Andrew Deavin M.Sc. Ph.D. Chairman, IFPMA Vaccine Regulatory Working Group GSK Biologicals

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1 Enabling access to vaccines through better National Regulatory Authority collaboration and harmonization of Clinical Trials Application regulatory procedures WHO Pre-ICDRA Workshop: Future for Medicines Regulation Session J: Worksharing November 29, 2010, Singapore Andrew Deavin M.Sc. Ph.D. Chairman, IFPMA Vaccine Regulatory Working Group GSK Biologicals 1

2 Agenda Considerations specific to clinical trials for vaccines Areas for Harmonization Fundamental Principles underlying the CTA regulatory review process for vaccines CTA regulatory review process Examples of regional CTA harmonization: EU and Africa What are the benefits of increased harmonization of clinical trial regulatory process? Conclusion and Moving Forward 2

3 Considerations specific to clinical trials for vaccines Prophylactic vaccines are for "healthy individuals Large subject numbers for a vaccine clinical trial often require multiple global trial sites Preventable communicable diseases do not know borders Vaccinating: Healthy people > pediatrics > infants Need to be sensitive to public perception Need to do trials that fit with country s vaccination schedule - they are not harmonized!! 3

4 Heterogeneous immunization schedules examples: European Countries Country 2m 3m 4m 5m 6m 12m 13m 14m 15m UK HibMenC DTP MenC Spain* Ireland Belgium France Hib & MenC Netherlands Portugal Italy Greece 1y+ Switzerland Germany 4

5 Areas for Harmonization of Clinical Trial Regulatory Process Key Principles Patient/volunteer safety is paramount It is not rate limiting to recruitment of volunteers/patients Allows visibility of procedure and accessibility of Regulators Enables innovation, i.e. it is not a barrier Enables participation in global clinical program Efficient ethics approval procedure, which runs in parallel with the regulatory procedure Procedural Aspects Regulatory procedures are clearly described This is particularly so for vaccines: Defined timelines are outlined and monitored Disease to ensure burden adherence will dictate where trials are undertaken Regulatory documentation is standardized The size and of appropriate trials required to the phase means of the almost clinical always and need product multistate development participation Mechanisms Immunology to manage and change vaccinology during are drug specialised development areas are so need defined to pool expertise Import approval is not a rate limiting step Good Clinical Practice (GCP) should enable the fundamental principles to be integrated in the ethical and regulatory review processes 5

6 Examples of Regional Harmonization Initiatives relating to Clinical Trial Applications EU Initiatives Clinical Trial Directive Voluntary Harmonization Procedure (VHP) 6

7 Clinical Trial Directive and Facilitation Group Key Provisions Provided consistency, for the first time, across the EU For example, one definition of an Investigational Medicinal Product (IMP) Harmonized data requirements: IMP Dossier (IMPD) Framework for timelines Clinical Trial Facilitation Group established in 2004 to facilitate harmonization For example, support in developing EU Clinical Trial Database (EudraCT) ( Areas for further harmony Country specific requirements Timelines can vary Still need separate reviews in each country 7

8 Voluntary Harmonization Procedure (VHP) for Clinical Trial Applications Joint member state response to Sponsor request V.1 pilot launched March 2009, V.2 March 2010 A leading designated member state consolidates all NRA questions into single list 3 approval steps: Request 5 days Assessment 60 days (max) Formal national authorisations ~30 days (max) Current scope: Multicenter CTs conducted in 3 Member States In 2009 there were 4491 new trials applied for in EU 933 were multi-state Less than 2.5% went through Voluntary Harmonization Procedure!! 8

9 Examples of Regional Harmonization Initiatives relating to Clinical Trial Applications African Initiative AVAREF (African Vaccine Regulatory Forum) Part of wider Regulatory Harmonization across Africa: 9

