Transcript Drug Regulatory Systems Strengthening (RSS) WHO Technical Briefing Seminar on Essential Medicines and Health Products 31 October 2013 WHO Headquarters, Geneva, Salle M 505 Dr Claudia.

Drug Regulatory Systems
Strengthening (RSS)
WHO Technical Briefing Seminar on Essential
Medicines and Health Products
31 October 2013
WHO Headquarters, Geneva, Salle M 505
Dr Claudia P Alfonso
Outline
 Global overview of vaccine production and immunization
 The WHO Regulatory Systems Strengthening (RSS)
Programme and the five-step capacity building model
 Assessments of national regulatory authorities (NRA) and
harmonized tool development
 NRA Institutional
Development Plans (IDP)
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 Link between WHO Prequalification and NRA assessment
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Global initiatives: coalition to support immunization
2015
2020
Decade of vaccines (DoV)
WHO reform
2011
2010
2000
Global Immunization Vaccine Strategy
2006 Measles
elimination
1999
IFFIm
2006
International Finance Facility
For Immunization
Global Alliance for
Vaccine & Immunization (GAVI)
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WHO
1987Vaccine prequalification (PQ)
1959
1947
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2015
UN Millennium Development Goals
(MDGs)
2000
Smallpox
1980
eradication
Polio eradication
1988
Universal Child Immunization (UCI) -1990
1990
Expanded Programme on Immunization - 1974
WHO Expert Committee on Biological Standardization (ECBS)
Global challenges
1. Demand for more vaccines
2. Raise of public awareness about
vaccines
3. New standards promoted by WHO
4. Anticipate new needs for
regulation vaccines
1. New initiatives and global coalition efforts:
GAVI, DoV, influenza, polio eradication,
measles immunization, introduction of
new vaccines, others
2. Public and media expectations increased
through media, internet and social
networks
3. Vaccine science requires new standards
5. Quality control systems
established in countries need
increased investment to be
sustained
4. Vaccines needs thorough regulations to
address specificity
6. Domestic production |not
consistent in volume and quality
has difficulty to meet cGMP
standards
6. Volume increasing and cGMP standards
raising too
7. Shift in vaccine market and
increase segmentation
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5. QC is more complex and expensive
7. EPI vaccines are traditionally produced by
developing countries while new vaccines
are produced by developed countries.
Vaccine demand increases while number of
producing countries decreases
Vaccine producing
1990: 63 countries
1997: 52 countries
2012: 44 countries
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Major vaccine producing countries 1997-2012
146 vaccine manufacturers, 95% global production in 16 countries
Denmark
Russia
Belgium
Bulgaria
France
Italy
China
Canada
USA
Cuba
Senegal
India
Japan
Korea
Indonesia
Brazil
Developing countries
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12 Developing countries
with emerging vaccine production or high potential
to account for 80-70% of the global production
Russia
Bulgaria
Egypt
Cuba
Mexico
Senegal
China
Iran
India
Viet Nam
Indonesia
Brazil
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Largest volume production
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UNICEF purchases 40% of global volume of vaccine doses
mainly EPI vaccines which represents only 5% of market value
Global Volume of Doses
Global Value of Doses
40%
5%
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Vaccines are different from drugs
 Biological products (Variation)
 Heat sensitive (Cold chain)
 Sensitive to light and freezing

Limited shelf life
 Mandated by public health programme (EPI or NIP)
 Targeted to healthy children and mothers
 Given| for prevention - recipient cannot judge treatment
 Pennies per dose, new vaccines are more expensive
 Limited number of products and manufacturers
 Given once or only a few times
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WHO Prequalification Principals
 Reliance on NRAs
 General understanding of the product
– presentations offered
– production process
– quality control methods
– quality system in place
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– clinical data
relevant to the target population
 Assurance of production consistency through compliance
with GMP
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WHO DEFINITION
OF VACCINES OF ASSURED QUALITY
 The National Regulatory Authority (NRA) is
able to regulate independently vaccines against
standards of quality, safety and efficacy (QSE)
in accordance with the WHO recommended
functions defined by WHO, and
 There are no unresolved confirmed reports of
quality-related problems.
