1. 3 rd ICIUM Conference 14-18 November 2011 Study on Quality Assurance for Essential Medicines other than ARVs, Antimalarial and Antituberculosis Medicines Joëlle Daviaud 1, Jean-Michel Caudron 2, Corinne Pouget 2, Monika Zweygarth 1, Abu Saleh 1, Carmen Perez Casas 1, Sophie Logez 1 1 The Global Fund to Fight AIDS, Tuberculosis and Malaria, Switzerland; 2 Quamed, Institute of Tropical Medicine, Antwerp, Belgium

2. 3 rd ICIUM Conference 14-18 November 2011 Global Fund’s procurement principles  Procure quality assured products  Conduct procurement processes in a transparent and competitive manner  In the most adequate form to support adherence (Fixed dose combinations, children forms)  At the lowest price  Adhere to National and  International Laws On average, 40 % percent of funds are used for medicines and health products procurement

3. 3 rd ICIUM Conference 14-18 November 2011 Overview of the Global Fund’s QA policy (issued 1 July 2009, last amended 14 December 2010): Clinical Criteria Medicines must be listed in WHO or national or institutional Standard Treatment Guidelines (or appropriate technical justification) Clinical Criteria Medicines must be listed in WHO or national or institutional Standard Treatment Guidelines (or appropriate technical justification) Quality Criteria All medicines must be authorized for use in recipient countries + Additional stringent criteria for all ARVs, anti-TB products and antimalarials Quality Criteria All medicines must be authorized for use in recipient countries + Additional stringent criteria for all ARVs, anti-TB products and antimalarials Quality Monitoring Grant recipients must organize: Monitoring quality all along the supply chain (storage, distribution) Systematic random quality control testing + + 2008: Decision to phase in stringent criteria for other Global Fund- financed medicines

4. 3 rd ICIUM Conference 14-18 November 2011 Category WHO-PQ: Prequalifi- cation Stringent Regulatory Authority (SRA) authorization Expert Review Panel (ERP): Time-limited advice National Medicines Regulatory Authority (NMRA) authorization Procurement as per principles of WHO Model Quality Assurance System for procurement agencies Antiretroviral, anti-TB, antiMalarial (ATM) medicines (if <2 WHO- prequalified or SRA- authorized) Other essential medicines Quality criteria for grant-funded medicines

5. 3 rd ICIUM Conference 14-18 November 2011 Monitoring compliance with quality criteria Grant recipients report all purchases of ARVs, anti-TB medicines and antiretrovirals, Bednets, Condoms and RDTS, received in the online PQR database (requirement of the grant agreement) Local Fund Agents verify all entries are verified against source documentation prior to each disbursement and at grant review for extension (“Phase 2” / periodic review) The Global Fund Secretariat detects and follows up non-compliances based on PQR data Procedures are in place to deal with: – Failure to obtain Global Fund agreement before procuring ERP-reviewed products – Non-compliance with the requirements of the Global Fund QA policy Less than 1% of Non Compliance purchase have been identified

6. 3 rd ICIUM Conference 14-18 November 2011 Procurement since July 2009, classified as per Global Fund QA Policy A: WHO- prequalified A and B B: SRA- autho- rized* Source: PQR data as at 31/10/2011 Second-line TB: USD 30 million First-line TB incl.streptomycin: US$ 48 million, 68% “A” or “B” GLC/GDF

7. 3 rd ICIUM Conference 14-18 November 2011 Aim To identify areas for improvement to inform policy development Study on QA status of donor-funded essential medicines Method: Desk review and survey: Publications and assessment reports Questionnaire on QA criteria for the procurement of essential medicines, focusing on opportunistic medicines Completed by 27 of 53 donors, implementers and organizations with procurement activities Five one-week country visits: Armenia, Burkina Faso, Cambodia, Nepal, Nicaragua Key informant interviews: representatives of facilities across levels of health care, regulatory authorities, local manufacturers, recipients of Global Fund grants, WHO country offices, disease programmes, procurement agents

8. 3 rd ICIUM Conference 14-18 November 2011 Main Outcome The global pharmaceutical market for non ATM medicines is at high-risk Poor regulations = weak protection of patients Predominance of price in purchase procedures, not linked with clear quality requirements More than 80% of Non ATM medicines purchased with Global Fund resources in 2010 are anti-infective, live saving medicines

9. 3 rd ICIUM Conference 14-18 November 2011 National medicines regulatory authorities (NMRAs) Legally responsible in country of use, but weak capacity National medicines regulatory authorities (NMRAs) Legally responsible in country of use, but weak capacity Donors Small market share, special requirements  Limited choice for some products Donors Small market share, special requirements  Limited choice for some products ( International) procurement agents Diverse capacity for QA  Competition on price and overall efficiency ( International) procurement agents Diverse capacity for QA  Competition on price and overall efficiency Small market share No clear QA criteria Over-reliance on QC MQAS principles: difficult to apply Delegation of QA Complex procurement channels Fast-tracked registration Challenges with QA of donor-funded essential medicines

