New problems of QC resulting from the program of clinical laboratory centralization are discussed. The one that seems to be most important is to evaluate what are the limits of instability caused by real conditions of sample storage and shipment from peripheral health care centers (PHCC) to central laboratory (CL) to be acceptable in clinical practice. All that occurs with samples from the moment of sampling in PHCC to testing in CL are considered as pre-analytical phase. The article states the fact of absence of conventional methods of quantitative evaluation of quality of the pre-analytical phase performance and its effect on clinical validity of the results. It is stressed that these instability investigations concerning all PHCC levels should precede the start of centralization policy. The aim of the study was to develop the procedure of calculation of analyte instability parameters based on statistical methods and to evaluate their clinical validity in accordance with GOST R standard 53079.4-2008. This national standard defines the highest admissible analyte instability parameters in the samples. The developed procedure includes also the algorithm of on-line incoming control checking in the CL to detect the samples containing analytes with out-of-range instability parameters. It is pointed that the method will ensure correct results only if working characteristics of all analytical systems used in both PHCC labs and regional CL correspond the national standard GOST R 531133.2-2008.