Evaluating the acceptability of vaccine and vaccination programmes: an individual and public health perspective

Transcription

1 The regulatory process Evaluating the acceptability of vaccine and vaccination programmes: an individual and public health perspective Annecy, Les Pensières July 7-9, 2008 Dr. Nora Dellepiane, Scientist WHO/IVB/QSS July 2008

2 Outline Vaccines of assured quality Recommended regulatory functions and source of vaccines. WHO support to strengthen regulatory functions New vaccines: New challenges WHO innovative approaches to support strengthening of regulatory capacity

3 Vaccines of assured quality

4 Contribution to World Health Organization Goal Ensure that 100% of vaccines used in all national immunization programmes are of assured quality Definition iti of Assured d quality vaccines National Regulatory Authority (NRA) independently controls the quality of vaccines in accordance with the six specified functions defined by WHO No unresolved confirmed reports of quality related problems Guided by Expert Committee on Standardization of Biologicals i l (ECBS) recommendations on safety, efficacy and quality issued in WHO Technical Report Series (TRS)

5 Recommended regulatory functions and source of vaccines. WHO support to strengthen regulatory functions

6 Regulatory functions depending on vaccine source Regulatory functions Regulation System Licensing AEFI monitoring UN agency Vaccine source Direct Procurement Lot release Functions Access to laboratory assured by NRA of Regulatory inspections producing Fuctions assured country and by NRA of Authorization of producing WHO PQ system clinical trials country Production

7 Regulatory guidance WHO norms and standards Global written standards Global measurement standards Support for the evidence base for standards

8 WHO Global written standards Technical specifications that help define safe and efficacious vaccines. These are intended to be scientific and advisory in nature Guidance for national regulatory authorities and manufacturers on international regulatory expectations for the production and quality control of vaccines, non-clinical and clinical evaluation of vaccines Facilitate international harmonisation of vaccine licensure Living documents revised in response to scientific advances

9 Use of WHO guidance and standards The WHO Recommendations on production and quality control of vaccines are used as: -thebasis of national regulations in many countries - the technical specifications against which compliance is assessed for the purposes of pre-qualification of vaccine supply by UN agencies

10 Process to strengthen NRAs The five step capacity building programme 1)Benchmarking 2)NRA assessment 3)Planning to address gaps (IDP) Planning to address gaps NRA Network of regulatory experts 4)Implementation pe e tato of pa plan, including training courses (GTN), technical inputs, in country workshops 5)Monitoring and evaluation NRA Training i i Assessment Institutional needs using joint development assessment plan p to to tools address gaps Technical (Drug (Drug& vaccine) support 5 days assessment GTN placement within 1-3 months Follow up up visits months (6-8 months in needs much improvement)

11 Country Status: country assessment of vaccine regulatory system conducted, September 1997 NRA assessments conducted & planned NRA assessments completed Not yet conducted T

12 Country Status: 86 country assessment of vaccine regulatory system conducted, Sept.1997 Dec 2007 NRA assessments conducted & planned NRA assessments completed Not yet conducted New assessments to be conducted in 2008

13 New vaccines: New challenges

14 The Vaccine Pipeline & PQ vaccines HIV/AIDS Future Malaria TB Underutilized Vaccines Cholera Typhoid Hib (conj) Dengue Mening (conj) HPV Rotavirus Pneumo (conj) YF Influenza JE Rubella HepB Measles Traditional EPI Tetanus Polio Pertussis Diphtheria // // Vaccine Development Pipeline

15 Key messages The vaccine development pipeline is especially buoyant; some complex products are under development; specialist regulatory oversight is needed WHO is committed to support countries to ensure and sustain that 100% of vaccines used in all national immunization programmes are of assured quality NRA strengthening activities and other innovative approaches are being applied to attain this goal

16 New challenges Regulation of new vaccines : Responsibility now falls more on Developing Countries using these vaccines and less on Industrialized Countries where they are produced Countries have insufficient i expertise and experience to assess data and dossiers (Manufacturing, preclinical and clinical data, etc.) NRAs must acquire new skills Clinical trials for new vaccines Are being run in ANY country, no matter the expertise/strength t th of their National Regulatory Authority Quality of the trials must be guaranteed

17 Responding to challenges 1. Development of new support mechanisms for regulatory authorities 2. Development of new regulatory pathways

18 New Support Mechanisms for National Regulatory Authorities Establishment of Developing Countries Vaccines Regulators Network (DCVRN) in 2004 Establishment of African Vaccine Regulatory Forum (AVAREF) in 2006 Development of new Global Training Network Courses and country workshops on a needs basis Sentinel Network to monitor safety during introduction of novel vaccines and DTP based combinations

19 New Regulatory Support Mechanisms 1. Establishment of the Developing Countries Vaccine Regulators Network (Global) Brazil, Cuba, China, India, Indonesia Korea, Russia, South Africa and Thailand

20 Objectives 1. Developing Countries Vaccine Regulators Network Promote and support the strengthening of the regulatory capacity of NRAs for the evaluation of clinical i l trial proposals and clinical i l trial data through expertise and exchange of relevant information. Modus Operandi Meetings twice a year Discuss critical aspects to be considered for the review of clinical data for registration of novel vaccines Develop procedures, forms and other relevant documents to harmonize regulation of clinical trials and evaluation of clinical trial data Exchange of information and mutual support Provide support to other countries in their region of influence (i.e. SA and Indonesia

