Application of 3Rs principles to assess the quality of DPT vaccine: Advantages and disadvantages

INTRODUCTION. Global vaccine manufacturers actively use modern alternative in vivo and in vitro tests to assess the potency of diphtheria and tetanus toxoids in the DPT vaccine, following 3Rs principles (replacement, reduction, refinement). At present, some in vivo tests have been completely replaced with alternative tests. In the Russian Federation, the 3Rs principles for quality assessment of DPT vaccine are practically not applied. The process of harmonization of the State Pharmacopoeia of the Russian Federation with the requirements of the regional pharmacopoeia of the Eurasian Economic Union (EAEU) necessitates the analysis of modern tests for quality assessment of DPT vaccines.

AIM. To conduct a comparative analysis of modern tests for potency determination of DPT vaccine components, assess advantages and disadvantages of tests, and identify problematic issues in harmonizing tests within the pharmacopoeia of EAEU.

DISCUSSION. In the European Union, the 3Rs principles are an integral part of the legislation. Due to investigations under the auspices of WHO and the European Directorate for the Quality of Medicines and Healthcare (EDQM), the use of laboratory animals have been completely excluded from some tests or replaced with more sparing tests that alleviate the suffering of animals. Alternative serological tests of DPT vaccine are considered sparing, but they include animals that are immunized for subsequent collection of blood samples. To establish alternative tests for potency assessment of diphtheria and tetanus toxoid, additional materials, reagents, standards, special equipment, and statistical software are required. They are multi-stage and a larger number of skilled specialists are needed. Alternative serological tests based on enzyme-linked immunosorbent assay (ELISA) have a certain advantage over the lethal challenge method: exclusion of toxins usage and determination of two types of protective antibodies in the blood serum samples obtained from one animal.

CONCLUSIONS. Despite the active development and implementation of in vitro tests for quality control of the diphtheria and tetanus components of the DPT vaccine, lethal challenge methods are more cost-effective, easy to perform and adapted to assess the direct protective effect of the vaccine. It should be noted that ELISA is the most promising test of the alternative tests applied for quality control of the DPT vaccine.

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