

9%

Indonesia

5%

Italy

3%

Others

13%

Russia

2%

USA

5%

Vaccine Sources in Poor Countries

(Relative % in US$)

656 Mill US$ of vaccines

(2003-2004)

1.61 Bn US$ of vaccines

(2003-2004)For 58 Poor and 50 MI WHO Member States (excl. China)

Vaccine Sources in MI Countries

(Relative % in US$)

Emerging Economies Becoming Major in

Vaccine Market% Share by volume % Share by value

*2011 – 2012 Data based on awards already made

Developing countriesIndustrialized countries

50

Major vaccine producing countries, 1997-2011146 vaccine manufacturers, 95% global production in 15 countries

Brazil

ChinaUSA

Senegal

Indonesia

India

Russia

France

Belgium

Italy

Canada

Japan

Korea

Denmark

Cuba

Developing countries

Emerging vaccine production in countries with high

potential to account for 80-70% global production

Brazil

South Africa

China

Mexico Senegal

Indonesia

IndiaViet Nam

Russia

Serbia

IranEgypt

Cuba

Countries with WHO prequalified vaccines

Impact and challenges• NRAs are critical to sustain new vaccine

introduction and to address quality, safety and efficacy issues • New vaccines with limited safety profile

• Sustaining new immunization policy through vaccine performance information (epidemiological data, safety profile, quality information)

• Investigating product quality defects and complaints leading to increased confidence in the new immunization programme

• Development of domestic vaccine production is limited without functional regulatory systems to address quality, safety and efficacy issues before, during and after licensure

Impact and challenges• Investment on a functional regulatory

system is cheap and always lead to increase confidence and credibility of the national immunization programme

• Sustaining global vaccine production requires investment in regulatory capacity and domestic production in developing countries

• Increased consultation between NRAs and Industry is needed to ensure optimal and timely use of new vaccines as well as to maintain public confidence in national immunization programmes

Acknowledgments and Credits

• The source of material used for this

presentation is the WHO NRA

Strengthening Programme database

containing information kindly provided

by the Member States

• Generation of all maps and graphs was

assisted by the IT support staff of the

WHO NRA Strengthening Programme