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

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

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

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

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

6. Vaccines prequalification- Required regulatory oversight L Lot to lot release Inspections at regular Intervals. Inform WHO of serious GMP deviations 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 Critical for countries: Critical for countries: allows to ensure quality of actual lots received

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

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

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)

10. Vaccine PQ- Evaluations and Reassessments

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: Hi gh 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. currecurre Current procedure lighterlighter Lighter procedure* * 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

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.

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

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.

17. WHO website link to PQ and expedited approval procedures http://www.who.int/immunization http://www.who.int/immunization standards/vaccine_quality/pq_su ppliers/en/index.html

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.

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

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.

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

22. PQS- Organizational Structure

23. PQS- Enpoint