Building capacity to regulate clinical trials for vaccines Dr. Liliana Chocarro

1. 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 ForumAVAREF (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 ForumAVAREF (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 AVAREFSeptember 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 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