1. Leveraging the prequalification process for national regulatory decision making Fimbo, A. M Tanzania Food and Drugs Authority

2. Outline ► WHO prequalification processes: ► Prequalification of medicines ► Prequalification of vaccines ► Prequalification of diagnostics ► Prequalification of QC laboratories ► Tanzania experience ► Integrating PQP procedures into NRA approval processes

3. 3 Prequalification of medicines ► Objective: ► To ensure quality, efficacy and safety of medicines procured by UN agencies ► Covers – prioritized medicines for HIV/AIDS, TB, malaria, influenza, reproductive health and acute diarrhoea (zinc) ► Over 240 medicines prequalified so far (http://www.who.int/mediacentre/factsheets/fs278/ en/index.html)http://www.who.int/mediacentre/factsheets/fs278/ en/index.html

4. 4 Prequalification of medicines ► Components: ► Invitation - Expression of interest ► Dossier submission ► Evaluation of Quality, Safety and Efficacy of prioritised essential medicines ► Inspection of manufacturers ► Decision making ► Monitoring of the products after their prequalification

5. 5 Prequalification of vaccines ► Official request and response ► Meeting with manufacturers ► Submission of Product Summary File (PSF) ► Initial testing of vaccine samples ► WHO site audits ► Report and outcome of assessment ► Over 200 vaccine products have been prequalified (as of 22 nd June 2011) (http://www.who.int/immunization_standards/vaccine_quality/PQ_vac cine_list_en/en/index.html)http://www.who.int/immunization_standards/vaccine_quality/PQ_vac cine_list_en/en/index.html

6. 6 Prequalification of diagnostics ► The WHO prequalification of diagnostics programme aims to increase access to affordable diagnostic technologies of assured quality that are appropriate for use in resource limited settings. ► The programme provides Member States, UN agencies and other partners with technical information and advice on the quality of currently available HIV/AIDS, malaria and hepatitis B and C test kits and technologies. ► http://www.who.int/diagnostics_laboratory/evaluations/en/

7. 7 Prequalification of diagnostics ► Submission of application ► Letter of agreement and payment of fees ► Dossier review ► Site inspection ► Laboratory evaluation ► Prequalification decision making ► 20 diagnostics have been prequalified as of 1 st May 2012 (http://www.who.int/diagnostics_laboratory/evaluations/120502_preq ualified_products_list_v1.pdf)

8. 8 Prequalification of QC Labs ► Invitation for Expression of Interest ► Submission of EOI and Lab info ► Screening and Evaluation of the Lab info ► Site inspection, report and outcome ► Results of assessment ► Monitoring of prequalified QC Labs (WHO TRS 961)

9. 9 Tanzania experience ► Tanzania Food and Drugs Authority (TFDA) is the regulatory authority in Tanzania (est. under the Food, Drugs and Cosmetics Act, No.1 of 2003 ► Together with other regulatory functions, TFDA has established systems & procedures for: ► Medicinal product review and marketing authorization ► Medical devices assessment and authorization ► Biological product review and marketing authorization ► GMP and GCP inspection ► QC Laboratory

10. 10 Evaluation and MA ► Applicants are required to submit dossier with a complete set of data on: ► Active pharmaceutical ingredient (API) ► Finished pharmaceutical product (FPP) ► Interchangeability (BE data) ► SPC and other details ► The TFDA Guidelines on Submission of Documentation for Registration of Human Medicinal Products have been developed for applicants to follow through when compiling data ► The requirements have been adopted from the WHO prequalification guidelines

11. Evaluation and MA ► Assessment tools have also been adopted from the WHO prequalification tools – used for assessment of dossiers ► Assessment timeline is 250 working days (Clients Service Charter) ► Both internal and external assessors are used ► Assessment involves a comprehensive review of all parts of the dossier for products that have not been prequlified or originate from stringent regulatory authorities

