Standardization of immunoassay for CRM-related proteins in Japan: from evaluating CRM 470 to setting reference intervals.

The Japan National Institute of Health (JNIH), in close collaboration with academic societies, commercial companies, and the Japan Society of Medical Technologists, has led in the attempt to standardize plasma protein assays since the mid 1980s. Under a framework of global standardization, they used WHO primary reference materials to reduce discrepancies in values reported for proteins assayed using different systems, thus laying the foundations for a protein immunoassay standardization system in Japan. With the introduction of CRM 470 in 1993, the Japanese Committee for Clinical Laboratory Standards (JCCLS) has taken the initiative in promoting the use of the new material and bringing about the re-evaluation of all systems of quality assurance in clinical laboratories. This eventually led to the establishment of reference intervals in Japanese populations of children and adults after preparation of assigned calibrators from CRM 470 for each assay system. Here we review the history of a series of projects carried out in Japan and describe several remaining problems, through which we will attempt to evaluate the potential value of protein immunoassay standardization.