1. 1 Regulatory capacity building and principles of Collaboration Procedure between the WHO Prequalification Programme and NMRAs Milan Smid WHO Prequalification of Medicines Programme

2. 2

3. 3 Outcomes of survey organized during the PQP Assessment training January, 2011 Copenhagen, Jan 19, 2012

4. 4 Regulatory approvals of PQ medicines in selected countries 18 medicines selected, 18 countries participated, March 2011 Copenhagen, Jan 19, 2012

5. 5 CTD format of dossier is mandatory or accepted Copenhagen, Jan 19, 2012

6. 6 Current content of registration dossier for API (Drug Substance) is identical or close to CTD Copenhagen, Jan 19, 2012

7. 7 Current content of registration dossier as regards FPP requirements (Drug Product) is identical or close to CTD Copenhagen, Jan 19, 2012

8. 8 Requirements on documentation of bioequivalence (concerning both demonstration of bioequivalence in vivo and in vitro) are in principle close to PQP Copenhagen, Jan 19, 2012

9. 9 Average length of registration assessment report (pages) Ghana Kenya Tanzania Uganda Zambia Zimbabwe Avg pages: 9.6 Armenia Belarus Cuba Ethiopia Georgia Mozambique Namibia Oman Saudi Arabia Sudan Thailand Copenhagen, Jan 19, 2012

10. 10 Average length of registration assessment report (pages) Ghana Kenya Tanzania Uganda Zambia Zimbabwe Avg pages: 19.5 Armenia Belarus Cuba Ethiopia Georgia Mozambique Namibia Oman Saudi Arabia Sudan Thailand Avg pages: 4.2 Copenhagen, Jan 19, 2012

11. 11 If special confidentiality arrangements are achieved, assessment reports are or could be made available to other regulatory authorities Copenhagen, Jan 19, 2012

12. 12 Do you utilize WHO Public Assessment Reports (WHOPARs) in support of taking decision about national registration Copenhagen, Jan 19, 2012

13. 13 GMP standard required by country regulations for manufacturers of finished dosage forms is equivalent to WHO or PIC/S GMP Copenhagen, Jan 19, 2012

14. 14 GMP inspections of manufacturers abroad are performed Copenhagen, Jan 19, 2012

15. 15 In case that GMP inspections of manufacturers abroad are organized, inspections are also performed in countries with stringent regulatory authorities Copenhagen, Jan 19, 2012

16. 16 Average length of GMP inspection report (pages) Ghana Kenya Tanzania Uganda Zambia Zimbabwe Avg pages: 10.4 Armenia Belarus Cuba Ethiopia Namibia Oman Saudi Arabia Sudan Thailand Copenhagen, Jan 19, 2012

17. 17 Inspection reports are available for each inspected manufacturer Copenhagen, Jan 19, 2012

18. 18 If special confidentiality arrangements are achieved, inspection reports are or could be made available to other regulatory authorities Copenhagen, Jan 19, 2012

19. 19 WHO Public Inspection Reports are regularly used as a source of information on GMP compliance, when planning inspections of manufacturers Copenhagen, Jan 19, 2012

20. 20 In the practice of your authority, does exist the difference between registration process of medicines, which are WHO prequalified or approved by stringent authorities, and other medicines? Copenhagen, Jan 19, 2012

21. 21 Does any publicly available document exist explaining the difference Copenhagen, Jan 19, 2012

22. 22 Can you demonstrate that prequalification has positive effect on duration of a national registration procedure in your country Copenhagen, Jan 19, 2012

23. 23 Collaboration Procedure between the WHO Prequalification Programme and NMRAs Copenhagen, Jan 19, 2012

24. 24 Background reasoning Although WHO prequalified medicines are thoroughly assessed and manufacturers are inspected according to WHO/international standards, to be used in recipient countries they have to be registered by NMRAs Registration may be facilitated by closer co-operation among WHO, NMRAs and manufacturers of prequalified medicines Prerequisite of facilitated national registration is the communication about confidential data and therefore procedure must be well defined and agreed by participating parties Common assessment and inspections are useful practice, but not always are applicable Copenhagen, Jan 19, 2012

