Implementation of the 3Rs Concept in Quality Control of Biologicals: Status and Prospects (Review)

INTRODUCTION. Many countries are implementing an increasing number of alternatives to animal testing in the research, development, and quality control of medicines under the concept of 3Rs (replacement, reduction, and refinement). However, the implementation of in vitro alternatives to in vivo methods into batch release testing of biologicals, primarily vaccines, is a challenging process. The introduction of the 3Rs principles into regulatory and industry standards requires a comprehensive analysis, including, among other things, a study of specific considerations for national frameworks. AIM. This study aimed to analyse the degree of global integration of the 3Rs principles in the quality control of biological medicinal products and to assess existing challenges and opportunities for a successful transition to non-animal quality control methods in the Russian Federation. DISCUSSION. The key advantages of in vitro biological methods over in vivo approaches for quality control of medicinal products include reduced variability, higher specificity, and shorter testing timelines. Analysis of assessments by regulatory authorities and pharmaceutical manufacturers regarding the opportunities and challenges in implementing the 3Rs principles has identified the following main arguments for replacing in vivo methods: ethical considerations, relevance of reducing testing time, decreased variability. The integration of in vitro methods is hindered by insufficient information on alternative approaches and the lack of harmonised regulatory frameworks for adopting 3Rs principles. For instance, the European Pharmacopoeia has eliminated all general safety testing of biological medicinal products in animals as part of its 3Rs implementation. Furthermore, the World Health Organization has developed guidelines for the phased discontinuation of animal testing in the quality control of biological products. CONCLUSIONS. The main challenges associated with 3Rs implementation include the difficulty of confirming the in vitro – in vivo correlation (particularly, by comparing in vivo and in vitro methods), the lack of regulatory harmonisation, and the insufficient regulatory support for manufacturers in adopting alternative methods. The international harmonisation of regulatory requirements is necessary to effectively address these issues and successfully implement the 3Rs principles in the quality control procedures for biologicals released in different countries, including the Russian Federation.