Documenting assay quality in TDM

Abstract

Key goals in providing therapeutic drug monitoring (TDM) services are consistency and accuracy of results. These concepts are often misunderstood, with a disproportionate emphasis placed on assay reproducibility, rather than calibration issues. Whilst TDM has been delivered using immunoassay kits, there has been some logic in developing assay-related target ranges locked into the calibrators supplied by diagnostic companies. However, with a growing number of laboratories turning to the use of high-performance liquid chromatography with mass-spectrometric detection (HPLC/MS) for TDM services, preparation of accurate calibrators assumes more importance, as the responsibility for calibrator accuracy usually rests with individual centres. The availability of HPLC/MS has also highlighted the differences between chromatographic and immunoassays for a number of analytes, including naturally occurring compounds. These quality issues, calibration accuracy and reproducibility of the methodology, will be discussed in the context of assay validation and documentation of performance to satisfy regulatory standards. Illustrations will draw on data from external proficiency testing schemes for a number of drug classes, and the development of assays for infrequently measured analytes. It will be concluded that there are increasing demands on laboratories to show that their measurements of drugs and endogenous compounds are consistent between laboratories, and that they provide clinicians with reliable information on which to base dose changes or diagnoses. It is the responsibility of laboratories to show that they have addressed these issues by documenting the processes involved.