ABNORMAL TOXICITY TEST VALIDATION FOR INSULIN SUBSTANCE STANDARDISATION

Abstract

Abnormal Toxicity test is obligatory in the Russian Federation for standardisation of biological origin substances, despite an ambiguous assessment of its expediency. Evaluation of abnormal toxicity of insulin by a standard technique is impossible because its introduction causes death of animals as a result of hypoglycemic shock. A change in pharmacopoeial technique defines need of its validation. On the example of substance of human genetically engineered insulin Rosinsulin (LLC «Zavod Medsintez») with mice males as biological test system the optimum conditions of the test were proposed. They include intraperitoneal introduction of glucose solution in 60 min, prior to intravenous administration of insulin. Indicators of intoxication, body weight and blood glucose level were monitored during the test for three bathes of insulin substance. Abnormal Toxicity test was validated on Robutness (with influence of small changes of volume of the entered solution of insulin and time between introduction of glucose and insulin solutions) and a Precision (intra-day and inter-day). Satisfactory results for all validation parameters were received.