The ICHQ3D guideline presents a process to assess and control elemental impurities in drug products using the principles of risk assessment. This risk assessment includes consideration of the impurity profile of the API. Therefore, PQT has decided to adopt the ICHQ3D guideline for the assessment of the elemental impurities information for new applications for both procedures: APIMF procedure and Prequalification of Active Pharmaceutical Ingredients procedure. The implementation of ICHQ3D for drug products is still under consideration within PQT.
Since the ICHQ3D guideline applies to the drug product, providing a risk assessment as part of the APIMF is not a mandatory requirement. However, many API manufacturers may wish to undertake a risk assessment, in order that this may be then used in an assessment of the drug product with respect to ICH Q3D
Therefore when submitting an APIMF, either through the APIMF procedure or as part of the API Prequalification procedure, the applicant has two possibilities:
- Option 1: Do not provide a risk management summary (RMS)
- Option 2: Provide a risk management summary (RMS) for elemental impurities that may be present in the final API
The selected option should be indicated by the applicant on the application form.
If no RMS is provided, only the elemental impurities that have been intentionally added will be investigated as part of the assessment and the need for the inclusion of controls for elemental impurities in the API specifications will be determined on this basis.
If a RMS is provided then this risk management summary will be considered as part of an assessment in line with ICHQ3D.
For an APIMF participating only in the APIMF procedure, the outcome of the RMS assessment will be recorded in the internal assessment report and remain available if needed for reference as part of an FPP assessment.
For APIs seeking prequalification, a statement indicating whether a risk assessment for elemental impurities has been provided will be mentioned on the CPQ. In case a RMS is submitted it will be annexed to the CPQ.
For those APIMFs that have been already accepted, the applicant can submit a RMS for elemental impurities at any time through the amendment procedure. There is no specific change category in the APIMF amendments guideline for such a revision but applicants should submit such a change as 11 (AIN). However for ongoing applications it should not be provided as part of responses, since these invariably delay the completion of the application.
For further information, please contact Dr Antony Fake at fakea@who.int and CC Dr Matthias Stahl at stahlm@who.int