regulatory capacity building and ndra approvals of prequalified products milan smid prequalification...

Regulatory capacity building and NDRA approvals of prequalified products

Milan Smid

Prequalification team

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Copenhagen, May 2014

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

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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, BMGF, GFATM, UNCoLSP, USFDA …

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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-up2 (Technical

assistance& consultancy

3 (Provision of information, standards and regulatory

expertise

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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

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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 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

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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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• 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• Collaborative registration procedures

Provision of information and regulatory expertise

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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

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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.

Africa• Botswana• Ethiopia• Ghana• Kenya

www.who.int/prequal/info_applicants/collaborative_registration_main.htm

Europe/Asia

• Georgia• Kyrgyzstan• Ukraine

• Madagascar• Mozambique• Namibia• Nigeria• Tanzania

• Uganda• Zambia• Zanzibar• Zimbabwe

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Principles of the process

1)

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.

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Principles of the process

2)

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

• Recognize• Verify• 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 maintained

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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: registration

PQ product is submitted for national registration to NMRA participating in the procedure

NMRA is informed about the interest to follow PQP

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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

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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

optimal. • 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

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)

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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

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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 welcome!

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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

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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.

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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

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

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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

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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

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Thank you for the attention

[email protected]

regulatory capacity building and ndra approvals of prequalified products milan smid prequalification...

Documents

regulatory capacity

regulatory expertise

combined slide

usfda slide

outcome slide

capacity building resources

training effect slide

pq team