ABSTRACT
Since 2011, the European Bioanalysis Forum has been discussing the topic of context-of-use for biomarker assays, in support of a cross-industry implementation of its principles. The discussions have led to the acknowledgement of the challenges that we face as an industry in implementing these principles. In addition to scientific recommendations, the European Bioanalysis Forum has addressed these challenges by providing recommendations on organizational design, and what works in both sponsor and contract research organizations, to support and enable context-of-use across biomarker strategies. Here, we highlight the key considerations for organizational design to help ensure that biomarker assays are characterized and validated according to the right context-of-use, to ensure that the right decisions based on the biomarker data can be made during drug development.
Subject(s)
Biological Assay , Biomarkers/analysisABSTRACT
Background: Inhibition of the enzyme dipeptidyl peptidase 4 (DPP-4) is a pharmaceutical treatment for type 2 diabetes. To demonstrate bioequivalence of enzyme inhibition of a new dosage form of the inhibitor vildagliptin, a method for enzyme activity was developed, validated and applied using liquid chromatography and tandem mass spectrometry (LC-MS/MS). Results: The method was validated fit for purpose, including accuracy, precision as well as the stability of the activity and the inhibition of DPP-4 in human plasma. Conclusion: A method for the determination of the activity and inhibition of DPP-4 was developed using LC-MS/MS readout; the characteristics and performance of the method met predefined acceptance criteria and were fit for the purpose of a bioequivalence clinical trial.
Subject(s)
Aniline Compounds/pharmacology , Dipeptidyl Peptidase 4/metabolism , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Aniline Compounds/chemical synthesis , Aniline Compounds/chemistry , Chromatography, Liquid , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Dipeptidyl-Peptidase IV Inhibitors/chemical synthesis , Dipeptidyl-Peptidase IV Inhibitors/chemistry , Humans , Molecular Structure , Tandem Mass SpectrometryABSTRACT
The entire world was severely affected by the outbreak of the SARS-CoV-2 virus. Early phase clinical research was no exception and clinical healthy volunteer trials were halted across the globe. To enable continuation of development of new drugs, we developed a testing strategy for nonsymptomatic trial participants in an early stage of the outbreak. A point-of-care polymerase chain reaction test combined with a gold standard polymerase chain reaction test and strict social distancing and hygiene measures limited the number of infected subjects entering our clinical research units and reduced further spread for the duration of the clinical trial. Thus, proving efficacy of this strategy to allow safe and effective continuation of early phase clinical trials during the COVID-19 pandemic.
