2. Prequalification of HIV/AIDS products and manufacturers

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

13. 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