47 research outputs found
Current regulatory requirements for non-clinical evaluation of prophylactic vaccines
Vaccines are subject to specific regulatory requirements for the evaluation of their quality, safety, and efficacy. In 2005, the World Health Organisation (WHO), as the main international organisation coordinating measures to combat infectious disease outbreaks, began developing documents on the evaluation of vaccine quality, safety, and efficacy. The worldβs leading regulatory authorities (FDA, EMA, etc.) have also issued recommendations for conducting non-clinical studies of vaccines.The aim of this study was a critical review of the regulatory requirements established by foreign national and international regulatory authorities for non-clinical evaluation of the safety and efficacy of vaccines.According to the study results, since the 2000s, the WHO and the worldβs leading regulatory authorities have produced more than 40 regulatory documents describing certain aspects of non-clinical studies of the safety and efficacy of vaccines. These documents can be divided into two groups: the first group addresses non-clinical studies of vaccines in general, and the second one dwells upon the evaluation of the quality, safety, and efficacy of specific types of vaccines. For the Russian guidelines on non-clinical evaluation of the quality, safety, and efficacy of immunobiologicals, the latest revision dates back to 2013 and does not provide any information on new medicinal products. Currently, work is underway to prepare the regulatory framework for medicines, including vaccines, in the Member States of the Eurasian Economic Union (EAEU). This review of regulatory documents on non-clinical safety and efficacy studies of vaccines may be useful in drafting harmonised guidelines for the relevant groups of vaccines in the EAEU. It may also be of use to developers, manufacturers, and researchers involved in the creation and non-clinical study of vaccines
Challenges in development and authorisation of gene therapy products
There are a lot of diseases known today, which are caused by genetic abnormalities. Advances in genetics and biotechnology brought about gene editing technologies that can produce almost any gene, which ultimately led to the emergence of a new class of medicines - gene therapy products (GTPs). The aim of the study was to analyse international experience in development and authorisation of GTPs. The review highlights the challenges in GTP development, related to the search for an optimal approach to therapeutic gene delivery to the target cells. Viral vectors were shown to be a promising gene delivery system, with adenovirus (AV) and adeno-associated virus (AAV) based products demonstrating the highest efficacy and safety. The paper reviews current approaches to gene editing that allow modification of AVs and AAVs to improve GTP efficacy and safety. These modifications are carried out with the aim of, e.g., including a large therapeutic gene into a viral vector, decreasing viral protein expression levels, and decreasing viral vector immunogenicity. The review summarises GTP authorisation procedures in the USA and the European Union, including data on FDA and EMA subcommittees and departments entrusted with advisory functions. The paper mentions that there is one Russian-produced GTP authorised in the Russian Federation, and some other GTPs are in the pipeline. Therefore, the Russian regulatory framework and the Eurasian regulations and recommendations should be updated in order to accommodate for GTP development and authorisation
Π‘ΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΡΠ΅ Π½ΠΎΡΠΌΠ°ΡΠΈΠ²Π½ΡΠ΅ ΡΡΠ΅Π±ΠΎΠ²Π°Π½ΠΈΡ ΠΊ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ Π²Π°ΠΊΡΠΈΠ½ ΠΏΡΠΎΡΠΈΠ² Π²ΠΈΡΡΡΠ½ΡΡ ΠΈΠ½ΡΠ΅ΠΊΡΠΈΠΉ
Scientific relevance. In recent years, the development of various vaccines based on novel platforms has underscored the significance of updating regulatory requirements for vaccines. Consequently, clinical trials of viral vaccines need harmonised approaches within national guidelines and the Eurasian Economic Union (EAEU) regulatory framework.Aim. This study aimed to analyse national and international requirements for clinical trials of the efficacy and safety of preventive viral vaccines.Discussion. This article presents an analysis of the guidelines issued by the WHO and leading regulatory authorities on different aspects of clinical trials of viral vaccines. These guidelines place particular emphasis on the immunogenicity of vaccines. The lack of well-established immune correlates of protection for most infections presents a significant problem for assessing the effectiveness of vaccines. Immunobridging studies may be conducted to expand vaccine indications to different populations (such as a new age group). The size of the prelicensure safety database should include data on at least 3,000 vaccinated study participants. For some vaccines, safety studies must assess the risk of disease onset or enhancement due to vaccination.Conclusions. The clinical trial requirements for viral vaccines have been substantially aligned by the WHO and major international regulatory authorities, thereby facilitating the development of harmonised national or EAEU guidelines.ΠΠΊΡΡΠ°Π»ΡΠ½ΠΎΡΡΡ. Π‘ ΡΡΠ΅ΡΠΎΠΌ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠΈ Π² ΠΏΠΎΡΠ»Π΅Π΄Π½Π΅Π΅ Π²ΡΠ΅ΠΌΡ ΠΌΠ½ΠΎΠΆΠ΅ΡΡΠ²Π° Π²Π°ΠΊΡΠΈΠ½ Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ Π½ΠΎΠ²ΡΡ
ΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΠ»Π°ΡΡΠΎΡΠΌ ΠΎΡΠΎΠ±ΠΎ Π±ΠΎΠ»ΡΡΠΎΠ΅ Π·Π½Π°ΡΠ΅Π½ΠΈΠ΅ ΠΏΡΠΈΠΎΠ±ΡΠ΅ΡΠ°Π΅Ρ ΠΎΠ±Π½ΠΎΠ²Π»Π΅Π½ΠΈΠ΅ Π½ΠΎΡΠΌΠ°ΡΠΈΠ²Π½ΡΡ
ΡΡΠ΅Π±ΠΎΠ²Π°Π½ΠΈΠΉ ΠΊ Π²Π°ΠΊΡΠΈΠ½Π½ΡΠΌ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ°ΠΌ. ΠΠΊΡΡΠ°Π»ΡΠ½ΠΎΠΉ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»ΡΠ΅ΡΡΡ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠ° Π³Π°ΡΠΌΠΎΠ½ΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΠΏΠΎΠ΄Ρ
ΠΎΠ΄ΠΎΠ² Π² ΡΠ°ΠΌΠΊΠ°Ρ
Π½Π°ΡΠΈΠΎΠ½Π°Π»ΡΠ½ΡΡ
ΡΡΠΊΠΎΠ²ΠΎΠ΄ΡΡΠ² ΠΈ Π½ΠΎΡΠΌΠ°ΡΠΈΠ²Π½ΡΡ
Π΄ΠΎΠΊΡΠΌΠ΅Π½ΡΠΎΠ² ΠΠ²ΡΠ°Π·ΠΈΠΉΡΠΊΠΎΠ³ΠΎ ΡΠΊΠΎΠ½ΠΎΠΌΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠΎΡΠ·Π° (ΠΠΠΠ‘), ΡΠ΅Π³Π»Π°ΠΌΠ΅Π½ΡΠΈΡΡΡΡΠΈΡ
ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠ΅ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ Π²ΠΈΡΡΡΠ½ΡΡ
Π²Π°ΠΊΡΠΈΠ½.Π¦Π΅Π»Ρ. ΠΠ½Π°Π»ΠΈΠ· Π½ΠΎΡΠΌΠ°ΡΠΈΠ²Π½ΡΡ
Π½Π°ΡΠΈΠΎΠ½Π°Π»ΡΠ½ΡΡ
ΠΈ ΠΌΠ΅ΠΆΠ΄ΡΠ½Π°ΡΠΎΠ΄Π½ΡΡ
ΡΡΠ΅Π±ΠΎΠ²Π°Π½ΠΈΠΉ, ΡΠ΅Π³Π»Π°ΠΌΠ΅Π½ΡΠΈΡΡΡΡΠΈΡ
ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠ΅ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΈ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΠΈ Π²Π°ΠΊΡΠΈΠ½ Π΄Π»Ρ ΠΏΡΠΎΡΠΈΠ»Π°ΠΊΡΠΈΠΊΠΈ Π²ΠΈΡΡΡΠ½ΡΡ
ΠΈΠ½ΡΠ΅ΠΊΡΠΈΠΎΠ½Π½ΡΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ.ΠΠ±ΡΡΠΆΠ΄Π΅Π½ΠΈΠ΅. ΠΡΠΎΠ²Π΅Π΄Π΅Π½ Π°Π½Π°Π»ΠΈΠ· ΡΠ°Π·ΡΠ°Π±ΠΎΡΠ°Π½Π½ΡΡ
ΠΡΠ΅ΠΌΠΈΡΠ½ΠΎΠΉ ΠΎΡΠ³Π°Π½ΠΈΠ·Π°ΡΠΈΠ΅ΠΉ Π·Π΄ΡΠ°Π²ΠΎΠΎΡ
ΡΠ°Π½Π΅Π½ΠΈΡ (ΠΠΠ) ΠΈ Π²Π΅Π΄ΡΡΠΈΠΌΠΈ ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΠ½ΡΠΌΠΈ ΠΎΡΠ³Π°Π½Π°ΠΌΠΈ ΡΡΠΊΠΎΠ²ΠΎΠ΄ΡΡΠ², ΠΊΠ°ΡΠ°ΡΡΠΈΡ
ΡΡ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
Π°ΡΠΏΠ΅ΠΊΡΠΎΠ² ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ Π²ΠΈΡΡΡΠ½ΡΡ
Π²Π°ΠΊΡΠΈΠ½. Π ΡΡΠΊΠΎΠ²ΠΎΠ΄ΡΡΠ²Π°Ρ
ΠΎΡΠΎΠ±ΠΎΠ΅ Π²Π½ΠΈΠΌΠ°Π½ΠΈΠ΅ ΡΠ΄Π΅Π»Π΅Π½ΠΎ Π²ΠΎΠΏΡΠΎΡΠ°ΠΌ ΠΈΠΌΠΌΡΠ½ΠΎΠ³Π΅Π½Π½ΠΎΡΡΠΈ Π²Π°ΠΊΡΠΈΠ½. Π‘ΡΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΠΏΡΠΎΠ±Π»Π΅ΠΌΠΎΠΉ Π΄Π»Ρ ΠΎΡΠ΅Π½ΠΊΠΈ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π²Π°ΠΊΡΠΈΠ½ ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΎΡΡΡΡΡΡΠ²ΠΈΠ΅ ΠΎΠ±ΠΎΡΠ½ΠΎΠ²Π°Π½Π½ΡΡ
ΠΈΠΌΠΌΡΠ½Π½ΡΡ
ΠΊΠΎΡΡΠ΅Π»ΡΡΠΎΠ² Π·Π°ΡΠΈΡΡ Π΄Π»Ρ Π±ΠΎΠ»ΡΡΠΈΠ½ΡΡΠ²Π° ΠΈΠ½ΡΠ΅ΠΊΡΠΈΠΉ. ΠΠΎΠΏΡΡΠΊΠ°Π΅ΡΡΡ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠ΅ ΡΠ²ΡΠ·ΡΡΡΠΈΡ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ ΠΈΠΌΠΌΡΠ½ΠΎΠ³Π΅Π½Π½ΠΎΡΡΠΈ Ρ ΡΠ΅Π»ΡΡ ΡΠ°ΡΡΠΈΡΠ΅Π½ΠΈΡ ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΈΠΉ Π½Π° Π΄ΡΡΠ³ΠΈΠ΅ ΠΏΠΎΠΏΡΠ»ΡΡΠΈΠΈ Π²Π°ΠΊΡΠΈΠ½ΠΈΡΡΠ΅ΠΌΡΡ
(Π½Π°ΠΏΡΠΈΠΌΠ΅Ρ, ΠΏΠΎ Π²ΠΎΠ·ΡΠ°ΡΡΡ). ΠΠ»Ρ ΡΠ΅Π³ΠΈΡΡΡΠ°ΡΠΈΠΎΠ½Π½ΠΎΠΉ ΠΎΡΠ΅Π½ΠΊΠΈ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΠΈ ΠΌΠΈΠ½ΠΈΠΌΠ°Π»ΡΠ½ΡΠΉ ΠΎΠ±ΡΠ΅ΠΌ Π²ΡΠ±ΠΎΡΠΊΠΈ Π΄ΠΎΠ»ΠΆΠ΅Π½ Π²ΠΊΠ»ΡΡΠ°ΡΡ Π½Π΅ ΠΌΠ΅Π½Π΅Π΅ 3000 Π²Π°ΠΊΡΠΈΠ½ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
. ΠΡΠΈ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠΈ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΠΈ Π΄Π»Ρ Π½Π΅ΠΊΠΎΡΠΎΡΡΡ
Π²Π°ΠΊΡΠΈΠ½ Π½Π΅ΠΎΠ±Ρ
ΠΎΠ΄ΠΈΠΌΠΎ ΠΎΡΠ΅Π½ΠΈΠ²Π°ΡΡ ΡΠΈΡΠΊ ΡΡΠΈΠ»Π΅Π½ΠΈΡ ΠΈΠ½ΡΠ΅ΠΊΡΠΈΠΎΠ½Π½ΠΎΠ³ΠΎ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ, ΡΠ²ΡΠ·Π°Π½Π½ΠΎΠ³ΠΎ Ρ Π²Π²Π΅Π΄Π΅Π½ΠΈΠ΅ΠΌ Π²Π°ΠΊΡΠΈΠ½Ρ, ΠΈ ΡΠ°Π·Π²ΠΈΡΠΈΡ Π²Π°ΠΊΡΠΈΠ½ΠΎΠΈΠ½Π΄ΡΡΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ.ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. Π’ΡΠ΅Π±ΠΎΠ²Π°Π½ΠΈΡ ΠΠΠ ΠΈ Π²Π΅Π΄ΡΡΠΈΡ
ΠΌΠΈΡΠΎΠ²ΡΡ
ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΠ½ΡΡ
ΠΎΡΠ³Π°Π½ΠΎΠ² ΠΊ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ Π²ΠΈΡΡΡΠ½ΡΡ
Π²Π°ΠΊΡΠΈΠ½ Π² ΡΠ΅Π»ΠΎΠΌ ΡΠ²Π»ΡΡΡΡΡ ΡΡ
ΠΎΠ΄Π½ΡΠΌΠΈ ΠΈ ΠΌΠΎΠ³ΡΡ ΡΠ°ΡΡΠΌΠ°ΡΡΠΈΠ²Π°ΡΡΡΡ ΠΊΠ°ΠΊ Π²Π·Π°ΠΈΠΌΠΎΠ΄ΠΎΠΏΠΎΠ»Π½ΡΡΡΠΈΠ΅ ΠΏΡΠΈ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠ΅ Π½ΠΎΠ²ΡΡ
, Π³Π°ΡΠΌΠΎΠ½ΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
Π² ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²ΠΈΠΈ Ρ ΠΌΠ΅ΠΆΠ΄ΡΠ½Π°ΡΠΎΠ΄Π½ΡΠΌΠΈ ΠΏΠΎΠ΄Ρ
ΠΎΠ΄Π°ΠΌΠΈ Π½Π°ΡΠΈΠΎΠ½Π°Π»ΡΠ½ΡΡ
ΡΡΠΊΠΎΠ²ΠΎΠ΄ΡΡΠ² ΠΈΠ»ΠΈ ΡΡΠΊΠΎΠ²ΠΎΠ΄ΡΡΠ² ΠΠΠΠ‘ ΠΏΠΎ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠΌ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡΠΌ
ΠΡΠΏΠ΅ΠΊΡΡ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² Π΄Π»Ρ Π»Π΅ΡΠ΅Π½ΠΈΡ Π³Π΅ΠΌΠΎΡΠΈΠ»ΠΈΠΈ
Hemophilia is an orphan disease associated with deficiency or complete lack of certain blood coagulation factors due to mutation of genes encoding their synthesis. Patients with hemophilia need continuous replacement therapy with coagulation factor products which are produced by recombinant DNA technology or derived from donated blood plasma. The development of new products or improvement of the production process of already authorised medicinal products involve clinical trials that have to include both previously treated and untreated patients of different age groups. The aim of the paper was to perform an analytical review of general hemophilia issues and major requirements for clinical trials of coagulation factor IX products based on the updated documents of the European Medicines Agency. The paper summarises the basic principles of conducting clinical trials of coagulation factor IX products that are submitted for marketing authorisation as βnewβ products, based on recommendations of Russian and international regulatory documents, including the updated guideline of the European Medicines Agency. It sums up product safety issues associated with undesirable immunogenicity resulting in formation of inhibitors that provoke allergic reactions or reduce the effectiveness of therapy. The harmonisation of the requirements for clinical trials during preparation and updating of documents by Russian manufacturers should be based on the analysis of the experience with hemophilia products and latest scientific achievements in the disease treatment. In that case it will facilitate the introduction of innovative efficacious hemophilia products into clinical practice.ΠΠ΅ΠΌΠΎΡΠΈΠ»ΠΈΡ β ΠΎΡΡΠ°Π½Π½ΠΎΠ΅ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠ΅, ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Π½ΠΎΠ΅ Π½Π΅Π΄ΠΎΡΡΠ°ΡΠΎΡΠ½ΠΎΡΡΡΡ ΠΈΠ»ΠΈ ΠΏΠΎΠ»Π½ΡΠΌ ΠΎΡΡΡΡΡΡΠ²ΠΈΠ΅ΠΌ ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²ΡΡΡΠΈΡ
ΡΠ°ΠΊΡΠΎΡΠΎΠ² ΡΠ²Π΅ΡΡΡΠ²Π°Π½ΠΈΡ ΠΊΡΠΎΠ²ΠΈ Π·Π° ΡΡΠ΅Ρ ΠΌΡΡΠ°ΡΠΈΠΈ Π³Π΅Π½ΠΎΠ², ΠΊΠΎΠ΄ΠΈΡΡΡΡΠΈΡ
ΠΈΡ
ΡΠΈΠ½ΡΠ΅Π·. ΠΠ°ΡΠΈΠ΅Π½ΡΠ°ΠΌ Ρ Π³Π΅ΠΌΠΎΡΠΈΠ»ΠΈΠ΅ΠΉ ΡΡΠ΅Π±ΡΠ΅ΡΡΡ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠ΅ ΠΏΠΎΡΡΠΎΡΠ½Π½ΠΎΠΉ Π·Π°ΠΌΠ΅ΡΡΠΈΡΠ΅Π»ΡΠ½ΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ°ΠΌΠΈ ΡΠ°ΠΊΡΠΎΡΠΎΠ² ΡΠ²Π΅ΡΡΡΠ²Π°Π½ΠΈΡ ΠΊΡΠΎΠ²ΠΈ, ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΡΠΌΠΈ Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΠΈΠΈ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ
ΠΠΠ ΠΈΠ»ΠΈ ΠΈΠ· ΠΏΠ»Π°Π·ΠΌΡ ΠΊΡΠΎΠ²ΠΈ Π΄ΠΎΠ½ΠΎΡΠΎΠ². ΠΡΠΈ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠ΅ Π½ΠΎΠ²ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² ΠΈ ΡΡΠΎΠ²Π΅ΡΡΠ΅Π½ΡΡΠ²ΠΎΠ²Π°Π½ΠΈΠΈ ΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΠΈΠΈ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄ΡΡΠ²Π° ΡΠ°Π½Π΅Π΅ ΡΡΠ²Π΅ΡΠΆΠ΄Π΅Π½Π½ΡΡ
Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² ΠΏΡΠΎΠ²ΠΎΠ΄ΡΡΡΡ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ, ΡΡΠ΅Π±ΡΡΡΠΈΠ΅ Π²ΠΊΠ»ΡΡΠ΅Π½ΠΈΡ ΠΊΠ°ΠΊ ΡΠ°Π½Π΅Π΅ Π»Π΅ΡΠ΅Π½Π½ΡΡ
, ΡΠ°ΠΊ ΠΈ ΡΠ°Π½Π΅Π΅ Π½Π΅Π»Π΅ΡΠ΅Π½Π½ΡΡ
ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
Π²ΠΎΠ·ΡΠ°ΡΡΠ½ΡΡ
Π³ΡΡΠΏΠΏ. Π¦Π΅Π»Ρ ΡΠ°Π±ΠΎΡΡ β Π°Π½Π°Π»ΠΈΡΠΈΡΠ΅ΡΠΊΠΈΠΉ ΠΎΠ±Π·ΠΎΡ ΠΎΡΠ½ΠΎΠ²Π½ΡΡ
ΡΡΠ΅Π±ΠΎΠ²Π°Π½ΠΈΠΉ ΠΊ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² ΡΠ°ΠΊΡΠΎΡΠ° ΡΠ²Π΅ΡΡΡΠ²Π°Π½ΠΈΡ ΠΊΡΠΎΠ²ΠΈ IX Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ ΠΎΠ±Π½ΠΎΠ²Π»Π΅Π½Π½ΡΡ
Π΄ΠΎΠΊΡΠΌΠ΅Π½ΡΠΎΠ² ΠΠ²ΡΠΎΠΏΠ΅ΠΉΡΠΊΠΎΠ³ΠΎ Π°Π³Π΅Π½ΡΡΡΠ²Π° ΠΏΠΎ Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΠΌ ΡΡΠ΅Π΄ΡΡΠ²Π°ΠΌ. ΠΡΠΈΠ²Π΅Π΄Π΅Π½Ρ ΠΎΡΠ½ΠΎΠ²Π½ΡΠ΅ ΠΏΡΠΈΠ½ΡΠΈΠΏΡ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² ΡΠ°ΠΊΡΠΎΡΠ° IX, ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»ΡΠ΅ΠΌΡΡ
Π΄Π»Ρ ΡΠ΅Π³ΠΈΡΡΡΠ°ΡΠΈΠΈ ΠΊΠ°ΠΊ Β«Π½ΠΎΠ²ΡΠ΅Β» ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΡ, Ρ ΡΡΠ΅ΡΠΎΠΌ ΡΠ΅ΠΊΠΎΠΌΠ΅Π½Π΄Π°ΡΠΈΠΉ, ΠΏΡΠΈΠ²Π΅Π΄Π΅Π½Π½ΡΡ
Π² ΠΎΡΠ΅ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΡ
ΠΈ ΠΌΠ΅ΠΆΠ΄ΡΠ½Π°ΡΠΎΠ΄Π½ΡΡ
Π΄ΠΎΠΊΡΠΌΠ΅Π½ΡΠ°Ρ
, Π²ΠΊΠ»ΡΡΠ°Ρ ΠΎΠ±Π½ΠΎΠ²Π»Π΅Π½Π½ΡΠΉ Π΄ΠΎΠΊΡΠΌΠ΅Π½Ρ ΠΠ²ΡΠΎΠΏΠ΅ΠΉΡΠΊΠΎΠ³ΠΎ Π°Π³Π΅Π½ΡΡΡΠ²Π° ΠΏΠΎ Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΠΌ ΡΡΠ΅Π΄ΡΡΠ²Π°ΠΌ. ΠΡΡΠ°ΠΆΠ΅Π½Ρ Π²ΠΎΠΏΡΠΎΡΡ, ΡΠ²ΡΠ·Π°Π½Π½ΡΠ΅ Ρ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΡΡ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ², ΠΊΠΎΡΠΎΡΡΠ΅ ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Ρ ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΠ΅ΠΌ Β«Π½Π΅ΠΆΠ΅Π»Π°ΡΠ΅Π»ΡΠ½ΠΎΠΉΒ» ΠΈΠΌΠΌΡΠ½ΠΎΠ³Π΅Π½Π½ΠΎΡΡΠΈ, ΠΏΡΠΈΠ²ΠΎΠ΄ΡΡΠ΅ΠΉ ΠΊ ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠΎΠ², ΠΏΡΠΎΠ²ΠΎΡΠΈΡΡΡΡΠΈΡ
ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ Π°Π»Π»Π΅ΡΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠ΅Π°ΠΊΡΠΈΠΉ ΠΈΠ»ΠΈ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΠ΅ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ. ΠΠ°ΡΠΌΠΎΠ½ΠΈΠ·Π°ΡΠΈΡ ΡΡΠ΅Π±ΠΎΠ²Π°Π½ΠΈΠΉ ΠΊ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ ΠΏΡΠΈ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠ΅ ΠΈ ΠΎΠ±Π½ΠΎΠ²Π»Π΅Π½ΠΈΠΈ ΠΎΡΠ΅ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΡ
Π΄ΠΎΠΊΡΠΌΠ΅Π½ΡΠΎΠ² Π½Π° ΠΎΡΠ½ΠΎΠ²Π°Π½ΠΈΠΈ Π°Π½Π°Π»ΠΈΠ·Π° ΠΎΠΏΡΡΠ° ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΡ Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ², ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΠ΅ΠΌΡΡ
Π΄Π»Ρ Π»Π΅ΡΠ΅Π½ΠΈΡ Π³Π΅ΠΌΠΎΡΠΈΠ»ΠΈΠΈ, Π° ΡΠ°ΠΊΠΆΠ΅ Π½ΠΎΠ²ΡΠ΅ Π½Π°ΡΡΠ½ΡΠ΅ Π΄ΠΎΡΡΠΈΠΆΠ΅Π½ΠΈΡ Π² ΠΈΠ·ΡΡΠ΅Π½ΠΈΠΈ ΡΠΊΠ°Π·Π°Π½Π½ΠΎΠΉ ΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΠΈ Π±ΡΠ΄ΡΡ ΡΠΏΠΎΡΠΎΠ±ΡΡΠ²ΠΎΠ²Π°ΡΡ Π²Π½Π΅Π΄ΡΠ΅Π½ΠΈΡ Π² ΠΌΠ΅Π΄ΠΈΡΠΈΠ½ΡΠΊΡΡ ΠΏΡΠ°ΠΊΡΠΈΠΊΡ ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² Π΄Π»Ρ ΡΡΠΏΠ΅ΡΠ½ΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ Π³Π΅ΠΌΠΎΡΠΈΠ»ΠΈΠΈ
Π Π΅Π³ΠΈΡΡΡΠ°ΡΠΈΡ Π½Π΅ΠΎΡΠΈΠ³ΠΈΠ½Π°Π»ΡΠ½ΡΡ Π±ΠΈΠΎΡΠ΅ΡΠ°ΠΏΠ΅Π²ΡΠΈΡΠ΅ΡΠΊΠΈΡ (Π±ΠΈΠΎΠΏΠΎΠ΄ΠΎΠ±Π½ΡΡ ) ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² Π² Π‘Π¨Π
European competent authorities began to elaborate scientific principles of development of non-innovator biotherapeutic (biosimilar) products in the early noughties, and in 2009 these principles were approved at the WHO International Conference in Seoul gathering participants from countries with a well-developed pharmaceutical industry. The USA adopted the law on biosimilar products in 2012, it was based on the documents and recommendations prepared by the EMA and approved by the WHO. In 2015, the FDA published the new revised versions of the guidelines dealing with biosimilar products. The US regulatory requirements for development and authorisation of biosimilar products are based on a step-by-step comparative assessment of biosimilar and innovator products in terms of their quality, efficacy, and safety in accordance with the WHO/EMA recommendations. At the same time the US regulatory requirements differ from those of other national authorities, including EMA (WHO), when it comes to the design of comparative quality studies (studies of productsβ physicochemical and biological properties), the assignment of International Non-Proprietary Names and the interchangeability of biosimilar products.ΠΠΎΠ΄Π³ΠΎΡΠΎΠ²ΠΊΠ° Π½Π°ΡΡΠ½ΡΡ
ΠΏΡΠΈΠ½ΡΠΈΠΏΠΎΠ² ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠΈ Π½Π΅ΠΎΡΠΈΠ³ΠΈΠ½Π°Π»ΡΠ½ΡΡ
Π±ΠΈΠΎΡΠ΅ΡΠ°ΠΏΠ΅Π²ΡΠΈΡΠ΅ΡΠΊΠΈΡ
(Π±ΠΈΠΎΠΏΠΎΠ΄ΠΎΠ±Π½ΡΡ
, Π±ΠΈΠΎΠ°Π½Π°Π»ΠΎΠ³ΠΎΠ²ΡΡ
) ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² Π±ΡΠ»Π° Π½Π°ΡΠ°ΡΠ° Π² ΠΠ²ΡΠΎΠΏΠ΅ Π² Π½Π°ΡΠ°Π»Π΅ 2000-Ρ
Π³Π³., Π² 2009 Π³. ΠΎΠ½ΠΈ Π±ΡΠ»ΠΈ ΡΡΠ²Π΅ΡΠΆΠ΄Π΅Π½Ρ Π½Π° ΠΌΠ΅ΠΆΠ΄ΡΠ½Π°ΡΠΎΠ΄Π½ΠΎΠΉ ΠΊΠΎΠ½ΡΠ΅ΡΠ΅Π½ΡΠΈΠΈ ΠΠΠ Π² Π‘Π΅ΡΠ»Π΅ Ρ ΡΡΠ°ΡΡΠΈΠ΅ΠΌ ΡΡΡΠ°Π½ Ρ ΡΠ°Π·Π²ΠΈΡΠΎΠΉ ΡΠ°ΡΠΌΠΈΠ½Π΄ΡΡΡΡΠΈΠ΅ΠΉ. Π Π‘Π¨Π Π·Π°ΠΊΠΎΠ½ ΠΎ Π±ΠΈΠΎΠΏΠΎΠ΄ΠΎΠ±Π½ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ°Ρ
ΠΏΡΠΈΠ½ΡΡ Π² 2012 Π³., Π·Π° ΠΎΡΠ½ΠΎΠ²Ρ Π±ΡΠ»ΠΈ Π²Π·ΡΡΡ Π΄ΠΎΠΊΡΠΌΠ΅Π½ΡΡ ΠΈ ΡΠ΅ΠΊΠΎΠΌΠ΅Π½Π΄Π°ΡΠΈΠΈ, ΠΏΠΎΠ΄Π³ΠΎΡΠΎΠ²Π»Π΅Π½Π½ΡΠ΅ ΠΠΠ ΠΈ ΠΎΠ΄ΠΎΠ±ΡΠ΅Π½Π½ΡΠ΅ ΠΠΠ. Π 2015 Π³. FDA ΠΎΠΏΡΠ±Π»ΠΈΠΊΠΎΠ²Π°Π»ΠΎ ΠΎΡΠ΅ΡΠ΅Π΄Π½ΡΡ ΡΠ΅Π΄Π°ΠΊΡΠΈΡ ΠΎΡΠ½ΠΎΠ²Π½ΡΡ
Π΄ΠΎΠΊΡΠΌΠ΅Π½ΡΠΎΠ², ΠΊΠ°ΡΠ°ΡΡΠΈΡ
ΡΡ Π±ΠΈΠΎΠΏΠΎΠ΄ΠΎΠ±Π½ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ². Π ΠΎΡΠ½ΠΎΠ²Π΅ Π½ΠΎΡΠΌΠ°ΡΠΈΠ²Π½ΡΡ
ΡΡΠ΅Π±ΠΎΠ²Π°Π½ΠΈΠΉ Π‘Π¨Π ΠΏΠΎ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠ΅ ΠΈ ΡΠ΅Π³ΠΈΡΡΡΠ°ΡΠΈΠΈ Π±ΠΈΠΎΠΏΠΎΠ΄ΠΎΠ±Π½ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² Π»Π΅ΠΆΠΈΡ ΠΏΠΎΡΠ°Π³ΠΎΠ²Π°Ρ ΡΡΠ°Π²Π½ΠΈΡΠ΅Π»ΡΠ½Π°Ρ ΠΎΡΠ΅Π½ΠΊΠ° Π±ΠΈΠΎΠΏΠΎΠ΄ΠΎΠ±Π½ΠΎΠ³ΠΎ ΠΈ ΠΎΡΠΈΠ³ΠΈΠ½Π°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² ΠΏΠΎ Π°ΡΡΠΈΠ±ΡΡΠ°ΠΌ ΠΊΠ°ΡΠ΅ΡΡΠ²Π°, ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΈ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΠΈ Π² ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²ΠΈΠΈ Ρ ΡΠ΅ΠΊΠΎΠΌΠ΅Π½Π΄Π°ΡΠΈΡΠΌΠΈ ΠΠΠ/ΠΠΠ. ΠΡΠΈ ΡΡΠΎΠΌ ΠΏΠΎ ΡΠ°ΠΊΠΈΠΌ Π²ΠΎΠΏΡΠΎΡΠ°ΠΌ, ΠΊΠ°ΠΊ Π΄ΠΈΠ·Π°ΠΉΠ½ ΡΡΠ°Π²Π½ΠΈΡΠ΅Π»ΡΠ½ΡΡ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ ΠΊΠ°ΡΠ΅ΡΡΠ²Π° (ΡΠΈΠ·ΠΈΠΊΠΎ-Ρ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠ²ΠΎΠΉΡΡΠ²), ΠΏΡΠΈΡΠ²ΠΎΠ΅Π½ΠΈΠ΅ ΠΠ΅ΠΆΠ΄ΡΠ½Π°ΡΠΎΠ΄Π½ΠΎΠ³ΠΎ Π½Π΅ΠΏΠ°ΡΠ΅Π½ΡΠΎΠ²Π°Π½Π½ΠΎΠ³ΠΎ Π½Π°ΠΈΠΌΠ΅Π½ΠΎΠ²Π°Π½ΠΈΡ ΠΈ Π²Π·Π°ΠΈΠΌΠΎΠ·Π°ΠΌΠ΅Π½ΡΠ΅ΠΌΠΎΡΡΡ Π±ΠΈΠΎΠΏΠΎΠ΄ΠΎΠ±Π½ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ², Π½ΠΎΡΠΌΠ°ΡΠΈΠ²Π½ΡΠ΅ ΡΡΠ΅Π±ΠΎΠ²Π°Π½ΠΈΡ Π‘Π¨Π ΠΎΡΠ»ΠΈΡΠ°ΡΡΡΡ ΠΎΡ Π½Π°ΡΠΈΠΎΠ½Π°Π»ΡΠ½ΡΡ
