The Use of Routine Process Capability for the Determination of Process Parameter Criticality in Small-molecule API Synthesis

Abstract

During the development of a pharmaceutical chemical process, it is vital to establish a control strategy that will ensure the process performance and fitness for use of the active pharmaceutical ingredient (API), which in turn is essential to the drug product performance and its fitness for use. As part of the control strategy, it is very important to understand and establish critical elements of the process, one of which is the establishment of the critical process parameters that impact the critical quality attributes (CQAs) of the API. In this paper, we are proposing a method for determining the criticality of a process parameter and whether it should be listed in the common technical document as critical. By using routine process control capability across a variety of operating conditions and equipment configurations, a risk-based approach is used to identify parameters that could have a potential of impacting the CQAs of the API. Beyond establishing criticality, and understanding the operational variability, the knowledge gathered from these approaches can also be used to facilitate the efficient mapping of a multivariate design space.