WHO medicines prequalification came into being in 2001. National regulators in recipient countries, UNICEF, and nongovernmental organizations wanted to know whether low-cost generic medicines that were becoming increasingly available, especially for treatment for HIV/AIDS, were quality-assured and could be procured safely. WHO could not immediately answer this question. So it created a review process whereby assessment criteria used by stringent regulatory authorities (SRAs) are applied to determine the safety, efficacy and quality of finished pharmaceutical products (FPPs). The term “prequalification” refers to the outcome: after WHO approval, an FPP is deemed “prequalified” and eligible to participate in UN procurement tenders.
Following expansion of WHO medicines prequalification, the WHO List of Prequalified Medicinal Products now includes FPPs medicines for HIV/AIDS, tuberculosis and malaria, childhood diarrhoea and for reproductive health. It lists not only what FPPs have been prequalified and when and in what therapeutic area, but also the dosage form and strength and where it is manufactured. The list is used principally by UN agencies and the Global Fund to Fight AIDS, Tuberculosis and Malaria. But it has become a vital tool for any agency or organization — national or international — involved in bulk purchasing of medicines.
When purchasing of products from the list, any procurement agency using the list of products and manufacturers that meet WHO norms and standards, should make sure that:
the most current edition of the list is used
the contracted manufacturer will supply the product as was prequalified in all aspects in the product dossier (including at least specifications, active pharmaceutical ingredient, formula, manufacturing method, etc.) that was assessed by WHO.
the product supplied by the manufacturer, was manufactured at the site as listed in the product dossier assessed by WHO and inspected by WHO (and as appears on the list).
WHO recommends that procurement agencies enter into an agreement or contract with the manufacturer before purchasing any products. The responsibilities of each party should be defined clearly in the agreement. The agreement should make provision for liability and remedies in case of breach of contract.
Additional prequalification outputs of value to procurement agencies
Other WHO medicines prequalification outputs are also of value to procurers:
- WHO List of Prequalified Active Pharmaceutical Ingredients (APIs) — this provides information on what APIs have been prequalified and when; where; with what packaging, re-test period or shelf life and storage conditions; although medicines procurers do not procure APIs, they may find it a useful reference when considering procurement of FPPs manufactured by the same applicant or at a site at which a prequalified API is manufactured
- WHO List of Prequalified Quality Control Laboratories (QCLs) — consulted by procurers who need to organize testing of medicines at a laboratory and wish to be assured that the laboratory selected meets international standards and can provide the type of testing required
- Prequalification Pipeline — summarizes FPPs and APIs that have been prequalified and what is currently under assessment; especially important for procurers who seek information on upcoming products for prequalification that represent, for example, a new dosage form
- FPPs and APIs eligible for prequalification — information on the FPP(s) or API(s) currently eligible for evaluation for prequalification
- Procedures and Fees — information on prequalification requirements for FPPs, APIs and QCLs
- Post-prequalification Procedures — information on what an FPP, API or QCL applicant must do to maintain prequalification status
- Prequalification Reports — WHO Public Assessment Reports describe the products that have been prequalified and WHO Public Inspection Reports describe the manufacturing sites and contract research organizations (and also the quality control laboratories) that have passed WHO inspection; they are often consulted by procurers seeking information on specific manufacturing sites
- Notices of Concern or Suspension — these alert procurers to quality issues relating to specific APIs or FPPs and that may concern products they have procured
- Collaborative Procedure for Accelerated Registration — describing an innovative WHO procedure that offers manufacturers the opportunity to get their products onto markets more quickly, and helps procurers to reduce delay in getting products to health care providers, patients and users
- Market Information — with links to reports and sources that contain information (including prices and volume) about who is procuring what
- Key Contacts — the key persons who can be contacted regarding different aspects of prequalification or collaborative registration.
Expert Review Panel
In some instances, procurers are faced with a dilemma: neither a prequalified nor a stringently-approved FPP exists for a certain product. Yet the product is urgently needed for a treatment programme or for promoting reproductive health. The Expert Review Panel (ERP) was created by WHO and the Global Fund to Fight AIDS, Tuberculosis and Malaria to respond to this situation. An independent advisory body of technical experts coordinated by WHO, ERP uses transparent, science-based criteria to assess the quality risks of FPPs that are neither prequalified nor SRA-approved. Assessment results are used to inform procurement decisions relating to (time-limited) procurement of the products assessed. To be eligible for ERP assessment, an FPP must generally be manufactured at a site that is compliant with Good Manufacturing Practices. Information about calls for submission of FPPs for ERP assessment can be found in the Market Information section.
The principal users of the ERP mechanism are the Global Drug Facility, the Global Fund to Fight AIDS, Tuberculosis and Malaria, UNFPA, UNICEF and WHO's procurement unit. But any procurer can request ERP evaluation of FPPs. (A fee is applied for evaluation of each FPP dossier and for evaluation of additional data, if this is required.)
Model Quality Assurance System and Assessment Tools
Evidently, medicines procurement agencies play a critical role in ensuring that only quality-assured products are procured using public funds. Procuring prequalified products, or requesting ERP review when these are not available, can greatly assist procurement agencies in this respect. But since they will need to procure many more medicines than can be covered by WHO prequalification and the ERP mechanism, it is vital that they have a quality assurance policy and system to govern procurement and distribution of all procured products. In the absence of these, the risk of sourcing substandard, counterfeit and contaminated pharmaceutical products increases, potentially leading to product complaints and product recalls and waste of money. Worst of all, patients could be harmed.
Although some procurement organizations have quality systems in place, the extent and appropriateness of these vary greatly. In particular, evaluation of product-specific data may not be undertaken and/or information on quality of products procured is lacking, while inspections of manufacturing sites may not be performed routinely to a consistent standard.
WHO therefore developed a Model Quality Assurance System (MQAS) to help procurement agencies formulate and implement an adequate quality assurance system. Development of the MQAS received input from many partners (such as the Global Fund to Fight AIDS, TB and Malaria). It was reviewed by the WHO Expert Committee on Specifications for Pharmaceutical Preparations (ECSPP) and subsequently revised, before receiving the Committee’s approval.
The MQAS focuses on key activities associated with procurement, including prequalification of products and manufacturers/suppliers, purchasing, storage and distribution of products. Procurement agencies involved in any of these key activities are advised to develop their own internal quality assurance systems on the basis of the MQAS. Organizations actively using the MQAS include the International Committee of the Red Cross, Médecins Sans Frontières, Quality Medicines for All, UNFPA, UNICEF and UNOPS. Although the guidelines are designed for procurement of pharmaceutical products can also be applied to procurement of diagnostic kits or medical devices.
Two tools are available to further assist procurement agencies in their efforts to ensure that products procured are quality-assured and use of their resources optimized. The Assessment Tool based on the Model Quality Assurance System for Procurement Agencies: Aide-memoire for Inspection developed by a number of procurement agencies (also adopted by ECSPP) seeks to promote better use of resources through coordination of procurement agency assessments and mutual recognition of findings. The tool is not a checklist, but serves as a document to help and remind inspectors as to what should be assessed during inspections of procurement agencies. Procurement agencies interested in self-assessment may also wish to refer to A Harmonized Self-assessment Tool for Procurement Agencies. It enables procurement agencies to assess themselves, to communicate the outcomes in a standardized way, and to take targeted measures for improvement.
GUIDANCE DOCUMENTS AND TOOLS