1. www.tfda.or.tz 1 GAVI MEETING Hyatt (Kilimanjaro) Hotel 5 th - 7 th, December 2012 Regulation of Vaccines: From Regulator’s perspective Hiiti B. Sillo Director General 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 ► Statutory organization under the MoHSW 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 which resulted into a merger of the then Pharmacy Board and National Food Control Commission ► TFDA began operations on 1 st July 2003

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5. TFDA ► TFDA is a semi autonomous body ► It sources it’s funding from internal revenue generation systems (i.e. fees collection), government subvention and donor funding (e.g. GF, WHO, FAO, USAID, HSPS DANIDA, CHAI etc.) ► There about 183 employees to date 5

6. www.tfda.or.tz 6 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 and vaccine manufacturers ► Import and export control ► Monitoring of adverse drug reactions (ADRs)

7. www.tfda.or.tz 7 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

8. www.tfda.or.tz 8 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

9. www.tfda.or.tz 9 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

10. www.tfda.or.tz 10 Registration of Vaccines (3)

11. www.tfda.or.tz 11 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 47 vaccines (human - 20 & vet - 27) have been registered

12. www.tfda.or.tz Abbreviated evaluation ► Internal procedure for evaluating medicinal products that have obtained marketing authorization from identified Regulatory Authorities incl. WHO prequalified products ► Conditions:- –Must be on the market in the countries of origin –Must be identical in terms of composition and approved SPC –Must be manufactured in the same facilities 12

13. www.tfda.or.tz 13 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.

14. www.tfda.or.tz 14 Inspection activities… ► Physical verification and checking of premises (MSD, hospitals, private pharmacies, vehicles, vessels or conveyances 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

15. www.tfda.or.tz 15 Safety monitoring ► 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.

16. www.tfda.or.tz 16 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 adverse events.

17. www.tfda.or.tz 17 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

18. www.tfda.or.tz 18 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

19. www.tfda.or.tz 19 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

20. www.tfda.or.tz 20 Current situation (1) ► There have been few reports of safety of products including AEFI ► 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) ► AEFI reports are usually received by EPI

21. www.tfda.or.tz 21 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)

22. www.tfda.or.tz 22 Harmonization initiatives ► 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

23. www.tfda.or.tz 23 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.

24. www.tfda.or.tz 24 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

25. www.tfda.or.tz 25 Missing link ► Collaboration between TFDA and EPI - needs to be strengthened ► AEFI surveillance system needs to be synchronized ► It had been agreed during AVAREF meetings to 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 can be used for the interaction

26. www.tfda.or.tz 26 Conclusion ► We need to strengthen collaboration & information sharing ► The National AEFI Advisory Committee has been recently established to advise on issues related to AEFI reporting and management ► 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.

27. www.tfda.or.tz 27 End of Presentation You can visit us at www.tfda.or.tz