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.

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 world’s 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 world’s 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.

According to the World Federation of Hemophilia (WFH), there are currently about 400 thousand patients with hemophilia in the world. Severe clinical manifestations of the disease associated with a genetically determined deficiency of blood clotting factor activity require continuous replacement therapy with blood clotting medicines. Long-term use of protein-based medicines often leads to the formation of specific antibodies, which causes a decrease in or loss of efficacy of the medicine or results in severe adverse reactions, including anaphylaxis. Therefore, it is important to search for new optimal approaches to hemophilia treatment, which requires the development of new blood clotting factor products, improvement of the production technology for already authorised products, as well as the use of non-factor products. The aim of the study was to present the results of the analysis of key issues related to the development and characteristics of plasma-derived and recombinant factor VIII products, new approaches to hemophilia A treatment, including the use of non-factor products. The review summarises current data on the etiology, clinical manifestations, and complications of hemophilia A treatment. It provides information on the blood clotting factor products (plasma-derived and recombinant) used as replacement therapy. It also provides information on advanced research projects for the development of new biotechnology-derived products which have good prospects of successful clinical use.

Эффективность применения препаратов на основе иммуноглобулинов плазмы и моноклональных антител для лечения и профилактики COVID-19

Разработка фармакопейного стандартного образца для количественного определения активности иммуноглобулина человека антирезус Rho(D)

Scientific relevance. Currently, two types of methods are used to evaluate the potency of diphtheria and tetanus toxoids: the gold standard, which involves administering toxins to immunised animals, and serological methods, which involve quantifying protective antibodies in the serum of immunised animals. International validation studies of serological methods for assessing the potency of diphtheria and tetanus toxoids have resulted in revisions to the relevant chapters of the WHO Manual for Quality Control of Diphtheria, Tetanus and Pertussis Vaccines, as well as the European, Japanese, and several other pharmacopoeias. Consequently, some diphtheria and tetanus vaccine manufacturers have substituted the potency evaluation methods that require administering toxins to animals with alternative serological methods.Aim. The study aimed to assess the suitability, reproducibility, and feasibility of an alternative enzyme immunoassay method (ELISA) for assessing the potency of diphtheria and tetanus components of diphtheria, tetanus, and whole-cell pertussis (DTwP) vaccines and to determine the possibility of implementing this method in Russia using standards and reagents manufactured in the country.Materials and methods. The study used combined vaccines for diphtheria prophylaxis, diphtheria toxin, and reference vaccines. The potency of diphtheria and tetanus toxoids was determined in guinea pigs and mice by the pharmacopoeial lethal challenge method and an alternative ELISA method.Results. ELISA and lethal challenge methods demonstrated comparable results of potency determination: 230 IU/mL vs 264 IU/mL (diphtheria toxoid), 188 IU/mL vs 160 IU/mL (tetanus toxoid), respectively. As opposed to the lethal challenge, the serological method allows testing the efficacy of several antigens in the same animals. The study showed the possibility of using purified diphtheria and tetanus toxoids manufactured in Russia as coating antigens. The authors obtained comparable antibody titres for each animal, using plates coated with international standards and Russian-made diphtheria and tetanus toxoids.Conclusions. The authors demonstrated the possibility of using ELISA to determine the potency of diphtheria and tetanus toxoids in DTwP vaccines. Moreover, the study demonstrated the suitability of Russian purified diphtheria and tetanus toxoids as coating antigens. Researchers should continue working on enzyme immunoassay validation with a view to harmonising national and international methods for assessing the potency of diphtheria and tetanus toxoid vaccines, as these efforts will not only facilitate the registration of foreign vaccines in Russia but also accelerate the approval of Russian vaccines in other countries.