Assessment of blood substitutes: II. In-vitro complement activation of human plasma and blood for safety studies in research, development, industrial production and preclinical analysis.

Animal safety study cannot predict the effects of blood substitutes in human response. Response of human, especially in immunology and complement activation, need not be the same as those in animals. We have earlier reported an in-vitro preclinical screening test based on testing the effects of modified hemoglobin on complement activation of human plasma or blood in vitro. In this test, modified hemoglobin is added to human plasma in a test tube. Complement activation is followed by the C3a levels. Since this directly measures the effect of modified hemoglobin on human plasma, it would be the closest response in human next to injecting this into human. Thus, this could be an important bridge before clinical use in patients. However, why wait for the completion of research, industrial production and preclinical animal studies? Why don't we do this test right at the beginning during the research stage? If a new system is found to cause complement activation at this stage, one can avoid tremendous waste of time and money in further development, industrial production and preclinical animal study. This paper analyzes this approach in research, development, industrial production and preclinical analysis.