Quality Tolerance Limits: A General Guidance for Parameter Selection and Threshold Setting.

The past years have sharpened the industry's understanding of a Quality by Design (QbD) approach toward clinical trials. Using QbD encourages designing quality into a trial during the planning phase. The identification of Critical to Quality (CtQs) factors and specifically Critical Data and Processes (CD&Ps) is key to such a risk-based monitoring approach. A variable that allows monitoring the evolution of risk regarding the CD&Ps is called a Quality Tolerance Limit (QTL) parameter. These parameters are linked to the scientific question(s) of a trial and may identify the issues that can jeopardize the integrity of trial endpoints. This paper focuses on defining what QTL parameters are and providing general guidance on setting thresholds for these parameters allowing for the derivation of an acceptable range of the risk.