ΡΠ΅ΠΊΠΎΠΌΠ΅Π½Π΄Π°ΡΠΈΠΉ Π΄ΡΡΠ³ΠΈΡ
ΡΡΡΠ°Π½, Π² ΡΠΎΠΌ ΡΠΈΡΠ»Π΅ ΠΠΠ (ΠΠΠ)
Π‘ΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΡΠ΅ Π½ΠΎΡΠΌΠ°ΡΠΈΠ²Π½ΡΠ΅ ΡΡΠ΅Π±ΠΎΠ²Π°Π½ΠΈΡ ΠΊΒ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ Π΄ΠΎΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ ΠΏΡΠΎΡΠΈΠ»Π°ΠΊΡΠΈΡΠ΅ΡΠΊΠΈΡ Π²Π°ΠΊΡΠΈΠ½
Vaccines are subject to specific regulatory requirements for the evaluation of their quality, safety, and efficacy. In 2005, the World Health Organisation (WHO), as the main international organisation coordinating measures to combat infectious disease outbreaks, began developing documents on the evaluation of vaccine quality, safety, and efficacy. The worldβs leading regulatory authorities (FDA, EMA, etc.) have also issued recommendations for conducting non-clinical studies of vaccines.The aim of this study was a critical review of the regulatory requirements established by foreign national and international regulatory authorities for non-clinical evaluation of the safety and efficacy of vaccines.According to the study results, since the 2000s, the WHO and the worldβs leading regulatory authorities have produced more than 40 regulatory documents describing certain aspects of non-clinical studies of the safety and efficacy of vaccines. These documents can be divided into two groups: the first group addresses non-clinical studies of vaccines in general, and the second one dwells upon the evaluation of the quality, safety, and efficacy of specific types of vaccines. For the Russian guidelines on non-clinical evaluation of the quality, safety, and efficacy of immunobiologicals, the latest revision dates back to 2013 and does not provide any information on new medicinal products. Currently, work is underway to prepare the regulatory framework for medicines, including vaccines, in the Member States of the Eurasian Economic Union (EAEU). This review of regulatory documents on non-clinical safety and efficacy studies of vaccines may be useful in drafting harmonised guidelines for the relevant groups of vaccines in the EAEU. It may also be of use to developers, manufacturers, and researchers involved in the creation and non-clinical study of vaccines.Π Π²Π°ΠΊΡΠΈΠ½Π°ΠΌ ΠΏΡΠ΅Π΄ΡΡΠ²Π»ΡΡΡΡΡ ΠΎΡΠΎΠ±ΡΠ΅ Π½ΠΎΡΠΌΠ°ΡΠΈΠ²Π½ΡΠ΅ ΡΡΠ΅Π±ΠΎΠ²Π°Π½ΠΈΡ Π΄Π»Ρ ΠΎΡΠ΅Π½ΠΊΠΈ ΠΈΡ
ΠΊΠ°ΡΠ΅ΡΡΠ²Π°, ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΈ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΠΈ. Π£ΡΠΈΡΡΠ²Π°Ρ, ΡΡΠΎ ΠΡΠ΅ΠΌΠΈΡΠ½Π°Ρ ΠΎΡΠ³Π°Π½ΠΈΠ·Π°ΡΠΈΡ Π·Π΄ΡΠ°Π²ΠΎΠΎΡ
ΡΠ°Π½Π΅Π½ΠΈΡ (ΠΠΠ) ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΎΡΠ½ΠΎΠ²Π½ΠΎΠΉ ΠΌΠ΅ΠΆΠ΄ΡΠ½Π°ΡΠΎΠ΄Π½ΠΎΠΉ ΠΎΡΠ³Π°Π½ΠΈΠ·Π°ΡΠΈΠ΅ΠΉ, ΠΊΠΎΠΎΡΠ΄ΠΈΠ½ΠΈΡΡΡΡΠ΅ΠΉ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠ΅ ΠΌΠ΅ΡΠΎΠΏΡΠΈΡΡΠΈΠΉ ΠΏΠΎ Π±ΠΎΡΡΠ±Π΅ Ρ Π²ΡΠΏΡΡΠΊΠ°ΠΌΠΈ ΠΈΠ½ΡΠ΅ΠΊΡΠΈΠΎΠ½Π½ΡΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ, Π½Π°ΡΠΈΠ½Π°Ρ Ρ 2005 Π³. ΠΠΠ Π½Π°ΡΠ°Π»Π° ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΡ Π΄ΠΎΠΊΡΠΌΠ΅Π½ΡΠΎΠ², ΠΊΠ°ΡΠ°ΡΡΠΈΡ
ΡΡ Π²ΠΎΠΏΡΠΎΡΠΎΠ² ΠΎΡΠ΅Π½ΠΊΠΈ ΠΊΠ°ΡΠ΅ΡΡΠ²Π°, Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΠΈ ΠΈ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π²Π°ΠΊΡΠΈΠ½. ΠΠ΅Π΄ΡΡΠΈΠΌΠΈ ΠΌΠΈΡΠΎΠ²ΡΠΌΠΈ ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΠ½ΡΠΌΠΈ ΠΎΡΠ³Π°Π½Π°ΠΌΠΈ (FDA, ΠΠΠ ΠΈ Π΄Ρ.) ΠΏΠΎΠ΄Π³ΠΎΡΠΎΠ²Π»Π΅Π½Ρ ΡΠ΅ΠΊΠΎΠΌΠ΅Π½Π΄Π°ΡΠΈΠΈ Π΄Π»Ρ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ Π΄ΠΎΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ Π²Π°ΠΊΡΠΈΠ½.Π¦Π΅Π»Ρ ΡΠ°Π±ΠΎΡΡ β ΠΊΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈΠΉ Π°Π½Π°Π»ΠΈΠ· Π½ΠΎΡΠΌΠ°ΡΠΈΠ²Π½ΡΡ
ΡΡΠ΅Π±ΠΎΠ²Π°Π½ΠΈΠΉ Π΄Π»Ρ Π΄ΠΎΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΎΡΠ΅Π½ΠΊΠΈ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΈ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΠΈ Π²Π°ΠΊΡΠΈΠ½, ΠΏΠΎΠ΄Π³ΠΎΡΠΎΠ²Π»Π΅Π½Π½ΡΡ
Π·Π°ΡΡΠ±Π΅ΠΆΠ½ΡΠΌΠΈ Π½Π°ΡΠΈΠΎΠ½Π°Π»ΡΠ½ΡΠΌΠΈ ΠΈ ΠΌΠ΅ΠΆΠ΄ΡΠ½Π°ΡΠΎΠ΄Π½ΡΠΌΠΈ ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΠ½ΡΠΌΠΈ ΠΎΡΠ³Π°Π½Π°ΠΌΠΈ.ΠΡΠΎΠ²Π΅Π΄Π΅Π½Π½ΡΠΉ Π°Π½Π°Π»ΠΈΠ· ΠΏΠΎΠΊΠ°Π·Π°Π», ΡΡΠΎ Π½Π°ΡΠΈΠ½Π°Ρ Ρ 2000-Ρ
Π³Π³. ΠΠΠ ΠΈ Π²Π΅Π΄ΡΡΠΈΠΌΠΈ ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΠ½ΡΠΌΠΈ ΠΎΡΠ³Π°Π½Π°ΠΌΠΈ ΠΌΠΈΡΠ° Π±ΡΠ»ΠΎ ΠΏΠΎΠ΄Π³ΠΎΡΠΎΠ²Π»Π΅Π½ΠΎ Π±ΠΎΠ»Π΅Π΅ 40 Π½ΠΎΡΠΌΠ°ΡΠΈΠ²Π½ΡΡ
Π΄ΠΎΠΊΡΠΌΠ΅Π½ΡΠΎΠ², Π² ΠΊΠΎΡΠΎΡΡΡ
ΠΎΠΏΠΈΡΠ°Π½Ρ ΡΠ΅ ΠΈΠ»ΠΈ ΠΈΠ½ΡΠ΅ ΡΡΠΎΡΠΎΠ½Ρ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ Π΄ΠΎΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΈ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΠΈ Π²Π°ΠΊΡΠΈΠ½. ΠΠΎΠΊΡΠΌΠ΅Π½ΡΡ ΠΌΠΎΠΆΠ½ΠΎ ΡΠ°Π·Π΄Π΅Π»ΠΈΡΡ Π½Π° Π΄Π²Π΅ Π³ΡΡΠΏΠΏΡ: Π΄ΠΎΠΊΡΠΌΠ΅Π½ΡΡ, ΠΏΠΎΡΠ²ΡΡΠ΅Π½Π½ΡΠ΅ ΠΎΠ±ΡΠΈΠΌ Π²ΠΎΠΏΡΠΎΡΠ°ΠΌ Π΄ΠΎΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ Π²Π°ΠΊΡΠΈΠ½, ΠΈ Π΄ΠΎΠΊΡΠΌΠ΅Π½ΡΡ, ΠΊΠ°ΡΠ°ΡΡΠΈΠ΅ΡΡ ΠΎΡΠ΅Π½ΠΊΠΈ ΠΊΠ°ΡΠ΅ΡΡΠ²Π°, ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΈ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΠΈ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½Π½ΡΡ
Π²ΠΈΠ΄ΠΎΠ² Π²Π°ΠΊΡΠΈΠ½. Π Π ΠΎΡΡΠΈΠΉΡΠΊΠΎΠΉ Π€Π΅Π΄Π΅ΡΠ°ΡΠΈΠΈ ΠΏΠΎΡΠ»Π΅Π΄Π½ΡΡ ΡΠ΅Π΄Π°ΠΊΡΠΈΡ ΡΠ΅ΠΊΠΎΠΌΠ΅Π½Π΄Π°ΡΠΈΠΉ Π΄Π»Ρ Π΄ΠΎΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΎΡΠ΅Π½ΠΊΠΈ ΠΊΠ°ΡΠ΅ΡΡΠ²Π°, Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΠΈ ΠΈ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΈΠΌΠΌΡΠ½ΠΎΠ±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² Π±ΡΠ»Π° ΠΎΠΏΡΠ±Π»ΠΈΠΊΠΎΠ²Π°Π½Π° Π² 2013Β Π³. ΠΈ Π½Π΅ ΡΠΎΠ΄Π΅ΡΠΆΠΈΡ ΠΈΠ½ΡΠΎΡΠΌΠ°ΡΠΈΠΈ ΠΎΡΠ½ΠΎΡΠΈΡΠ΅Π»ΡΠ½ΠΎ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² ΠΏΠΎΡΠ»Π΅Π΄Π½Π΅Π³ΠΎ ΠΏΠΎΠΊΠΎΠ»Π΅Π½ΠΈΡ. Π Π½Π°ΡΡΠΎΡΡΠ΅Π΅ Π²ΡΠ΅ΠΌΡ ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΡΡΡ ΡΠ°Π±ΠΎΡΠ° ΠΏΠΎ ΠΏΠΎΠ΄Π³ΠΎΡΠΎΠ²ΠΊΠ΅ Π½ΠΎΡΠΌΠ°ΡΠΈΠ²Π½ΠΎ-ΠΏΡΠ°Π²ΠΎΠ²ΠΎΠΉ Π±Π°Π·Ρ, ΠΊΠ°ΡΠ°ΡΡΠ΅ΠΉΡΡ Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΡ
ΡΡΠ΅Π΄ΡΡΠ², Π² ΡΠΎΠΌ ΡΠΈΡΠ»Π΅ Π²Π°ΠΊΡΠΈΠ½, Π½Π° ΡΠ΅ΡΡΠΈΡΠΎΡΠΈΠΈ Π³ΠΎΡΡΠ΄Π°ΡΡΡΠ²Β β ΡΠ»Π΅Π½ΠΎΠ² ΠΠ²ΡΠ°Π·ΠΈΠΉΡΠΊΠΎΠ³ΠΎ ΡΠΊΠΎΠ½ΠΎΠΌΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠΎΡΠ·Π° (ΠΠΠΠ‘). ΠΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Π½ΡΠΉ Π² ΡΡΠ°ΡΡΠ΅ Π°Π½Π°Π»ΠΈΠ· Π½ΠΎΡΠΌΠ°ΡΠΈΠ²Π½ΡΡ
