1. 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

2. 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.

3. 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

4. 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)

9. 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

10. 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

11. 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

13. Assistances provided in individual countries 2006-2011

14. 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

15. 3) 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

16. 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

17. 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

18. 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

19. 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

20. 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.

21. 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

22. 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.

23. 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.

24. 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

25. 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

26. 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

27. Procedure drafted in wide consultation and available for comments:
Pilot testing starting with 10 interested countries:
Botswana
Ghana
Kenya
Namibia
Nigeria
Tanzania
Uganda
Zambia
Zanzibar
Zimbabwe

28. 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

29. 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!

30. Thank you for the attention smidm@who.int