Контроль над бронхиальной астмой в России: результаты многоцентрового наблюдательного исследования НИКА

Summary. Asthma control level was evaluated in 1 000 patients treated in 26 outpatient centers at 12 cities of Russian Federation. Asthma control level was assessed clinically and with special questionnaires ACQ-5 and ACT. Results were referred to GINA criteria. Well-controlled asthma was found in 23 % of patients, partly controlled and poorly controlled asthma was diagnosed in 25 % and 42 % of patients, respectively. Attendant physicians misestimated asthma control level in 49 % of cases. ACQ-5 and ACT questionnaires equally improved estimation of asthma control (64 % and 60 % of adequate estimates, respectively) however, ACT questionnaire demonstrated systematic bias to overestimated asthma control when compared to GINA criteria.Резюме. В исследовании была проведена оценка уровня контроля над бронхиальной астмой (БА) у 1 000 больных из 26 амбулаторных лечебных учреждений 12 городов Российской Федерации. Уровень контроля оценивался клинически и с применением специализированных опросников ACQ-5 и ACT. В качестве референтного метода оценки применялась оценка симптомов и показателей спирометрии в соответствии с критериями GINA. В целом контролируемая БА отмечалась у 23 % больных, частичный контроль и неконтролируемое течение заболевания – у 35 % и 42 % соответственно. При диагностике уровня контроля лечащие врачи совершали ошибки в 49 % случаев. Применение тестов ACQ-5 и ACT давало более высокое и примерно сопоставимое качество оценки контроля (64 % и 60 % адекватных оценок), но при этом у ACT отмечалась систематическая погрешность в сторону завышения уровня контроля над БА по сравнению с критериями GINA

Biosimilars: development and investigation using achievements in modern biotechnology

Biosimilars are biological drug products that have an equivalent clinical profile with innovator biotherapeutics but are developed under a reduced program. To this end, specific comparability approaches are followed based on reverse engineering that involves a thorough analysis of the innovator biotherapeutics and the development of the version of the latter, which should be as much as possible similar with respect to structural and functional characteristics with the innovator. This approach includes the evaluation and comparison between the biosimilar and innovator biologic with respect to the molecular structure and impurity profile and of biological activity in in vitro settings as well as pharmacokinetic, pharmacodynamic, and immunogenicity characteristics on human subjects. Where considered necessary, animal studies or phase 3 clinical studies might be performed when residual uncertainties remain in terms of biosimilarity, that could not have been resolved in the previous tests and trials. Any potentially inevitable differences should be insignificant for safety and efficacy. The state-of-the-art methods of biotechnology and analytics, when applied in line with the appropriate scientific and regulatory requirements, can allow developing similar biologics where no difference in the clinical profile exists with the respective innovator product. Available experience demonstrates the lack of major problems due to the incomparability between the biosimilar and corresponding reference biologics when applicable scientific standards and regulatory recommendations are met

Трансплантация фекальной микробиоты: возможные терапевтические подходы и вопросы правового регулирования

Since Ilya Metchnikoff’s studies, both medical science and clinical practice have accumulated a large amount of evidence that human intestinal microbiota possesses a unique characteristics for our existence. However, only recently, scientists have achieved the actual breakthrough in this field of human physiology, and we start to understand the precise mechanisms of the complex interplay of microbial activity with human homeostasis and discover numerous new functions of intestinal microbes. In this regard, a novel medical technology evolves since 1958, so called fecal microbiota transplantation (FMT), which is the administration of donor feces to the patients suffering from different kinds of diseases. Such infusion of donor feces restores the natural balance of gut commensal germs. FMT is most efficacious in severe or recurrent Clostridium difficile infection. FMT has been also reported to cure diarrhea and constipation caused by different conditions, such as multiple sclerosis, Crohn ’s disease etc. In the U.S. and Canada as well as in other countries FMT is of uttermost interest of not merely clinical practitioners but lately also of regulatory authorities. The paper also addresses the possibility of application the Russian pharmaceutical legislation to FMT.Начиная с работ Ильи Мечникова, в медицинской науке и практике накоплено большое количество доказательств влияния состояния кишечной микробиоты на здоровье человека. Однако лишь в последние годы в исследованиях в этой области произошел качественный перелом: мы стали понимать механизмы влияния микробиоты на гомеостаз, а также выяснять все новые функции живущих в нас микроорганизмов. На этом фоне с 1958 г. развивается трансплантация фекальной микробиоты (ТФМ) от здоровых доноров пациентам с различными заболеваниями, которая восстанавливает нарушенный баланс кишечных микроорганизмов. Наибольшую эффективность данный метод проявляет при терапии тяжелых кишечных инфекций, вызываемых Clostridium difficile. Также ТФМ показала потенциальную эффективность при диарее и запоре различного генеза, рассеянном склерозе, болезни Крона и др. В США, Канаде и других странах ТФМ является предметом интереса не только врачей-клиницистов, но и с недавних пор - регуляторных, органов. В статье также рассматривается возможность применения российского законодательства в сфере обращения лекарственных средств к этому новому методу

