Full assessment of an active pharmaceutical ingredient (api) that has not been assessed previously by WHO or by a stringent regulatory authority (SRA) incorporates:
- full assessment of the API master file (APIMF)
- inspection of the manufacturing site(s) of the API to verify compliance with GMP, or evidence of compliance with WHO or stringent GMP requirements is provided by the applicant, and WHO GMP inspection is waived.
The required technical content of the APIMF is described in the WHO guidance on submission of documentation on the quality of a multisource (generic) finished pharmaceutical products. The APIMF itself should follow the structure and format of the Common Technical Document (CTD), agreed within the framework of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (commonly known as ICH).
The manufacturing site(s) of any API for which prequalification is sought must undergo inspection to verify compliance with WHO Good Manufacturing Practices (GMP). Manufacturers who submit an application for prequalification should therefore request inspection by WHO of the relevant manufacturing site(s) so that compliance with WHO GMP can be assessed. However, applicants whose manufacturing site(s) have already undergone a WHO GMP inspection, or inspection by an SRA may submit evidence of this inspection as part of their application for API prequalification, in lieu of a request for inspection by WHO. Such evidence includes but is not limited to, GMP certificates, inspection reports, and corrective and preventive action reports, and the most recently completed product quality review report. The relevant inspection must have been performed within two years of submission of application and relevant to the specific API for which evaluation by WHO is now being requested.
Irrespective of their GMP status, all applicants must submit a site master file (SMF) for each manufacturing site. An SMF is a document prepared by the manufacturer containing information with respect to the production and/or control of pharmaceutical manufacturing operations carried out at a named site, and to any closely integrated operations at adjacent and/or nearby buildings. If only part of the API production is carried out at a site ― such as analysis or packaging ― the SMF need describe only that operation.