The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products / Ведомости Научного центра экспертизы средств медицинского применения
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Стресс-исследования и фотостабильность как часть данных по фармацевтической разработке лекарственного средства
Get PDFDrug stress studies are conducted in order to identify drug degradation products under the influence of stress conditions. The principles of stress studies depend on characteristics of an active substance. The following factors accelerating chemical reactions are being used: temperature, light, moisture, pH, oxygen, carbon dioxide. The obtained results are required for the development of impurity identification and assay methods as well as for the choice of appropriate conditions for drug manufacture and storage.Стресс-исследования лекарственных средств проводят с целью установления продуктов деградации лекарственных веществ под действием стресс-условий. Характер стресс-исследований зависит от свойств действующего вещества. Используют факторы, ускоряющие химические реакции: температуру, свет, влагу, рН среды, кислород, углекислый газ. Представленные данные необходимы для разработки методик определения посторонних примесей и количественного определения, для выбора надлежащих условий производства и хранения лекарственных средств
ЭКСПЕРТНАЯ ОЦЕНКА ДОКЛИНИЧЕСКИХ ИССЛЕДОВАНИЙ ПЕРВИЧНОЙ И ВТОРИЧНОЙ ФАРМАКОДИНАМИКИ ЛЕКАРСТВЕННЫХ СРЕДСТВ
Get PDFThe article dwells upon the results of comparative analysis of the Russian national requirements and EAEU regulations dealing with evaluation of preclinical pharmacological studies. It highlights historical aspects of elaboration of regulatory requirements and scientific and methodological recommendations for conducting and evaluating preclinical pharmacological studies. According to the EAEU Rules of registration and evaluation of medicinal products for human use, the Common Technical Document has to include information on primary pharmacodynamics, secondary pharmacodynamics, safety pharmacology studies, and pharmacodynamic drug interactions, which are subject to evaluation during examination of the preclinical study results. The national guideline on evaluation of medicines does not contain any clear indication of the subject of examination in primary and secondary pharmacodynamic studies, which can make it difficult to prepare a registration dossier in the format of a Common Technical Document. The article formulates basic approaches to expert evaluation of the results of preclinical studies of primary and secondary pharmacodynamics of medicines. It determines the basics of expert evaluation which covers methodological framework of the research, results of the research, characteristics of the safety profile, extrapolation of preclinical data, characteristics of risk factors and of the predictable clinical safety profile for patients
Рентгеновская порошковая дифрактометрия. Практическое применение в экспертизе лекарственных средств
Get PDFMethod of X-ray phase analysis based on obtaining and analyzing the diffraction pattern resulting from the diffraction of x-rays scattered by electrons of the atoms of the irradiated polycrystalline sample. Using this method in the framework of a pre-registration examination the study of pharmaceutical substances temosolomide, form I of valacyclovir hydrochloride monohydrate and quetiapine fumarate (form I) to confirm their authenticity. The results obtained allowed to conclude that the claimant substance temosolomide is not primary, and the substance of valacyclovir does not meet the stated requirements in terms of "Authenticity".Метод рентгенофазового анализа основан на получении и последующем анализе дифракционной картины, возникающей в результате дифракции рентгеновских лучей, рассеянных электронами атомов облучаемого поликристаллическо-го образца. С использованием этого метода в рамках предрегистрационной экспертизы проведено исследование фармацевтических субстанций темозоломида, формы I валацикловира гидрохлорида моногидрата и кветиапина фумарата (форма I) с целью подтверждения их подлинности. Полученные результаты позволили заключить, что представленная заявителем субстанция темозоломида не является первичной, а субстанция валацикловира не удовлетворяет заявленным требованиям по показателю «Подлинность»
Роль фармакопеи в условиях глобализации экономики стран и пути ее развития
