1. The WHO Prequalification of Medicines Programme Capacity building agenda Dr Milan Smid Technical Briefing Seminar October, 2013, Geneva

2. 2 Technical briefing seminar Geneva, October 2013 WHO Prequalification of Medicines Programme To increase access to priority medicinal products of acceptable unified standards 1.Prequalification of medicines (FPPs and APIs) –Evaluation of quality, safety and efficacy based on submitted data –Inspections of manufacturers and clinical testing sites –Listing and follow-up of prequalified medicinal products Variations, Inspections, Sampling and testing, Requalification 2.Prequalification of Quality Control Laboratories –Inspections and evaluations –Testing projects 3.Capacity building

3. 3 Technical briefing seminar Geneva, October 2013 Capacity building - objectives Good quality submissions for PQ supported by compliance with "good practices" –platform for improvement of drug development, manufacturing, documentation and quality control Fast regulatory approvals of PQ medicines in recipient countries –technical education of regulators as a platform for strengthening expertise, regulatory efficiency and networking Reliable quality monitoring –technical education of staff of QCLs to strengthen expertise, effectiveness of quality monitoring and networking PQP standards and PQP example support strengthening of regulatory systems and capacity of manufacturers in general

4. 4 Technical briefing seminar Geneva, October 2013 Capacity building - stakeholders WHO PQP supports generation of expertise for development, manufacture, control or regulation of medicines National Regulatory Authorities (NRAs) Quality control laboratories (QCLs) Contract Research Organizations (CROs) Manufacturers

5. 5 Technical briefing seminar Geneva, October 2013 Capacity building – team work 1) Trainings of different set-up and PQ advocacy 2) Technical assistance & advice 3) Provision of information, standards and regulatory expertise

6. 6 Technical briefing seminar Geneva, October 2013 1) Trainings - seminars and workshops –General: PQ procedures and WHO requirements –Problem oriented, e.g.: –HIV/AIDS, TB, antimalarial or RH products –Pharmaceutical development/paediatric dosage forms, BE/BCS –Manufacture of sterile medicines –Quality of APIs –Bioequivalence testing –Trainings of NRA staff and manufacturers frequently combined –Collaboration with third parties frequent involved –Support is given to trainings organized by others –Focus on "training of trainers" –WHO training materials used, when available (GMP, GPCL)

7. 7 Technical briefing seminar Geneva, October 2013 Main partners in organization of trainings International Pharmaceutical Federation (FIP) European Directorate for the Quality of Medicines & Healthcare (EDQM) National Regulatory Authorities in South Africa, Tanzania, Estonia, Ethiopia, Ukraine, Morocco, Brazil, Jordan, Ghana, Egypt, Indonesia, Kenya, Uganda, China National Quality Control Laboratories in Morocco and Tanzania East Africa Community (EAC) Association of Southeast Asian Nations (ASEAN) Ministry of Health China, Pakistan, Iran, Morocco Program for Appropriate Technology in Health (PATH) United Nations Population Fund (UNFPA) European Medicines Agency (EMEA) Drug Information Association (DIA) Therapeutic Goods Agency Australia (TGA) Roche Pharmaceuticals

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15. 15 Technical briefing seminar Geneva, October 2013 Training by doing Training of regulatory staff by involvement in PQP activities –Involvement of assessors from NRAs in PQ assessment –Involvement of inspectors from NRAs in PQ inspections –Rotations of experts from NRAs in WHO HQ

16. 16 Technical briefing seminar Geneva, October 2013 2) Technical Assistance Key objective: Facilitate prequalification of priority medicines Provision of consultants to advice on –GMP or GCP compliance –Data development and compilation of dossier Assistances are separated from the assessment / inspections Assistances may include specific trainings Assistance is provided in principle free of charge

17. 17 Technical briefing seminar Geneva, October 2013 Conditions for provision of technical assistance Manufacturers: Found to be capable and willing to improve Commitment to participate in the prequalification programme Location in a developing country Products: Inclusion in the list of expression of interest Poor representation on the Prequalification list Prioritised for Public Health purpose

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19. 19 Technical briefing seminar Geneva, October 2013 Assistances provided in individual countries 2006-2012

20. 20 Technical briefing seminar Geneva, October 2013 Technical assistances in WHO regions 2006-2012

21. 21 Technical briefing seminar Geneva, October 2013 3) Provision of information and regulatory expertise Information related to individual PQ products or manufacturers / CROs http://www.who.int/prequal –Product list and pending procedures –Public assessment reports (WHOPAR, SPC, PIL) –Public inspection reports (WHOPIR – APIs and FPPs) –Notice of concern / suspension –Guidelines and standards –PQ laboratories –Training materials Published training materials and standards / CDs Availability of non-WHO standards (Ph.Eur., ICH) Technical Briefing Seminars in Geneva

22. 22 Technical briefing seminar Geneva, October 2013 Support to rational regulation and development of regulatory systems Concentration on priority issues most relevant for public health in countries relevant for PQP Mostly on invitation of WHO offices or national governmental institutions Improved effectiveness and efficiency of work Co-operation with partners and work-sharing –Facilitated by common standards and administrative requirements

