ICH S3A Q & A Focus on Microsampling and Their Related Information

Abstract

For toxicokinetic (TK) evaluation in non-clinical studies, it is often necessary to use satellite animals in rodents, owing to the volume of blood required for measurement of drugs. However, with the recent increases in the sensitivity of analytical instruments, it is now possible to evaluate TK with a smaller volume of blood by using a microsampling technique. As the application of microsampling can permit the evaluation of TK in the main study animals, it is possible to directly evaluate the relationship between the toxicology data and drug exposure in the same animals, and to reduce the number of animals or their pain, thereby contributing to the replacement, refinement and reduction of animals (3Rs) in research. To accelerate inclusion of this technique in TK studies, the ICH decided, in 2014, to make a Q & A for the S3A guideline, which was finalized in November 2017; the Japanese version was issued in March 2019. This Q & A describes points to consider when applying the microsampling technique for TK evaluation. Microsampling techniques have been used more often in non-clinical studies for applications for investigational new drugs (INDs) as well as new drug applications (NDAs) in Europe and the United States than in Japan. In UK, the National Centre for the Replacement Refinement & Reduction of Animals in Research has established a microsampling working group to share and publicize the knowledge of the industry. In Japan, an AMED research group has been conducting joint research projects on the practical application of microsampling, and its achievements have been evaluated in detail at academic meetings. This review introduces the background to ICH S3A Q & A, outlines the contents, and describes the recent progress in microsampling in Japan and other countries.