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? How we do it? Snapshot updates from Prequalification of medicines Prequalification of vaccines Prequalification of diagnostics and devices Opportunities for the new joint prequalification programme Future vision on prequalification Conclusions

3. 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 Science and technologies 3

4. 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 4

5. How we do it? Although WHO is NOT a regulator it uses the same scientific principles to assess the products safety, quality and efficacy/performance as do national regulators - scientific assessment of documentary evidence for quality, safety and efficacy - site inspections for GMP, GLP and GCP - control of variations to products and their manufacturing processes - post-approval monitoring of quality and safety 5

6. 6 Prequalification is NOT stand alone activity Many other technical work areas support and link to prequalification (medicines, vaccines, 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. First ever joint PQ progress report published 7

8. Medicines (PQRx) 8

9. 9 Prequalification of Medicines  Since 2001 the UN Prequalification Programme managed by WHO is ensuring that medicines procured with international funds are of assessed and inspected for quality, efficacy and safety, involves Prequalification programme for medicines (finished dosage forms) Prequalification of active pharmaceutical ingredients (APIs) Prequalification of quality control (QC) laboratories  The Prequalification Programme is an action plan for expanding access to priority essential medicines in the following four areas: - HIV/AIDS - Tuberculosis - Malaria - Reproductive Health - Selected individual products for other diseases (Flu, Zinc sulphate)

10. Highlights – finished dosage forms Products 397 FPPs prequalified over time (since 2001) 347 prequalified FPPs listed on the website 48 FPPs prequalified in 2012 (35 in 2011), including 16 “firsts” i.e. product types not previously prequalified (20 in 2011) Re-assessment and variations 44 prequalified FPPs undergoing requalification review 521 variation submissions to prequalified FPPs and 80 variations to API master files assessed in 2012 Pipeline Over 150 products under assessment 82 new applications received in 2012 (68 in 2011), 73 accepted after screening 10

11. API prequalification Prequalified APIs (since 2011) 40 prequalified APIs from India (31), China (8) and Italy (1) listed on the WHO website 20 APIs prequalified in 2012 (8 in 2011) Important “firsts” in 2013: - Prequalification of a contraceptive API (June) - Acceptance of semi-synthetic artemisinin (May) Pipeline 38 applications received in 2012 42 APIs under assessment 11

12. Quality Control labs Prequalified QCLs (since 2004) Total of 27 prequalified laboratories in all six WHO regions listed on the website 5 laboratories prequalified in 2012 (6 in 2011), including the first one in China Pipeline 33 laboratories working towards prequalification 5 expressions of interest for laboratory prequalification received in 2012 12

13. Vaccines (PQVx) 13

14. Prequalified vaccines and pipeline 129 prequalified vaccines listed on the website Total of 14 vaccines under assessment 7 new submissions in 2012 — one completed, six ongoing Variation control 53 manufacturers’ annual reports reviewed in 2012, giving rise to review of 448 variations Guidance on variations and variation reporting by manufacturers published for comment in February 2013 Re-assessment 12 prequalified vaccines reassessed in 2012 14

15. Monitoring, complaints, safety reports Random testing 154 vaccine lots tested by WHO-contracted laboratories in 2012 Follow-up of potential quality issues 15 complaints investigated in 2012 9 reports of AEFI communicated to WHO in 2012 (7 in 2011), of which 7 were serious. None was linked to a quality defect, 3 were due to programmatic error 15

16. Collaboration with NRAs 109 meetings with NRAs in 2012 Confidentiality and collaboration agreements with 6 NRAs in 2012 Developing Country Vaccine Regulators Network (DCVRN) One meeting held in Thailand in 2012 One webex-based meeting held in 2012 Annual 3-month secondments of 2 DCVRN representatives to Geneva (from Thailand and Indonesia in 2012) 16

17. Diagnostics (PQDx) 17

18. Priority products Current priorities –HIV rapid tests –CD4 technologies –HIV Viral Load and Early infant diagnosis tests –Malaria rapid tests –Adult male circumcision devices New Priorities –Hepatitis rapid tests –TB tests –Multiplex HIV-HCV and HIV-syphilis rapid tests

19. Recent progress Products prequalified in 2010 1 Products prequalified in 2011 10 Products prequalified in 2012 8 Products prequalified in 2013 8 Total products prequalified to date 27 Additional products anticipated for 2013 4 - 5 Products closed / withdrawn 56 Products submitted an application to PQ 185

20. Challenges Different categories of IVDs regulated differently –HIV IVDs, particularly for blood screening, attract greatest stringency –Degree of stringency is risk-based –Risk classification is different in different settings –Different regulatory versions of the same product Still poor understanding and implementation of quality management systems at manufacturing site Inadequate product dossier to demonstrate performance claims including –Inadequate demonstration of product stability Both in-use and transportation stability –Inadequate lot release procedures –Inadequate customer service

21. 21 What WHO PQ can offer to the regulators and industries in the regions? Regulators –Capacity building/training – improved technical knowledge and skills –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

22. 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 Increase in efficiency and reach out Better coordinated and more efficient working within the organization, with national/regional regulators and other partners Potential efficiency savings (admin costs etc.) … 22

23. 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 23

24. 24 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