Due to expiration of patents for most highly demanded biotechnological preparations there is a tendency for the increase in the number of applications for marketing authorisation of biosimilar preparations (biosimilars). In the Russian Federation, the process of bringing biosimilars to the market has just started. It should be expected that in the upcoming years the global tendency for brining biosimilars of previously authorized preparations will become real in Russia. In this regard there is a need for developing national requirements for drugs submitted for marketing authorization as biosimilars. In the present article the authors propose for consideration main approaches for selecting criteria for confirmation of biosimilarity in terms of their quality assessment and determining the amount of studies required to confirm the similarity and comparability of physical, chemical and biological properties of biosimilars in comparison with the originator.

The article describes results of comparative evaluation of two pharmacopoeial methods used for quantitative determination of tannins in herbal drugs: the titrimetric method of the State Pharmacopoeia of the USSR (XIth edition) that is described in the draft general monograph «Determination of tannins in herbal drugs» to be included in the State Pharmacopoeia of the Russian Federation, XIII edition, and the spectrophotometric method of the European Pharmacopoeia. Basic metrological characteristics of the methods were determined using oak bark as sample herbal drug. Both methods were used to test the quality of 9 herbal drug samples in which tannins were present as the main group of biologically active substances. It was revealed that the determined amount of tannins depends on the method used; and content limits are different for the two methods. Experiments were undertaken with the addition of pyrogallol. A modification of the titrimetric method of the State Pharmacopoeia of the USSR (XIth edition) was considered with a view of increasing tannins yield from herbal drugs; conclusions were made regarding the need to change the tannins limit for the modified method.

Optimization of pharmacotherapy (selection of optimal doses and dosing intervals) is a major objective of clinical pharmacology. This objective may be achieved, in part, by implementation of modern pharmacokinetic approaches and the use of therapeutic drug monitoring that consists in selection of an appropriate dose level and dosing interval based on information about drug concentrations at certain timepoints. This is particularly important for drugs with a narrow therapeutic range. The authors of the article advocate the usefulness of therapeutic drug monitoring in treating exacerbation of trigeminal neuralgia with carbamazepin and evaluate practical relevance of development of a new phenotyping method that could be used to increase pharmacotherapy efficiency and safety.

Perindopril is a prodrug which is converted to an active metabolite perindoprilat in the human organism. The present study led to the development of a fast and easily reproducible procedure for simultaneous detection of perinoprilat and its metabolite in plasma using HPLC with mass-spectrometric detector (LC-MS). Detection of the target substance was performed using atmospheric pressure electrospray ionization (API-ES) techniques in negative polarity in two modes: SIM1, ion, m/z=368,10 for perindopril and SIM2, ion, m/z=339,30 for perindoprilat. Retention time of perindopril was about 2,4 min, for perindoprilat - about 1,4 min. Sample processing was performed using solid-phase extraction. The method’s limit of quantification was equal to 1 ng/ml for perindopril and 1 ng/ml for perindoprilat. The developed procedure was used to analyse pharmacokinetics and bioequivalence of medicines containing 8 mg of perindopril. Values of all calculated pharmacokinetic parameters had no statistically meaningful differences. Confidence intervals obtained fall within bioequivalence criterion (80-125% for AUC and 75-133% for Сmax и Cmax/AUC). The medicines under analysis were found to be bioequivalent.

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The article describes arginase’s role in pathogenesis of endothelial dysfunction and a number of cardio-vascular diseases. Arginase catalyzes the hydrolysis of L-arginine, the substrate for nitric oxide synthesis, to L-ornithine and urea. Two isoforms of arginase were found in the human organism. Arginase I is located in the cells cytoplasm and is predominantly expressed in the liver. Arginase II is a mitochondrial protein that is expressed in the kidney, prostatic gland and vascular wall. Arginase II hydrolyzes L-arginine, thereby reducing the synthesis of nitric oxide and leading to the development of endothelial dysfunction and a number of cardio-vascular disorders. Arginase is a promising pharmacological target in the treatment of endothelial dysfunction and a number of cardio-vascular diseases, though the development of highly-selective arginase II inhibitors is still a difficult task.

According to EMA, advanced therapy medicinal products include, inter alia, therapeutic systems containing nucleic acids used for replacement or repair of genetic defects. Alipogen tiparvovec, a medicine containing genetic material for treatment of hereditary deficiency of lipoprotein lipase, meets these criteria. The article summarizes pathophysiological principles of this medicine action in subjects with lipoprotein lipase deficiency. The article describes the results of preclinical research conducted in mice and cats. Clinical trials revealed its efficiency in patients with hereditary lipoprotein lipase deficiency, however the period during which the drug proved efficient was rather short. Nevertheless the data obtained from alipogen tiparvovec clinical trials were convincing enough for EMA to permit its application in clinical practice.

