Availability of a risk-based approach in process-based QA inspection in GLP studies

Abstract

We evaluated the risk of issues in experimental procedures in typical GLP toxicity studies using a risk-based approach and examined its application in process-based quality assurance (QA) inspection.

Risk assessment was performed similarly to a healthcare failure mode and effects analysis. As typical toxicity studies, we selected a 4-week repeated dose toxicity study (4W) and a bacterial reverse mutation assay (Ames test). The experimental procedures in these studies were identified and possible issues were listed. We evaluated the degree of severity and the occurrence of possible issues, and criticality was calculated based on the severity and occurrence. The risk of possible issues was evaluated based on criticality. We examined whether the testing department could detect possible issues classified as high risk.

Many issues in both studies were classified as low risk. Almost all high-risk cases were issues involving computerized systems (4W) or records (Ames test). It was considered that the QA inspection did not need to be performed for all experimental procedures in each study because almost all high-risk cases would be detectable by the testing department.

We conclude that process-based QA inspection is applicable to all experimental procedures in both studies. However, it is necessary to assess the possible issues at each facility, because the possible issues of each facility differed according to the implementation system, test articles, and other factors. We consider that a risk-based approach is useful for determining the applications of process-based inspection.