Prequalification of Medicines Overview & update

1. Prequalification of Medicines Overview & update Wondiyfraw Z. Worku WHO Prequalification of Medicines Programme Assessors training, Copenhagen January 2011 PQP-overview & update January 2011

2. Agenda • PQP and its activities • Paths towards prequalification • PQ process flow • Some numbers and achievements • Our future and challenges • Summary PQP-overview & update January 2011

3. UN Prequalification Programme for Priority Essential Medicines • A UN action plan since 2001 to expand access to priority essential medicines for • HIV, Malaria, TB, • RH, selected Influenza products and Zinc products for Acute diarrhoea • To ensure quality, safety and efficacy of medicines procured using international funds • Propose a list of prequalified products and manufacturers meeting international norms and standards PQP-overview & update January 2011

4. UN Prequalification Programme for Priority Essential Medicines • Also since recently, to propose list of prequalified APIs and their manufacturers • Ensure that international norms and standards are applied at all the steps of the Prequalification Programme. • Help the national medicine regulatory authorities to build up capacity in assessment, inspection and quality control meeting international norms and standards. • Develop local possibilities of manufacturing and clinical studies by offering customized technical assistance. PQP-overview & update January 2011

5. UN Prequalification Programme for Priority Essential Medicines • Principally for generic products • Similar programmes run by WHO: • Prequalification of Vaccines • http://www.who.int/immunization_standards/vaccine_quality/pq_system/en/index.html • Prequalification of diagnostic products • http://www.who.int/diagnostics_laboratory/evaluations/en/ PQP-overview & update January 2011

6. Why PQ? • Many of the UN and other procurement agencies lack sufficient means to ensure safety, efficacy and quality of procured medicines and other medical items. • Many of the receiving and exporting countries do not have/did not have well established regulatory system. • Increasing demand for generic medicines-several players- substandard products • A number of reports on sub standard Anti Tb and Malaria products • Need for common-international standard. PQP-overview & update January 2011

7. Similarities with NMRAs • Like NMRAs, the prequalification programme performs - Dossier assessments - Inspections - Quality control testing (mostly through post approval sampling) - Also post approval pharmacovigilance activities (through sister units within EMP/QSM) PQP-overview & update January 2011

8. Differences from NMRAs • Priority therapeutic areas • Assessments and inspections by international experts • Marketing authorization is not issued. • Prequalification of APIs • Prequalification of quality control laboratories • Provides technical assistance to applicants • No fees PQP-overview & update January 2011

9. Prequalification activities • Prequalification of medicinal products and APIs • Review of quality and safety/efficacy documentation • Inspection of manufacturing sites and CROs • Prequalification of quality control laboratories • To identify suitable laboratories for quality testing of products procured using international funds • Also for quality survey of products • Technical assistance and capacity building • Help manufacturers to meet dossier and GMP requirements • To build capacity of national medicine regulatory authorities PQP-overview & update January 2011

10. Organogram PQP-overview & update January 2011

11. Paths for inclusion of a product in the list of prequalified products • Prequalification of multisource generic products • Full review and inspection by PQP • Prequalification of innovators • Approval based on marketing authorization issued by an NMRA in ICH region and associated countries • Prequalification of generic products approved by SRA • Approval based on SRA marketing authorization • For established generic products • Recognition of temporary approvals / scientific opinions • USFDA PEPFAR approval/tentative approval • EMA article 58 • Hcnda Access programme PQP-overview & update January 2011

12. The assessment process • Coordinated by Dr. Matthias Stahl, • Quality assessors • BE assessors • Clinical assessors • Support staff • Six full time in-house and one rotational assessor. • More than 50 temporary advisors (pool of external assessors) • Six sessions per annum (every other month) here in CPH. • More than 30 assessors per session. PQP-overview & update January 2011

13. International standards for prequalification • Primarily WHO guidance documents and standards • PQ main generic and variation guidelines • The WHO Bioequivalence and bio waiver guidelines • The WHO Stability guideline • International Pharmacopoeia • WHO GMP and GCP Guidelines • ICH guidelines • Other guides issued by SRAs such as USFDA and EMA • Other recognized pharmacopoeias • BP, EP, JP, USP PQP-overview & update January 2011

