1. 3rd WHO Prequalification Stakeholders Meeting
WHO Prequalification of Diagnostics, Medicines and Vaccines - 3rd Consultative Stakeholders Meeting
Building capacity to regulate clinical trials for vaccines
Dr. Liliana Chocarro
IVB,QSS, Regulatory Pathways
WHO HQ, Geneva
3rd WHO Prequalification Stakeholders Meeting

2. Vaccine clinical trials in developing countries
Sponsor
(manufacturer
Or NGO)
Clinical research center
Ethics Committee
approval
Commencement of trial
Importation and release of clinical batches
N RA

3. Selection of target countries
Endemic area (no justification for phase I)
Existing clinical research center with cap
Regardless of:
Qualifications of IRB members
Existence of a national regulatory process for authorization and inspection

4. Regulatory challenges: authorization of vaccine trials
US manufacturers are not obliged to follow the IND procedure if products are only for export, therefore USFDA will not have access to clinical development plan for approval
European NRAs may not review clinical trial (CT) applications if done outside of the EC
Other NRAs do not take into consideration trials in third countries in their regulatory framework

5. Regulatory challenges: inspections of clinical trials
USFDA will seldom perform a GCP inspection of trials in Africa
European NRAs only do GCP inspections in the EC, and EMEA will do GCP inspections in developing countries within the framework of Scientific Opinion, or IF the assessor of the registration dossier finds a "trigger". Consequence of non compliance: no use of data
NRAs from developing countries do not perform GCP inspections in third countries

6. The vision
Developing countries that are target for clinical trials and introduction of new vaccines will have the regulatory mechanisms in place to perform quality reviews in a timely manner

7. WHO 's initiatives
Raise awareness on regulatory challenges and to propose approaches to strengthen regulation of clinical trials in target countries
Promote communication among sponsors/regulators/ ethics committees/ research centres to achieve coordination among stakeholders
Facilitate capacity building activities and availability of expertise for regulatory review of clinical trial applications and inspection of clinical trials
Strengthen links and collaboration between regulators from manufacturing and trial host countries
Advocate the need to support regulatory processes with NGOs involved in clinical development of new vaccines

8. Developing Country Vaccine regulator's Network (DCVRN)
Establishment: Bangkok, Thailand, 17 September 2004
Mission : to promote and support the strengthening of the regulatory capacity of NRAs of participating and other developing countries for evaluation of clinical trial proposals (including preclinical data and product development processes) and clinical trial data through expertise and exchange of relevant information.
Member countries: RSA, India, Indonesia, Thailand, South Korea, China, Russia, Cuba, Brazil

9. DCVRN: main achievements
Member countries introduced improvements in the national system for regulation of clinical trials
DCVRN and non-DCVRN countries benefited from scientific sessions on clinical development of new vaccines and assessment of clinical data
Development of GCP inspection course (transferred to GTN)
DCVRN countries in the process to develop an IND-like system
Detected misuse of bridging studies
Raises issues for further consideration by QSS (for discussion at ECBS, gaps in guidelines, other interaction with Norms and Standards)

10. The "regional approach" for evaluation of vaccines
Development of (harmonized) procedures for regulation of clinical trials
Joint review of CT application
Joint inspections of clinical trials
Identification of regional needs for training on evaluation of vaccines

11. African Vaccine Regulatory Forum AVAREF (September 2006)
Provide information to regulators of countries that are target for clinical trials of priority vaccines
Promote communication and collaboration between NRAs and Ethics committees
Strengthen links between regulators of manufacturing and trial host countries
Provide a resource of expert advise to regulators to support their regulatory system for evaluation of vaccines.
Identify needs for expert support

12. African Vaccine Regulatory Forum AVAREF (September 2006)
Participants: NRAs and Ethics Committees nominated according to established criteria (Countries: Ghana, Gambia, Mali, Burkina Faso, Senegal, Nigeria, Malawi, Botswana, Zimbabwe, Kenya, Uganda, Ethiopia, Gabon, Cameroon, South Africa, Rwanda, Zambia, Tanzania, Mozambique
Experts: independent experts designated by WHO, FDA/CBER, DCVRN, EMEA
Topics: Priority vaccines in CTs or near introduction (Malaria, HIV, Mening, Rotavirus, etc)

13. Second plenary meeting AVAREF September 2007, Ouagadogou
Regulatory oversight of clinical trials in Africa, by USFDA, EMEA, Health Canada (source of most vaccines in trials)
Roles of NRAs and Ethics Committees
IRBs, Independent ECs
Role of NRA to ensure qualifications of ECs
Confidentiality provisions/use of external advise for regulatory reviews
Report on implementation of regulatory procedures
Sessions on HIV, Malaria, HPV, Mening A
Satellite meetings with Malaria relevant countries for planning of capacity building activities
Recommendations for training, support, regulatory documents and others

14. AVAREF: outcome higlights
Malaria project: 7 countries will use harmonized format for CT application for joint review facilitated by WHO
EMEA, USFDA, Health Canada to evaluate regulatory framework and other ways to support African NRA
Inventory of status of regulation of CTs in member countries
Endorsement to link registration and regulation of clinical trials

15. Development of training courses
Authorization of Clinical Trials
GCP inspections
Evaluation of clinical data for registration of new vaccines

16. Coordination with other WHO units
Medicines department
Sharing of guidance documents, regulatory model procedures, training programs to harmonize whenever possible
Ethics
Support to AVAREF (plenary and satellite activities)
Clinical Trial registry platform
Joint project to link registration-regulation of clinical trials

17. The status of CT regulation in developing countries
The vision
The status of CT regulation in developing countries
Developing countries that are target for clinical trials and introduction of new vaccines will have the regulatory mechanisms in place to perform quality reviews in a timely manner

18. The way forward
Collaboration between regulatory bodies to avoid gaps in oversight, ensuring quality of clinical data for priority vaccines
Strengthen regulatory mechanisms in developing countries
NGOs committed to further clinical development will support regulatory strengthening in involved developing countries