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Ensuring vaccine quality for use in national immunization
programmes: concept evolution
Training
1996
Benchmarking
1997
Assessment Technical
support
1997
1998
Monitoring
Progress
2004
Impact
2011
Regulatory Systems Strengthening
60 functional NRAs, 80% of all producing countries, 97% vaccines of assured quality
Bench Marking
Development of
NRA assessment
tool
1
Assessment of
NRA
Development of
Institutional
Development Plan
(IDP)
Providing
technical support,
Training/Learning,
networking,
Monitoring
progress and
impact
2
3
4
5
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Revised
indicators
(2-3 years)
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Re-assessment
Every 2-5 years
Functional NRA
WHO NRA Five-Step Capacity Building
Model
Applicants
Dossier
(manufacturer or
distributor)
Vaccine regulatory process
Pre-marketing phase
Post Marketing phase
Market distribution
Licensing/Registration=evaluation process
Product
Evaluation
Lot release
testing
Application
testing
Quality
Safety
Efficacy
Post marketing
AEFI
surveillance
Laboratory
access
Licensing Regulatory
inspections
facility
Inspections
Authorization clinical trials
(Ethical review process, compliance against GLP, GMP, GCP)
Marketing Authorization
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monitoring
Regulatory function
to implement
Vaccine source
UN agency
Procure
Produce
Regulatory system (RS)
√
√
√
Marketing authorization
and licensing (MA)
√
√
√
Pharmaco-vigilance (PV)
including AEFI
monitoring
√
√
√
Undertaken
by WHO on
behalf of UN
agencies or
producing
countries
√
√
√
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Lot release (LR)
Laboratory access (LA)
Regulatory inspections
(RI)
Oversight or clinical trials
(CT)
Undertaken
by the
producing
country
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Chronology of indicators in the WHO NRA assessment
tool for vaccines
NRA ASSESSMENT TOOLS: 1999, 2001, 2002, 2004 & 2007
Progress of the number of total & critical indicators and sub-indicators
200
183
173
180
181
173
164
160
140
128
120
100
88**
80
70**
63
60
61
54
54
32
40
20
4*
4*
2001
2002
53
51
45
38
0
1999
2004
2007
2011
NRA assessment tools
Total indicators
*Critical but not for Pre-qualification (PQ)
**Critical as required for vaccine PQ
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Total critical indicators
Total sub-indicators
Total critical sub-indicators
Harmonized tool: regulatory functions
1. NATIONAL REGULATORY SYSTEM
2. REGISTRATION AND MARKETING AUTHORIZATION
3. LICENSING ACTIVITIES
4. POST-MARKETING SURVEILLANCE (+ LOT RELEASE FUNCTION)
5. OVERSIGHT OF CLINICAL TRIALS
6. INSPECTIONS AND ENFORCEMENT ACTIVITIES
7. LABORATORY ACCESS AND TESTING
8. VIGILANCE AND RISK MANAGEMENT
9. CONTROL OF PROMOTION AND ADVERTISING
10. CONTROL OF NARCOTICS, PSYCHOTROPIC SUBSTANCES AND
PRECURSORS
11. PHARMACEUTICAL PERSONNEL
National Regulatory System,
18 | Status of vaccine indicators
Regulatory functions: former and harmonized tool
PAHO TOOL
1. SISTEMA NACIONAL DE
REGULACIÓN
MEDICINES TOOL
Module 2 - NATIONAL
REGULATORY SYSTEM
2. AUTORIDAD REGULADORA Module 3 - NATIONAL
NACIONAL
REGULATORY AUTHORITY
3. REGISTRO SANITARIO
Module 4 - MARKETING
AUTHORIZATION
4. LICENCIAMIENTO DE
PRODUCTORES
Module 5 - LICENSING OF
MANUFACTURERS
Module 6 - LICENSING OF
IMPORTERS, EXPORTERS,
WHOLESALERS AND
DISTRIBUTORS
Module 7 - LICENSING OF
PHARMACIES AND RETAIL
OUTLETS
Module 8 - REGISTRATION OF
PHARMACY PERSONNEL
National Regulatory System,
19 | Status of vaccine indicators
MEDICAL DEVICES &
DIAGNOSTICS
VACCINES TOOL
WHO-PAHO
HARMONIZED TOOL
NRS: NATIONAL REGULATORY RS: NATIONAL REGULATORY
SYSTEM
SYSTEM
1.NATIONAL REGULATORY
SYSTEM
MA: MARKETING
AUTHORIZATION (MA) FOR
MEDICAL DEVICES AND
DIAGNOSTICS
2.REGISTRATION AND
MARKETING
AUTHORIZATION
LI: LICENSING OF
MANUFACTURERS,
IMPORTERS, DISTRIBUTERS
AND RETAILERS OF MEDICAL
DEVICES AND DIAGNOSTICS
FUNCTION 1: MARKETING
AUTHORIZATION AND
LICENSING ACTIVITIES
3.LICENSING ACTIVITIES
11.PHARMACEUTICAL
PERSONNEL
(HEALTH/REGULATORY??)
