Regulatory capacity building and NDRA approvals of prequalified products

Transcription

1 Regulatory capacity building and NDRA approvals of prequalified products Milan Smid WHO Prequalification Team

2 Principal objective of PQP capacity building: To facilitate availability of quality priority medicines Good quality submissions and compliance with "good practices" Strengthening of regulatory functions and fast approvals of PQd medicines Reliable quality monitoring PQP builds capacity in general: PQP technical expertise is used in support of capacity building of regulators, quality control laboratories and manufacturers WHO/PQP standards and PQP example support strengthening of regulatory systems and manufacturing capacity Focus on regulators in: Countries recipient PQ medicines Major producing countries without stringent regulation Other countries of specific need 2

3 Capacity building resources All PQ team is involved Close co-operation with WHO colleagues, many collaborating organizations, pool of external experts Funding coming from several donors, especially UNITAID, BMGF, GFATM, UNCoLSP, USFDA 3

4 Frequent partners in capacity building European Directorate for the Quality of Medicines & Healthcare (EDQM) International Pharmaceutical Federation (FIP) United Nations Population Fund (UNFPA) National Regulatory Authorities in UK, Canada, 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, Morocco Program for Appropriate Technology in Health (PATH) European Medicines Agency (EMEA) Drug Information Association (DIA) Therapeutic Goods Agency Australia (TGA) Roche Pharmaceuticals.. 4

5 Key capacity building approaches 2) Technical assistance & consultancy 1) Training activities of different set-up 3) Provision of information, standards and regulatory expertise 5

6 Trainings: individualized and collective (seminars and workshops) Training of regulators integrated into core PQP activities NMRA assessors in PQ assessment NMRA inspectors in PQ inspections NMRAs professionals in quality monitoring of medicines Rotations of assessors and inspectors from NMRAs Joint problem solving Joint assessments Collaborative registrations Informal audits of manufacturers, QCLs and CROs with training effect 6

7 Seminars and workshops Frequent collaboration with third parties 7

8 Seminars and workshops Trainings of NRA staff and manufacturers frequently combined 8

9 Why trainings with combined audience of regulatory and regulated professionals? Need to combine objectives due to agreements with donors PQ of prioritized medicines is key PQT deliverable Common technical understanding needed by manufacturers and regulators Facilitation of communication On site problem solution Less expensive Easier to measure the outcome 9

10 Seminars and workshops General: PQ procedures and WHO requirements Technical, to reflect identified needs, e.g.: Product specific: HIV/AIDS, TB, antimalarial or RH products Pharmaceutical development/paediatric dosage forms Quality of APIs, Stability testing Manufacture of sterile medicines Bioequivalence testing and GCP Dissolution and water determination, microbiological testing, HPLC analyses, quality management system 10

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13 Provision of information and regulatory expertise Information related to individual PQ products or manufacturers /CROs 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 Collaborative registration procedures 13

14 Support to rational regulation, development of regulatory systems, regulatory networking and worksharing Combined with acceleration of access to Pqed medicines Current projects Collaborative registrations of prequalified medicines Collaborative registrations of SRA approved essential medicines Support to regulatory worksharing ZaZiBoNa Technical assistance to manufacturers combined with regulatory strengthening in Nigeria 14

15 Strategies used to cope with increasing demands? Concentration on priority issues most relevant for public health Benefiting from information available from trusted parties Co-operation with partners in order to increase regulatory capacity Facilitated by comparable standards and administrative requirements Co-operation can be formal or informal, both have its pros and cons 15

16 Collaborative procedure between WHO Prequalification of Medicines Programme and national medicines regulatory authorities in the assessment and accelerated national registration of WHO-prequalified medicinal products 16

17 Procedure drafted in wide consultation and approved by WHO advisory expert committee in October Approved by WHO Executive Board in May

18 Why? Need to facilitate availability of WHO prequalified medicines by acceleration of national registrations Provide assurance that nationally registered medicine is the same as prequalified Propose a model for regulatory co-operation and information sharing 18

19 National registration process is supported by provision of WHO assessment and inspection reports 19

20 Principles of WHO Collaborative Procedure Voluntary for manufacturers and NMRAs and does not interfere with national decision making process and regulatory fees. Interested NMRAs sign confidentiality undertaking, commit to follow principles of the process and strive to register in 90 days. Product and registration dossier in countries are 'the same' as approved by PQP. Co-operation among PQ holder (manufacturer), NMRA in interested country and PQT overcomes confidentiality issues, ensures information flow and product identity WHO-PQT shares with interested regulators detailed outcomes of its assessment and inspections to support their decision making in exchange for accelerated registration process 'Harmonized product status' is monitored and maintained 20

