Background The new ICH Q3D guideline has been recently developed to define and provide a global policy for evaluating and limiting elemental impurities in drug products. Thus, a risk assessment and appropriate control of elemental impurities according to this guideline have become necessary.

Purpose The purpose of this study was to explain the risk assessment approach for limiting the presence of elemental impurities in the drug substance.

Material and methods According to the guideline ICH Q3D, the identification of elemental impurities of concern and their potential sources of occurrence is realised. The possible levels of elemental impurities were determined based on the published literature and provided information from suppliers. For high-risk elemental impurities, class 1 and class 2A, they we determined by the ICP-MS method. The determined level was then compared with the Permitted Daily Exposure defined in ICH Q3D. All of these assessment results were summarised into one single assessment sheet for each manufacturing step.

Results The potential sources of elemental impurities have been identified and several possible sources of class 1 and 2A elemental impurities have been identified. Based on the information in the assessment sheet, an appropriate control point in the manufacturing process and control method were determined. Additionally, the information was included in the assessment sheet to show the control strategy.

Conclusion The risk analysis approach provides a complete risk assessment of potential elemental impurities in the drug substance. All potential sources of elemental impurities of concern for the manufacturing process of the drug substance were mapped together with the control strategy in the proposed assessment sheet. This assessment sheet is considered to also be useful for the life-cycle management of the drug substance.

References and/or acknowledgements Dr Mamouni Alaoui Faiçal.

No conflict of interest.