14. Expression of interest (EOI) Process flow Application for prequalification Dossier, Samples & SMF Information requested Applicant Screening Application accepted for assessment GMP Review of GMP Certification, Inspection reports, Site Master Files (SMF). Information requested Information requested Corrective and preventative actions Assessment Applicant Inspection Manufacturer Accepted Accepted WHOPIR Final decision on prequalification Variations Complaints Random sampling Requalification WHOPAR Listing on WHO website PQP-overview & update January 2011

15. Invitation for Expression of interest (EOI) • A list of medicines invited for prequalification • Priority public health medicines • We can only accept product dossiers for medicines included in this list • List prepared by WHO clinical experts (HIV, TB, Malaria, RH, Influenza, Zinc) • Based on inclusion in treatment guidelines and/or WHO model list of essential medicines • Revised as needed to capture new developments PQP-overview & update January 2011

16. WHOPAR and WHOPIR • PQ transparency • As per WHA Resolution WHA57.14, dated 22 May 2004 • Also the pipeline (dossier status sheet) • WHOPAR • Assessment history • Discussion on the review outcomes • Approved SmPC, PIL and labels • Prepared by team of experts (Clinical, BE and Quality assessors) • WHOPIR • For FPP, API, CRO and QC lab inspections • Scope and dates of inspection • Summary of observations and findings • Conclusion PQP-overview & update January 2011

17. Variations • Part of the prequalification status maintenance activity • To ensure that changes will not negatively impact the product in terms of quality, safety and efficacy • Guideline primary based on the EU guide • Discussions ongoing on possible revision • Mostly handled by in-house assessors • Growing activity as the number of prequalified products has increased • Time lines shortened PQP-overview & update January 2011

18. Requalification • Every 5 years or when requested, as per PQ procedure • Guideline adopted by the WHO Expert Committee in 2009 • Verification of acceptability of the product in terms of • current norms and standards • consistency of the product quality • First set of products have been identified and applicants are requested to submit the necessary data PQP-overview & update January 2011

19. Prequalification of APIs • Procedure approved by the WHO Expert Committee in 2009 • Separate from the APIMF procedure • GMP compliance is mandatory • Does not require submission of the corresponding FPP dossier • A separate list of prequalified APIs and their manufacturers will be posted on our website • Same guideline- PQ Generic guide • Launched in October 2010 (as pilot programme) • Initially for those APIs for which we already have approved APIMFs • Will soon be expanded to invite other APIs included in our EOI • Expected to be of importance to NMRAs and procurement agencies PQP-overview & update January 2011

20. Major achievements in 2010 • Revision of our main guideline for multi source generic products • To harmonize requirements and formats with other regulators (adoption of CTD) • To provide further details to requirements • Revision of development, process validation and stability requirements for prequalification • Growing number of PhInt monographs • Improvement in internal handling of variations • High number of prequalified products despite declining submission PQP-overview & update January 2011

21. Major Achievements 2010, contd • Undertook manufacturer survey • First manufacturers meeting took place in July 2010 • Studies to determine the value of PQ to manufacturers (ongoing) • Joint assessment of one HIV and one second line TB product dossiers with EAC countries • Capacity building and promotion of regional harmonization • Facilitating national registration • No duplication of efforts • Incentive for manufacturers • Two products manufactured by Varichem were prequalified PQP-overview & update January 2011

22. List of products included in WHO prequalified products list • Prequalified generics and innovators as of December 31st 2010: 252 products (assessed and inspected by PQ) • Total listed as of December 31st 2010 (including those listed based on USFDA/EMA/HCnda approvals): 350 products PQP-overview & update January 2011

23. Inspections PQP-overview & update January 2011

24. Prequalified / interested quality control laboratories Prequalified QCLs: • South Africa, RIIP+CENQAM (2005) • Algeria, LNCPP (2005) • South Africa, Adcock Ingram (2007) • Morocco, LNCM (2008) • Kenya, NQCL (2008) • India, Vimta Labs (2008) • France, CHMP (2008) • Vietnam, NIDQC (2008) • Kenya, MEDS (2009) • Singapore, HSA (2009) • Singapore, TÜV (2009) • Canada, K.A.B.S. Laboratories (2010) • Ukraine, CLQCM (2010) • Ukraine, LPA (2010) • Peru, CNCC (2010) • Uruguay, CCCM (2010) • Bolivia, CONCAMYT (2010) PQP-overview & update January 2011

