Rotavirus infection is a widespread cause of severe gastroenteritis in children in low-income countries. Specific prophylaxis in young children has become the most important means of combating severe rotavirus gastroenteritis. The review presents current data on the molecular biology and genetic diversity of rotaviruses, interaction of viral proteins with host cell receptors, molecular aspects of infectivity and pathogenesis of rotavirus infection, and the development of immunity. It addresses a new approach to the epidemiology of rotavirus infection which regards it as a manageable infection, it illustrates the specificity of the epidemic process based on data gained from extensive experience in vaccination, and summarises relevant information on the introduction of rotavirus vaccines into the international healthcare practice. The paper summarises risks associated with the use of vaccines based on the analysis of WHO statistics, scientific publications on the epidemiology of rotavirus infection, and the results of vaccination. It analyses approaches of the competent authorities of some countries to the tactics of vaccination against rotavirus infection and the WHO stance on the use of existing vaccines for the prevention of rotavirus infection. A conclusion was made that it is necessary to further improve the tactics of vaccine prevention of rotavirus infection in Russia, to study the incidence of idiopathic intussusception, and to conduct further studies aimed at characterisation of existing and newly emerging genotypes of rotavirus.

The rotavirus infection causes acute gastroenteritis and is a major cause of lethal severe dehydrating diarrhoea in children under 5 years of age worldwide. Live attenuated rotavirus vaccines are the only means of preventing severe forms of the disease. The aim of the study was to analyse the twenty-year international experience of prophylactic immunisation against rotavirus infection. The paper summarises safety and efficacy data on the long-term use of Rotarix® (Belgium) and RotaTeq® (USA) for the prevention of rotavirus infection in the WHO European Region, the European Union and other countries. It addresses the development of correlates of immune protection for vaccines as well as evaluation of efficacy and safety of the new vaccines Rotavac® and Rotasiil® (India) in clinical trials. The authors analysed international experience of using the vaccines in countries that do not keep records of infant mortality from diarrhoea. The study summarises the results of clinical studies on the use of new vaccines prequalified by WHO in 2018 in regions with high rates of infant mortality from diarrhoea. It was demonstrated that vaccination not only reduces the rates of hospital admission of immunised children, but also contributes to the development of herd immunity. Rotarix® and RotaTeq® vaccines are authorised or included in the national immunisation schedules of many countries, but this type of vaccination is not mandatory in most of these countries. Vaccination coverage in the EU countries is about 24 %. Alternative vaccination schemes using live attenuated vaccines based on strains derived from newborn children, and parenteral rotavirus vaccines which do not replicate in the intestine may help reduce existing risks. It was concluded that the introduction of live rotavirus vaccines in immunisation schedules should be accompanied by the analysis of incidence of intussusception of the small intestine before and after the introduction of mass immunisation, and by active pharmacovigilance.

The management of post-approval changes to registration dossiers for medicinal products is one of the most important factors for ensuring sustainable quality, safety and effi cacy of medicines. Competent authorities that use the module format of the registration dossier, i. e. the regulatory authorities of the European Union, USA and other members of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), and the Eurasian Economic Union (EEU), issue guidelines on changes to registration dossiers for pharmaceuticals and biologicals (immunological products). Vaccines (fi nished dosage forms) and vaccine antigens (active ingredients) are a specifi c group of immunobiological products which have great prophylactic importance for healthcare, and which are associated with challenging development and specifi c methods of manufacturing and quality control. The procedure of introducing post-approval variations to dossiers for immunobiological medicinal products is poorly refl ected in the current Russian and EEU regulations. The World Health Organization (WHO) established a procedure described in the «Guidelines on procedures and data requirements for changes to approved vaccines». The purpose of the present study was to compare current Russian and international legislation in terms of regulatory requirements for post-approval сhanges to dossiers for immunobiological products. The Federal State Budgetary Institution «Scientifi c Centre for Expert Evaluation of Medicinal Products» of the Ministry of Health of the Russian Federation is drafting Guideline on introducing CC BY 4.0 Внесение изменений в документы регистрационных досье на вакцины: анализ нормативно-методических подходов... Post-approval Variations to Dossiers for Vaccines: Analysis of Regulatory and Methodological Approaches Used... Ведомости Научного центра экспертизы средств медицинского применения 2019. Т. 9, № 1 The Bulletin of the Scientifi c Centre for Expert Evaluation of Medicinal Products 2019. V. 9, No. 1 42 ОБЗОРЫ / REVIEWS post-approval changes into dossiers for immunobiological medicines. The draft includes a detailed review of various categories of changes based on their importance, and a list of conditions and required documents for specifi c groups of medicines. This article summarises scientifi c and methodological approaches to evaluation of changes introduced in registration dossiers for vaccines in order to further improve the regulatory framework of the Russian Federation and the EEU.