23. 23 Technical briefing seminar Geneva, October 2013 WHO Projects Organized in Cooperation with SFDA in China 23 Focus on quality and safety of medicines, sponsored by Bill and Melinda Gates Foundation (BMGF) –To improve TB control in China by increasing national capacity to produce fixed-dose combination (FDC) anti- TB medicines of assured quality and to regulate TB FDC drugs Global Fund to Fight HIV/AIDS, TB and Malaria (GFATM) –To improve the quality of anti-TB, HIV/AIDS and malaria medicine produced in China to ensure improved accessibility and patient outcomes

24. Zazibona – ‘look to the future’ (Zambian ‘nyanja’ language) Pilot of collaborative registration procedure in four mutually co-operating regulatory authorities Zambia, Zimbabwe, Botswana and Namibia Testing the applicability of collaboration in exchange of assessment and inspection reports on generic medicines (not submitted for WHO-PQP) among NMRAs in participating countries

25. 25 Geneva, October 2013 WHO Collaborative Procedure to facilitate and accelerate registrations of prequalified medicines Procedure drafted in wide consultation and approved by WHO advisory expert committee in October 2012. Approved by WHO Executive Board in May 2013. Pilot ongoing from June 2012, currently 14 participating NMRAs from 13 countries. Africa Botswana Ghana Kenya www.who.int/prequal/info_applicants/collaborative_registration_main.htm Europe/Asia Georgia Kyrgyzstan Ukraine Madagascar Namibia Nigeria Tanzania Uganda Zambia Zanzibar Zimbabwe

26. 26 Geneva, October 2013 1) Being asked by PQP holder (manufacturer), PQP shares full PQP assessment and inspection outcomes with NMRAs participating in the scheme and provides advice to facilitate national regulatory decisions (registrations, variations, withdrawals). Applicable only for medicines assessed by PQP. PQP holder provides consent with information sharing. Principles of the process

27. 27 Geneva, October 2013 2) It is up to discretion of participating NMRAs how to benefit from shared information. However, participating NMRAs commit to adopt registration decision within 90 days from having available full PQP assessment and inspection outcomes. NMRAs have the right to –decline to adopt procedure for individual medicines –decide differently from PQP, but keep PQP informed and clarify reasons for deviation. Principles of the process

28. 28 Geneva, October 2013 Recognize Verify Organize RB second review and inspections Consider in decision making Use as quality assurance of national assessment and decision Options for participating regulators

29. 29 Geneva, October 2013 Voluntary for manufacturers and NMRAs and does not interfere with national decision making process and regulatory fees Product and registration dossier in countries are 'the same' as approved by PQP. Co-operation among PQP holder (manufacturer), NMRA in interested country and PQP is necessary to overcome confidentiality issues, assure information flow and product identity 'Harmonized product status' is monitored and maintained Principles of the process

30. 30 Geneva, October 2013 Manufacturer informs PQP about national submission and gives consent with information sharing Participating NMRA confirms its interest to participate in procedure for specific product PQP shares with participating NMRA outcomes of assessment and inspections Participating NMRA reviews WHO PQP outcomes, decides within 90 days decides upon the national registration and informs PQP about its decision Steps of the procedure: registration PQ product is submitted for national registration to NMRA participating in the procedure NMRA is informed about the interest to follow PQP

31. 31 Geneva, October 2013 13 procedures successfully terminated by registration in 6 countries: Ghana 5Kenya 1 Zimbabwe 3Uganda 1 Namibia 2Nigeria 1 10 different prequalified products (9 ARVs, 1 RH) 3 companies involved (all Indian) None procedure 100% typical Experience with the procedure

32. 32 Geneva, October 2013 What is 'the same product' ? Applicability for pending national registrations? Submissions of reduced registration dossiers in resource limited settings? Use of other languages than English? Quality control of registration samples? NMRAs administrative capacity and competence? Role of NMRAs and Drug Boards? Mednet as information system: suitable, but not optimal. Synchronization of national and PQ variations? Learning and challenges

33. 33 Geneva, October 2013 Manufacturers –Harmonized data for PQ and national registration –Facilitated interaction with NMRAs in assessment and inspections –Accelerated and more predictable registration –Easier post-registration maintenance Procurers –Faster start of procurement and wider availability of PQ medicines –Assurance about 'the same' medicine as is prequalified (website) Win-win outcomes for all stakeholders 33

34. 34 Geneva, October 2013 NMRAs –Availability of WHO assessment and inspection outcomes to support national decisions and save internal capacities –Opportunity to learn from PQP assessors and inspectors –Demonstrating NMRA efficiency –Having assurance about registration of 'the same' medicine as is prequalified –Quality control by same methods and specifications –Easier post-registration maintenance WHO –Prequalified medicines are faster available to patients –Feed-back on WHO prequalification outcomes Win-win outcomes for all stakeholders 34

35. 35 Geneva, October 2013 The collaborative registration of PQed medicines is in its infancy, but starts to produce results Procedure provides model for inter-regulatory information exchange to those NMRAs and manufacturers, who want to cooperate Extension of mechanism to SRA approved PQed products to be explored in co-operation with SRAs and manufacturers. Extension to 'originators' in principle not impossible. Newcomers to the network are welcome! Status Quo

36. 36 Technical briefing seminar Geneva, October 2013 Thank you for the attention smidm@who.int