Π΄ΠΎΠΊΡΠΌΠ΅Π½ΡΠΎΠ² ΠΏΠΎ Π΄ΠΎΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠΌ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡΠΌ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΈ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΠΈ Π²Π°ΠΊΡΠΈΠ½ ΠΌΠΎΠΆΠ΅Ρ Π±ΡΡΡ ΠΏΠΎΠ»Π΅Π·Π΅Π½ Π΄Π»Ρ ΠΏΠΎΠ΄Π³ΠΎΡΠΎΠ²ΠΊΠΈ Π³Π°ΡΠΌΠΎΠ½ΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΡΠ΅ΠΊΠΎΠΌΠ΅Π½Π΄Π°ΡΠΈΠΉ ΠΏΠΎ ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²ΡΡΡΠΈΠΌ Π³ΡΡΠΏΠΏΠ°ΠΌ Π²Π°ΠΊΡΠΈΠ½ Π² ΡΠ°ΠΌΠΊΠ°Ρ
ΠΠΠΠ‘, Π° ΡΠ°ΠΊΠΆΠ΅ ΡΠ°Π·ΡΠ°Π±ΠΎΡΡΠΈΠΊΠ°ΠΌ, ΡΠ°ΡΠΌΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄ΠΈΡΠ΅Π»ΡΠΌ ΠΈ ΡΡΠ΅Π½ΡΠΌ-ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠΌ, Π·Π°Π½ΠΈΠΌΠ°ΡΡΠΈΠΌΡΡ ΡΠΎΠ·Π΄Π°Π½ΠΈΠ΅ΠΌ ΠΈ Π΄ΠΎΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡΠΌΠΈ Π²Π°ΠΊΡΠΈΠ½
ΠΠ±ΡΠ°Ρ Ρ Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠ° Π°Π΄ΡΡΠ²Π°Π½ΡΠΎΠ² ΠΈ ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌ ΠΈΡ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ (ΡΠ°ΡΡΡ 1)
One of priority issues of the present-day healthcare system is development of new vaccines and improvement of existing ones due to decreasing immunocompetence of the population, emergence of new infections and reemergence of old ones which were previously thought to be under control. Adjuvants have proven to be integral and important components of modern vaccines, as they enhance immune response to the vaccine antigen. However, despite a lot of effort put into their development, only a small number of adjuvants are currently used in clinical practice. The aim of the study was to systematise literature data on the adjuvantsβ mechanisms of action, their specific structure, composition, and stimulation effects that mediate their immunoadjuvant properties. The paper summarises data on adjuvants used as components in licensed vaccines, describes their characteristics, analyses molecular mechanisms of their action in order to establish correlation between their structure and activity, which is important for the development of more efficacious and safe adjuvants. The paper cites advanced developments aimed at enhancing stimulation effects of existing adjuvants. It concludes by stating that the key research area aimed at improving vaccination efficacy is the study of mechanisms that contribute to the development of effective protection against infectious agents, as well as analysis of how to use adjuvants to stimulate the bodyβs defensive mechanisms, primarily by impacting the innate immunity.ΠΠΊΡΡΠ°Π»ΡΠ½ΠΎΠΉ ΠΏΡΠΎΠ±Π»Π΅ΠΌΠΎΠΉ ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΠΎΠ³ΠΎ Π·Π΄ΡΠ°Π²ΠΎΠΎΡ
ΡΠ°Π½Π΅Π½ΠΈΡ ΡΠ²Π»ΡΠ΅ΡΡΡ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠ° Π½ΠΎΠ²ΡΡ
Π²Π°ΠΊΡΠΈΠ½ ΠΈ ΡΠΎΠ²Π΅ΡΡΠ΅Π½ΡΡΠ²ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠΆΠ΅ ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΠ΅ΠΌΡΡ
Π² ΠΌΠ΅Π΄ΠΈΡΠΈΠ½ΡΠΊΠΎΠΉ ΠΏΡΠ°ΠΊΡΠΈΠΊΠ΅, ΡΡΠΎ ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½ΠΎ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΠ΅ΠΌ ΠΈΠΌΠΌΡΠ½ΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π½Π°ΡΠ΅Π»Π΅Π½ΠΈΡ, ΠΏΠΎΡΠ²Π»Π΅Π½ΠΈΠ΅ΠΌ Π½ΠΎΠ²ΡΡ
ΠΈΠ½ΡΠ΅ΠΊΡΠΈΠΉ ΠΈΠ»ΠΈ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΠ΅ΠΉ Β«ΡΡΠ°ΡΡΡ
Β», ΠΊΠΎΡΠΎΡΡΠ΅ ΡΠ°Π½Π΅Π΅ ΡΡΠΈΡΠ°Π»ΠΈΡΡ ΠΏΠΎΠ±Π΅ΠΆΠ΄Π΅Π½Π½ΡΠΌΠΈ. ΠΠ΅ΠΎΡΡΠ΅ΠΌΠ»Π΅ΠΌΠΎΠΉ ΠΈ Π²Π°ΠΆΠ½ΠΎΠΉ ΡΠ°ΡΡΡΡ ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΡΡ
Π²Π°ΠΊΡΠΈΠ½ ΡΠ²Π»ΡΡΡΡΡ Π°Π΄ΡΡΠ²Π°Π½ΡΡ, ΠΊΠΎΡΠΎΡΡΠ΅ ΡΡΠΈΠΌΡΠ»ΠΈΡΡΡΡ ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ ΠΈΠΌΠΌΡΠ½Π½ΠΎΠ³ΠΎ ΠΎΡΠ²Π΅ΡΠ° Π½Π° Π°Π½ΡΠΈΠ³Π΅Π½ Π²Π°ΠΊΡΠΈΠ½Ρ. ΠΠ΄Π½Π°ΠΊΠΎ, Π½Π΅ΡΠΌΠΎΡΡΡ Π½Π° ΠΌΠ½ΠΎΠ³ΠΎΡΠΈΡΠ»Π΅Π½Π½ΡΠ΅ ΡΡΠΈΠ»ΠΈΡ ΠΏΠΎ ΠΈΡ
ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠ΅, Π² Π½Π°ΡΡΠΎΡΡΠ΅Π΅ Π²ΡΠ΅ΠΌΡ Π² ΠΌΠ΅Π΄ΠΈΡΠΈΠ½ΡΠΊΠΎΠΉ ΠΏΡΠ°ΠΊΡΠΈΠΊΠ΅ ΠΏΡΠΈΠΌΠ΅Π½ΡΠ΅ΡΡΡ Π»ΠΈΡΡ Π½Π΅Π±ΠΎΠ»ΡΡΠΎΠ΅ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²ΠΎ Π°Π΄ΡΡΠ²Π°Π½ΡΠΎΠ². Π¦Π΅Π»Ρ ΡΠ°Π±ΠΎΡΡ β ΡΠΈΡΡΠ΅ΠΌΠ°ΡΠΈΠ·Π°ΡΠΈΡ Π΄Π°Π½Π½ΡΡ
Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΡ ΠΏΠΎ Π°Π½Π°Π»ΠΈΠ·Ρ ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠΎΠ² Π΄Π΅ΠΉΡΡΠ²ΠΈΡ Π°Π΄ΡΡΠ²Π°Π½ΡΠΎΠ², ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠ΅ΠΉ ΠΈΡ
ΡΡΡΡΠΊΡΡΡΡ, ΡΠΎΡΡΠ°Π²Π° ΠΈ ΡΡΠΈΠΌΡΠ»ΠΈΡΡΡΡΠΈΡ
ΡΡΡΠ΅ΠΊΡΠΎΠ², ΠΊΠΎΡΠΎΡΡΠ΅ ΠΎΠΏΠΎΡΡΠ΅Π΄ΡΡΡ ΠΈΡ
ΠΈΠΌΠΌΡΠ½ΠΎΠ°Π΄ΡΡΠ²Π°Π½ΡΠ½ΡΠ΅ ΡΠ²ΠΎΠΉΡΡΠ²Π°. ΠΠ±ΠΎΠ±ΡΠ΅Π½Ρ ΡΠ²Π΅Π΄Π΅Π½ΠΈΡ ΠΎΠ± Π°Π΄ΡΡΠ²Π°Π½ΡΠ°Ρ
, Π²Ρ
ΠΎΠ΄ΡΡΠΈΡ
Π² ΡΠΎΡΡΠ°Π² Π·Π°ΡΠ΅Π³ΠΈΡΡΡΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
Π²Π°ΠΊΡΠΈΠ½, ΠΏΡΠΈΠ²Π΅Π΄Π΅Π½Π° ΠΈΡ
Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠ°, ΠΏΡΠΎΠ°Π½Π°Π»ΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Ρ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΠ΅ ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΡ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ Π°Π΄ΡΡΠ²Π°Π½ΡΠΎΠ² Ρ ΡΠ΅Π»ΡΡ ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΈΡ Π²Π·Π°ΠΈΠΌΠΎΡΠ²ΡΠ·ΠΈ ΠΈΡ
ΡΡΡΡΠΊΡΡΡΡ ΠΈ ΠΏΡΠΎΡΠ²Π»ΡΠ΅ΠΌΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ, ΡΡΠΎ ΡΠ²Π»ΡΠ΅ΡΡΡ Π²Π°ΠΆΠ½ΡΠΌ Π΄Π»Ρ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠΈ Π±ΠΎΠ»Π΅Π΅ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΡΡ
ΠΈ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΡΡ
Π°Π΄ΡΡΠ²Π°Π½ΡΠΎΠ². ΠΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Ρ ΡΠ²Π΅Π΄Π΅Π½ΠΈΡ ΠΎ ΠΏΠ΅ΡΡΠΏΠ΅ΠΊΡΠΈΠ²Π½ΡΡ
ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠ°Ρ
ΠΏΠΎ ΡΠΎΠ²Π΅ΡΡΠ΅Π½ΡΡΠ²ΠΎΠ²Π°Π½ΠΈΡ ΡΠΆΠ΅ ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΠ΅ΠΌΡΡ
Π°Π΄ΡΡΠ²Π°Π½ΡΠΎΠ² Ρ ΡΠ΅Π»ΡΡ ΡΡΠΈΠ»Π΅Π½ΠΈΡ ΠΈΡ
ΡΡΠΈΠΌΡΠ»ΠΈΡΡΡΡΠ΅Π³ΠΎ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ. Π‘Π΄Π΅Π»Π°Π½ Π²ΡΠ²ΠΎΠ΄ ΠΎ ΡΠΎΠΌ, ΡΡΠΎ ΠΊΠ»ΡΡΠ΅Π²ΡΠΌ Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½ΠΈΠ΅ΠΌ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ Π² ΠΎΠ±Π»Π°ΡΡΠΈ ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π²Π°ΠΊΡΠΈΠ½Π°ΡΠΈΠΈ ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΈΠ·ΡΡΠ΅Π½ΠΈΠ΅ ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠΎΠ², ΡΠΏΠΎΡΠΎΠ±ΡΡΠ²ΡΡΡΠΈΡ
ΡΠ°Π·Π²ΠΈΡΠΈΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΠΉ Π·Π°ΡΠΈΡΡ ΠΎΡ Π²ΠΎΠ·Π±ΡΠ΄ΠΈΡΠ΅Π»Π΅ΠΉ ΠΈΠ½ΡΠ΅ΠΊΡΠΈΠΈ, Π° ΡΠ°ΠΊΠΆΠ΅ ΡΠΏΠΎΡΠΎΠ±ΠΎΠ² ΡΡΠΈΠΌΡΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π·Π°ΡΠΈΡΠ½ΡΡ
ΡΠ΅Π°ΠΊΡΠΈΠΉ ΠΎΡΠ³Π°Π½ΠΈΠ·ΠΌΠ° Ρ ΠΏΠΎΠΌΠΎΡΡΡ Π°Π΄ΡΡΠ²Π°Π½ΡΠΎΠ², Π² ΠΏΠ΅ΡΠ²ΡΡ ΠΎΡΠ΅ΡΠ΅Π΄Ρ ΠΏΡΡΠ΅ΠΌ Π²ΠΎΠ·Π΄Π΅ΠΉΡΡΠ²ΠΈΡ Π½Π° ΡΠΈΡΡΠ΅ΠΌΡ Π²ΡΠΎΠΆΠ΄Π΅Π½Π½ΠΎΠ³ΠΎ ΠΈΠΌΠΌΡΠ½ΠΈΡΠ΅ΡΠ°
