The WHO Prequalification of Medicines Programme Capacity building agenda Dr Milan Smid Technical Briefing Seminar October, 2013, Geneva
WHO Prequalification of Medicines Programme • To increase access to priority medicinal products of acceptable unified standards • 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 • Prequalification of Quality Control Laboratories • Inspections and evaluations • Testing projects • Capacity building
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
Capacity building - stakeholders • WHO PQP supports generation of expertise for development, manufacture, control or regulation of medicines Manufacturers Contract Research Organizations (CROs) Quality control laboratories (QCLs) National Regulatory Authorities (NRAs)
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
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)
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
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
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
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
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
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
WHO Projects Organized in Cooperation with SFDA in China 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 23
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
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. • Europe/Asia • Georgia • Kyrgyzstan • Ukraine • Uganda • Zambia • Zanzibar • Zimbabwe • Africa • Botswana • Ghana • Kenya • Madagascar • Namibia • Nigeria • Tanzania www.who.int/prequal/info_applicants/collaborative_registration_main.htm
Principles of the process 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 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.
Options for participating regulators • Recognize • Verify • Organize RB second review and inspections • Consider in decision making • Use as quality assurance of national assessment and decision
Principles of the process • 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
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 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
Experience with the procedure • 13 procedures successfully terminated by registration in 6 countries: Ghana 5 Kenya 1 Zimbabwe 3 Uganda 1 Namibia 2 Nigeria 1 • 10 different prequalified products (9 ARVs, 1 RH) • 3 companies involved (all Indian) • None procedure 100% typical
Learning and challenges • 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?
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)
Win-win outcomes for all stakeholders • 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
Status Quo • 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!
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