Outline

1. Drug Regulatory Systems Strengthening (RSS)WHO Technical Briefing Seminar on Essential Medicines and Health Products31 October 2013WHO Headquarters, Geneva, Salle M 505Dr Claudia P Alfonso

2. 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) • Link between WHO Prequalification and NRA assessment

4. Global initiatives: coalition to support immunization Decade of vaccines (DoV) 2020 WHO reform 2015 2011 2010 Global Immunization Vaccine Strategy 2000 2006 2015 2006 Measles elimination IFFIm International Finance Facility For Immunization UN Millennium Development Goals (MDGs) 2000 Global Alliance for Vaccine & Immunization (GAVI) 1999 Polio eradication 1988 WHO Vaccine prequalification (PQ) 1987 Universal Child Immunization (UCI) -1990 Smallpox eradication 1959 1980 1990 Expanded Programme on Immunization - 1974 WHO Expert Committee on Biological Standardization (ECBS) 1947

5. Global challenges Demand for more vaccines Raise of public awareness about vaccines New standards promoted by WHO Anticipate new needs for regulation vaccines Quality control systems established in countries need increased investment to be sustained Domestic production not consistent in volume and quality has difficulty to meet cGMP standards Shift in vaccine market and increase segmentation • New initiatives and global coalition efforts: GAVI, DoV, influenza, polio eradication, measles immunization, introduction of new vaccines, others • Public and media expectations increased through media, internet and social networks • Vaccine science requires new standards • Vaccines needs thorough regulations to address specificity • QC is more complex and expensive • Volume increasing and cGMP standards raising too • EPI vaccines are traditionally produced by developing countries while new vaccines are produced by developed countries.

6. Vaccine demand increases while number of producing countries decreases Vaccine producing 1990: 63 countries 1997: 52 countries 2012: 44 countries

7. Major vaccine producing countries 1997-2012 146 vaccine manufacturers, 95% global production in 16 countries Denmark Russia Belgium Canada Bulgaria France Italy China USA Japan Cuba Korea India Senegal Indonesia Brazil Developing countries

8. 12 Developing countries with emerging vaccine production or high potential to account for 80-70% of the global production Russia Bulgaria China Iran Egypt Cuba Viet Nam India Mexico Senegal Indonesia Brazil Largest volume production

9. 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%

10. 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

11. WHO Prequalification Principals • Reliance on NRAs • General understanding of the product • presentations offered • production process • quality control methods • quality system in place • clinical data relevant to the target population • Assurance of production consistency through compliance with GMP

12. 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.

13. Ensuring vaccine quality for use in national immunization programmes: concept evolution Training Benchmarking Assessment Impact Technical support Monitoring Progress 1996 1997 1997 1998 2004 2011 Regulatory Systems Strengthening 60 functional NRAs, 80% of all producing countries, 97% vaccines of assured quality

14. WHO NRA Five-Step Capacity Building Model Functional NRA 2 1 5 3 4 Revised indicators (2-3 years) Re-assessment Every 2-5 years

15. Vaccine regulatory process Applicants Dossier (manufacturer or distributor) Pre-marketing phase Post Marketing phase Market distribution Licensing/Registration=evaluation process Product Evaluation Post marketing AEFI surveillance Lot release testing Application testing Laboratory access Regulatory inspections Licensing facility Quality Inspections Safety monitoring Authorization clinical trials (Ethical review process, compliance against GLP, GMP, GCP) Efficacy Marketing Authorization

17. Chronology of indicators in the WHO NRA assessment tool for vaccines

18. 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

19. Regulatory functions: former and harmonized tool

20. Regulatory functions: former and harmonized tool

22. 2013 NRA STATUS PER WHO REGION

25. GRACIAS MERCI