Prequalification of HIV/AIDS products and manufacturers

Background: Why prequalification? What are the problems? Millions of people living with HIV/AIDS, no access to treatment Procurement and supply of substandard and counterfeit products in different countries Weak/absent QA systems Money invested – lost Duplication of work by different agencies Risk: Sourcing of poor quality products, risk to patients, treatment failure, resistance

Prequalification: How to get started? Quality Assurance systems QSM, MQAS NGOs and other organizations Draft 1, 2 and 3 in process General Procedure for Prequalification Standard Operating Procedures Norms and standards for product dossiers and manufacturing sites

Expected outcome Partners: WHO role: Outcome: UNICEF, UNFPA, UNAIDS, WHO, supported by the World Bank WHO role: Managing the project and provide technical support, norms and standards on product assessment, GCP, GLP, GMP Outcome: List of products and manufacturers meeting international norms and standards Harmonization, co-operation, training, capacity building – NDRAs, WHO, PAs, NGOs Facilitate access to treatment

Prequalification procedure Invitation for EOI – voluntary participation Guidelines for product dossier compilation Screening and assessment of dossiers and product samples SMF and manufacturing site inspection Reports on outcome of assessments Assessment of additional data and information, follow up inspection Quality control testing of samples Listing the outcome Ongoing assessment and monitoring

Product data and information Innovator products Assessment report from DRA, CPP, Batch certificate, changes Multisource products Full dossier with data and information on quality and bio-equivalence including API details, specifications, stability data, formulation, manufacturing method, packaging, labelling etc Sample for analysis Assessment teams: DRA assessors from Canada, Denmark, France, Germany, Philippines, Sweden, Switzerland, Zimbabwe and others

Manufacturing sites and samples GMP compliance Team of inspectors: WHO plus PIC/S member DRA plus local DRA inspector(s) Premises, equipment, QA, materials, validation, QC, documentation Product and site specific – data verification (BMR, specifications, bio batch, validation report, dossier) Samples tested for compliance with dossier specifications and test methods

Current status Started March 2001 Four EOIs including ARVs, antibiotics, anticancer, antifungal products Ongoing assessments and follow-up (products and manufacturing sites) March 2004: 268 product dossiers received and assessed from various manufacturers for innovator and multi-source products Samples tested at three independent laboratories List of prequalified products and manufacturers published Second tender published

Problems experienced Non prequalified products (although under assessment) supplied to several countries Product dossiers lacking data and information API: source of API, synthesis, specifications, method validation, stability Pharmaceutical development data Formulation and manufacturing process, validation, stability No bioequivalence studies or incomplete study reports No pharmacopoeia monographs in many cases

Problems experienced (cont) Manufacturing sites not meeting GMP Poor design, layout and construction Lack of validation (process, utilities, equipment etc) Hormones, antibiotics such as penicillin, in same areas Lack of raw data Cross-contamination and mix-ups Lack of quality control on materials Manufacturers have to perform studies to generate data e.g. stability, bioequivalence Validation of manufacturing processes Upgrading of manufacturing facilities Different requirements and standards: local market versus export

Discussion and conclusion To date, only 97 (37%) products listed as meeting the requirements after several assessments and additional data – including innovator products Remaining products under assessment or withdrawn Manufacturing sites: Limited number complying Evident: Many products marketed not meeting international requirements Differences in requirements from country to country Lack of assessment and quality control in countries where needed most

Recommendation 14th edition of the list published – to continue to facilitate access to wide range of products meeting international standards Ongoing quality control, monitoring, assessment and re-qualification Mechanisms be put in place to curb supply of counterfeit and substandard medicines Harmonization in assessments and increased capacity building Ensure safe, effective, quality HIV/AIDS products are purchased and supplied