1. 1 WHO Prequalification of Medical Products (medicines, vaccines, diagnostics and medical devices) Dr Lembit Rägo Regulation of Medicines and Other Health Technologies Essential Medicines and Health Products World Health Organization Geneva Switzerland ragol@who.int

2. 2 Content Why we do it and how we do it? Organizational context Snapshot of activities Prequalification of medicines Prequalification of vaccines Prequalification of in vitro diagnostics and devices Prequalification of APIs Opportunities for the new joint prequalification programme Future vision on prequalification Conclusions

3. What is special about medical products? Advances in science and technology create new increasingly sophisticated medical products Neither health professionals nor patients/customers are able to assess the quality, safety and efficacy/performance of these products without special education and training Result - medical products belong to most regulated products In national settings subject to marketing approval registration by competent authorities/national (regional) regulatory authorities 3

4. Why we do it? Modern health systems depend a lot on availability and ACCESS to safe, effective quality medical products Medical products (medicines, vaccines, diagnostics, devices) Scientific assessment of quality, safety and efficacy (performance) Regulatory Approval Prequalification Innovation: Science and technologies 4

5. How we do it? WHO uses the same scientific principles to assess the products safety, quality and efficacy/performance as well-resourced national regulators: - scientific assessment of documentary evidence for quality, safety and efficacy - site inspections for GMP/QMS, GLP and GCP - Independent laboratory evaluation for IVDs - control of variations to products and their manufacturing processes - post-approval monitoring of quality and safety - where possible cooperating and relying on other regulators decisions avoiding duplication 5

6. 6 Prequalification is NOT stand alone activity Many other technical work areas support and link to prequalification (medicines, vaccines, in vitro diagnostics and medical device s) Outside EMP – Disease oriented departments/programs, IVB Department, Strategic Advisory Group of Experts (SAGE) on Immunization; Regional and Country Offices Inside EMP – Norms and standards work/Quality Assurance, Safety/Vigilance, Activities to combat SFFC medical products, NRA strengthening, Policy, Innovation and technology transfer

7. Structure of the new WHO/HQ regulatory unit 7 Regulation of Medicines and other Health Technologies Lembit Rägo Norms and Standards David Wood Regulatory systems strengthening Nora Dellepiane Prequalification Lembit Rägo a.i. Safety and Vigilance Clive Ondari Medicines - Lembit Rägo Vaccines – David Wood In Vitro Diagnostics – Irena Prat Medical devices – Adriana Velazquez

8. New prequalification team: five functional groups PQT Coordinator Medicines assessment Matthias Stahl Vaccines assessment Carmen Rodriquez Diagnostics assessment Irena Prat Inspections services Deus Mubangizi Technical assistance and laboratory services Milan Smid 8

9. Major activities Prequalification of PRODUCTS –Medicines (HIV/AIDS, malaria, TB, antivirals, RH, NTD etc.) –Vaccines –In vitro diagnostics, medical devices Prequalification of Active Pharmaceutical Ingredients (APIs) Prequalification of Quality Control Laboratories (for medicines) Training and capacity building (regulators/manufacturers) Scientific advice and technical assistance to manufacturers 9

10. 10 Vaccines: Different starting point for PQ GMP Reliance on NRA Meeting WHO requirements and tender specifications Consistency of final product characteristics Clinical data

11. Polio end-game strategy The Strategic Advisory Group of Experts on Immunization (SAGE), recommended in 2012 the withdrawal of the type 2 component of oral polio vaccine (OPV) from routine immunization programmes in all countries, facilitated by the introduction of at least one dose of IPV Weekly epidemiological record wer 8901 Registration of IPV and bOPV in all countries Mapping regulatory status at global level and regulatory pathways to facilitate license at global level

12. Revision of procedure: Alignment with medicines procedure WHO NRA Manufacturers Agreement Joint review Facilitated license

13. 13 Total Volume of HIV Test Procurement PQ vs non-PQ (all assay types, all data) % PQ6979868183 % Non PQ3121141917

14. 14 Progress has exceeded expectations, due in part to the willingness of manufacturers previously involved with PQP to participate. Prequalification of APIs 1 Jan 20111 Jan 20121 Jan 201328 Feb 2014 Cumulative number of applications received 23674113 Cumulative number of APIs Prequalified 082856

15. Prequalified/interested QCLs (31 December 2013) 15

16. 16 Trainings in medicines and QC labs area: More than 1900 participants annually

17. First ever joint PQ progress report published 17 http://apps.who.int/prequal/ http://www.who.int/immunization_standards /vaccine_quality/pq_system/en/ http://www.who.int/diagnostics_laboratory/ evaluations/en/

18. 18 What WHO PQ can offer to the regulators and industries in the regions? Regulators –Capacity building/training – improved technical knowledge and skills incl. rotational fellows from NRAs –Practice and experience for collaboration and cooperation –Offers a lot of practical tools and guidelines –Helps to build more credible regulatory systems –Save resources Industries –Access to international funds –Better quality production/products/regulatory knowledge – better access to markets –Better image, more trust from procurement and regulators

19. Several mechanisms to help national approval of prequalified products launched 19 –Joint assessment of selected products with interested national regulators (so far two rounds with EAC regulators). "Two in one" or PQ and NRA assessment together –Collaborative Registration Procedure (CRP) which enables to exchange confidential regulatory information about PQd products. "Second built on the first" – NRA decision making based on PQ assessment

20. Opportunities for the new joint prequalification programme "One structure, one entry" – more clear for all internal and external parties/partners Harmonization and alignment between product streams, learning from best practices, streamlined PQ for IVDs Increase in efficiency and reach out Better coordinated and more efficient working within the organization, with national/regional regulators and other partners e.g. confidentiality arrangements for PQT with EU EMA and TGA under way Potential efficiency savings (admin costs etc.) … 20

21. Future vision on prequalification Consolidating the programmes for better efficiencies, communication and reach out Increasing collaboration with NRAs for better access to safe and effective quality products through shorter timelines for approvals Facilitating harmonization and regulatory convergence Building national and regional regulatory capacities using both continuity and change Transferring PQ functions to individual and regional NRAs/NRA networks – from pilots to step by step transfer of certain functions/product categories 21

22. 22 PQP is a powerful and effective mechanism to promote access to quality medical products PQP saves lives PQP is not a replacement for national regulatory systems but a (time limited) mechanism to promote access to quality medicines PQP is a major proactive contributor to capacity building both for regulators and local manufacturers PQP promotes collaboration and cooperation among regulators, including relying on each others work and reducing duplications Conclusions

23. Selected references Ellen F. M. ‘t Hoena, Hans V. Hogerzeil, Jonathan D. Quick, Hiiti B. Sillo. A quiet revolution in global public health: The World Health Organization’s Prequalification of Medicines Programme. Journal of Public Health Policy, 16 January 2014 Isabel Ortega Diego, Antony Fake, Matthias Stahl, Lembit Rägo. Review of Quality Deficiencies Found in Active Pharmaceutical Ingredient Master Files Submitted to the WHO Prequalification ofn Medicines Programme. Pharm Pharm Sci (www.cspsCanada.org) 17(2) 169 - 186, 2014 Nora Dellepiane, David Wood. Twenty-five years of the WHO vaccines prequalification programme (1987–2012): Lessons learned and future perspectives. Vaccine, 2014 (in press) Wondiyfraw Z Worku, John Gordon, Matthias MS Stahl, Lembit Rägo. Deficiencies in generic product dossiers as submitted to the WHO prequalification of Medicines Programme. Journal of Generic Medicines 9(2) 63–74, 2012 23