Methods of control diphtheria vaccine safety

Abstract

Vaccination success depends not only on the timely coverage of threatened contingents, but also on the quality of vaccines. Every day, the requirements for security guarantees vaccines and their use guarantees of security increases. For the fast, reliable and independent scientific assessment of vaccine safety issues, WHO in 1999 created the Global Advisory Committee on Vaccine Safety. To enhance the capacity of pharmaceutical supervision in relation to vaccines in 2012 it was developed the Global Vaccine Safety Initiative. The main directions of the Global Vaccine Safety programs are considered in this review. It’s noted more strict requirements of Ukrainian pharmaceutical industry to produce public immunization drugs regulated Supplements to the State Pharmacopoeia of Ukraine, in comparison with other countries. This review considered diphtheria vaccine safety monitoring in the process of production according to the recommendations of the World Health Organization (WHO), described a subcutaneous method for determining the specific toxicity of the combined purified toxoid, characterized an intracutaneous method of determining of the presence of diphtheria toxin in each sample of the combined purified toxoid, that additionally used by some manufacturers. The definition of diphtheria toxin in dilutions of purified toxoid is presented.  This review considered diphtheria vaccine safety monitoring in the process of production according to the recommendations of the World Health Organization (WHO), described a subcutaneous method for determining the specific toxicity of the combined purified toxoid, characterized an intracutaneous method of determining of the presence of diphtheria toxin in each sample of the combined purified toxoid, that additionally used by some manufacturers. The definition of diphtheria toxin in dilutions of purified toxoid is presented.  As methods for determination of diphtheria toxin must be able to detect even a small amount of toxin it's examined the WHO's proposal to use an intradermal method on guinea pigs and tests on cell cultures. Attention is drawn to the fact that the determination of specific toxicity in cell culture can be carried out at presence of the approval of this method of a national control authority and sensitivity rates no less than in experiments on guinea pigs. The determining of specific toxicity of ready vaccine by subcutaneous method is described. The publication gave a test for elevated toxicity of the final product by intraperitoneal infection of mice and guinea pigs. It’s cited the WHO recommendations aimed at removing the possibility of recovery of the refined toxin toxicity.  Checking vaccines toxicity, pyrogenicity, sterility, allergenicity, teratogenicity, mutagenicity and immunogenicity mainly performed on laboratory animals. The review examined the unreliability of animal experiments and the need to find alternative methods for determining the toxicity without their use particularly in light of the “3R”concept. Methods for determining diphtherial toxin using cell cultures is considered,  namely, colony overlay test (COT), tests using a monolayer of HeLa cell culture, a culture of Vero cells (kidney cells of african green monkeys ), a culture of CHO cells (cells of Chinese hamster ovary), which are based on the toxin cytopathic effect on sensitive cell culture. Their advantages and disadvantages are listed.  An alternative method for the quantitative detection of C. diphtheriae toxin using the polystyrene plate coated with monoclonal antibody to the part of the diphtheria toxin which defines its binding to the cell, is described. It’s regarded the cytotoxic effect of diphtheria toxin on cells of the immune system of mice and guinea pigs: splenocytes, adhesive phagocytes i B- lymphocytes.