WHO Prequalification of Diagnostics, Medicines and Vaccines - 3rd Consultative Stakeholders Meeting

1. WHO Prequalification of Diagnostics, Medicines and Vaccines - 3rd Consultative Stakeholders Meeting WHO prequalification of vaccines and vaccine delivery devices Drs. Umit Kartoglu and Nora Dellepiane WHO HQ, Geneva- 4 February 2008 3rd WHO Prequalification Stakeholders Meeting

2. Vaccines prequalification- Purpose • A service provided to UN purchasing agencies. • Provide Independent opinion/ advice on the quality, safety and efficacy of vaccines for purchase • Ensure that candidate vaccines are suitable for the target population and meet the needs of the programme • Ensure continuing compliance with specifications and established standards of quality 3rd WHO Prequalification Stakeholders Meeting

3. Vaccines prequalification-Principles GMP Clinical data Consistency of final product characteristics Meeting WHO requirements and tender specs Reliance on NRA 3rd WHO Prequalification Stakeholders Meeting

4. Vaccines prequalification- Reliance on NRA • The responsible National Regulatory Authority (usually that of the producing country) is independent andfunctional: • Meets all the critical indicators required for prequalification purposes following a WHO independent assessment • The status of the NRA is reassessed at regular intervals 3rd WHO Prequalification Stakeholders Meeting

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

6. Vaccines prequalification- Required regulatory oversight Critical for countries: allows to ensure quality of actual lots received L Inspections at regular Intervals. Inform WHO of serious GMP deviations Lot to lot release Post-marketing surveillance for safety and efficacy Inform WHO in case of reports of serious AEFI Regulatory Actions: Inform WHO in case of withdrawals or recalls of lots and license suspensions 3rd WHO Prequalification Stakeholders Meeting

7. Vaccines prequalification- Evaluation procedure • Review of quality data • Review of efficacy and safety data with focus on data relevant for the target population in the recommended schedules • Production consistency at commercial scale • Compliance with GMP • Compliance with WHO recommendations • Compliance with UN tender specifications • Programmatically suitable presentation 3rd WHO Prequalification Stakeholders Meeting

8. Vaccines Prequalification- Impact of the project Assured Quality Replacing country's Regulatory oversight NRA and Manufacturer strengthened Seal of quality Requirement for procurement 3rd WHO Prequalification Stakeholders Meeting

9. Vaccines Prequalification- Features • Pre- evaluation meetings with mfgs and NRAs • 3 deadlines for submissions, joint reviews • 12 months evaluation (time taken by manufacturer excluded) • Clock stop system • Increased portfolio of vaccines • Prioritization system defined by UN agencies • PQ status valid for 2 to 5 years • Information published on WHO website (updated monthly) 3rd WHO Prequalification Stakeholders Meeting

10. Vaccine PQ- Evaluations and Reassessments 3rd WHO Prequalification Stakeholders Meeting

11. Vaccines PQ- Addressing the challenges • Provision for fast-track procedure in case of emergency vaccines (six months) • Addressing seasonal and pre-pandemic influenza vaccines (expedited procedure) • Provision for parallel evaluation with NRA for high priority vaccines • Increased human resources • Guidance documents produced • Strengthening quality assurance system • SOPs • Quality database • Testing database • Collaboration with EDM and EHT for development of common database for monitoring submissions

12. Vaccines PQ- The way forward • Sustainability of the process: risk based approach: Current procedure curre High risk: products from manufacturers with limited/no experience with the PQ process/ the product in question, and/or the NRA is borderline with respect to functionality Medium risk: manufacturer with or more prequalified vaccines and experience with product in question, or manufacturer is new to the system but supported by a JV with a with a well established mfg and NRA is functional. Low risk: Manufacturer is well established, more than one product prequalified, and may or may not have experience with product in question but has good research and development infrastructure. NRA is functional. Lighter procedure* lighter * Strict compliance with post-marketing commitments and close FU of functionality of NRA

13. Building on vaccine PQ system to expedite MAA process in receiving countries • Countries require that only licensed vaccines be used • Manufacturers are asked to submit dossiers and pay fees • Licensing timelines may be very long • Expertise for review not always available • Confidentiality not always guaranteed • Use of vaccine in country sometimes delayed pending evaluation 3rd WHO Prequalification Stakeholders Meeting

14. Procedure for expedited approval of prequalified vaccines used in NIP Intent of the procedure: • To comply with national regulations and international standards. • To continue to provide timely access to vaccines that meet standards of assured quality. • To enable countries to put more emphasis on post marketing surveillance system (AEFI). • Focuses on regulatory approval process and does not affect any post-approval activities in place. 3rd WHO Prequalification Stakeholders Meeting

15. Procedure for Expedited Approval of Prequalified Vaccines used in NIP Scenario 1: Countries sourcing from UN agencies For an expedited approval of WHO-prequalified vaccines that are sourced from UN procurement agency. Scenario 2: Countries procuring directly For an expedited approval of WHO-prequalified vaccines that are procured directly. Provides guidance as to how NRAs of these countries can build on the processes in place for the WHO prequalification to expedite the granting of regulatory approval for such products 3rd WHO Prequalification Stakeholders Meeting

16. Proposed implementation plan- SEARO 2008 • Review national regulations, procurement process, vaccine import procedures, and any other processes as required. • Adapt and adopt guidelines as part of national regulatory process applied to vaccines for use in NIP. • Ensure smooth transition period. • Encourage manufacturers to start the process. • Receive applications from manufacturers • Review applications and notify WHO & the manufacturer (with copy to UN procurement agency if relevant). • Add product information to national approved drug list. • Encourage other manufacturers and repeat the process until all pre-qualified vaccines (suppliers) receive expedited regulatory approval. 3rd WHO Prequalification Stakeholders Meeting

17. WHO website link to PQ and expedited approval procedures http://www.who.int/immunizationstandards/vaccine_quality/pq_suppliers/en/index.html 3rd WHO Prequalification Stakeholders Meeting

18. Performance, Quality and Safety (PQS)Background- The interested parties • WHO: takes the duty to specify and verify cold chain and other products for immunization. • UN procurement agencies: are products fit for purpose? • Client countries:what’s the performance of the product, and where should it be used? • Industry:a fair basis for tendering and investing in development. 3rd WHO Prequalification Stakeholders Meeting

19. PQS Background- Product Information Sheets (PIS) -Collaboration between UNICEF Supply Division and WHO -Performance specifications and test procedures for immunization-related products, including cold chain equipment. - Main information for buyers of products used in NIP - Conform products listed - Last PIS eddition 2000 3rd WHO Prequalification Stakeholders Meeting

20. PQS- Product categories • E01 > Cold rooms, freezer rooms and related equipment. • E02 > Transport (guidance only – includes refrigerated vehicles) • E03 > Refrigerators and freezers, including solar (PV) systems. • E04 and E11 > Cold boxes, vaccine carriers and biological specimen carriers. • E05 > Ice packs • E06 > Temperature monitoring devices. • E08 and E13 > Single-use injection devices (AD syringes for immunization and curative services). • E10 > Waste management equipment. 3rd WHO Prequalification Stakeholders Meeting

21. PQS- Procedures • PQS works on a cost-recovery basis. • SOPs that detail the procedure (writing/amending specs, product review and disqualification, test laboratory accreditation) • Product evaluation: Compliance with an ISO standard. • All pre-qualified products subject to annual review. • All product data sheets and guidelines web-based. http://www.who.int/immunization_standards/vaccine_quality/pqs/en/index.html 3rd WHO Prequalification Stakeholders Meeting

22. PQS- Organizational Structure

23. PQS- Enpoint