10. 3 rd ICIUM Conference 14-18 November 2011 Assessment of manufacturing sites Insufficient capacity to assess domestic sites Rarely done for foreign sites Post-marketing surveillance Poor capacity for medicines control In developed countries: Resources and independent technical expertise for global pharmaceutical QA are becoming increasingly scarce Trend towards harmonized, risk-based approaches for maximum impact Less stringent requirements for products for export Weaknesses at regulatory level Authorization for medicines use: Weak requirements Difficulties to properly assess the quality of generic medicines Waivers, fast-tracking In many grant recipient countries (developing countries): Lack of human, financial and technical resources:

11. 3 rd ICIUM Conference 14-18 November 2011 Quality monitoring Difficulty to confirm the identity of the product supplied (e.g. WHO prequalified) Confusion between quality assurance and quality control Inappropriate QC protocols (costly and not necessarily efficient) Lack of internationally recognized standards and/or manufacturers’ specifications Weaknesses at procurement level Product selection and prequalification Poor knowledge and understanding of norms and standards Difficult access to technical references (pharmacopoeias, WHO technical report) Poor quality of information submitted by suppliers; challenge to verify the veracity of the information

12. 3 rd ICIUM Conference 14-18 November 2011 All medicines should meet appropriate quality standards. Many implementers call for an appropriate and global answer to the problem. No double standards: Logistic and ethical dilemma to maintain multiple QA systems Advocate for a harmonization of QA policies among donors who have the capacity to influence the market Policy implementation should include resource mobilization to promote quality assurance Need more efficient procurement and supply systems Situation will not change as long as drug regulatory authorities have not strengthened their capacity and responsibilities of all actors are better defined and respected Critical responsibility: check, control and audit delegated activities Key stakeholders’ comments

13. 3 rd ICIUM Conference 14-18 November 2011 Towards a harmonized approach with partners WHO and Global Fund joint meeting on Quality Assurance for Essential Medicines 30-31 August 2011 Participants from 16 International Organizations: Centrale Humanitaire Médico-Pharmaceutique (CHMP) Crown Agents European Commission, DG Humanitarian Aid and Civil Protection Global Fund IDA Foundation International Committee of the Red Cross (ICRC) Institute of Tropical Medicine ( QUAMED) Management Sciences for Health (MSH) Médecins sans Frontières (MSF) Partnership for Supply Chain Management (PFSCM) UNICEF Supply Division United Nations Office for Project Services (UNOPS) United Nations Population Fund (UNFPA) USAID, Bureau for Global Health World Health Organization (WHO) World Bank

14. 3 rd ICIUM Conference 14-18 November 2011 Possible approaches for QA of essential medicines Which standards to apply to which products? Step-wise, risk-based? ApproachAdvantagesChallenges WHO- prequalification (PQ) Stringent assessment & follow-up of issues in countries Limited capacity of WHO-PQ Cost - incentives for manufacturers to reach and maintain PQ status? Stringent regulatory auth. (SRA) approval Stringent assessmentCost – no incentives for manufacturers operating in non- stringent environment Time-limited risk assessment Increased availability & competition of expertly QA’d products Interim solution Less stringent when not linked to WHO-PQ / SRA approval Regulatory approval in country of use Responsible authority Best placed for post-market surveillance Weak capacity and enforcement in most recipient countries Qualification of procurement agencies (PAs) Holistic approach to QA Recognized standard (MQAS) Role of international PAs Current diverse QA capacity Commercial orgs–conflict of interest? Role of national procurement bodies?

15. 3 rd ICIUM Conference 14-18 November 2011 Joint Global Fund-WHO meeting on QA of essential medicines A common approach with harmonized criteria is needed and was agreed by all participants: – Efficient use of scarce, technical resources – Maximum market impact (even if still limited – market niche) – Avoiding confusion and double standards Specific criteria can be established once a risk classification is finalized – Consider medicines in each class and associated risks – Define appropriate mechanisms to mitigate these risks Recipient countries must be involved – Responsibility of NMRAs remains – Avoid double standards (donor-funded vs. other medicines)

16. 3 rd ICIUM Conference 14-18 November 2011 Next steps 1.Donors and procurement agencies will continue to work towards common quality requirements for non-ATM medicines 2.Risk categorization of essential medicines by WHO in 2012 3.Towards Qualification of Procurement Agencies: A working group of donors and procurement agencies, facilitated by Global Fund, will develop a common tool for assessment of procurement agencies, based on the WHO Model Quality Assurance System (Q3 2012) WHO will formalize the tool, ultimately to serve for independent qualification of procurement agents (Q4 2012)

17. 3 rd ICIUM Conference 14-18 November 2011 THANK YOU