25. 25 Principles of proposed process Availability of PQP assessment, inspection outcomes and advice to facilitate national regulatory decisions making (registrations, variations, withdrawals) No interference with national legislation, decision making process and regulatory fees Co-operation among product manufacturer (PQP holder), NMRA in interested country and PQP to overcome confidentiality issues and assure information flow Procedure applicable for individual products Procedure voluntary for manufacturers and NMRAs Copenhagen, Jan 19, 2012

26. 26 Steps of the procedure: agreement NMRA confirms to WHO PQP its interest to participate in collaborative procedure and respect its conditions - Annex 1 Copenhagen, Jan 19, 2012

27. 27 Steps of the procedure: agreement Interested NMRAs agree to participate in the procedure PQP lists committed NMRAs on its website Copenhagen, Jan 19, 2012

28. 28 Steps of the procedure: registration /1 1. Manufacturer submits to participating authority the application for national registration of the medicinal product, which underwent WHO PQP assessment/ inspections and is prequalified, and informs the authority about the interest to follow the collaborative procedure - Annex 2 2. Manufacturer informs WHO PQP about the application for national registration and, for each product, provides written agreement to exchange of information between the participating authority and WHO PQP - Annex 3 Copenhagen, Jan 19, 2012

29. 29 Steps of the procedure: registration /2 3. Participating authority informs WHO PQP about its interest to apply the procedure for given medicinal product - Annex 4 4. WHO PQP provides participating authority with the assessment/inspection outcomes and provides additional explanation, if requested 5. Participating NMRA reviews WHO PQP assessment and inspection outcomes and within 90 days decides upon the national registration. Participating NMRA informs WHO PQP about the outcome of national registration and, when divergent from PQP decision, provides explanation - Annex 5 Copenhagen, Jan 19, 2012

30. 30 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 Copenhagen, Jan 19, 2012

31. 31 Steps of the procedure: post-registration 1.PQP provides participating authorities with variation assessment reports and post-prequalification inspection reports, when regulatory action is deemed to be justified 2.Participating authorities inform PQP about the outcome of national variation procedures, if they have reached a decision different from that reached by PQP, or they reached a decision which results in national registration conditions being inconsistent with prequalification conditions 3.WHO PQP informs participating NMRA about withdrawals, suspensions or de-listings of prequalified medicinal products 4.Participating authority informs PQP about national de- registration (for any reason) of a prequalified medicinal product Copenhagen, Jan 19, 2012

32. 32 Steps of the procedure: post-registration PQP informs NMRAs about important variations NMRAs inform PQP about variations and decisions leading to inconsistency with PQP conditions WHO PQP informs NMRA about withdrawals, suspensions or de-listings of prequalified medicinal products NMRAs inform PQP about national de-registration Variations De-registrations and de-listings Copenhagen, Jan 19, 2012

33. 33 Steps taken Principles of procedure pre-discussed with several African NMRAs Procedure drafted and internally agreed by PQP team Draft discussed at different fora with NMRAs and manufacturers and amended – UNFPA/WHO workshops in Tanzania, Namibia – Regulatory assessors familiar with PQP in Copenhagen Pilot to be organized with volunteering NMRAs and manufacturers – Pilot sponsored by Gates Foundation as one of PQP project activities (2011-2012) Copenhagen, Jan 19, 2012

34. 34 Piloting the procedure Intention to pilot the procedure with several already PQ products; possibility to include parallel submissions later Identification of 2-3 piloting countries (NMRAs) in Africa and South-East Asia Identification of 2-3 products of 2 manufacturers to volunteer in pilot project Review of experience at the meeting of participating countries and manufacturers Copenhagen, Jan 19, 2012

35. 35 Win-win outcomes for all stakeholders NMRAs –Availability of WHO assessment and inspection outcomes to support national decisions –Opportunity for learning from experienced assessors –Saving internal capacities –Demonstrating NMRA efficiency WHO –Prequalified medicines are faster available to patients Procurers –Faster start of procurement Manufacturers –Harmonized data for PQ and national registration –Facilitated interaction with NMRAs in assessment and inspections –Accelerated registration Copenhagen, Jan 19, 2012

36. 36 Comments? Copenhagen, Jan 19, 2012

37. 37 Thank you for the attention smidm@who.int Copenhagen, Jan 19, 2012