ΠΡΡΠ°Π½Π½ΡΠ΅ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΡ, ΠΏΡΠΈΠ½ΡΠΈΠΏΡ ΠΈΡ ΡΠ΅Π³ΠΈΡΡΡΠ°ΡΠΈΠΈ ΠΈ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΡ
One of the most complicated issues of modern medicine is diagnosis, treatment and prevention of rare diseases. In the structure of rare diseases the vast majority accounts for genetically determined disorders. The introduction of genetic testing methods helped to identify a lot of hereditary diseases, that currently reach the number of 8,000 cases and according to estimations the frequency of their detection is about to increase. Medicinal products for diagnosis or treatment of rare diseases form the group of orphan drugs. Biologicals are the most effective medicinal products in the whole group, due to their ability to bind specifically with the Β«target receptorΒ», which allows to use them as targeted drugs. Another advantage of biologicals, compared with preparations of chemical origin, is their low toxicity. Orphan drug provision is the most severe issue because the treatment of severe forms of rare diseases may require the prescription of an expensive drug. Manufacturing of orphan drugs may be unprofitable for the reason of the low prevalence of rare diseases. Therefore, the availability of orphan drugs for patients depends on the amount of state participation in manufacture stimulation. In various countries regulatory requirements for the recognition of a disease as a rare disease, and marketing authorization procedures for orphan drugs are developed with due regard to the social and economic characteristics of the country. The article presents the analysis of the regulatory requirements for various countries for the detection of rare diseases, and a common approach to marketing authorization procedure for the drugs used in treatment of rare diseases, exemplified by biological orphan preparations.ΠΠ΄Π½ΠΎΠΉ ΠΈΠ· Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ ΡΠ»ΠΎΠΆΠ½ΡΡ
ΠΏΡΠΎΠ±Π»Π΅ΠΌ ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΠΎΠΉ ΠΌΠ΅Π΄ΠΈΡΠΈΠ½Ρ ΡΠ²Π»ΡΠ΅ΡΡΡ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠ°, Π»Π΅ΡΠ΅Π½ΠΈΠ΅ ΠΈ ΠΏΡΠΎΡΠΈΠ»Π°ΠΊΡΠΈΠΊΠ° ΡΠ΅Π΄ΠΊΠΈΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ. Π ΡΡΡΡΠΊΡΡΡΠ΅ ΡΠ΅Π΄ΠΊΠΈΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ ΠΏΡΠ΅ΠΎΠ±Π»Π°Π΄Π°ΡΡΠ΅Π΅ ΠΌΠ΅ΡΡΠΎ Π·Π°Π½ΠΈΠΌΠ°ΡΡ Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈ ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Π½ΡΠ΅ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ. ΠΠ½Π΅Π΄ΡΠ΅Π½ΠΈΠ΅ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠ΅ΡΡΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΠΏΠΎΡΠΎΠ±ΡΡΠ²ΠΎΠ²Π°Π»ΠΎ Π²ΡΡΠ²Π»Π΅Π½ΠΈΡ Π±ΠΎΠ»ΡΡΠΎΠ³ΠΎ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π° Π½Π°ΡΠ»Π΅Π΄ΡΡΠ²Π΅Π½Π½ΡΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ, ΡΠΈΡΠ»Π΅Π½Π½ΠΎΡΡΡ ΠΊΠΎΡΠΎΡΡΡ
Π² Π½Π°ΡΡΠΎΡΡΠ΅Π΅ Π²ΡΠ΅ΠΌΡ Π΄ΠΎΡΡΠΈΠ³Π°Π΅Ρ 8000 ΠΈ ΠΏΡΠΎΠ³Π½ΠΎΠ·ΠΈΡΡΠ΅ΡΡΡ ΡΠ²Π΅Π»ΠΈΡΠ΅Π½ΠΈΠ΅ ΡΠ°ΡΡΠΎΡΡ ΠΈΡ
Π²ΡΡΠ²Π»Π΅Π½ΠΈΡ. ΠΠ΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΠ΅ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΡ, ΠΏΡΠ΅Π΄Π½Π°Π·Π½Π°ΡΠ΅Π½Π½ΡΠ΅ Π΄Π»Ρ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ ΠΈΠ»ΠΈ ΠΏΠ°ΡΠΎΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π»Π΅ΡΠ΅Π½ΠΈΡ ΡΠ΅Π΄ΠΊΠΈΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ, ΠΎΡΠ½ΠΎΡΡΡ ΠΊ Π³ΡΡΠΏΠΏΠ΅ ΠΎΡΡΠ°Π½Π½ΡΡ
. ΠΠ°ΠΈΠ±ΠΎΠ»Π΅Π΅ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΡΠΌΠΈ ΠΈΠ· ΡΡΠΎΠΉ Π³ΡΡΠΏΠΏΡ ΡΠ²Π»ΡΡΡΡΡ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΡ. ΠΡΠΎ ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½ΠΎ ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΡΡ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈ ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΡΡ Ρ Β«ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠΌ-ΠΌΠΈΡΠ΅Π½ΡΡΒ», ΡΡΠΎ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΠ΅Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°ΡΡ ΠΈΡ
Π² ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½Π½ΠΎΠ³ΠΎ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ. ΠΡΠ΅ ΠΎΠ΄Π½ΠΈΠΌ ΠΏΡΠ΅ΠΈΠΌΡΡΠ΅ΡΡΠ²ΠΎΠΌ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ², ΠΏΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Ρ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ°ΠΌΠΈ Ρ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΏΡΠΎΠΈΡΡ
ΠΎΠΆΠ΄Π΅Π½ΠΈΡ, ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΈΡ
Π½ΠΈΠ·ΠΊΠ°Ρ ΡΠΎΠΊΡΠΈΡΠ½ΠΎΡΡΡ. ΠΠ΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΠΎΠ΅ ΠΎΠ±Π΅ΡΠΏΠ΅ΡΠ΅Π½ΠΈΠ΅ ΠΎΡΡΠ°Π½Π½ΡΠΌΠΈ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ°ΠΌΠΈ ΡΠ²Π»ΡΠ΅ΡΡΡ Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ ΠΎΡΡΡΠΎΠΉ ΠΏΡΠΎΠ±Π»Π΅ΠΌΠΎΠΉ, ΠΏΠΎΡΠΊΠΎΠ»ΡΠΊΡ Π΄Π»Ρ Π»Π΅ΡΠ΅Π½ΠΈΡ ΡΡΠΆΠ΅Π»ΡΡ
ΡΠΎΡΠΌ ΡΠ΅Π΄ΠΊΠΈΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ ΠΌΠΎΠΆΠ΅Ρ ΠΏΠΎΡΡΠ΅Π±ΠΎΠ²Π°ΡΡΡΡ Π½Π°Π·Π½Π°ΡΠ΅Π½ΠΈΠ΅ Π΄ΠΎΡΠΎΠ³ΠΎΡΡΠΎΡΡΠ΅Π³ΠΎ Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΠΎΠ³ΠΎ ΡΡΠ΅Π΄ΡΡΠ²Π°. ΠΡΠΎΠΌΡΡΠ»Π΅Π½Π½ΠΎΠ΅ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄ΡΡΠ²ΠΎ ΠΎΡΡΠ°Π½Π½ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² ΠΌΠΎΠΆΠ΅Ρ Π±ΡΡΡ Π½Π΅ΡΠ΅Π½ΡΠ°Π±Π΅Π»ΡΠ½ΡΠΌ Π² ΡΠΈΠ»Ρ ΠΌΠ°Π»ΠΎΠΉ ΡΠ°ΡΠΏΡΠΎΡΡΡΠ°Π½Π΅Π½Π½ΠΎΡΡΠΈ ΡΠ΅Π΄ΠΊΠΈΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ. ΠΠΎΡΡΠΎΠΌΡ Π΄ΠΎΡΡΡΠΏΠ½ΠΎΡΡΡ ΠΎΡΡΠ°Π½Π½ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² Π΄Π»Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Π·Π°Π²ΠΈΡΠΈΡ ΠΎΡ ΡΡΠ°ΡΡΠΈΡ Π³ΠΎΡΡΠ΄Π°ΡΡΡΠ²Π° Π² ΡΡΠΈΠΌΡΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠΈ ΠΈΡ
ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄ΡΡΠ²Π°. Π ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΡΡΡΠ°Π½Π°Ρ
Π½ΠΎΡΠΌΠ°ΡΠΈΠ²Π½ΡΠ΅ ΡΡΠ΅Π±ΠΎΠ²Π°Π½ΠΈΡ Π΄Π»Ρ ΠΏΡΠΈΠ·Π½Π°Π½ΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ ΡΠ΅Π΄ΠΊΠΈΠΌ ΠΈ ΡΠ΅Π³ΠΈΡΡΡΠ°ΡΠΈΠΈ ΠΎΡΡΠ°Π½Π½ΠΎΠ³ΠΎ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ° ΡΠ°Π·ΡΠ°Π±Π°ΡΡΠ²Π°ΡΡΡΡ Ρ ΡΡΠ΅ΡΠΎΠΌ ΡΠΎΡΠΈΠ°Π»ΡΠ½ΡΡ
ΠΈ ΡΠΊΠΎΠ½ΠΎΠΌΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠ΅ΠΉ ΡΡΡΠ°Π½Ρ. Π ΡΠ°Π±ΠΎΡΠ΅ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½ Π°Π½Π°Π»ΠΈΠ· Π½ΠΎΡΠΌΠ°ΡΠΈΠ²Π½ΡΡ
ΡΡΠ΅Π±ΠΎΠ²Π°Π½ΠΈΠΉ ΡΠ°Π·Π½ΡΡ
ΡΡΡΠ°Π½ Π΄Π»Ρ Π²ΡΡΠ²Π»Π΅Π½ΠΈΡ ΡΠ΅Π΄ΠΊΠΈΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ ΠΈ ΠΎΠ±ΡΠΈΡ
