Fate of Impurities Studies
Reactive intermediates and by-products have the potential to be present in APIs, and when such impurities have potential for genotoxicity they must be consistently reduced to trace levels as per ICH guideline M7. We have the tools and experience to track the fate of such API impurities (where they land during workup and API isolation), and to recommend workup modifications to ensure consistent removal.
Case Study: Residual Intermediate Possessing Genotoxicity Potential
A client requested that we perform a fate study on a genotoxic process impurity that was still present at a substantial level going into the final, API-generating step of their manufacturing process. We investigated how the impurity fared during the reaction, conducted a detailed kinetic study of the impurity’s destruction during a critical stage of the workup, and designed a simple in-process check to confirm removal of the impurity at a 10-fold lower level than that which would have met the ICH M7 guideline limit. The documented study was used to support the client’s CMC submission.