10 WHO capacity building for Sub-Saharan Africa NRAs: AVAREF AVAREF= African Vaccine Regulatory Forum, hosted by WHO AFRO, 19 member countries created in 2006 Objective : to establish a system to support African NRAs in the assessment of clinical trial applications and monitoring of clinical trials as well as to evaluate clinical data in registration dossiers In addition to annual AVAREF meetings: Specialized workshops (GCP, inspections, ) Facilitation of joint reviews of clinical trial applications by host and observers countries with assistance from tech. experts THE GAMBIA GUINEA BISSAU MAURITANIA SIERRA LEONE GUINEA LIBERIA COTE DTVOIRE MALI BURKINA BENIN TOGO GHANA EQUATORIAL GUINEA NIGER NIGERIA CAMEROON GABON CHAD REP. OF THE CONGO ANGOLA NAMIBIA CENTRAL AFRICAN REPUBLIC DEMOCRATIC REPUBLIC OF THE CONGO SUDAN RWANDA BURUNDI ZAMBIA BOTSWANA MALAWI ZIMBABWE SWAZILAND LESOTHO SOUTH AFRICA ERITREA UGANDA ETHIOPIA KENYA TANZANIA MOZAMBIQUE DJIBOUTI Current countries intelligence Established regulatory procedures for clinical trials Regulatory procedures for clinical trials in progress No regulatory procedures for clinical trials Status unknown 10

11 Process for review of CTAs: GSK experience AVAREF Sept. 2007: Proposal for Joint review of Clinical trial application(cta) by the 7 target countries: KENYA Standardized format & timelines Technical assistance from 2 delegates from Belgium FAHMP Individual NRA approvals Of the 7 host countries, only four had established processes for NRA approval of clinical trials June 4, 2008: Pre-submission meeting facilitated by WHO with representatives from Tanzania, Kenya, Malawi and Ghana July 2008 : Pre-submission meetings with Gabon and Burkina-Faso NRA BURKINA-FASO GHANA GABON WHO MALAWI TANZANIA Mozambique August 2008: CTA submission to 7 NRAs based on agreed harmonized format 11

12 Joint review meeting : October out of 7 countries participated in the Joint Review process (Mz out) 2 ½ days closed NRAs meeting with Belgian NRA technical experts + WHO ½ day debriefing meeting with sponsor No major show-stoppers from the meeting but consolidated list of 46 questions to the sponsor Questions received formally from 5 out of 7 NRAs (all but Gabon) drawn from the consolidated list

13 Phase III Efficacy Study, approval timelines NRA Approvals Jan & May 2009 MoH Approval April 2009 NRA Approvals June 2009 MoH Approval Feb NRA Approvals Apr NRA Approval Apr MoH Approval Jan NRA approval 3 to 8 Months after Joint Review meeting (1) ClinicalTrials.gov web site. Efficacy of GSK Biologicals' Candidate Malaria Vaccine Against Malaria Disease in Infants and Children in Africa. Available from: [Assessed: 11 June 2009] (2) MARA & ARMA web site. Maps. Map adapted from Duration of Malaria Transmission Season. Available from: [Assessed: 11 June WHO 2009] Pre-ICDRA, Session J: 29 Nov. 2010, Singapore 13

14 Conclusion from GSK experience of AVAREF process Close collaboration with NRAs foster mutual understanding and pave the way towards licensure NRAs and sponsor learning experience & led to adjustments/revisions in CTA processes in trial countries However despite careful planning and preparation, still unpredictable timelines Lack of local political commitment to NRAs and Ethics Committees strengthening contribute to slow process, which could be improved Strengthening AVAREF is key to promote & pursue NRAs and IRBs capacity building in the area of CT oversight in Sub-Saharan Africa 14

15 What are the benefits of increased harmonization of clinical trial regulatory process? Increases standardization so facilitating recognition of each others approvals Consistent GCP implementation Enable earlier clinical trial start up so lead to fast approval and faster access to the eventual vaccine Global clinical trials negate the need to do additional bridging studies in relation to potential ethnic differences Early involvement with the vaccine will help to build grass root expertise and experience with the vaccine Expedite eradication/reduction of disease burden 15

16 Movement towards Harmonization China Japan South Korea (+ Others) Tripartite Agreement EU Voluntary Harmonization Procedure AVAREF in Africa striving for harmonization, including for CTA review and requirements 16

17 Conclusion and Moving Forward GCP Harmonization is work in progress There are regional initiatives underway which help to facilitate regional harmonization of clinical trial regulatory review process Our Ask? Continued Political Will towards harmonization Universal harmonization of principles e.g. GCP Increased harmonization of regulatory review process for clinical trial application Increased CT harmonization will ensure people (wherever they live) gain faster access to life saving preventative medicines 17

18 Thank you 18