Ways to Reduce the Level of Contamination at the Stages of Tableted Chemical Cholera Vaccine Production

Abstract

Objective of the study was an assessment of the degree of contamination of cholera chemical vaccine at the stages of preparation and determination of the ways to reduce it.Materials and methods. Liquid and lyophilized components of the cholera chemical vaccine used in the study: cholerogen-anatoxin and O-antigens of Vibrio cholerae 569B and V. cholerae M-41 strains, as well as auxiliary substances (sucrose, talc, calcium stearate, starch). Granulation was carried out in a device that works on a fluidized bed principle, GPCG 2 (GLATT, Germany). Subsequent tabletizing of the mixture was performed using MiniTabT compression machine (LUXNER, Germany). Studies were conducted on the evaluation of “microbiological purity” at the stages of manufacturing of the cholera chemical vaccine, tablets coated with an enteric coating. Positive or negative growth of microorganisms on Petri dishes with nutrient media was determined on visual inspection.Results and conclusions. The dynamics of changes in microbial contamination at certain technological stages of vaccine production has been revealed. It is shown that the solutions of antigens in the process of separation are subject to microbial contamination which is associated with the use of ammonium sulfate during precipitation and non-sterile water at the stage of dialysis. Sterility of semi-finished products has been achieved through twophase filtration of choleragen-anatoxin and sterilization of O-antigens of V. cholerae 569B and V. cholerae M-41 strains with flowing steam at (100±1) °C for 30 minutes. In order to decrease microbial contamination at the stage of granulation additional fine filters were installed in the air-supply system. Further on comparative assessment of microbial purity of vaccine batches obtained using both, direct compression and preliminary granulation, was carried out. It has been experimentally demonstrated that granulation of the components of a tablet mixture of cholera vaccine leads to a decrease in the level of bacterial contamination and improves the microbiological purity of the finished dosage form.