Regulatory capacity building and NDRA approvals of prequalified

Regulatory capacity building and NDRA
approvals of prequalified products
Milan Smid
Prequalification team
Principal objective of PQP capacity building:
To facilitate availability of quality priority medicines
• Good quality submissions and compliance with "good
• 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
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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,
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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
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Key capacity building approaches
1) Training activities
of different set-up
2) Technical
assistance & 3) Provision of information,
standards and regulatory
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individualized and collective (seminars and workshops)
• Training of regulators integrated into core PQP
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
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Seminars and workshops
• Frequent collaboration with third parties
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Seminars and workshops
• Trainings of NRA staff and manufacturers frequently combined
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Why trainings with combined audience of
regulatory and regulated professionals?
• Need to combine objectives due to agreements with
• 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
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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
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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
Copenhagen, May 2014
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
Copenhagen, May 2014
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 16 participating
NMRAs from 15 countries.
• Botswana
• Ethiopia
• Ghana
• Kenya
• Georgia
• Kyrgyzstan
Zimbabwe • Ukraine
Copenhagen, May 2014
Principles of the process
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,
- 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.
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Principles of the process
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.
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Options for participating regulators
Organize R/B second review and/or inspections
Consider in decision making
Use as quality assurance of national assessment
and decision
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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
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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
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
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Experience with the procedure
• 20 procedures successfully terminated by
registration in 7 countries:
Ghana 5
Zimbabwe 5
Namibia 4
Tanzania 2
Kenya 1
Uganda 1
Nigeria 2
• 14 different prequalified products
(9 ARVs, 1 RH, 1 antimalarial, 1 TB)
• 6 PQ holders involved, all from India
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Number of finalized procedures
according to time bands
Days from accepting supportive PQ data to national registration
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Percentage of finalized procedures
according to time bands
Days from accepting supportive PQ data to national registration
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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
• Synchronization of national and PQ variations?
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Win-win outcomes for all stakeholders
• Manufacturers
– Harmonized data for PQ and national registration
– Facilitated interaction with NMRAs in assessment and
– 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)
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Win-win outcomes for all stakeholders
– Availability of WHO assessment and inspection
outcomes to support national decisions and save
internal capacities
– Opportunity to learn from PQP assessors and
– 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
– Prequalified medicines are faster available to patients
– Feed-back on WHO prequalification outcomes
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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
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Zazibona – ‘look to the future’
(Zambian ‘nyanja’ language)
Pilot of collaborative registration procedure in
four mutually co-operating regulatory
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
Copenhagen, May 2014
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
• to test the mechanism of co-operation among
regulatory authorities for potential use by others
• to improve information sharing and/or networking.
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Zazibona – enabling factors
• No language barriers and geographically close
• Partially overlapping pharmaceutical markets
• All meeting capacity constraints and fighting backlog of
• Agencies/ministries able to adopt necessary decisions
• All members of SADC and having good contacts among
• Having semi-harmonized guidelines and similar speed in
implementation of international standards
• Co-operating with PQP and participating in PQP
collaborative registration procedure
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Agreed steps
• Agreement of HoA backed by MoH on pilot of mutual
• Several meetings of assessors to support AR sharing and
develop experience
• BE (comparator, sourcing, BW) and stability conditions
• DMFs, pharmacopoeias, product information, communication
• Meeting with inspectors to agree on exchange of
inspection reports and inspection planning
• Regular interaction among assessors, inspectors and
HoA to cultivate joint work
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• 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
• 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
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Thank you for the attention
Copenhagen, May 2014