The WHO Prequalification of Medicines Programme Capacity building agenda Dr Milan Smid WHO QSM Technical Briefing Seminar 1st November, 2012, Geneva Microbiological training, Nov 2011, Jordan

PQP 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 Next we will have a short session on Self-inspection. We then turn to the topic of Personnel. Personnel should be seen by the pharmaceutical manufacturer as its most valuable resource. It is sometimes its most difficult one to manage. Inspectors need to be sure that there are sufficient human resources, with people who have the correct qualifications and acceptable levels of experience. An important issue for you to check is the conflict of interest that can arise if Quality Control is not properly independent of Production. For this reason a full day is required for this subject. This will be followed by a half-day session on Equipment. If you would like to have any particular piece of equipment discussed please write its name down and hand it to me at the end of this module. If possible we will discuss the item during the Equipment module. We shall then spend a full day on Premises. Here we are going to be looking at some of the fundamental issues, including the effect of the external environment, on a company’s ability to manufacture products in the appropriate conditions. This will be followed by a half-day session on Materials. Experience has shown that many problems arise as a result of the selection of unsuitable or impure materials. Many developing countries have financial constraints that work against using materials of the right quality.

team work: WHO HQ, RO, WCO + partners Capacity building team work: WHO HQ, RO, WCO + partners 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)

Training by doing for regulators 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 Manufacturers: Commitment to participate in the prequalification programme Found to be capable and willing to improve Location in a developing country Not supported by other international organization Products: Inclusion in the list of expression of interest Poor representation on the Prequalification list Prioritised for Public Health purpose

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

Assistances provided in individual countries 2006-2011

Project of assistance to Nigerian manufacturers – why Nigeria? Pro-active Collaborating and committed state authorities In Africa one of strongest pharmaceutical sectors, companies producing and exporting range of products relevant for PQ About 70% of medicines imported, donors require PQ Companies committed and having common representation (PGMAN) Understanding of financial implications of prequalifying medicinal products and suggesting solutions Able to agree upon 'Project of assistance' Strive for prequalification of specific medicines Cost sharing Follow improvement plans

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

Generalized objectives of both projects Achieve quality assured production of TB FDC, HIV and malaria drugs in China and strengthen their role on domestic market and increase export opportunities Implement new GMP standards Move towards WHO prequalification. WHO prequalification functions as a gate-keeping mechanism to enter international tenders and procurement is growing No direct financial support to manufacturers through this project but technical assistance 18

Accelerated procedure for registration of WHO-prequalified medicines Collaboration Procedure between the WHO Prequalification Programme and NMRAs = Accelerated procedure for registration of WHO-prequalified medicines Pilot initiated in June 2012 Procedure approved by WHO Expert Committee for Specifications of Pharmaceutical Preparations in October 2012

Background reasoning (1) 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. Re-assessment and re-inspections of prequalified medicines place demands on NMRAs. Slow registration delays availability to patients. Specific national registration requirements sometimes discourage manufacturers to register and import needed medicines.

Background reasoning (2) Registration of prequalified medicines may be facilitated by closer co-operation among WHO, NMRAs and manufacturers and by provision of full outcomes of PQP assessment and inspections. Prerequisite of facilitated national registration is the communication of confidential data and therefore procedure must be well defined and agreed by all participating parties Common assessment and inspections are useful practice, but not always are applicable Bangkok, November 2012

Principles of proposed process Procedure voluntary for manufacturers and NMRAs and providing benefits to both parties. No interference with national legislation, decision making process and regulatory fees – availability of PQP expertise. Being asked by PQP holder (manufacturer), full PQP assessment and inspection outcomes and advice will be shared with interested NMRAs to facilitate national regulatory decisions making (registrations, variations, withdrawals). Applicable only for medicines assessed by PQP.

Principles of proposed process Co-operation among PQP holder (manufacturer), NMRA in interested country and PQP necessary to overcome confidentiality issues, assure information flow and product identity. Registration dossier in countries in principle the same as approved by PQP. Each participating authority commits to adopt registration decision within 90 days from having available full PQP assessment and inspection outcomes and has the right to decline to adopt procedure for individual medicines decide differently from PQP, but keep PQP informed and clarify the reasons for deviation.

Steps of the procedure: agreement Interested NMRAs agree to participate in the procedure and designate focal persons PQP lists committed NMRAs on its website and gives to focal persons access to restricted-access website

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

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

Procedure drafted in wide consultation and available for comments: http://www.who.int/entity/medicines/areas/quality_safety/quality_assurance/PQProcedure-assessmentandacceleratednationalreg-QAS12-497_01062012.pdf Pilot testing starting with 10 interested countries: Botswana Ghana Kenya Namibia Nigeria Tanzania Uganda Zambia Zanzibar Zimbabwe

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 and pharmacovigilance WHO Prequalified medicines are faster available to patients Feed-back on WHO prequalification outcomes

Win-win outcomes for all stakeholders Procurers Faster start of procurement and wider availability of PQ medicines Assurance about 'the same' medicine as is prequalified 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 Ultimate beneficiaries are patients!

Thank you for the attention smidm@who.int