No full textThe article reviews the process of development and the role of national and regional pharmacopoeias in the context of globalization of world economies. Three major paths of globalization identified are: enlargement of national pharmacopoeias’ area of influence, formation of supranational (regional and supraregional) pharmacopoeias and harmonization of pharmacopoeias. The article draws a conclusion on interrelation of national and regional pharmacopoeias that aim to contribute to each other’s development. Harmonization of pharmacopoeias should follow the path of alignment of test methods and analytical procedures and at the same time accommodate national factors and priorities of countries that are involved in harmonization.В статье рассмотрены процессы развития и роль национальных и региональных фармакопей в условиях глобализации мировой экономики. Выделены три основных направления развития процессов глобализации: расширение территории влияния национальных фармакопей, создание наднациональных (региональных и надрегиональных) фармакопей и гармонизация фармакопей. Сделан вывод о взаимосвязи национальных и региональных фармакопей, которые должны способствовать развитию друг друга. Гармонизация фармакопей должна идти по пути унификации методов и методик анализа, но в то же время учитывать национальные факторы и приоритеты стран-участниц гармонизации
Перспективы использования полиморфизма C3435T гена P-гликопротеина ABCB1 в персонализированной медицине
No full textThe article reviews scientific literature on C3435T polymorphism in the ABCB1 gene which encodes P-glycoprotein (an ATP-binding cassette transporter which is responsible for energy-dependent transport of substrates across cellular membranes and whose primary role consists in the prevention of penetration of various substances, such as xenobiotics, through biological barriers. C3435T polymorphism in the ABCB1 gene could be regarded as a promising pharmacogenetic biomarker which could be used in diagnostic testing after approval of the corresponding test methods. The authors of the article collected and systematized scientific data available in the electronic media (NCBI PubMed, eLIBRARY.ru) regarding medicines (such as digoxin, fexofenadine, loperamide, amlodipine, statins, etc.) for which there are integrated pharmacogenetic data on the effect of C3435T polymorphism in the ABCB1 gene on pharmacokinetic parameters, as well as on the efficacy and safety of treatment. It was demonstrated that ABCB1 gene polymorphism is of great importance for personalised medicine, however, there is a lack of awareness about all the factors that affect the bioavailability of medicines, and this precludes a significant progress in the use of ABCB1 genotyping in the near future
Регуляторные подходы к оценке биоаналогов для лечения ревматических заболеваний
No full textThe article discusses the design of development programmes for biosimilars used to treat patients with rheumatic diseases. It analyses the most popular definitions of biosimilars that are used in Russia and abroad, as well as regulatory approaches to establishing biosimilarity. The authors describe the design of confirmatory clinical trials and draw attention to the fact that equivalence margins need to be justified on both clinical and statistical grounds. The article substantiates the need to continuously improve the requirements for and approaches to the assessment of the programmes’ applicability to biosimilars evaluation.Рассмотрены вопросы планирования программ разработки биоаналогичных препаратов, которые применяют для терапии пациентов с ревматическими заболеваниями. Проанализированы основные определения биоаналогичных препаратов, применяемые в Российской Федерации и за рубежом, а также регуляторные подходы к признанию биоаналогичности. Описан дизайн подтверждающих клинических исследований. Отмечено, что обоснование границ эквивалентности должно строиться как на клинических, так и на статистических предпосылках. Обоснована необходимость постоянного совершенствования требований и подходов к оценке достаточности программ изучения этих препаратов
ЛЕКАРСТВЕННЫЕ СРЕДСТВА, СОДЕРЖАЩИЕ ЗМЕИНЫЙ ЯД: ИСТОРИЯ РАЗВИТИЯ, НОМЕНКЛАТУРА, ОЦЕНКА ПОДЛИННОСТИ
Get PDFThe article presents general data on the chemical composition and properties of snake venoms, as well as the history of their use in medical practice. It considers the differences characteristic of the venom of snakes belonging to different systematic groups. It demonstrates that venoms remain a valuable source of new medicines. The article compares existing methods of venom analysis (immunological, chromatographic, electrophoretic, mass spectrometric). Particular attention is paid to specific metho-dological aspects of identification testing depending on the object and purpose of the analysis. The article also compares different modifications of the precipitation reaction. It highlights the advantages and disadvantages of existing methods. The affordability and simplicity of immunological methods accounts for their wide use in the analysis of poisons in biological media which helps to determine the cause of poisoning. While greater informativeness of instrumental methods makes them a perfect toll for detailed examination of poison composition during poisons research and comparison. The authors of the article performed a retrospective analysis of data obtained in identification testing of snake venoms during the period from 2006 to 2017. It has been established that manufacturer specifications for individual medicinal products in some cases do not contain instructions on the use of a specific type of precipitation reaction or the description of test procedures. It was concluded that some modifications should be made to the existing method, the choice of conditions for sample preparation should be considered, or alternative methods for identification of snake venoms in medicinal products should be developed