ΠΏΠΎΠ΄Ρ
ΠΎΠ΄ΠΎΠ² ΠΊ ΡΠ΅Π³ΠΈΡΡΡΠ°ΡΠΈΠΈ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ², ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΠ΅ΠΌΡΡ
Π΄Π»Ρ Π»Π΅ΡΠ΅Π½ΠΈΡ ΡΠ΅Π΄ΠΊΠΈΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ Π½Π° ΠΏΡΠΈΠΌΠ΅ΡΠ°Ρ
Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΎΡΡΠ°Π½Π½ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ²
ΠΠ΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΠ΅ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΡ ΡΠ°ΠΊΡΠΎΡΠ° VIII, Π°ΠΊΡΡΠ°Π»ΡΠ½ΡΠ΅ Π²ΠΎΠΏΡΠΎΡΡ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠΈ, ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΠΈ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΡ (ΡΠ°ΡΡΡ 2)
Continuous replacement therapy with clotting factor products can lead to serious complications in haemophilia A patients. One of potential reasons of such complications is an undesirable immune response to a blood clotting factor VIII (FVIII) product, which undermines the treatment effectiveness. The aim of the study was to systematise and summarise data on undesirable immunogenicity of plasma-derived and recombinant FVIII products, formation of immunological tolerance, and modern approaches to the development of clinical trial programmes for such products. The analysis was based on scientific literature, as well as Russian and international guidelines, including the updated document of the European Medicines Agency. The paper presents clinical trial data on pharmacokinetics, efficacy, and safety of FVIII products, including data on manifestations of unwanted immunogenicity. It highlights molecular mechanisms of interaction between inhibitors and FVIII, and analyses the main factors (genetic characteristics, immune status of patients, dosage regimen, etc.) affecting the frequency and intensity of the immune response to the product. The authors summarised approaches to the clinical trial design, including selection of patients and studied parameters. They substantiate the need for post-authorisation studies to collect additional clinical data on both efficacy and safety of the routine use of the product, including additional assessment of immunogenicity and other adverse reactions. It is concluded that the successful use of high-quality FVIII products ensures by harmonisation of requirements of Russian and international regulatory documents.ΠΠΎΡΡΠΎΡΠ½Π½Π°Ρ Π·Π°ΠΌΠ΅ΡΡΠΈΡΠ΅Π»ΡΠ½Π°Ρ ΡΠ΅ΡΠ°ΠΏΠΈΡ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ°ΠΌΠΈ ΡΠ²Π΅ΡΡΡΠ²Π°Π½ΠΈΡ ΠΊΡΠΎΠ²ΠΈ ΠΏΡΠΈ Π³Π΅ΠΌΠΎΡΠΈΠ»ΠΈΠΈ Π ΠΌΠΎΠΆΠ΅Ρ ΠΏΡΠΈΠ²Π΅ΡΡΠΈ ΠΊ ΡΠ΅ΡΡΠ΅Π·Π½ΡΠΌ ΠΎΡΠ»ΠΎΠΆΠ½Π΅Π½ΠΈΡΠΌ, ΠΎΠ΄Π½ΠΎΠΉ ΠΈΠ· ΠΏΡΠΈΡΠΈΠ½ ΠΊΠΎΡΠΎΡΡΡ
ΡΠ²Π»ΡΠ΅ΡΡΡ ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ Β«Π½Π΅ΠΆΠ΅Π»Π°ΡΠ΅Π»ΡΠ½ΠΎΠ³ΠΎΒ» ΠΈΠΌΠΌΡΠ½Π½ΠΎΠ³ΠΎ ΠΎΡΠ²Π΅ΡΠ° Π½Π° Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΠΉ ΠΏΡΠ΅ΠΏΠ°ΡΠ°Ρ ΡΠ°ΠΊΡΠΎΡΠ° ΡΠ²Π΅ΡΡΡΠ²Π°Π½ΠΈΡ ΠΊΡΠΎΠ²ΠΈ VIII (FVIII), ΡΡΠΎ ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ ΠΏΠΎΡΠ΅ΡΠ΅ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠΌΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ. Π¦Π΅Π»Ρ ΡΠ°Π±ΠΎΡΡ β ΡΠΈΡΡΠ΅ΠΌΠ°ΡΠΈΠ·Π°ΡΠΈΡ ΠΈ ΠΎΠ±ΠΎΠ±ΡΠ΅Π½ΠΈΠ΅ ΡΠ²Π΅Π΄Π΅Π½ΠΈΠΉ ΠΎ ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΠΈ Π½Π΅ΠΆΠ΅Π»Π°ΡΠ΅Π»ΡΠ½ΠΎΠΉ ΠΈΠΌΠΌΡΠ½ΠΎΠ³Π΅Π½Π½ΠΎΡΡΠΈ ΠΏΠ»Π°Π·ΠΌΠ΅Π½Π½ΡΡ
ΠΈ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ
Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² FVIII, ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΠΈ ΠΈΠΌΠΌΡΠ½ΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠΎΠ»Π΅ΡΠ°Π½ΡΠ½ΠΎΡΡΠΈ, ΠΎ ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΡΡ
ΠΏΠΎΠ΄Ρ
ΠΎΠ΄Π°Ρ
ΠΊ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠ΅ ΠΏΡΠΎΠ³ΡΠ°ΠΌΠΌΡ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ ΡΡΠΈΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ Π΄Π°Π½Π½ΡΡ
Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΡ, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΌΠ΅ΠΆΠ΄ΡΠ½Π°ΡΠΎΠ΄Π½ΡΡ
ΠΈ ΡΠΎΡΡΠΈΠΉΡΠΊΠΈΡ
ΡΡΠΊΠΎΠ²ΠΎΠ΄ΡΡΠ², Π²ΠΊΠ»ΡΡΠ°Ρ ΠΎΠ±Π½ΠΎΠ²Π»Π΅Π½Π½ΡΠΉ Π΄ΠΎΠΊΡΠΌΠ΅Π½Ρ ΠΠ²ΡΠΎΠΏΠ΅ΠΉΡΠΊΠΎΠ³ΠΎ Π°Π³Π΅Π½ΡΡΡΠ²Π° ΠΏΠΎ Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΠΌ ΡΡΠ΅Π΄ΡΡΠ²Π°ΠΌ. Π ΠΎΠ±Π·ΠΎΡΠ΅ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Ρ Π΄Π°Π½Π½ΡΠ΅ ΠΎΠ± ΠΎΡΠ΅Π½ΠΊΠ΅ Π² Ρ
ΠΎΠ΄Π΅ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² FVIII ΡΠ°ΡΠΌΠ°ΠΊΠΎΠΊΠΈΠ½Π΅ΡΠΈΠΊΠΈ, ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΈ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΠΈ, Π² ΡΠΎΠΌ ΡΠΈΡΠ»Π΅ ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΠΉ Π½Π΅ΠΆΠ΅Π»Π°ΡΠ΅Π»ΡΠ½ΠΎΠΉ ΠΈΠΌΠΌΡΠ½ΠΎΠ³Π΅Π½Π½ΠΎΡΡΠΈ. ΠΡΠΎΠ±ΠΎΠ΅ Π²Π½ΠΈΠΌΠ°Π½ΠΈΠ΅ ΡΠ΄Π΅Π»Π΅Π½ΠΎ ΡΠ°ΡΡΠΌΠΎΡΡΠ΅Π½ΠΈΡ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΡ
ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠΎΠ² Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΡ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠΎΠ² ΠΈ FVIII. ΠΡΠΎΠ°Π½Π°Π»ΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Ρ ΠΎΡΠ½ΠΎΠ²Π½ΡΠ΅ ΡΠ°ΠΊΡΠΎΡΡ (Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠΈ, ΡΠΎΡΡΠΎΡΠ½ΠΈΠ΅ ΠΈΠΌΠΌΡΠ½Π½ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΡ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠ°, ΡΠ΅ΠΆΠΈΠΌ Π΄ΠΎΠ·ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ° ΠΈ Π΄Ρ.), Π²Π»ΠΈΡΡΡΠΈΠ΅ Π½Π° ΡΠ°ΡΡΠΎΡΡ ΠΈ Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΠΎΡΡΡ ΠΈΠΌΠΌΡΠ½Π½ΠΎΠ³ΠΎ ΠΎΡΠ²Π΅ΡΠ° Π½Π° ΠΏΡΠ΅ΠΏΠ°ΡΠ°Ρ. ΠΠ·Π»ΠΎΠΆΠ΅Π½Ρ ΠΏΠΎΠ΄Ρ
ΠΎΠ΄Ρ ΠΊ Π΄ΠΈΠ·Π°ΠΉΠ½Ρ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ, Π² ΡΠΎΠΌ ΡΠΈΡΠ»Π΅ ΠΊΠ°ΡΠ°ΡΡΠΈΠ΅ΡΡ ΠΎΡΠ±ΠΎΡΠ° ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² ΠΈ Π²ΡΠ±ΠΎΡΠ° ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»Π΅ΠΉ Π΄Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ. ΠΠ±ΠΎΡΠ½ΠΎΠ²Π°Π½Π° Π½Π΅ΠΎΠ±Ρ
ΠΎΠ΄ΠΈΠΌΠΎΡΡΡ ΠΏΠΎΡΡΡΠ΅Π³ΠΈΡΡΡΠ°ΡΠΈΠΎΠ½Π½ΡΡ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ Ρ ΡΠ΅Π»ΡΡ ΡΠ±ΠΎΡΠ° Π΄ΠΎΠΏΠΎΠ»Π½ΠΈΡΠ΅Π»ΡΠ½ΡΡ
ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
Π΄Π°Π½Π½ΡΡ
, ΠΊΠ°ΡΠ°ΡΡΠΈΡ
ΡΡ ΠΊΠ°ΠΊ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ, ΡΠ°ΠΊ ΠΈ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΠΈ ΡΡΡΠΈΠ½Π½ΠΎΠ³ΠΎ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΡ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ°, Π²ΠΊΠ»ΡΡΠ°Ρ Π΄ΠΎΠΏΠΎΠ»Π½ΠΈΡΠ΅Π»ΡΠ½ΡΡ ΠΎΡΠ΅Π½ΠΊΡ ΠΈΠΌΠΌΡΠ½ΠΎΠ³Π΅Π½Π½ΠΎΡΡΠΈ ΠΈ Π΄ΡΡΠ³ΠΈΡ
