Medicines


Before prequalification of an active pharmaceutical ingredient (API)  or finished pharmaceutical product (FPP)  can be granted, WHO must assess whether the relevant manufacturing site(s) operate(s) in compliance with WHO Good Manufacturing Practice (GMP). This may be by an initial on-site inspection or by leveraging the outputs of inspections conducted by national medicines regulatory authorities operating to equivalent standards and stringency to those of WHO Prequalification.

Inspections of API or FPP manufacturing sites are restricted to GMP compliance in relation to the products submitted for prequalification. All inspections are performed as a sampling exercise: that is, not each and every element of WHO GMP or all parts of a site will be examined, but only those elements of direct relevance to the product(s) submitted. 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 (CRO) that conducted a clinical study and bioanalytical or bioequivalence study for the product may also be necessary. Generally, this clinical study will have taken the form of a bioequivalence study, aimed at demonstrating therapeutic equivalence (i.e. efficacy and safety) with the innovator product. CRO inspections are therefore study-specific i.e. each CRO inspection is linked to a trial  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.

An API manufacturing site may be inspected as part of the assessment of an API for prequalification, or as part of the assessment of an FPP for prequalification.

WHO also conducts inspections of 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.

In case a site has recently been inspected by a stringent national regulatory authority or body operating to equivalent standards and stringency to those of WHO, the company may apply for a desk assessment in lieu of an on-site inspection. If the application is accepted, then Inspection Services will request a list of documents to be provided for assessment. Following the desk assessment, the site will be informed on the outcome and if deemed compliant a WHOPIR will be published.

Under exceptional circumstances (e.g. natural disasters, travel restrictions) when an on-site inspection or a desk assessment cannot be performed and the company must be inspected, Inspection Services may decide to conduct a distant assessment based on QRM principles, using IT tools and systems, provided the company could accommodate this assessment. In this case Inspection Services will liaise with the company and upon agreement will make the necessary arrangements to carry out the assessment.

Other types of inspection

As well as initial inspections and study-specific inspections for prequalification, Inspection Services may also conduct:

  • follow-up inspections of API and FPP manufacturing sites and QCLs: to verify that corrective and preventive actions have been implemented by the manufacturers or QCLs
  • routine surveillance inspections of API and FPP manufacturing sites: to verify that they continue to comply with WHO Good Manufacturing Practice (GMP)
  • routine surveillance inspections of QCLs: to verify that that the QCLs continue to comply with WHO Good Practices for Pharmaceutical Quality Control Laboratories, WHO Good Practices for Pharmaceutical Microbiology Laboratories and WHO GMP.
  • special (for cause) inspections of API and FPP manufacturing sites, and CROs: focusing on the specific causes (alert, complaint, etc.) that triggered the inspection.