Tiered approach to metabolite quantification: regional practices reviewed by Japan Bioanalysis Forum discussion group.

Abstract

2015 Tiered approach; familiarization is essential A tiered approach [1–3] is an idea of step-bystep characterization of analytical methods in coordination with the stage of drug development and the importance of the analytical results obtained. It is thought that this approach contributes to the optimization of the framework of bioanalytical laboratories by adding flexibility to the analytical methods [4]. Nevertheless, it appears that bioanalysts are not ready to use this tiered approach in their day-to-day work because bioanalytical method validation guidances or guidelines, which are in force in the USA, Europe, Brazil and Japan, do not provide a framework for this approach (although the Japanese guidelines do outline the concept of a tiered approach). In addition, bioanalytical experts in industry or regulatory authorities have not provided detailed scientific requirements for different assay types or stages of drug development [4]. The tiered approach is often accompanied with the idea of case-by-case consideration. This makes it hard for those who are not familiar with this concept to understand the whole picture. The common question is how to implement the tiered approach practically (timing and characterization details of the analytical methods). This question seems to show that detailed models of works for the tiered approach are necessary in drug discovery and development stages. Though one of the ultimate goals for the tiered approach is to add flexibility to the bioanalytical works, we considered that it is useful to be familiarized with the approach at first through the typical workflow model. Complete understanding would contribute to more flexible usage of the methods. This activity may help remove certain hurdles toward general acceptance of the tiered approach in laboratory works [4]. Accordingly, a voluntary discussion group (named DG2013–03) of Japan Bioanalysis Forum (JBF), consisting of eight Japanese researchers from pharmaceutical companies and a contract research organization, tried to get the birds-eye-view of the tiered approach in accordance with drug discovery and development stages with emphasis on metabolite research [5]. This activity was intended to provide detailed scientific requirements in assay type or stage of drug development as described above. As an outcome of JBF DG2013–03, this report outlines tiered characterization of the analytical methods in metabolite quantification in relation to actual regional practices in Japan.