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.
The progress of the COVID-19 pandemic initiated research to develop vaccines against this novel coronavirus infection. The WHO and national regulatory authorities in many countries have elaborated guidelines to speed up the development and authorisation of COVID-19 vaccines.The aim of the study was to analyse international and Russian regulatory recommendations for the development and fast-track approval of COVID-19 vaccines in the context of the pandemic, as well as to summarise the preliminary published results of the first stages of preclinical and clinical studies. The paper analyses approaches to fast-track approval of medicines in the face of the pandemic in Russia, the European Union, and the United States. It summarises regulatory requirements for the quality of COVID-19 vaccines, as well as for preclinical, and clinical studies. It describes the first results of COVID-19 vaccine development. The analysed regulatory documents allow for accelerated authorisation due to reduction of time spent on evaluation of vaccine quality, safety, and efficacy. Another option is the so-called conditional marketing authorisation when a vaccine is registered based on incomplete preclinical and clinical data provided that all the studies will be completed after the vaccine authorisation. The paper summarises the results of clinical trials of COVID-19 vaccines. The few published preliminary results of the first phases of COVID-19 vaccine clinical trials demonstrate the vaccines’ good tolerability, safety, and immunogenicity. Evaluation of adenovirusbased vaccines showed that almost half of the volunteers had had high antibody titers to adenovirus before the study, which resulted in milder adverse reactions and low immunogenicity. In addition, the immune response was weaker in the older group of subjects (45–60 years) as compared to the subjects younger than 45 years. The results of the analysis of regulatory requirements for the development and marketing authorisation of COVID-19 vaccines in the context of the pandemic, as well as of national and international regulatory approaches to vaccine development and authorisation can be used as a basis for the development of Russian requirements for COVID-19 vaccines in the context of the pandemic.
Эффективность применения препаратов на основе иммуноглобулинов плазмы и моноклональных антител для лечения и профилактики COVID-19Федеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской Федерации, 127051, г. Москва, Российская Федерация РезюмеРазвитие пандемии COVID-19 инициировало поиск эффективных препаратов для лечения и профилактики инфекции. Особое значение для борьбы с пандемией играют сроки внедрения препаратов в клиническую практику. Поэтому в странах с развитыми системами здравоохранения (ЕС, США, Российская Федерация и др.) выдача разрешения на применение препаратов для лечения и профилактики COVID-19 осуществляется на условиях нормативных требований, регламентирующих оборот лекарственных средств в чрезвычайных ситуациях. Данное разрешение выдается на основании результатов ограниченных клинических данных с тем условием, что оценка безопасности и эффективности будет проведена после выдачи разрешения в пострегистрационном периоде в полном объеме.Пандемия COVID-19 совершила революцию в дизайне клинических исследований и скорости их проведения, включая адаптивные исследования фаз I, II и III, которая привела к одобрению биологических препаратов для лечения и профилактики COVID-19 в рекордно короткие сроки в большинстве стран с развитой фарминдустрией. При этом органы здравоохранения (и/или регуляторные органы) или международные организации осуществляют постоянный мониторинг безопасности и эффективности применяемых лекарственных средств и при необходимости вносят корректировки (изменение показаний и дозы, прекращение применения препарата и др.).С начала пандемии, фактически в условиях, когда было разрешено применение препаратов на основании очень ограниченных данных, начались исследования с целью обоснования безопасности и эффективности применения препаратов иммуноглобулинов и моноклональных антител для лечения и профилактики COVID-19.По мере появления новых данных вносились изменения, касающиеся показаний к применению, доз и других характеристик препаратов иммуноглобулинов и моноклональных антител для лечения и профилактики COVID-19. В обзоре представлен критический анализ результатов оценки безопасности и эффективности применения препаратов иммуноглобулинов и моноклональных антител, особенности их применения в условиях пандемии COVID-19.
At the end of 2019, an outbreak of a new coronavirus began in the city of Wuhan (Hubei Province) in the People's Republic of China. The outbreak turned into a pandemic. In the shortest possible time, national and international manufacturers developed preventive COVID-19 vaccines, and the population was vaccinated. During pandemics, accelerated approval of vaccines is an important factor that shortens the time to market with the aim of mass vaccination. The experience of rapidly developing and introducing vaccines into routine practice is not only important for managing the current pandemic, but also valuable in case of extremely likely future ones. The aim of this study was to analyse the main issues associated with assessing the safety and efficacy of vaccines for COVID-19 prevention during their registration and widespread use amid the pandemic and ongoing SARS-CoV-2 evolution. The vaccines for COVID-19 prevention were developed and introduced into healthcare practice very rapidly and under the circumstances of the pandemic, and the use of these vaccines has surfaced a number of concerns requiring further research. The most important issues identified in the performed analysis include, but are not limited to the need for accelerated assessment of the safety and immunogenicity of new vaccines; the lack of immune correlates of protection against SARS-CoV-2; the waning of antibody immunity over time, motivating the need to determine revaccination and post-recovery vaccination timelines; and the emergence of mutant SARS-CoV-2 variants. One of noteworthy aspects is the need to develop recommendations for updating the strain composition of registered COVID-19 vaccines. According to the conclusions, the level of herd immunity, including vaccine-induced protection, plays a certain role in virus evolution during the pandemic. If COVID-19 becomes seasonal, which is a probable scenario, regular revaccination can be essential.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.