3rd Stakeholders Meeting on Prequalification Geneva, 4th February 2008

1. 3rd Stakeholders Meeting on Prequalification Geneva, 4th February 2008 Update and Future Directions of Prequalification of Diagnostics Dr Gaby Vercauteren Coordinator, Diagnostics and Laboratory Technology Essential Health Technologies Health Systems and Services

2. The aim of prequalification of diagnostics • To promote and facilitate access to safe and appropriate diagnostic technologies of good quality in an equitable manner.

3. WHO's Diagnostics activities • Assessment of the performance and operational characteristics of test kits • HIV tests since 1988 • Hepatitis B tests since 2000 • Hepatitis C test kits since 2000 • Chagas tests since 2002 • Syphilis tests since 2001 • Malaria tests since 2002. • CD4 technologies ad hoc in 1996 and 2003 • Alternatives to viral load started 2005 • Provide technical information on various diagnostics

4. Global market for diagnostics is changing Trends • Outsourcing of production • Move to countries with less stringent regulations • Confusion about licensing of products • Re-branding of test kits (OEM) • Same name, but different production site, different quality norms • Easy to operate tests/methods • Near patient testing, hard to reach populations, non lab environments, tasks shifting • Humanitarian projects- initiative from companies • Availability of funds for diagnostics

5. WHO's response • Review of the prequalification process for diagnostics • As a more comprehensive approach was required ... • Align with global standards for assuring quality of diagnostics

6. Prequalification of Diagnostics – New approach • Through a rigorous process identify diagnostics that meet the quality standards • Harmonize the WHO prequalification process • More stringent dossier assessment of diagnostics • Inspection of the QMS at production site (ISO 13485/GMP) • Laboratory assessment of performance characteristics • Building capacity at country level (NRA and NRLs) and establishing post-market surveillance for priority diagnostics • Partnering with well known regulatory authorities and with key technical partners

7. PQ strategic plan Objective 1: • increase number of diagnostics reviewed each year by expanding technical managerial and administrative capacity, and by improving efficiency of the PQ process Objective 2a : • Create and/or refine norms and standards for prequalifying diagnostics Objective 2b: • Prequalify diagnostics

8. PQ strategic plan Objective 2c: • Increase country capacity to effectively regulate diagnostics and diagnostics manufacturers to submit products for prequalification Objective 3 : • Ensure financial sustainability of UN Prequalfication programme after project completion

9. Priority Diagnostics • HIV • Malaria • TB • Ongoing and new diagnostic markers

10. WHO - ensuring improved access, quality & appropriate use of Diagnostics WHO departments and teams • Essential Health Technologies, (EHT) • Diagnostics and Laboratory technology; (DLT) • HIV department (HIV) • Stop TB, (STB) • TB strategy and operations (TBS) • UNDP/World Bank/WHO special Programme for Research and Training in Tropical Diseases, (TDR) • Product Development and Evaluation, (PDE) • Global Malaria Programme,(GMP), SCM • WPRO : Malaria, other vector borne diseases; (MVP) Key priority for 2007-2012 Prequalification of Diagnostics

11. Achievements 2007 • New team in place • Expanded procedures developed • Forms-instructions-protocols • Process documents developed • SOP – check lists- letters • Quality Management System applied • Communication strategy

12. Achievements 2008 start new process • Applications and dossier assessments, inspections, lab evaluations, HIV, malaria diagnostics • Plan and organize field sites VL and CD4 tests • Increase communication to key stakeholders and industry about PQ

13. Achievements 2007 Diagnostics and Laboratory Technology • New team established in January 2007 …. But

14. Department of Essential Health Technologies *

15. PQ of diagnostics : Staffing 2006 2007

16. Prequalification project management team • Diagnostics-Medicines and Vaccines • Bi-monthly meetings • 1 day meeting reviewed the 3 PQ processes: • Similarities • Differences • Opportunities for efficiency (web-based applications, tracking, etc) • Malaria diagnostics working group • Regular meetings • Improved collaboration

17. The communication strategy • Communications mapping and analysis • Annual stakeholders meeting • Annual prequalification report • Prequalification web pages (FAQs) • Communications specific for target audiences • Manufacturers • Donors • NRA - NRL • Users • Buyers

18. Key Messages Different elements of the case will be emphasized according to the different target audiences. Prequalification of diagnostics: • facilitates the procurement of appropriate, quality diagnostics at reasonable cost for resource limited countries by UN and other agencies involved in procurement • reduces expenditure of human and financial resources on poor-quality, ineffective diagnostic technologies • contributes to the scaling-up of prevention and treatment programs, slowing of drug resistance and treatment failures • Empowers people at risk and/or infected with HIV/AIDS or malaria by assuring that the patient receives an appropriate diagnosis and consequently optimal treatment.

