If an active pharmaceutical master file (APIMF) had already been assessed and accepted by an Authority applying stringent standards, an abridged rather than a full assessment of the APIMF will be carried out when the relevant API is submitted for prequalification. This avoids duplication of regulatory work.
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.
The applicant should request that WHO conduct an abridged assessment,by reviewing the relevant authorities assessment report, rather than undertaking its own assessment of the APIMF. Currently, this includes APIMFs previously assessed and accepted by the US Food and Drug Administration (US FDA), or the European Directorate for the Quality of Medicines (EDQM): i.e. applicants may request review of the relevant assessment report, in lieu of assessment by WHO.
Ensuring that the details of the APIMF submitted to WHO correspond to the details assessed and accepted by the agency applying stringent standards, as detailed in its assessment reports, is critical to the success of an application submitted for abridged assessment. The authority may have conducted multiple rounds of assessment, and/or multiple changes may have been made since approval was granted. The chronological summary of assessments should therefore be outlined clearly in the application, and any changes that have been made over time to the details of the APIMF should be described clearly.
If the details of the API submitted to WHO and of the API accepted by the SRA differ, these should be detailed in the submission. Only differences that are not significant are allowable.
After the application for prequalification has been received, WHO will contact the agency (e.g. US FDA or EDQM) and request access to the relevant assessment report.
If a Good Manufacturing Practices inspection of the API's sites or sites of manufacture has been carried out within the past two years by a member of the Pharmaceutical Inspection Cooperation Scheme (PICs) the applicant may submit evidence of this inspection, with a request that inspection be waived, as part of its application for prequalification. 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. If recent evidence of compliance with GMP cannot be provided, the applicant should request inspection of the manufacturing site(s) of the API.
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.
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)