QTLs at SCOPE 2023

One of the sessions we’re looking forward to most at SCOPE next week is the panel discussion on “The place of Quality Tolerance Limits (QTLs) in a changing regulatory environment”. That’s because we’re currently helping one of our biggest customers go through the process of implementing QTLs, with all the challenges that involves, including process changes and upskilling staff.

We believe QTLs are and will continue to be important because they are a critical component of an effective Quality Management System (QMS) for clinical trials. They provide an objective way to measure and monitor the quality of data collected from trials and help ensure compliance with applicable regulations.

Definitions are important, so for those who don’t know what a QTL is, it’s a specific limit that is set for a given parameter, such as a laboratory test value, that is considered to be acceptable or unacceptable. If the measured value is outside the specified tolerance limit, then it may be considered unacceptable and may require corrective action.

QTLs have a place in the QMS to ensure that clinical trials produce quality data that will answer the scientific questions of the trial as well as trial participant safety. Since the ICH E6 (R2) revision, the use of QTLs has been removed from the guideline, however, this does not mean that they should not be used in clinical trials. Regulatory authorities still recognize their importance, and their use is still relevant. The ICH E9 (R1) addendum provides guidance on how best to use QTLs in clinical trials.

The first step in implementing QTLs is to ensure that they are appropriate for the specific trial. This means that they should be based on the scientific objectives of the trial and the data that will be collected. For example, if the trial is assessing a particular biomarker, then the QTL should be set for that biomarker. It is also important to ensure that the QTLs are based on valid scientific evidence and that they are correctly implemented.

Once the appropriate QTLs have been established, the next step is to monitor them throughout the trial. This may involve regular sampling and testing of the data collected to ensure that the data is within the specified limits. If the data is outside the limits, then corrective action should be taken. This could include modifying the protocol or data collection method to ensure that the data falls within the acceptable range.

Finally, it is important to ensure that the QTLs are regularly reviewed and updated if necessary. This will ensure that they remain valid and relevant to the trial and that they are not over- or under-applied. This will also help to ensure that data collected is of high quality, risks are managed, and that regulatory compliance is maintained.

In conclusion, QTLs still have a place in the QMS for clinical trials. While the ICH E6 (R2) revision does not specifically call out their use, regulatory authorities still recognize their importance. It is important to establish appropriate QTLs that are based on valid scientific evidence and to monitor and review them regularly. This will help to ensure high quality data, appropriate risk management, and regulatory compliance.