19. Objectives To increase awareness and maintain manufacturers' interest in submitting products for PQ and to encourage manufacturers to prepare PQ submissions adequately. To urge manufacturers to focus on producing priority diagnostics, appropriate for resource-limited settings and to cater to both paediatric and adult populations. To encourage compliance with GMS. To encourage manufacturers to ensure adequate product maintenance and customer service locally. Messages PQ enables product to be included in UN Bulk Purchasing Scheme and reinforces global image of quality diagnostic. Adequate submissions result in timely PQ. Products that are not appropriate for resource limited countries or that are not considered priority will not be eligible for PQ. Compliance with GMS is necessary for PQ. PQ, in addition to local customer service will help to establish the diagnostic product in the market. Manufacturers

20. Objectives To urge donors to contribute to the purchase of not only medicines, but also diagnostics. To maintain and increase financial support for diagnostics PQ. Messages Prevention and treatment scale-up initiatives rely on access to quality, affordable diagnostics. The purchase of prequalified diagnostics is cost efficient spending of public funds. The purchase of prequalified diagnostics should be a requirement. Donors

21. Diagnostics Procurement Issues Promote use of pre-qualified diagnostics • Advocate for selected tendering of pre-qualified products • Advocate for link buyers and users • Technical guidance on procurement issues • Generic specifications • Maintenance contracts • Post-market surveillance mechanisms

22. Communication Updates • Update prequalification of diagnostics • Issue 1 (general) • Issues 2- 8 ( topics identified, issues in preparation) • AIDS conference; Mexico 3-8 August 2008 • Organize briefing session

23. WHO webpages www.who.int/diagnostics_laboratory

24. Prequalification of Diagnostics Process Rejected Manufacturer submits application Application is screened Manufacurer pays fee and submits dossier Accepted Rejected Dossier is reviewed Accepted Laboratory Evaluation Manufacturing Site Inspection Meets WHO requirements Meets WHO requirements Does not meet WHO requirements Does not meet WHO requirements Review of all information Product is prequalified (eligible to tender with UN)

25. Achievements 2007: Key Process Documents

26. Challenges for the dossier review • Web based application system (lower priority) • Lack of stability data • Insufficient performance data • Lack or rudimentory Quality Managment System ( ISO 13485) RESPONSE…. • Guidance document on stability testing (CLSI) • Guidance document on performance data • Instructions for compilation of a dossier address these issues (organize some sessions)

27. Terminology What is a Quality Management System? • 'The system should ensure consistency and improvement of working practices, which in turn should provide products and services that meet customer's requirements. • ISO 9000 series is the most commonly used international standard that provides a framework for an effective quality management system.'

28. International Organization for Standardization who uses ISO 13485? • US FDA Quality System (FDA 21 CFR Part 820) regulation now 'harmonized' with ISO 9001 and ISO 13485 (minor variations) • European Union • Therapeutic Goods Administration (TGA ) Australia • Health Care Canada • Global Harminization Task Force (GHTF) • Australia-Canada-EU-Japan-USA • Asian Harmonization Working Party (AHWP) • 16 Asian countries, including China, Korea, … • Alliance with GHTF

29. Quality Management of the project Continual Improvement of The Quality Management System Management responsibility Analysis of feedback Resource management Satisfaction Customers Customer requirements Prequalification Assessment

30. Achievements 2007 Quality Management Explained • policies, processes and procedures required for planning and execution of the prequalification assessment • integrates WHO processes and appliesa process approach • enables DLT to identify, measure, control and improve the prequalification processes that will lead to improved performance

31. Challenges for Countries and for the PQ Dx programme Procurement Issues • Malaria • Large variety of rapid malaria diagnostic tests available, … but which test to choose ? • HIV • Procurement HIV tests more established • Gaps in availability of pediatric diagnostics

32. Potential inspections in 2008 • Priority for diagnostics currently procured by UN (Web buy list) • 32 HIV tests (20 rapid, 7 EIA and 5 confirmatory) • 53 Malaria tests (53 rapid) • Additional 7 manufacturers are of interest • Rapid tests have priority • 40 sites manufacture rapid tests

33. Inspections (site visits only) 2008 • Time per inspection mission: • 3 days on site of manufacture +2 days travelling time per mission • 5 days:1 site – 1 product, 6 days: 1 site- 2 products, 9 days: 2 sites – 2 products • Inspection team consists of • One WHO DLT staff member • 2 externally sourced inspectors • Inspector/s from the National Regulatory Authority

34. Priority setting for laboratory assessment of diagnostics • Serological tests • HIV rapid tests • Malaria rapid tests • TB rapid tests (2009 …) • HIV incidence tests • CD4 technologies • Viral load and early detection in infants • filter paper approach • Alternatives

35. Conclusion: A more efficient programme • Application process • Generates valuable information • formalizes procedure and screens out products which are not UN priority or substandard • streamlines scheduling • Dossier review • screens out applicants with poor quality management • Assessment of QMS of production of diagnostics through site inspection • ensures a consistent product each time • Laboratory evaluation • (operational characteristics and performance) • PQ Diagnostics Programme operates under an internal QMS

36. Capacity building • Capacity building National Regulatory Authorites • Pilots South Africa, China • Generic regulations • Strengthened national capacity for inspections • Capacity building National Reference Laboratories • Performance assessments • Batch release testing • Pilot Post-market surveillance • QA programmes for users • Tools to record problems • Guidance on Procurement and supply management • Selection of diagnostics • Tendering processes GFATM, UN agencies, key players

37. Update the business plan • Review of the business plan for prequalfication of diagnostics based on real costs • Short term – next 2 years • Longer term

38. Future directions • Expand range of diagnostics • TB • STI's – HPV tests • HIV incidence tests • Capacity building • NRA • NRL • Guidance to address found weaknesses • Expand Post market surveillance • Guidance on Procurement and supply management • Selection of diagnostics • Tendering processes GFATM, UN agencies, key players

39. Diagnostics and Laboratory Technology (DLT) Team Thank you