Π½Π΅ΠΆΠ΅Π»Π°ΡΠ΅Π»ΡΠ½ΡΡ
ΡΠ΅Π°ΠΊΡΠΈΠΉ. Π‘Π΄Π΅Π»Π°Π½ Π²ΡΠ²ΠΎΠ΄ ΠΎ ΡΠΎΠΌ, ΡΡΠΎ ΡΡΠΏΠ΅ΡΠ½ΠΎΡΡΡ Π²Π½Π΅Π΄ΡΠ΅Π½ΠΈΡ Π² ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΡΡ ΠΏΡΠ°ΠΊΡΠΈΠΊΡ ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΡ
Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² FVIII ΠΎΠ±Π΅ΡΠΏΠ΅ΡΠΈΠ²Π°Π΅ΡΡΡ Π³Π°ΡΠΌΠΎΠ½ΠΈΠ·Π°ΡΠΈΠ΅ΠΉ ΡΡΠ΅Π±ΠΎΠ²Π°Π½ΠΈΠΉ, ΠΈΠ·Π»ΠΎΠΆΠ΅Π½Π½ΡΡ
Π² ΠΎΡΠ΅ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΡ
ΠΈ ΠΌΠ΅ΠΆΠ΄ΡΠ½Π°ΡΠΎΠ΄Π½ΡΡ
Π½ΠΎΡΠΌΠ°ΡΠΈΠ²Π½ΡΡ
Π΄ΠΎΠΊΡΠΌΠ΅Π½ΡΠ°Ρ
ΠΠΌΠΌΡΠ½Π½ΡΠΉ ΠΎΡΠ²Π΅Ρ ΠΏΡΠΈ ΠΈΠΌΠΌΡΠ½ΠΈΠ·Π°ΡΠΈΠΈ ΠΏΡΠΎΡΠΈΠ²ΠΎΠ²ΠΈΡΡΡΠ½ΡΠΌΠΈ Π²Π°ΠΊΡΠΈΠ½Π°ΠΌΠΈ
The review is devoted to specific aspects of the development of post-vaccination immunity following immunisation with different types of antiviral vaccines, as well as to ways of increasing immunogenicity of vaccines and effectiveness of preventive vaccination. Vaccines containing highly purified and recombinant antigens obtained using modern technologies have lower reactogenicity and a higher safety profile, but are less immunogenic compared to live vaccines. Effective vaccines have not been developed for many viral infections yet. Therefore, it is critical to search for ways to enhance immunogenic properties of vaccines in order to increase the efficiency of vaccination, and to develop new vaccine formulations that provide reliable protection of the body against infection. The aim of the paper was to analyse specific aspects of immune response development following immunisation with antiviral vaccines, and approaches to increasing their immunogenicity using adjuvants. It reviews different types of antiviral vaccines, as well as specific aspects of immune response development depending on the nature of a specific antigen. The paper substantiates the use of adjuvants to enhance and regulate the induced immune response. It analyses mechanisms that determine the stimulating effect of adjuvants and summarises data on the adjuvants used in the licensed vaccines for human use. The authors highlight the need for further research to increase the efficiency of vaccination and suggest that one of potential solutions is the use of adjuvants based on recombinant human cytokines.ΠΠ±Π·ΠΎΡ ΠΏΠΎΡΠ²ΡΡΠ΅Π½ Π²ΠΎΠΏΡΠΎΡΠ°ΠΌ, ΡΠ²ΡΠ·Π°Π½Π½ΡΠΌ Ρ ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΡΠΌΠΈ ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΏΠΎΡΡΠ²Π°ΠΊΡΠΈΠ½Π°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΈΠΌΠΌΡΠ½ΠΈΡΠ΅ΡΠ° ΠΏΡΠΈ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠΈ ΡΠ°Π·Π½ΡΡ
ΡΠΈΠΏΠΎΠ² ΠΏΡΠΎΡΠΈΠ²ΠΎΠ²ΠΈΡΡΡΠ½ΡΡ
Π²Π°ΠΊΡΠΈΠ½, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΏΡΠΎΠ±Π»Π΅ΠΌΠ°ΠΌ ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΡ ΠΈΠΌΠΌΡΠ½ΠΎΠ³Π΅Π½Π½ΠΎΡΡΠΈ Π²Π°ΠΊΡΠΈΠ½ ΠΈ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π²Π°ΠΊΡΠΈΠ½ΠΎΠΏΡΠΎΡΠΈΠ»Π°ΠΊΡΠΈΠΊΠΈ. ΠΠ°ΠΊΡΠΈΠ½Ρ, ΡΠΎΠ΄Π΅ΡΠΆΠ°ΡΠΈΠ΅ Π²ΡΡΠΎΠΊΠΎΠΎΡΠΈΡΠ΅Π½Π½ΡΠ΅ ΠΈ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΠ΅ Π°Π½ΡΠΈΠ³Π΅Π½Ρ, ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΡΠ΅ Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΡΡ
ΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΠΈΠΉ, Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΡΡΡΡΡ Π±ΠΎΠ»Π΅Π΅ Π½ΠΈΠ·ΠΊΠΎΠΉ ΡΠ΅Π°ΠΊΡΠΎΠ³Π΅Π½Π½ΠΎΡΡΡΡ ΠΈ Π±ΠΎΠ»Π΅Π΅ Π²ΡΡΠΎΠΊΠΈΠΌ ΠΏΡΠΎΡΠΈΠ»Π΅ΠΌ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΠΈ, Π½ΠΎ ΡΠ²Π»ΡΡΡΡΡ ΠΌΠ΅Π½Π΅Π΅ ΠΈΠΌΠΌΡΠ½ΠΎΠ³Π΅Π½Π½ΡΠΌΠΈ, ΠΏΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Ρ ΠΆΠΈΠ²ΡΠΌΠΈ Π²Π°ΠΊΡΠΈΠ½Π°ΠΌΠΈ. ΠΠ»Ρ ΠΌΠ½ΠΎΠ³ΠΈΡ
ΠΈΠ½ΡΠ΅ΠΊΡΠΈΠΎΠ½Π½ΡΡ
Π²ΠΈΡΡΡΠ½ΡΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ Π΄ΠΎ Π½Π°ΡΡΠΎΡΡΠ΅Π³ΠΎ Π²ΡΠ΅ΠΌΠ΅Π½ΠΈ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΡΠ΅ Π²Π°ΠΊΡΠΈΠ½Ρ Π½Π΅ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠ°Π½Ρ. ΠΠΎΠΈΡΠΊ ΠΏΡΡΠ΅ΠΉ ΡΡΠΈΠ»Π΅Π½ΠΈΡ ΠΈΠΌΠΌΡΠ½ΠΎΠ³Π΅Π½Π½ΡΡ
ΡΠ²ΠΎΠΉΡΡΠ² Π²Π°ΠΊΡΠΈΠ½ Π΄Π»Ρ ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π²Π°ΠΊΡΠΈΠ½Π°ΡΠΈΠΈ ΠΈ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠ° Π½ΠΎΠ²ΡΡ
Π²Π°ΠΊΡΠΈΠ½Π½ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ², ΠΎΠ±Π΅ΡΠΏΠ΅ΡΠΈΠ²Π°ΡΡΠΈΡ
Π½Π°Π΄Π΅ΠΆΠ½ΡΡ Π·Π°ΡΠΈΡΡ ΠΎΡΠ³Π°Π½ΠΈΠ·ΠΌΠ° ΠΎΡ ΠΈΠ½ΡΠ΅ΠΊΡΠΈΠΈ, ΡΠ²Π»ΡΠ΅ΡΡΡ Π°ΠΊΡΡΠ°Π»ΡΠ½ΡΠΌ. Π¦Π΅Π»Ρ ΡΠ°Π±ΠΎΡΡ β ΠΏΡΠΎΠ²Π΅ΡΡΠΈ Π°Π½Π°Π»ΠΈΠ· ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠ΅ΠΉ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΠΈΠΌΠΌΡΠ½Π½ΠΎΠ³ΠΎ ΠΎΡΠ²Π΅ΡΠ° Π½Π° ΠΏΡΠΎΡΠΈΠ²ΠΎΠ²ΠΈΡΡΡΠ½ΡΠ΅ Π²Π°ΠΊΡΠΈΠ½Ρ ΠΈ ΠΏΠΎΠ΄Ρ
ΠΎΠ΄ΠΎΠ² ΠΊ ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΡ ΠΈΡ
ΠΈΠΌΠΌΡΠ½ΠΎΠ³Π΅Π½Π½ΠΎΡΡΠΈ Ρ ΠΏΠΎΠΌΠΎΡΡΡ Π°Π΄ΡΡΠ²Π°Π½ΡΠΎΠ². Π Π°ΡΡΠΌΠΎΡΡΠ΅Π½Ρ ΡΠΈΠΏΡ ΠΏΡΠΎΡΠΈΠ²ΠΎΠ²ΠΈΡΡΡΠ½ΡΡ
Π²Π°ΠΊΡΠΈΠ½, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠΈ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΠΈΠΌΠΌΡΠ½Π½ΠΎΠ³ΠΎ ΠΎΡΠ²Π΅ΡΠ° Π² Π·Π°Π²ΠΈΡΠΈΠΌΠΎΡΡΠΈ ΠΎΡ ΠΏΡΠΈΡΠΎΠ΄Ρ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π°Π½ΡΠΈΠ³Π΅Π½Π°. ΠΠ±ΠΎΡΠ½ΠΎΠ²Π°Π½Π° ΡΠ΅Π»Π΅ΡΠΎΠΎΠ±ΡΠ°Π·Π½ΠΎΡΡΡ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΡ Π°Π΄ΡΡΠ²Π°Π½ΡΠΎΠ² Π΄Π»Ρ ΡΡΠΈΠ»Π΅Π½ΠΈΡ ΠΈ ΠΌΠΎΠ΄ΡΠ»ΡΡΠΈΠΈ ΠΈΠ½Π΄ΡΡΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠ³ΠΎ ΠΈΠΌΠΌΡΠ½Π½ΠΎΠ³ΠΎ ΠΎΡΠ²Π΅ΡΠ°. ΠΡΠΎΠ°Π½Π°Π»ΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Ρ ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΡ, ΠΎΠ±ΡΡΠ»Π°Π²Π»ΠΈΠ²Π°ΡΡΠΈΠ΅ ΡΡΠΈΠΌΡΠ»ΠΈΡΡΡΡΠΈΠΉ ΡΡΡΠ΅ΠΊΡ Π°Π΄ΡΡΠ²Π°Π½ΡΠΎΠ². ΠΠ±ΠΎΠ±ΡΠ΅Π½Ρ ΡΠ²Π΅Π΄Π΅Π½ΠΈΡ ΠΎΠ± Π°Π΄ΡΡΠ²Π°Π½ΡΠ°Ρ
, Π²Ρ
ΠΎΠ΄ΡΡΠΈΡ
Π² ΡΠΎΡΡΠ°Π² Π·Π°ΡΠ΅Π³ΠΈΡΡΡΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
Π²Π°ΠΊΡΠΈΠ½ Π΄Π»Ρ ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ°. ΠΠ±ΠΎΠ·Π½Π°ΡΠ΅Π½Π° Π½Π΅ΠΎΠ±Ρ
ΠΎΠ΄ΠΈΠΌΠΎΡΡΡ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ Π΄Π°Π»ΡΠ½Π΅ΠΉΡΠΈΡ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ Π² ΠΎΠ±Π»Π°ΡΡΠΈ ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π²Π°ΠΊΡΠΈΠ½Π°ΡΠΈΠΈ, ΠΎΠ΄Π½ΠΈΠΌ ΠΈΠ· Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½ΠΈΠΉ ΠΊΠΎΡΠΎΡΡΡ
ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ Π² ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ Π°Π΄ΡΡΠ²Π°Π½ΡΠΎΠ² Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ
ΡΠΈΡΠΎΠΊΠΈΠ½ΠΎΠ² ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ°