The WHO Prequalification of Medicines Programme Capacity building agenda Dr Milan Smid

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 TBS, Nov 3, 2011

TBS, Nov 3, 2011

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. TBS, Nov 3, 2011

Capacity building - stakeholders WHO support to the generation of expertise for development, manufacture, control or regulation of medicines Manufacturers Clinical Research Organizations (CROs) Quality control laboratories (QCLs) National Regulatory Authorities (NRAs) TBS, Nov 3, 2011

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 TBS, Nov 3, 2011

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) TBS, Nov 3, 2011

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 TBS, Nov 3, 2011

TBS, Nov 3, 2011

TBS, Nov 3, 2011

TBS, Nov 3, 2011

TBS, Nov 3, 2011

TBS, Nov 3, 2011

Topics of workshops 2006-2010 TBS, Nov 3, 2011

Therapeutic focus of workshops 2006-2010 (I-VIII) TBS, Nov 3, 2011

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 TBS, Nov 3, 2011

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 TBS, Nov 3, 2011

Conditions for provision of technical assistance Manufacturers: Commitment to participate in the prequalification programme Found to be capable and willing to improve 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 TBS, Nov 3, 2011

2006-2011 (I-IX) TBS, Nov 3, 2011

Assistances provided in individual countries 2006-2011 (I-VI) TBS, Nov 3, 2011

Technical assistances in WHO regions 2006-2011 (I-VI) TBS, Nov 3, 2011

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 (PhEur, ICH) Technical Briefing Seminars in Geneva TBS, Nov 3, 2011

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 effectivity and efficiency of work Co-operation with partners and work-sharing Facilitated by common standards and administrative requirements TBS, Nov 3, 2011

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 TBS, Nov 3, 2011 24

implement new GMP standards 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 (TA) TBS, Nov 3, 2011 25

Monitoring of capacity building outcomes Feedback from participants of trainings Pool of assessors, inspectors and trainers New applications for prequalification or authorization Quality of submissions and compliance with requested standards of good practices Reliability of laboratory quality control Improvement in efficiency of regulatory processes and inspections TBS, Nov 3, 2011

Thank you for the attention smidm@who.int TBS, Nov 3, 2011