For the purpose of prevention and treatment of various diseases, herbal medicinal products are used along with a wide range of small molecule drugs. Herewith herbal preparations are not only herbs and combined herbal products, but also various galenic and new galenic preparations and individual biologically active compounds derived from plants. The growth of demand for herbal medicinal product, the changing requirements of the regulatory system to their safety and effectiveness during the procedure of registration puts certain tasks to improve this procedure. The article provides an overview of the literature data on contemporary requirements for safety and efficacy assessment of herbal preparations. Analysis of approaches to conducting preclinical and clinical studies of herbal preparations in Russia and the international community led to certain conclusions on the degree of their harmonization and possible unification.

In recent years health care professionals came to understanding that any medical technology should be a subjected of expert evaluation. One of the key issues in the evaluationt of medical technologies is the ability to transfer effectiveness data to efficacy. Effectiveness and efficacy are also a part of translational (operational) research, transferring from basic knowledge to clinical practice. Effectiveness and efficacy studies, as well as translational research usually allow to evaluate the reasonability of the use of medical technology in a defined group of population in terms of clinical outcomes and costs. The problem of fragmented biomedical data can be solved by means of conducting translational (operational) research in which medical technology is evaluated from the perspective of fundamental science. The translation process takes quite a long time, but eventually gives a holistic and comprehensive idea about the investigational medical technology, which will allow its correct implementation into clinical practice and health care system.

One of the principle ways of improving the process of the expert evaluation of medicines is the optimization of expert evaluation timing and creation the system, preventing the occurrence of errors. For this purpose the experts of the Federal State Budgetary Institution «Scientific Center for Expert Evaluation of Medicinal Products» of the Ministry of Health of the Russian Federation are working on establishment of the concept of creating the information system that would meet all the requirements. The main objectives of the measures taken are the optimization of expert evaluations processes management, automation of manual operations associated with working activities of an expert, specific recommendations for the implementation of collection and storage of primary data, both obtained from analytical instruments and introduced by experts. The authors have considered general principles of «automated expert workplace» concept, the challenge of information technologies elaboration in the sphere of drug development, evaluation and circulation. The role of information systems at each stage of drug life cycle has been defined. A number of optimum approaches to organizing automated expert workplace have been identified.

Nternational practices comprise integrated common approaches to validation of information systems, used in pharmaceutical industry by various organizations and that affect the results of their work. The purpose ofvalidation is to assure that the results, obtained with the help of an information system are reliable. Validated system ensures accurate results and reduces the risk of errors. The article describes basic principles of the validation of pharmaceutical information systems. The principles are constituted on the basis of international requirements of OMCL system and international standards of ISO system. The article provides the classification information systems used in pharmaceutical organizations. It also describes basic concepts of validation of information systems, such as version management, validation testing, change management, requirement consideration. Basic requirements for application of risk management system to creation of concept devoted to pharmaceutical information system validation are also provided.

The analysis of national and foreign normative documents regulating modern requirements for preservative quality assessment has been performed. The need for elaboration of modern requirements for quality assessment and standardization of preservatives used in the production of immunobiological preparation in accordance with the good manufacturing and laboratory practice (GMP and GLP) has been justified. The conducted analysis has shown that the most common preservatives in immunobiological preparations are thiomersal, phenol and formaldehyde. The requirements for these preservatives have been elaborated and systematized. International and national assay methods and requirements for thiomersal, phenol, formaldehyde, have been characterized. The results of the studies have been used in elaboration of general chapters related to the assay of thiomersal, phenol and formaldehyde in immunobiological preparations. The projects of general chapters have been approved the minutes of the Board of the Ministry of Health of the Russian Federation on the State Pharmacopoeia and proposed for inclusion in the State Pharmacopoeia of the Russian Federation XIII edition. The constant increase in the range of immunobiological preparations shows the need for further research of preservatives as a part of their content, as well as for studying their properties, mechanism of action and combinations with other preservatives.

A pharmacoeconomic study is a comprehensive scientific and research activity, which should take into account specific characteristics of a research subject as well as nosology based on common methodological approaches of pharmacoeconomics,. The growing significance of the results obtained when performing pharmacoeconomic analysis involves higher requirements to the quality pharmacoeconomic studies, which is largely stipulated by the methodology used. The analysis of the features that have influence when conducting pharmacoeconomic studies has been studied as exemplified by chronic kidney disease. The aspects of the choice of effectiveness criteria for pharmacoeconomic analysis when performing the analysis of «cost-effectiveness», when analyzing «impact on the budget», have been described. It has been shown that the specificity of the analyzed disease is reflected at all stages of pharmacoeconomic studies: elaboration of study design, choice of performance criteria, determination of the research costs profile, implementation of particular methods of pharmacoeconomic analysis, interpretation of the results of pharmacoeconomic evaluation. It was found that pharmacoeconomic analysis of renal replacement therapy in patients with chronic kidney disease is the most specific.