1. Update and future directions for prequalification of medicines WHO HQ, Geneva, 4 February 2008 Dr Lembit Rägo Coordinator Quality Assurance and Safety: Medicines Medicines Policy and Standards Health Systems and Services

2. Prequalification of medicines  Established in 2001  Started with HIV/AIDS products, later TB, malaria and selected reproductive health products were added  Based on WHO normative guidelines, widely discussed and transparent  Open to both innovative and generic medicines  Carried out by global pool of regulators for the benefit of all stake holders – outcome list of prequalified products as a public good  Capacity building and training important component  Continues to face old, but also meets new challenges

3. Which medicines and why PQ Programme deals with?  Application to include a product on Expression of Interest (EOI) Lists published comes from WHO disease oriented programs  Products should be of high public health value  Products must be in line with WHO treatment guidelines  Products must be in line with Essential Medicines List  Rare exceptions from these principles, if justified

4. Constantly updated web site: http://www.who.int/prequal/

5. Highlights of 2007  Total number of prequalified products reached 156  Increased work load for maintenance  Relatively small number of new products prequalified  "New comers" – usually low quality submissions  Applicants "fatigue" – not enough new products applied  Boosting quality control laboratories prequalification  Strengthening programme, increasing transparency  Substantially increased delivery of trainings and technical assistance (+100% increase)

6. Trainings

7. News example

8. HIV/AIDS  In total 360 assessment reports were written in 2007

9. TB products  In total 87 assessment reports were written in 2007

10. Inspections – finished product manufacturers  Inspections of finished products manufacturers increased during 2007 reaching 26

11. Submission of product dossiers 200520062007 HIV 67 42 23 TB 17 9 17 Malaria 3 5 6 NO NEW SUBMISSIONS in 2007 of some priority products: -2nd-line anti-tuberculosis products -paediatric anti-retroviral products

12. Proactive steps in 2007 – 2nd-line TB  Scientific advice on design appropriate of bio- equivalence studies  Detailed guidance to perform dissolution studies to implement biowaiver (to replace BE- study, if feasible)  Development of Pharmacopoeia monographs for anti-tuberculosis medicines  Situation (gap) analysis on the potential of tb- manufacturers to develop new products

13. Proactive steps in 2007 – Malaria  Proactive working with applicants (pre- submission review, reminders, coordinate submission of additional data, meetings for solving problems)  Scientific advice on design appropriate of bio- equivalence studies  Research (adverse reactions database, complicated quality issues)  Development of Pharmacopoeia monographs for antimalarial medicines

14. Proactive steps in 2007– paediatric medicines  To support appropriate dosage and formulation design by manufacturers: First Essential Medicines List for Children WHO guidance on preferred ARV medicines for the children; model to design proper strengths of fixed-dose combination products for different weight/age Consultation with other regulators (such as US FDA)  Two training courses on "Development of Paediatric Medicines" in 2007, third prepared for India in April 2008

15. To ensure sustainability of supplies of good quality priority products: challenges  Continue developing WHO standards and guidelines  Guidance on development and analytical control of TB and antimalarial medicines  Close the information gap for paediatric medicines  Implement comprehensive sampling and testing programme  Develop a comprehensive programme for providing technical assistance to potential new manufacturers  If manufacturers are to be persuaded to make the human and technological investments needed to enhance quality of medicines, financial incentives must be built into procurement mechanisms.

16. Future directions: short-term  Technical guidance, regulatory advise and technical assistance to manufacturers has to increase  Increasing efficiency: shorter timelines, pro-active follow- up and communication for priority products  Continuing human resource development – new assessors/inspectors identified and trained Trainings organized for assessors to achieve better consistency and the same level of technical skills  Continuing developing capacity building element in the programme Second rotational post to be considered  Increased communication and information exchange with regulators (both from well resourced and less resourced countries)

17. Future directions: long-term  Long-term strategy to be finalized during 2008  Promoting and facilitating production of quality medicines in developing countries continued  Structured co-operation with regulatory agencies further developed to avoid duplications using several tools Memorandums of understanding, confidentiality agreements Collaboration agreements  Promoting harmonization continued - potential to work with some regional harmonization initiatives to be explored  Exploring potential of contracting certain functions to national regulators/quality control laboratories

18. Instead of conclusions  Prequalification - a good engine to pull quality of medicines into international agenda  It challenges the still existing reality "poor quality medicines for poor"  How best keep it going as huge unfinished agenda is ahead?