Application of a Joint Risk Assessment Platform to Identify Suitable Drug Substance and Drug Product Process Options

The final selection of a robust drug substance process in combination with a drug product process can be extremely challenging, especially in cases in which the crystal form and powder properties of the active pharmaceutical ingredient (API) directly impact the development of a robust and economic drug product process.  For such cases, it is necessary to assess and manage the overall risk of a given drug substance (API) + drug product combination instead of analyzing drug substance and drug product risks independently.  In this presentation a case study is described in which a joint risk assessment platform was organized to rank combinations of various API crystal form inputs with drug product processes.  The joint risk assessment was executed in the following phases:  planning, data collection for each API + drug product option, data review and scoring, and final API + drug product ranking and review.  Data collected from lab feasibility studies on each option were utilized to help more accurately score the perceived processing risks in each unit operation.  The risks were scored using a failure modes and effects analysis (FMEA) quality risk assessment tool.  Through the joint risk assessment approach, appropriate API + drug product options were identified to help the drug substance and drug product teams effectively direct resources toward processes that have the highest chance of successfully delivering a commercially manufactured drug product.