Reference materials used for specific safety evaluation of human immunoglobulin and human albumin products: features of development, certification and application

Abstract

Human immunoglobulin and human albumin products can negatively affect patients’ health. The residual content of haemagglutinins, anti-D antibodies, prekallikrein activator, as well as the level of anticomplementary activity, are controlled during both production and testing for compliance with normative documentation. Methods for their quantitative evaluation are based on the effects of erythrocytes hemolysis or agglutination and on the amidolytic product properties of cascade reactions. These methods require the obligatory use of reference materials (RMs). The development of RMs, acting as the carrier of the quantitative characteristics of the human immunoglobulins and human albumin impurities, is fraught with the difficulty of selecting a candidate, substantiating the certification methodology, and determining the relevant characteristics. In this research, we used human immunoglobulin solutions with normalized haemagglutinin content, anti-D antibodies or anti-complementary activity in a different range, whose quality was studied using haemagglutination and chromogenic methods, and the complement fixation test. Methodological approaches to the RM development and certification were justified using system analysis and forensic audit methods. The results demonstrate the necessity of using RMs to assess the stability of analytical work by applying anti-complementary activity determination, haemagglutinin content or anti-Dantibody methods. It is established that RMs allow the quantitative content of haemagglutinins, anti-D antibodies and prekallikrein activator to be established. The value of the CRM characteristics should be approximated to the qualitative composition of these impurities in the analysed products, but in amounts not detectable (to produce negative RM components) or exceeding permissible maxima (to produce positive RM components).