1. www.tfda.or.tz 1 EPI ANNUAL EVALUATION MEETING Kunduchi Beach Hotel 13 - 16 th, December 2010 Registration, Inspection and Vaccine Safety Fimbo, A. M Tanzania Food and Drugs Authority

2. www.tfda.or.tz 2 Outline ► About TFDA ► Roles of TFDA ► Registration of vaccines ► Inspection of vaccines ► Vaccine safety ► Harmonization initiatives ► Conclusion

3. www.tfda.or.tz 3 TFDA ► Established under the Tanzania Food, Drugs and Cosmetics Act, No.1, 2003. ► Followed a repeal of Pharmaceuticals & Poisons Act, 1978 and Food (Control of Quality) Act, 1988

4. www.tfda.or.tz 4 Roles of TFDA (1) ► TFDA is responsible for regulating and ensuring quality, safety & efficacy of food, drugs (human, veterinary, herbal and vaccines), medical devices & cosmetic products through: ► Evaluation & registration of such products ► Registration & licensing of premises ► GMP inspection of drug manufacturers ► Import and export control ► Monitoring of adverse drug reactions (ADRs)

5. www.tfda.or.tz 5 Roles of TFDA (2) ► QC Lab. testing/analysis of products manufactured or imported into Tanzania ► Registration and control of clinical trials ► Control of product promotion ► Public education on issues related to safety, quality & efficacy of all products regulated by TFDA

6. www.tfda.or.tz 6 Registration of Vaccines (1) ► Section 51 (1) of the 2003 Act, mandates the TFDA to register all medicines including vaccines ► The Authority considers the following factors before approving products: ► That the availability of the product is in the public interest ► It is safe, efficacious and of acceptable quality; ► The premises and manufacturing operation complies with the current GMP requirements ► The product complies with any other requirements as may be prescribed by the Authority

7. www.tfda.or.tz 7 Registration of Vaccines (2) ► Guidelines for Application for Registration of Biologicals of 2004 is a standard doc used by applicants when applying vaccines for registration ► The guidelines amongst other things outlines the requirements for registration of vaccines to include: ► Submission of data on the chemistry, manufacturing and quality of immunogenic substance ► Data on the chemistry, manufacturing and quality of finished product ► Pre-clinical toxicological data ► Clinical safety and efficacy data

8. www.tfda.or.tz 8 Registration of Vaccines (3)

9. www.tfda.or.tz 9 Registration of Vaccines (4) ► Validity of registration is 5 years ► The TFDA may by giving reasons in writing refuse, suspend, cancel or revoke the registration of a vaccine, or amend the conditions of its registration. ► So far a total of 79 vaccines (human & vet) have been registered ► There are about 7 human vaccine and 11 vet vaccine manufacturers approved by TFDA

10. www.tfda.or.tz 10 Inspection of Vaccines ► Various sections of the main Act, 2003 mandates the TFDA to conduct inspection and enforcement activities. ► Amongst the activities include: ► Registration of premises/outlets to stock, distribute and dispense medicines incl. vaccines ► Issuance of license/permit to stock, distribute and sell/sale medicines incl. vaccines.

11. www.tfda.or.tz 11 Inspection activities… ► Physical verification and checking of premises (MSD, hospitals, private pharmacies, vehicles, vessels or conveyance etc) for compliance to the law ► Conducting GMP inspection of manufacturers of medicines incl. vaccines ► Controlling importation and exportation of products incl. inspecting PoEs. ► Destruction of unfit products ► Conducting GCP inspection of clinical trials/sites

12. www.tfda.or.tz 12 Safety monitoring (1) ► TFDA uses two systems to monitor safety of medicines incl. vaccines: ► Passive surveillance ► Active surveillance ► The mandate to monitor safety is provided under section 5 (1) (c) of TFDA Act, 2003. ► The National Guidelines for Monitoring Medicines Safety is a standard document used.

13. www.tfda.or.tz 13 Safety monitoring (2)

14. www.tfda.or.tz 14 Safety monitoring (3)

15. www.tfda.or.tz 15 Passive surveillance (1) ► Passive surveillance (spontaneous or voluntary reporting) system involves: ► ADR reporting forms (used to collect safety data) ► Existence of zonal pharmacovigilance centers (MNH, Bugando, Mbeya & KCMC) ► Existence of a National PV Center (TFDA HQ) responsible for receiving safety data, detecting, assessing and preventing adverve events.

