(466e) Strategy and Process for Effective Scale-up On the Removal of Pd During the Synthesis of A Drug Substance

Metal catalyst, for example Pd or its derivatives, are commonly used during the synthesis of small molecule drug substance.  Due to the toxic nature of these catalysts, their levels are highly controlled at the final drug substance stage.  Generally, rejection of metal catalyst is not easy and requires multiple steps of purifications.  However, from time to time the approach of metal removal could be highly empirical with a minimum understanding on the fundamentals.  Given than, it would be very desirable to address the issue through a more fundamental approach to ensure the efficiency and consistency of catalyst removal upon scale-up.

In our presentation, we share our experience during the development of drug substance for the removal of Pd catalyst.  A dual approach, incorporating both the solubilization method and adsorption method are employed and fully integrated into the process.  For solubilization, the critical control points are identified to be mixing and cake washing.  For adsorption, the most cost-effective adsorbents are shown to be carbon and filtrol.  Pd rejection consistency and efficiency are fully demonstrated at the pilot plant scale after implementing the proper procedures with the findings.