1. Prequalification team
Regulatory capacity building and NDRA approvals of prequalified products
Milan Smid
Prequalification team
Microbiological training, Nov 2011, Jordan

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
Map of regions – regulators and manufacturers/ QCLs

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 …
Stress:
QSM: norms and standards, SSFFCs, regulatory support, pharmacovigilance
experts from SRAs
Microbiological training, Nov 2011, Jordan

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
……………..
Benefits of collaboration with partnering organizations
financial share
share of workload
More experts available
Microbiological training, Nov 2011, Jordan

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

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
Assessment sessions – each 2 months ? Assessors from developing countries
Inspections – producing country and observers
Data about rotations? 17 or 18 – mostly Afro
Microbiological training, Nov 2011, Jordan

7. Seminars and workshops
Frequent collaboration with third parties
Microbiological training, Nov 2011, Jordan

8. Seminars and workshops
Trainings of NRA staff and manufacturers frequently combined
Microbiological training, Nov 2011, Jordan

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

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
Microbiological training, Nov 2011, Jordan

12. Microbiological training, Nov 2011, Jordan

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

14. Support to rational regulation, development of regulatory systems, regulatory networking and worksharing
Emerging projects:
'Prequalification' of key regulatory functions relevant for regulation of generic medicines
Systematic development of competencies of regulatory professionals in areas relevant for regulation of generic medicines
Pilot of distant learning approaches
Microbiological training, Nov 2011, Jordan

15. 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 Approved by WHO Executive Board in May 2013.
Pilot ongoing from June 2012, currently 16 participating NMRAs from 15 countries.
Africa
Botswana
Ethiopia
Ghana
Kenya
Madagascar
Mozambique
Namibia
Nigeria
Tanzania
Europe/Asia
Georgia
Kyrgyzstan
Ukraine
Uganda
Zambia
Zanzibar
Zimbabwe
Microbiological training, Nov 2011, Jordan

16. Principles of the process1)
Being asked by PQ holder (manufacturer), PQT shares full PQ 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/inspected by PQP
- PQ holder provides consent with information sharing
- Voluntary for manufacturers and NMRAs and does not interfere with national decision making process and regulatory fees.

17. Principles of the process2)
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.

18. Options for participating regulators
Recognize
Verify
Organize R/B second review and/or inspections
Consider in decision making
Use as quality assurance of national assessment and decision

19. Outcomes of the process
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
Microbiological training, Nov 2011, Jordan

20. 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
Template documents for each step.
Participating NMRA reviews WHO PQP outcomes, decides within 90 days decides upon the national registration and informs PQP about its decision
Microbiological training, Nov 2011, Jordan

21. Experience with the procedure
20 procedures successfully terminated by registration in 7 countries:
Ghana 5 Kenya 1
Zimbabwe 5 Uganda 1
Namibia 4 Nigeria 2
Tanzania 2
14 different prequalified products
(9 ARVs, 1 RH, 1 antimalarial, 1 TB)
6 PQ holders involved, all from India

22. Number of finalized procedures according to time bands
Days from accepting supportive PQ data to national registration

23. Percentage of finalized procedures according to time bands
Days from accepting supportive PQ data to national registration

24. 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?
Microbiological training, Nov 2011, Jordan

25. 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)

26. 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

27. Newcomers to the network are welcome!
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!
Microbiological training, Nov 2011, Jordan

28. 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
Not be involved in regulatory collaboration schemes demonstrates inefficiency and lack of professionalism
Recent experience from assessment report sharing exercise
Microbiological training, Nov 2011, Jordan

29. 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.
Current focus on registration assessment
Microbiological training, Nov 2011, Jordan

30. Zazibona – enabling factors
No language barriers and geographically close
Partially overlapping pharmaceutical markets
All meeting capacity constraints and fighting backlog of applications
Agencies/ministries able to adopt necessary decisions
All members of SADC and having good contacts among themselves
Having semi-harmonized guidelines and similar speed in implementation of international standards
Co-operating with PQP and participating in PQP collaborative registration procedure
Differences in interpretation can be bigger than differences in guidelines themsekves – in the bacgroung Who-(PQP) and SADC guidelies
Current focus on registration assessment, but inspections, maintenance, QC and PhV later …
Microbiological training, Nov 2011, Jordan

31. Agreed steps
Agreement of HoA backed by MoH on pilot of mutual collaboration
Several 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
Similar issues like IGDRP , EU multistate procedures …
CTD, ARs WHO/PQP model
Differences in standards not considered essential, with exception of – BE (compartor and its sourcing and BW) and stability!
DMFs, Product information, pharmacopoeias parked to future. A Not priority
To ne overcome – IT tool – Mednet,
Microbiological training, Nov 2011, Jordan

32. Summary
Capacity building of national regulators is core PQP agenda integrated into all PQP activities
PQP capacity building is not isolated agenda, reacts on identified needs and focuses on technical competence
Scope of capacity building is influenced by priorities of donors, but also reflects needs of NMRAs in developing countries
External partners and experts play important role
Outcomes are measured by deliverables and indicators of projects funded to PQP and QSM

33. Thank you for the attention