25. Quality survey of Antimalarial medicines in Sub-Saharan Africa 2010 PQP-overview & update January 2011 To evaluate quality of ACTs and Sulfadoxine/Pyrimethamine Cameroon, Ethiopia, Ghana, Kenya, Nigeria, Tanzania To estimate quality at different points of the distribution system To identify possible causes for any findings To propose possible strategies and implementation plans to address the problems identified by the study

26. Collected samples by products935 samples PQP-overview & update January 2011

27. Results 83 samples of PQ products • AL (Novartis, Ajanta, Ipca) • A&A co-pack (Cipla, Guilin, Ipca) PQP-overview & update January 2011

28. Quality survey of anti TB medicines • Armenia, Azerbaijan, Belarus, Kazakhstan, Ukraine, Uzbekistan • Countries with high multidrug-resistant and extensively drug-resistant TB • Rifampicin caps, Isoniazid tabl/inj, Rifampicin/Isoniazid tablets, Kanamycin inj powder, Ofloxacin tabl/infusion PQP-overview & update January 2011

29. 291 samples from 33 manufacturers and 90 sampling sites Results PQP-overview & update January 2011

30. Results continued • 38 samples of WHO-prequalified products • Isoniazid/Rifampicin tablets • 75/150mg, Lupin India (18), Sandoz Private India (17) • 30/60mg (2) and 60/60mg (1) Macleods Pharmaceuticals India • None of WHO-prequalified products failed to comply with specifications PQP-overview & update January 2011

31. Technical assistance to applicants • More than 60 technical assistance missions have been organized and delivered PQP-overview & update January 2011

32. Trainings • More than 65 trainings have been delivered PQP-overview & update January 2011

33. Trainings (contd) • More than 3130 assessors, inspectors and manufacturers have been trained PQP-overview & update January 2011

34. Rotational post within WHO PQP team • A full time P3 position, on rotational basis (one participant every three months) • A unique arrangement for assessors from national medicine regulatory authorities (developing countries) • Opportunity for further development in regulatory skills and exposure to the WHO Medicines area of work • Several assessors from Ethiopia, Kenya, Tanzania, Uganda, Zimbabwe, Zambia and Ukraine have participated. PQP-overview & update January 2011

35. The future • Additional therapeutic areas may be included • Prequalification of API continued • Requalification continued • Revision of our variation guide • Continue with capacity building and harmonization activities including joint assessments • Continue with our technical assistance missions PQP-overview & update January 2011

36. Challenges • Declining number of submissions • Slow progress with respect to RH, TB and Malaria dossiers • Increasing demand vs limited capacities • Additional therapeutic areas • Prequalification of APIs • Additional support to procurement agencies (risk assessment for interim procurement decisions) • Increasing demand for technical assistance • From initial dossier compilation to prequalification • GMP compliance PQP-overview & update January 2011

37. Info rich & user friendly website • Notice of concerns & related info • Prequalification lists • Procedures & Guidelines • Prequalification of APIs • Inspection info • Trainings and meetings • Public assessment and inspection reports www.who.int/prequal PQP-overview & update January 2011

38. Summary • Prequalification of priority essential medicines • Promoting access to safe, effective and quality medicines • Prequalification of APIs and • Prequalification of quality control laboratories • Provides technical assistance to applicants • NMRAs capacity building • International standards are applied • Assessment and inspections by international experts • Mainly for multisource generics and innovator products approved in ICH region • Has issued a revised CTD based guideline for multisource pharmaceutical products • Can serve as resource document for NMRAs • Active participation in regional regulatory harmonization efforts • Joint assessments • Complete information on the web, transparent • www.who.int/prequal PQP-overview & update January 2011

39. Thank you PQP-overview & update January 2011