Statistical quality control methods in standardization of BCG vaccines.

The quality control of the BCG vaccine lacks the requirements of exact statistical methods, although the principles of bioassay have been required in the control of other biological products for a long time. For a remedy and to eliminate controversies in the interpretation of the laboratory results of BCG products valid statistical control is needed. In the four major laboratory test systems generally used to control: the viability of the BCG products, the residual virulence of the BCG strains, the allergenic potency and 4) the immunogenic potency of the BCG vaccines the following statistical methods should be required: estimations of the unbiased point and 95% confidence interval of the viable units 10(6)/ml, the mean residual virulence, the mean allergizing and protective capacity in appropriate models, the expressions of the relative potency of the in vitro viability and the in vivo test systems to a Reference Preparation, hypothesis tests using the unbiased estimates for the comparison of the estimated parameters of the controlled vaccines (Anova) and testing the stability of the viability (Regranal), multiple comparison with the ranked estimates to diminish Type I error in rejected null hypotheses, test of concordance between the sets of ranked parameters of the different test systems. Valid models will promote the standardization of the BCG vaccine, will ensure the objective statistical inference of the control results, the interpretation of the immunogenicity and reactogenicity of the BCG vaccines and the understanding of the epidemiological processes in tuberculosis.