The World Health Organization’s Prequalification Team: Medicines (PQTm) ensures that active pharmaceutical ingredients (APIs) and finished pharmaceutical products (FPPs) are safe, appropriate and meet stringent quality standards. It does so by assessing product dossiers (for FPPs) or master files (for APIs), inspecting manufacturing and clinical sites, and organizing quality control testing of products. These activities form part of the broad access agenda of WHO’s Department of Essential Medicines and Health Products which seeks to expand access to quality-assured medicines. In addition to medicines, WHO prequalification also covers in vitro diagnostics, vaccines and vector control products.
APIs that meet assessment and inspection criteria are added to the WHO List of Prequalified Active Pharmaceutical Ingredients. FPPs that meet assessment and inspection criteria are added to the WHO List of Prequalified Medicinal Products.
PQTm also prequalifies quality control laboratories (QCLs), specifically those QCLs that carry out chemical and microbiological testing of medicines. QCLs whose analytical activities are found to comply with the standards recommended by WHO are added to the WHO List of Prequalified Quality Control Laboratories.
The standards used to evaluate FPPs and APIs, and their manufacturing sites, are based on the principles and practices agreed by the world’s leading regulatory agencies and adopted by the WHO Expert Committee on Specification for Pharmaceutical Preparations.
PQTm’s other main areas of activity are:
- training (for manufacturers, regulators and QCLs)
- provision of technical assistance (for manufacturers and QCLs)
- implementation of the collaborative procedure for registration.
On this website, for the sake of simplicity, reference is often made to WHO, rather than to WHO PQTm, when describing activities undertaken to evaluate products and QCLs for prequalification.
The WHO Prequalification Team: medicines (PQTm) assesses information submitted in support of finished pharmaceutical products (FPPs) or active pharmaceutical ingredients (APIs) to determine whether they meet the requirements and standards for WHO prequalification. The master file (MF) of an API may be assessed either because it is linked to an FPP, or because the API itself has been submitted for prequalification.
Generally, before prequalification of an active pharmaceutical ingredient (API) or finished pharmaceutical product (FPP) can be granted, WHO must inspect the relevant manufacturing site(s) to assess compliance with WHO Good Manufacturing Practice (GMP). Inspections of API or FPP manufacturing sites are product-specific and performed as a sampling exercise: that is, not each and every element of WHO GMP is examined, but only those elements of direct relevance to the product(s) submitted for prequalification. More than one product may be assessed in a single inspection.
In the case of a generic FPP submitted for prequalification, inspection of the contract research organization(s) (CRO(s)) that conducted clinical studies for the product may also be necessary. CRO inspections are study-specific: that is, each CRO inspection is linked to a study that was undertaken in relation to a specific product. During inspection of a CRO, compliance with WHO Good Clinical Practices for Trials on Pharmaceutical Products and WHO Guidance for Organizations Performing In Vivo Bioequivalence Studies is assessed, and data verification performed.
WHO also inspects quality control laboratories (QCLs) that have applied for prequalification. QCL inspections are carried out to assess adherence to WHO Good Practices for Pharmaceutical Quality Control Laboratories (GPQCL), WHO Good Practices for Pharmaceutical Microbiology Laboratories and WHO GMP.
Post-prequalification inspections are undertaken routinely to verify that manufacturing sites are maintaining WHO GMP standards, or, in the case of complaints, as part of an investigation. Similarly, routine inspections of QCLs verify continued adherence to GPQCL, WHO Good Practices for Pharmaceutical Microbiology Laboratories and WHO GMP. CRO inspections are mainly study-specific, and therefore not subject to post-prequalification inspection.
The immediate aim of WHO medicines prequalification is to increase the availability of quality-assured medicines and of proficient medicines testing. In the immediate- to longer-term it aims to build the capacity of countries to produce and regulate quality-assured medicines. It therefore carries out many activities that help manufacturers, contract research organizations (CROs) regulators and medicines quality control laboratories (QCLs) to enhance their respective skills and expertise. All of these activities benefit from the rich experience gained by medicines prequalification staff during the past 15 years.
How is capacity built?
Capacity is built through:
- hands-on training for regulators, including participation in the Collaborative procedure for Accelerated Registration
- hands-on training for QCL staff
- organization of training workshops for regulators, QCL staff and regulators
- provision of feedback and support to manufacturers during evaluation for prequalification
- organization of technical assistance for manufacturers, CROs and QCLs
- issuing of medicines prequalification guidance for consultation by manufacturers, regulators and QCLs
- dissemination of prequalification information.