РЕНТГЕНОВСКАЯ ПОРОШКОВАЯ ДИФРАКТОМЕТРИЯ: КОНТРОЛЬ КАЧЕСТВА ЛЕКАРСТВЕННЫХ СРЕДСТВ
Get PDFX-ray powder diffraction is one of the methods used for detection and analysis of polymorphic forms of pharmaceutical substances. The article elucidates the concept of polymorphism, briefly explains physical characteristics of this phenomenon, conditions of polymorphic transformations and the prevalence of polymorphic forms among drug substances. It should be noted that polymorphism is observed in drug substances belonging to different pharmacologic classes. Polymorphic forms of the same drug substance have different solubility, melting point, resistance to oxidation and to other destructive processes, and, consequently, different surface properties which affect both the rate of absorption of the drug substances and their stability as components of dosage forms. This calls for the need to control the quality of drug substances for potential presence of polymorphic forms. The use of diffraction methods for examination of cryomodified forms of various biologically active compounds obtained by evaporation and subsequent precipitation at low temperatures resulted in obtaining polycrystalline substances with new properties. The article provides results of examination of crystalline modifications of phenazepam in the form of α- and β-polymorphs, tilorone, fabomotizole, zolendronic acid and dehydroepiandrosterone. It was demonstrated that the use of X-ray diffraction analysis for examination and quality control of polymorphic forms of drugs is a necessary component of identification testing
Определение видимых механических включений в лекарственных формах для парентерального применения и глазных лекарственных формах
No full textThe present article describes the approaches to the choice of methods for assessing the content of visible particles in parenteral and ophthalmic dosage forms, recognized in general pharmacopoeia monograph «Visible particles in parenteral dosage forms and ophthalmic dosage forms», as well as a special approach to the assessment of visible particles in individual preparations according to the batch volume, package type, the amount of drug in a package, drug nature etc., requiring unusual conditions and evaluation criteria.Описаны подходы к выбору методик оценки содержания видимых механических включений в парентеральных и глазных лекарственных формах, принятые в общей фармакопейной статье «Видимые механические включения в лекарственных формах для парентерального применения и глазных лекарственных формах», а также особый подход к оценке видимых механических включений в отдельных лекарственных препаратах в зависимости от объема серии, вида упаковки, объема препарата в упаковке, природы лекарственного средства и др., требующих нестандартных условий и критериев оценки
Методики фенотипирования изофермента CYP3A4, применяемые для персонализации фармакотерапии
No full textThe article reviews existing methods of determining CYP3A4 isoenzyme activity. The authors assess the significance of CYP3A4 activity determination and the applicability of these methods in clinical practice to adjust drugs doses and minimize risks of adverse reactions. The article demonstrates the possibility of developing a method for simultaneous determination of several CYP3A4 substrates which is necessary to rule out potential errors arising upon introduction of other P450 cytochrome enzymes into metabolism of some endogenous substrate. It is suggested that blood should no longer be used as a biological object in the study in order to decrease the method’s invasiveness.Проведен обзор существующих методов фенотипического определения активности изофермента CYP3A4, а также оценены актуальность проблемы оценки активности данного изофермента и возможность использования данных методов в клинической практике для корректировки доз назначаемых препаратов с целью минимизации риска возникновения нежелательных реакций. Показана возможность разработки методики совместного определения нескольких субстратов CYP3A4, которая необходима для нивелирования ошибки, которая может возникнуть при включении прочих изоферментов цитохрома P450 в метаболизм какого-либо эндогенного субстрата. Предложено исключить использование крови в качестве биообъекта исследования с целью снижения инвазивности метода