WHO Prequalification Programme: example of available regulatory expertise for some medicinal products

1. Mi WHO Prequalification Programme: example of available regulatory expertise for some medicinal products Milan Smid Quality Assurance and Safety: Medicines Prequalification Programme

2. UN Prequalification Programme for Priority Essential Medicines • Action plan of UN from 2001 for expanding access of priority medicines to patients with • HIV/AIDS • Malaria • Tuberculosis • Reproductive health • Potentially other categories of products • Antiviral medicines efficacious for avian flue • Paediatric formulations

3. Elements of Prequalification Programme Objective: • To ensure quality, efficacy and safety of medicines procured using international funds (e.g. GFTAM, UNITAID) Components: • Evaluation of Quality, Safety and Efficacy of prioritised Essential medicines, inspections of manufacturers and monitoring of the products after their prequalification. • Prequalification of quality control laboratories. • Building capacity of regulators, manufacturers and quality control laboratories.

4. How prequalification is organized? • WHO PQT working in co-operation with partners • UNICEF • UN Population Fund (UNFPA) • UNAIDS • World Bank • Anti-malarial and anti-TB products: Roll Back Malaria and Stop TB (Global Drug Facility); HIV/AIDS Department

5. How prequalification is organized? • WHO manages and organizes the programme on behalf of the United Nations: • provides technical and scientific support to assessment, inspections (GMP, GCP, GLP) and quality control (GPCL) • involvement of qualified assessors and inspectors mostly from NRAs of ICH and associated countries and PIC/S inspectorates • guarantees that international norms and standards are applied all through the process • supports capacity of NRA in developingcountries to evaluate, inspect and control the quality of medicines • involvement of qualified assessors and inspectors from NRAs in developing countries • by involvement of manufacturers from development countries into the project supports their capacity to produce according to international norms and standards

6. Assessment of products • Innovator products • If approved by stringent authorities like US FDA and EMEA • Based on availability of assessment reports, WHO Certificate of Pharmaceutical Product (CPP), batch certificate and continuous update on product changes after prequalification • Confidence in scientific expertise of well-established RAs,

7. Assessment of products • Multisource products Assessment of • Quality: information on starting materials and finished product, (API details, specifications, stability data, formulation, manufacturing method, packaging, labelling etc.) • Efficacy and safety: Report of bio-equivalence or clinical study demonstrating interchangeability with reference product • Inspection of manufacturers and CROs • Laboratory analysis in case of need Monitoring after prequalification

8. Essential steps of PQ procedure • Expression of interest (EOI) is published • Interested parties submit dossiers • Dossiers receive initial screening • Full dossiers are assessed • Inspections are conducted at manufacturing sites and at CROs • Samples are tested, if needed • If outcome is positive, pharmaceutical product is listed on the website, including product information (SPC, PIL), assessment report (WHOPAR) and inspection report (WHOPIR)

9. Essential steps of monitoring of PQ product • Variations to the dossier of prequalified product • Sampling and Testing • Reinspections • Reevaluation • De-listing or suspension (if and when appropriate)

10. Outcomes of PQ procedure Information in public domain (homepage) • Lists of PQ medicinal products • WHOPAR (SPC, PIL, labelling) • WHOPIR (both FPP and API) • Information on progress of assessment procedure and inspections • Supportive documents: WHO guidelines, description of PQ procedure Restricted information (available based on consent of applicant with information sharing) • Complete WHOAR • Complete WHOIR • Deficiency letters and prequalification letter

12. Prequalified medicinal products according to therapeutic categoriesStatus 30.8.07, in total 189 products

13. Prequalified medicinal products (source of expertise indicated for listed products)Status 30.8.07, in total 189 products

14. Number of prequalified products manufactured in individual countries (N=206)

15. Contribution of PQ to capacity building • Organization of trainings • general and problem specific (HIV/AIDS, TB and antimalarial products, pediatric dosage forms, BE, BE/BCS) • Trainings of NRA staff and manufacturers frequently combined • Involvement of assessors from NRAs into PQ assessment • Involvement of inspectors from NRAs into PQ inspections • 3 months rotations of experts from NRAs in WHO HQ – PQT • Provision of Technical assistance and/or Regulatory guidance • Technical assistance and Prequalification of Quality Control Laboratories • Development of standards • Provision of information • Technical Briefing Seminar (Geneve, 26.Nov–1.Dec 2007)