21 1. African Vaccine Regulators Forum (AVAREF) established in 2006 Objectives To provide information to regulators of countries that are target for clinical trials To promote communication/collaboration between NRAs and Ethics committees and among regulators in the Region and others To provide a resource of expert advise to regulators To identify needs for expert support to NRAs Modus Operandi One plenary meeting per year (2 to date) plus support activities between meetings; joint WHO/HQ/AFRO activity 19 countries involved; NRA and National Ethics Committee representatives ti

22 AVAREF achievements An historical moment : For the 1st time in Africa, regulators and ethics committee members from Burkina Faso, The Gambia, Ghana, Ethiopia and Mali conducted an inspection of Good Clinical Practice (GCP) inspection of phase II observer- blind, randomized, active controlled clinical trial of meningococcal a conjugate vaccine at the Centre for Vaccine Development (CVD), Bamako, Mali; January, 2007

23 Training Planning workshops for NRA strengthening g Twenty six countries The Gambia, Ghana, Nigeria, Ethiopia, Uganda and Kenya (Addis January 2005) Senegal, Mali, Niger, Benin, Togo, RCA, Cameroon, Burkina Faso and Guinea (Ouagadougou May 2005) Angola, Botswana, DRC, Malawi, Mozambique, Namibia, Rwanda, South Africa, Tanzania, Zambia and Zimbabwe (Gaborone Dec 2005)

24 Training Workshops and courses Evaluation of clinical trials, Pretoria, March 2005 Regulatory Procedures for Evaluation of Vaccines (Addis Sept. 2005) Regulatory forum on clinical evaluation of rotavirus vaccines (Botswana Dec. 2005) Joint review of CTA of Conjugate Meningitis A vaccine (Banjul Jun 2006) Vaccine Regulation (in French), M bour, Senegal, March 2006 Surveillance of AEFIs (in French) in Senegal (2006), Tunis (2007) and (in English) in Cape Town (RSA), 2006 Authorization & Inspection of Clinical Trials in French in Ouidah in December 2006, and in English in Harare in July 2007 Good Clinical Practices in English in Harare in July 2007 Joint Inspection of Men. A Clinical Trials, Bamako, Mali, Jan. 2007** African trainees sent in 2006 to GTN courses on lot relase in Lyon, France, and on GMP in Seoul, Korea

25 New GTN courses GMP inspections. Training Center: KFDA, Korea Testing of Hib conjugate vaccines. Training Center: NVI, The Netherlands Authorization of Clinical Trials (Itinerant) GCP inspection course (Itinerant) Evaluation of Clinical data (Updated 2008) (Itinerant) Lot Release (Updated 2007). Training Centers: AFSSAPS (in French) CDL Kasauli (in English) Product Evaluation (under development)

26 2. New Regulatory Pathways Collaboration with EMEA for the establishment of Scientific Opinion procedure (Art. 58) Procedure for expedited review of imported prequalified vaccines for use in immunization programmes Considering i feasibility of establishing mutual support mechanism between NRAs in Asia for the regulation of JE vaccines

27 Procedure for expedited review of PQd vaccines It is intended for countries that source their vaccines through UN agencies, or who use the WHO prequalification as a basis for selection of vaccines for use in their national immunization programmes, importing them through direct procurement. It provides guidance on how NRAs of such countries can expedite the regulatory review for such products. Not intended to affect in any way post-approval activities in place in these countries Countries intending to use the procedure should ensure that their national regulations contain provisions to allow to shorten the normal regulatory approval process.

28 Criteria for use Scenario 1 Scenario 2 For an expedited approval vaccines WHO-prequalified that are sourced through UN procurement agency. For an expedited approval of WHO-prequalified vaccines that are procured directly.

29 Requirements for licensing vaccines from PQ sources Scenario 1 Scenario 2 1. Check prequalification status 1. Same as in scenario 1 2. Submit product samples, product 2. Same as in scenario 1 inserts, NRA lot release certificates 3. Same as in scenario 1 from the country of origin, a list of 4. Same as in scenario 1in addition to countries where the product is licensed and marketed, and summary lot protocols of three final lots. 3. Visual inspection on samples 4. Review protocols (check specifications), labels, boxes and inserts against WHO model. Ensure presence of VVM 5. Prepare report of compliance (noncompliance) 6. If compliant, issue Certificate of Approval 7. Inform manufacturer and WHO 8. If novel vaccine with limited clinical data, review of clinical data may be needed ensure consistency with national tender specifications if different 5. Same as in scenario 1 6. Same as in scenario 1 7. Same as in scenario 1 8. Same as in scenario 1

30 Outcome and timeframes for expedited review procedure Scenario 1 Scenario 2 1. Waiver of fees from countries is requested 2. Total timeframe for evaluation should not exceed 30 days unless clinical i l data need to be reviewed, in which case timeframe is extended to 120 days 3. If info submitted by manufacturer is not complete, clock is halted awaiting. Completion. 4. Inform WHO that the procedure is being adopted. WHO will keep NRA informed of updates regarding PQ status. 5. Procedure applies to vaccines used in NIP 1. Same as in scenario 1 2. Same as in scenario 1. If country has testing capabilities and vaccine samples will be tested as part of the registration process, 90 days instead of 30 will be the timeframe for completion of procedure, except when clinical data need to be reviewed (120 days) 3. Same as in scenario 1 4. Same as in scenario 1; 5. Same as in scenario 1 6. Same as in scenario 1 6. Countries should not stop use of PQ vaccines not yet registered in the country

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