12. 12 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

13. Abbreviated evaluation ► Procedure adopted after gaining experience in evaluating products from such countries ► Also after taking part in the prequalification process for medicines including working at WHO HQ as part of rotational programme for staff who participate in the assessment of dossiers in Copenhagen ► And from positive market experience and results of PMS studies conducted in Tanzania

14. 14 Vaccines MA ► Vaccines that are in the EPI list are the ones accepted for assessment ► Applicants are required to submit dossier with a complete set of data on: ► Chemistry, manufacturing and quality of immunogenic substance ► Chemistry, manufacturing and quality of finished product ► Pre-clinical toxicology data ► Clinical safety and efficacy data ► SPC and other details ► The TFDA Guidelines for Application for Registration of Biologicals have been developed ► The requirements have been adopted from the ICH, AVAREF and WHO guidelines

15. Medical devices MA (Evaluation and approval - based on risk) ClassRisk LevelExamples ALow riskSurgical retractors/ tongue depressors BLow – moderate riskHypodermic Needles/ suction equipment CModerate – high riskLung ventilator/bone fixation plate DHigh riskHeart valves/ implantable defibrillator

16. 16 Medical devices MA ► For general devices – these are assessed based on risk ► Applicants are required to submit dossier with a complete set of data on: ► Summary technical documentation ► Device details ► SPC and other details ► The TFDA Guidelines on Submission of Documentation for Registration of Medical Devices is used by applicants when compiling data ► The requirements have been adopted from the GHTF and WHO guidelines

17. In-Vitro Diagnostics (IVDs) ► For IVDs the WHO guidelines for registration of IVDs have been adopted/adapted ► Project for PMS of diagnostics is now underway in TZ – plans to sample and test selected IVDs in the country ► Involves TFDA, PHLB, NHQAL-TC and MSD ► Aims at determining quality status of approved IVDs, increasing collaboration and adopting WHO prequalification guidelines on IVDs

18. GMP and GCP audits ► TFDA authorizes products that are manufactured at a GMP compliant facility ► TFDA GMP guidelines have been developed ► Adopted from the WHO guidelines ► Same principles, methods and norms are followed when conducting audits

19. GMP and GCP audits ► TFDA staff take part as observers in joint audits with WHO Auditors ► WHO prequalified sites are recognized by TFDA ► Audit is usually not conducted at WHO approved facilities unless otherwise when necessary (i.e. different line not falling under WHO prequalifed products)

20. GMP and GCP audits ► GCP inspection of CROs (BE sites) is usually not done ► Only GCP inspection of clinical trials conducted at trial sites in TZ is done ► GMP inspection of API manufacturers is also not done ► TFDA relies on WHO reports on GCP inspection outcomes for CROs and API manufacturers approved by WHO

21. 21 QC Laboratory ► TFDA laboratory established in 2000 has the capacity to handle most of the analytical work ► Minilab Kits (for primary screening) placed in centers throughout the country ► The lab has been prequalified by WHO (http://apps.who.int/prequal/lists/PQ_QCLabsList.p df) ► Has recently obtained SADCAS accreditation (ISO/IEC 17025)

22. QC Laboratory ► The Lab assists TFDA in making decision on: ► Products to be approved for MA ► PMS samples that meet/do not meet quality testing requirements ► Suspicious samples picked from POEs and market ► Counterfeit products confiscated from the market

23. Integrating PQP procedures ► Procedures used by NRAs and PQP are almost the same ► PQP pools resources (HR, finances and materials) for product review, site inspections and decision making ► PQP guidelines and procedures can be adopted and integrated into NRA procedures for decision making

24. Integrating PQP procedures ► This will minimize the use of already limited resources in emerging RAs ► Same products submitted to WHO for PQ are also submitted to NRAs for MA ► At least prequalified products can be waived from long review processes by NRAs ► It would enhance the harmonization of procedures and shorten the review and approval timelines

25. Summary ► The WHO PQP has greatly assisted TFDA to develop guidelines and procedures for approving medicines, vaccines and medical devices. ► Other emerging NRAs can adopt the PQP procedures to spare the limited resources and use them effectively for other regulatory functions