21 Sharing of expertise vs. recognition of decision in the world consisting of independent states Acceptance of decision is formal legal act, frequently requiring international treaties may modify liabilities of involved parties and requires legal specification of acceptance and non-acceptance, arbitration mechanisms etc. Acceptance of expertise is sovereign and complex regulatory decision of NRA based on scientific arguments and confidence may be applied case to case is followed by formal independent decision according to national legislation and mandate of NRA 21

22 Registration in countries by WHO-PQT collaborative registration process From June 2012 participate 25 NMRAs from 24 countries Africa Botswana Burkina Faso Burundi Cameroon DR Congo Ethiopia Ghana Ivory coast Kenya Madagascar Malawi Mozambique Namibia Nigeria Senegal Sierra Leone Tanzania Uganda Zambia Zanzibar Zimbabwe Europe/Asia Armenia Georgia Kyrgyzstan Ukraine 22

23 Presentation of participating NMRAs on PQT website 23

24 WHO-PQT collaborative registration process 24

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26 Options for participating regulators Decide on use of the process for individual products Conclude differently from WHO PQT - if justified. Recognize Verify Organize R/B second review and inspections Consider in decision making Use as quality assurance of national assessment and decision 26

27 58 registrations in 12 countries, 51 pending applications ( ) 27

28 45 (78%) approved within 4 months 27 (47%) approved within 3 months Median time to registration is 93 days 28

29 Win-win outcomes for all stakeholders 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) 29

30 Win-win outcomes for all stakeholders NMRAs Having data well organized in CTD in line PQ requirements Availability of WHO assessment and inspection outcomes to support national decisions and save internal capacities Having assurance about registration of 'the same' medicine as is prequalified or understanding the deviations Quality control by same methods and specifications Easier post-registration maintenance Demonstrating NMRA efficiency Opportunity to learn from PQP assessors and inspectors Having a model process for mutual co-operation in registrations WHO Prequalified medicines are faster available to patients Feed-back on WHO prequalification outcomes 30

31 New developments Revision of the Procedure and extension to vaccines Draft in the first round commented by vaccine manufacturers Extended pilot for vaccines under preparation WHO Expert Committees involved Scheduled meeting with participating countries Analogous process considered for in vitro diagnostics Similar model of the procedure piloted to facilitate registrations of medicines approved by SRAs Applicable both for innovators and generics Process constructed in collaboration with associations of industry, relevant SRAs and companies 31

32 Collaborative registration of SRA approved medicines Piloted scheme

33 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 33

34 Zazibona - perspective Regulatory collaboration in exchange of assessment and inspection reports to reduce regulatory workload to accelerate registrations of needed products to develop mutual confidence in regulatory collaboration to test the mechanism of co-operation among regulatory authorities for potential use by others to improve information sharing and/or networking 34

35 Agreed steps Agreement of HoA backed by MoH on pilot of mutual collaboration and HoA interaction Quarterly meetings of assessors to support AR sharing and develop experience BE (comparator, sourcing, BW) and stability conditions DMFs, pharmacopoeias, product information, communication platform Meeting with inspectors to agree on exchange of inspection reports and inspection planning Regular interaction among assessors, inspectors and HoA to cultivate joint work 35

36 Worksharing model applied by ZaZiBoNa (and EAC EOI) 36

37 Outcomes within less than 2 years Harmonized assessment criteria and documents, suggestions for harmonization of guidelines Defined a worksharing process with max 180 days Zazibona regulatory time Worksharing results: 61 primary consolidated assessment reports 55 AR ready for sharing with others 9 positive opinions - 6 products registered in approx 9 months 10 withdrawals and 7 rejections (BE not demonstrated) 38 pending positions waiting for applicant s response 37

38 Technical assistance to manufacturers combined with regulatory strengthening in Nigeria Agreement among WHO, NMRA and manufacturers association Assistance to selected manufacturers combined with trainings, both in cooperation with NMRA Stepwise process to demonstrate results: GMP pre-inspections Data maturity to start BE or palatability trials Submission for prequalification 38

39 Thank you for the attention 39