Regulated Drug Bioanalysis For Human Pharmacokinetic Studies And Therapeutic Drug Management

Abstract

Regulated drug bioanalysis (i.e., determination of drug concentrations in biological matrices for regulated studies) usually refers to animal toxicokinetics, bioavailability/bioequivalence and clinical pharmacokinetic studies. However, there is another important regulated drug bioanalysis – therapeutic drug management (TDM). In the USA, TDM is regulated by Clinical Laboratory Improvement Amendments. In this article, we review and compare human pharmacokinetic sample analysis and TDM sample analysis. The US FDA/Bioanalytical Method Validation Guidance and the American Association for Clinical Chemistry/TDM Roundtable Recommended Generic Assay Validation Guidance are also compared. Some regulated drug bioanalysis issues, such as terminology, validation concepts and acceptance criteria, are discussed. Fostering interaction between bioanalysts from pharmaceutical science and clinical chemistry and reducing the regulatory gaps between different agencies for drug bioanalysis is our objective.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Acknowledgements

The authors are grateful to C Hammett-Stabler, Department of Pathology and Laboratory Medicine, University of North Carolina, for providing some information on the American Association for Clinical Chemistry Therapeutic Drug Management Generic Assay Validation Guidance. The authors thank E Lin, the former Drug Studies Unit Director, and L Benet, Department of Bioengineering and Therapeutic Sciences, University of California, for providing comments during preparation of the manuscript.