16. www.tfda.or.tz 16 Passive surveillance (2) ► Existence of a Pharmacovigilance Technical Committee (PVTC) responsible for advising the TFDA on safety issues related to medicines and vaccines. ► Use of global databases for sharing safety data within the country and outside (WHO – Vigibase & Vigiflow) ► The system depends on the initiative and motivation of the reporters

17. www.tfda.or.tz 17 Passive surveillance (3)

18. www.tfda.or.tz 18 Passive surveillance (4)

19. www.tfda.or.tz 19 Active surveillance (1) ► Active measures are taken to find adverse effects other than the encouragement of health professionals and others to report safety concerns. ► Examples ► Sentinel approach ► Cohort event monitoring ► Registries ► Case control studies

20. www.tfda.or.tz 20 Active surveillance (2) ► CEM is mainly used. ► Involves collecting safety data using special forms for special categories of medicines and diseases ► A designated database (CEMFlow) is used to manage safety data ► A very effective system for identifying signals at an early stage of introducing medicines to the market

21. www.tfda.or.tz 21 Current situation (1) ► Reporting of safety data including AEFI has been very disappointing ► The rate of underreporting is very high ► Approx 30 – 50 reports of AEs related to medicines are received in 1 year ► Atleast 200 reports/1 million inhabitants are required to generate a signal (WHO) ► No AEFI reports have been received ever since the introduction of a PV system

22. www.tfda.or.tz 22 Current situation (2) ► Reasons could be: ► Reliant on goodwill of reporters (voluntary reporting) ► Fear to report by health professionals – afraid of being blamed for mismanagement of patients ► Workload to healthcare professionals ► Safety reporting not given priority (not included in supportive supervision, CCHPs etc)

23. www.tfda.or.tz 23 Harmonization initiative (1) ► TFDA is taking part in the harmonization process that involves clinical trials of vaccines in Africa ► The harmonization process has been set up by countries in collaboration with WHO under the auspices of a Forum named African Vaccine Regulatory Forum (AVAREF) since Sept 2006. ► About 19 countries are engaged with AVAREF at the moment: Botswana, Burkina Faso, Cameroon, Ethiopia, Kenya, Gambia, Ghana, Gabon, Uganda, Tanzania, Mali, Malawi, Nigeria, South Africa, Senegal, Rwanda, Mozambique, Zambia and Zimbabwe

24. www.tfda.or.tz 24 Harmonization initiative (2) ► The Forum meets every year: ► AVAREF 1 – Accra, Ghana – 2006 (inception) ► AVAREF 2 – Ouagadougou, B/Faso - 2007 ► AVAREF 3 – Zanzibar, Tanzania - 2008 ► AVAREF 4 – Abuja, Nigeria - 2009 ► AVAREF 5 – Nairobi, Kenya - 2010 ► AVAREF 6 – Planned for either Mozambique, Zimbabwe, Malawi or Senegal - 2011

25. www.tfda.or.tz 25 Objectives of AVAREF ► To provide information to countries targeted for clinical trials of vaccines, on vaccine candidates and timelines. ► To promote communication and collaboration between NRAs in countries where vaccines are developed and ECs and NRAs in countries targeted for vaccine clinical trials. ► To provide expertise to African NRAs, especially, on development of procedures for authorization and monitoring of clinical trials as well as the evaluation of data. ► To promote vaccine development and access, in line with the Global Immunization and Strategy and Vision (GIVS), as well as the goals of the IVB/HQ and IVD/AFRO programmes.

26. www.tfda.or.tz 26 Major achievements ► Joint reviews and joint inspections conducted (Conjugate meningitis A and Malaria vaccines) ► Development of African Common Clinical Trial Guidelines (ACCTG) ► Integration of ethical review, regulation and registration of clinical trials ► Model regulatory procedures developed and adopted by many countries

27. www.tfda.or.tz 27 Missing link ► Collaboration between TFDA and EPI - needs to be strengthened ► AEFI surveillance system needs be synchronized ► It was agreed during last AVAREF meeting that WHO should organize a forum for the interaction between NRAs and EPIs to bridge communication gaps. ► Annual African Regional Conference on Immunization/ Task Force on Immunization meeting platforms will be used for the interaction

28. www.tfda.or.tz 28 Conclusion ► We need to strengthen collaboration ► Effective systems for sharing information should be established ► AEFI reports should be shared to allow for regulatory measures to be taken: ► Warning manufacturers ► Change of product labelling ► Product withdrawal from the market etc.

29. www.tfda.or.tz 29 End of Presentation You can visit us at www.tfda.or.tz