If an active pharmaceutical master file (APIMF) was accepted previously by WHO during prequalification of a finished pharmaceutical product (FPP), an abridged rather than a full assessment of the APIMF will be carried out when the relevant API is submitted for prequalification.
An abridged assessment has two components:
- abridged assessment of the APIMF
- the manufacturing site or sites undergo WHO GMP inspection or evidence of compliance with WHO or stringent GMP requirements is provided, and WHO GMP inspection is waived.
Under an abridged assessment an APIMF is generally reviewed only with respect to key information and for conformity with administrative requirements.
Before submitting an application for API prequalification, the applicant should ensure that the details of the APIMF held by WHO are up to date. This is likely to necessitate submission of an APIMF amendment. Once the APIMF has been completed, and a revised and updated APIMF accepted by WHO, an application for API prequalification can be submitted.
Even if an APIMF undergoes abridged assessment, WHO may request further information to enable it to verify that the APIMF meets all WHO prequalification requirements.
The manufacturing site(s) involved in the preparation 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 carried out within the past three years by a member of the Pharmaceutical Inspection Cooperation Scheme (PICs) 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.
All applicants must submit a site master file (SMF) for each manufacturing site, irrespective of that site's GMP status. 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.
Use of ICHQ3D guideline in the assessment of active pharmaceutical ingredient master files (APIMFs) submitted in support of a finished pharmaceutical product (FPP) or prequalified active pharmaceutical ingredient (API) submitted to PQTm (25 January 2019)