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.

APIMF

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).

Manufacturing site

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. 

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.