Quality Tolerance Limits: A Review of Industry Trends

An expectation for the use of quality tolerance limits (QTLs) was formally established in the International Conference for Harmonization (ICH) E6 (R2) GCP guideline published in 2016. The aim of QTLs, as indicated in the guideline, is to “identify systematic issues that can impact subject safety or reliability of trial results. Detection of deviations from the predefined quality tolerance limits should trigger an evaluation to determine if action is needed.”

CluePoints released a QTL module into its risk-based quality management (RBQM) platform in 2019, which has provided an excellent opportunity to view industry trends related to QTL adoption.

Overall, 31.6% of organizations actively using the platform for centralized monitoring since 2019 have also implemented QTLs. A total of 115 studies have used QTLs thus far, and the rate of adoption has increased steadily each year as depicted in Figure 1 below. In 2019, only 5.9% of studies added to the platform included QTLs. However, this increased to 17.2% by 2021 and jumped to 37.7% in 2022.

For studies using QTLs, there is a median of two QTLs implemented per study. The most commonly observed range of QTLs per study is one to three, with only 25% of the studies implementing four or more QTLs to date.

The QTLs implemented thus far are distributed across three general categories as follows:

Compliance QTLs primarily focus on missed assessments (e.g., supporting key study objectives), as well as errors in randomization. Enrollment and retention QTLs focus on study and/or treatment discontinuations, along with enrollment trends (e.g., unbalanced by region, demographics, etc.). Safety QTLs focus on adverse events (e.g., adverse events related to the investigational product or specific laboratory results).

It is clear that the rate of QTL adoption within the industry is now rapidly increasing, and particularly among those organizations that are already conducting RBQM and centralized monitoring. We will continue to monitor QTL adoption trends along with emerging best practices in the coming year.