Regulatory functions: former and harmonized tool
PAHO TOOL
MEDICINES TOOL
MEDICAL DEVICES &
DIAGNOSTICS
VACCINES TOOL
5. VIGILANCIA DEL MERCADO
Module 9 - POST-MARKETING
SURVEILLANCE AND CONTROLS
PMS: POST- MARKETING
SURVEILLANCE
6. FARMACOVIGILANCIA
Module 11 PHARMACOVIGILANCE
VR: VIGILANCE AD RISK
MANAGEMENT ACTIVITIES ON
MEDICAL DEVICES AND
DIAGNOSTICS
Module 10 - CONTROL OF
MEDICINES PROMOTION AND
ADVERTISING
PR: CONTROL OF PROMOTION
AND ADVERTISSEMENT FOR
HEALTH PRODUCTS
Module 12 - CLINICAL TRIALS
CT: OVERSIGHT OF CLINICAL
TRIALS on IVDs and MD
FUNCTION 6: REGULATORY
5.OVERSIGHT OF CLINICAL
OVERSIGHT OF CLINICAL TRIALS TRIALS
IE: INSPECTIONS AND
ENFORCEMENT ACTIVITIES
FUNCTION 5: REGULATORY
INSPECTIONS
6.INSPECTIONS AND
ENFORCEMENT ACTIVITIES
Module 14 - QUALITY CONTROL LABORATORY ACCESS AND
LABORATORY
TESTING
FUNCTION 4: LABORATORY
ACCESS
7.LABORATORY ACCESS AND
TESTING
7. CONTROL DE ENSAYOS
CLÍNICOS
8. INSPECCIONES REGULADORAS Module 13 - REGULATORY
Y ACTIVIDADES DE
INSPECTIONS AND
FISCALIZACION
ENFORCEMENT ACTIVITIES
9. LABORATORIO NACIONAL DE
CONTROL DE CALIDAD
FUNCTION 2: POST-MARKETING
ACTIVITIES INCLUDING
SURVEILLANCE OF ADVERSE
EVENTS FOLLOWING
IMMUNIZATION (AEFI)
WHO-PAHO HARMONIZED
TOOL
4.POST-MARKETING
SURVEILLANCE (includes vaccine
lot release function)
8.VIGILANCE AND RISK
MANAGEMENT
9.CONTROL OF PROMOTION AND
ADVERTISING
FUNCTION 3: NRA LOT RELEASE
Module 15 - CONTROL OF
NARCOTICS, PSYCHOTROPIC
SUBSTANCES AND PRECURSORS
National Regulatory
Module 16System,
- INTERNATIONAL
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20 Status of vaccine
COOPERATION
AND
indicators
HARMONIZATION
10.CONTROL OF NARCOTICS,
PSYCHOTROPIC SUBSTANCES
AND PRECURSORS
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2013 NRA STATUS PER WHO REGION
Functional
Not functional
Grand Total
AFR
5
41
46
AMR
4
31
35
EMR
7
15
22
EUR
33
20
53
SEAR
4
7
11
WPR
7
20
27
Grand Total
60
134
194
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GRACIAS
MERCI