Estimating the Uncertainty of Structured Pharmaceutical Development and Manufacturing Process Execution Risks Using a Prospective Causal Risk Model (PCRM)

by Mark F. Witcher
Volume 18, Open Access (Sep 2019)

While many risk analysis methods describe how execution or performance risks originate and propagate through pharmaceutical and biopharmaceutical manufacturing processes and systems, few provide methods for efficiently estimating the uncertainty of an execution risk’s occurrence. This article describes prospective causal risk modeling (PCRM) for estimating the risk’s uncertainty of failures associated with executing processes, particularly when little process performance information or data is available. Building upon a basic unit of risk, the process-based system risk structure (SRS) approach is combined with PCRM to provide a method of carrying out quality risk management (QRM) exercises that properly assess both the severity and uncertainty of process execution risks. After the risks are structured using an SRS, PCRM provides a straightforward and effective method for using subjective human judgement and thought experiments to evaluate the risk process’s causal mechanisms for analyzing, evaluating, and controlling the uncertainty, including its likelihood of occurrence, of significant risks associated with developing and manufacturing pharmaceuticals. Using an SRS/PCRM-based QRM exercise, a wide variety of process execution risks can be efficiently evaluated and accepted or rejected so that important risks requiring mitigation can be identified for additional evaluation, control, and eventual acceptance.

Witcher M. Estimating the uncertainty of structured pharmaceutical development and manufacturing process execution risks using a prospective causal risk model (pcrm). BioProcess J, 2019; 18.

Posted online Sep 18, 2019.