In recent years, the presence of metal impurities has become a major issue in the drug-making industry, and thus, the need for its effective removal. The time pressure associated for drug candidates to quickly reach the market has greatly increased the number of metal-catalysed reactions progressing from lead optimization to early scale-up.

For almost two years now, the International Conference on Harmonisation (ICH) has been working on its Q3D guidelines for metal elemental impurities in new drugs and new formulations containing known ingredients. After many revisions and improvements, the final version or the Q3D guidelines was finally accepted and signed off by the ICH Steering Committee in December 2014, hence requiring that the entire manufacturing industry and supply chain follow these regulations. The implementation phase is currently scheduled for January 2016.

Our partner SiliCycle Inc. has made a white paper on this subject. The paper illustrates 4 phases to consider:

  1. Identify potential sources of elemental impurities
  2. Determine the possibility of occurrences of elemental impurities in a final drug
  3. Evaluate the concentration of elemental impurities according to the established potential daily exposure (PDE)
  4. Control by developing a plan to reduce or limit elemental impurities in a final drug

Download the white paper hereafter, below the classification is illustrated.