Высоковариабельные лекарственные препараты - особенности исследования биоэквивалентности

At present a specific group of medicines - highly variable medicines - is distinguished based on intraindividual variability data (CVintra > 30%). It is quite difficult to confirm therapeutic equivalence of highly variable medicines by pharmacokinetic bioequivalence studies, and quite a large number of subjects need to be included into the study in order to confirm bioequivalence within standard limits of 80-125%. Variability may be caused by many factors which include physiological and pathophysiological differences in absorption and metabolism processes; factors associated with properties of the active substance and factors associated with the finished product. In general factors impacting variability in bioequivalence studies could be divided into controllable and uncontrollable. The influence of controllable factors can be neutralized by proper performance of the bioequivalence study or proper development of the finished product. The influence of uncontrollable factors cannot be neutralized, and due to these factors medicines can be recognized as highly variable. This article provides a definition of a highly variable medicine, describes reasons for high variability and outlines current regulatory recommendations for and approaches to studying bioequivalence of highly variable medicines, proposes recommendations for designing such studies.В настоящее время относительно значений внутрииндивидуальной вариабельности (CVintra более 30%) выделяют особую группу лекарственных препаратов - высоковариабельные лекарственные препараты. Высоковариабельные лекарственные препараты вызывают определенные затруднения при подтверждении терапевтической эквивалентности путем проведения фармакокинетических исследований биоэквивалентности и требуют включения относительно большого числа субъектов исследования для подтверждения биоэквивалентности в стандартных границах 80-125%. Вариабельность может быть обусловлена многими факторами, которые включают физиологические и патофизиологические различия в процессах абсорбции и метаболизма; факторы, ассоциированные со свойствами действующего, и факторы, ассоциированные с готовой лекарственной формой. В целом факторы, влияющие на вариабельность в исследованиях биоэквивалентности, можно разделить на контролируемые и неконтролируемые. Влияние контролируемых факторов можно исключить надлежащим проведением исследования биоэквивалентности или надлежащей разработкой готового лекарственного препарата. Исключить влияние неконтролируемых факторов не представляется возможным, именно они и являются причиной отнесения лекарственных препаратов к высоковариабельным. В статье представлено определение высоковариабельного препарата, отражены причины высокой вариабельности, описаны существующие в настоящее время регуляторные рекомендации и подходы к изучению биоэквивалентности высоковариабельных лекарственных препаратов, сформулированы рекомендации в отношении дизайна исследований таких препаратов

Fecal microbiota transplantation: therapeutical approaches and regulatory framework

Since Ilya Metchnikoff’s studies, both medical science and clinical practice have accumulated a large amount of evidence that human intestinal microbiota possesses a unique characteristics for our existence. However, only recently, scientists have achieved the actual breakthrough in this field of human physiology, and we start to understand the precise mechanisms of the complex interplay of microbial activity with human homeostasis and discover numerous new functions of intestinal microbes. In this regard, a novel medical technology evolves since 1958, so called fecal microbiota transplantation (FMT), which is the administration of donor feces to the patients suffering from different kinds of diseases. Such infusion of donor feces restores the natural balance of gut commensal germs. FMT is most efficacious in severe or recurrent Clostridium difficile infection. FMT has been also reported to cure diarrhea and constipation caused by different conditions, such as multiple sclerosis, Crohn ’s disease etc. In the U.S. and Canada as well as in other countries FMT is of uttermost interest of not merely clinical practitioners but lately also of regulatory authorities. The paper also addresses the possibility of application the Russian pharmaceutical legislation to FMT

Highly variable medicines - specific aspects of bioequivalence studies

At present a specific group of medicines - highly variable medicines - is distinguished based on intraindividual variability data (CVintra > 30%). It is quite difficult to confirm therapeutic equivalence of highly variable medicines by pharmacokinetic bioequivalence studies, and quite a large number of subjects need to be included into the study in order to confirm bioequivalence within standard limits of 80-125%. Variability may be caused by many factors which include physiological and pathophysiological differences in absorption and metabolism processes; factors associated with properties of the active substance and factors associated with the finished product. In general factors impacting variability in bioequivalence studies could be divided into controllable and uncontrollable. The influence of controllable factors can be neutralized by proper performance of the bioequivalence study or proper development of the finished product. The influence of uncontrollable factors cannot be neutralized, and due to these factors medicines can be recognized as highly variable. This article provides a definition of a highly variable medicine, describes reasons for high variability and outlines current regulatory recommendations for and approaches to studying bioequivalence of highly variable medicines, proposes recommendations for designing such studies