The Active Pharmaceutical Ingredients Starting Material (APISM) and Other Materials in API Manufacture: Scientifically-Based Principles for the Common Technical Dossier

Until now, no clear guidance has been available from any authority on a key aspect of drug applications/marketing authorizations, namely, the determination of a suitable starting point for the description of the synthesis of the active pharmaceutical ingredient (API). This paper describes, for the first time, a fully scientifically-based proposal for such guidance. It is intended as a recommendation to the International Conference on Harmonization (ICH) expert working group developing guidance with respect to the definition of the “API Starting Material” (APISM) within the Common Technical Document (CTD) initiative. The authors recommend a similar approach to be used in the ICH to define the starting point in the API synthesis, after which full Current Good Manufacturing Practice (cGMP) principles should apply.