At present a specific group of medicines - highly variable medicines - is distinguished based on intraindividual variability data (CV_intra > 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.

Drug licensing is the most crucial factor for effective market regulation of pharmaceuticals. The rapid development of the pharmaceutical industry, emergence of new scientific data, and changes in composition of medicinal products drive the need for introduction of variations in original registration dossiers. The process of such variation approval implemented in a particular country is the key factor in assessing the effects of the variation on the quality, safety and efficacy of the medicinal product, and sets a timelines for their realization. The present article describes existing classifications of variations, which are adopted in the European Union (EU), USA and Russia. Also the article concerns the upcoming changes in Russia in the scope of Eurasian Economic Union establishment and the necessity of harmonizing the procedure with the European Union.

The approaches to the selection of the optimal chromatographic conditions to assess the content of high molecular weight aggregates in glatiramer acetate - compounds belonging to nonbiological medicines of complex chemical structure - are described. It is found that accelerated aggregate formation occurs under stringent conditions, and in this case it is accompanied by a change in the molecular weight distribution of a basic compound. The number of aggregates formed relatively small. Samples not subjected to accelerated aging are substantially free of aggregates. Clarification of the composition and the molecular weight of the resulting units, as well as an assessment of their stability, is the subject of further research, which will recommend approaches to standardization of pharmaceutical preparations containing glatiramer acetate.

Carbamazepine is the drug of first choice in the treatment of trigeminal neuralgia, epilepsy and other neurological diseases. Carbamazepine is known to have a narrow therapeutic range, and hereby the auto-induction of its metabolism with prolonged use cause the reduction of its therapeutic efficacy. Phenotyping of patients by the rate of carbamazepine metabolism allows to perform individual drug dose adjustment and to avoid the occurrence of adverse drug effects. In order to implement the mentioned approach, the method for simultaneous determination of carbamazepine and carbamazepine-10,11-epoxide in human serum using HPLC-MS/MS was developed.

In terms of pharmacotherapy, pregnancy is a specific phase of life that is different from all the other phases of the life of medical, ethical and legal framework. The article examines the scientific, ethical and regulatory principles of inclusion of pregnant women in the clinical trials of drugs, the necessity for them is justified from the point of clinical pharmacology. The clinical value assessment studies regarding the expected benefits to the possible risks during the pharmacotherapy in pregnancy necessitates the development of this scientific direction.

The article presents generalized information about the program of the World Health Organization (WHO) related to International Nonproprietary Names (INN) of biological and biotechnological drugs. It reflects general principles for selecting INN for biological and biotechnological preparations, immunoglobulins (sera), preparations for gene therapy, glycosylated proteins and peptides, non-glycosylated proteins peptides and proteins, hybrid proteins, blood preparations, monoclonal antibodies, skin substitutes, transgenic products, vaccines, biosimilars. The conclusion was made about the need for an early solution to the global problem of assigning INN to biological and biotechnological drugs, while the number of authorized products remains relatively small.

The article presents basic opportunities of the practical use of an official website of an institution engaged in the activities of expert evaluation in the sphere of drug circulation ex exemplified by the Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products» of the Ministry of Health of the Russian Federation. It overviews promising approaches to optimization of informational and functional content of a specialized web source. It also demonstrates various ways to determine real user interest to published materials and topics. The article describes the solutions for showing the institution’s opportunities in global communications network with maximum productivity.

During the lifecycle of a medicine - from its development to consumption - the developer has to go through several stages, such as obtaining the exclusive right for a medicine, obtaining permission to produce the medicine, obtaining permission to distribute and use the medicine, i.e. the developer has to patent and register the invention and obtain a marketing authorization for it. In order to accomplish these procedures that fall within the remit of the Federal Service for Intellectual Property and the Ministry of Health of Russia, developers have to submit documents described in relevant legislative acts. The article describes the patenting procedure used by the Federal Service for Intellectual Property, including examination as to form and substantive examination. It also addresses some problems associated with patenting medicines and their state authorization. A conclusion is drawn on the importance of searching for unexpired patents and their analysis in order to prevent situations in which developers of medicines infringe the rights of others.

The present article describes the results of a comparative analysis of methods for determining the antimicrobial activity of chlorophyllipt. It mentions the aspects of serial dilution method and shows the advantages of using agar culture medium for subsequent recording of test results performed by the mentioned methods. The possibility of an equivalent use of cup and test-tube methods for the assessment of antimicrobial activity of chlorophyllipt in the form of alcohol and oil extracts has been confirmed. The necessity of exact compliance with the standards of laboratory procedures and initial verification of culture media quality was noted. During the experimental study of the antimicrobial activity of chlorophyllipt, using 4 types of microorganisms, the feasibility of using S. aureus. strain as a test microorganism has been confirmed. The experiment has shown that the choice of the method does not affect the result of the test in terms of «antimicrobial activity» and it only depends on the characteristics of the sample.

The review contains summary information about possible impurities, determination of which is described by draft monograph «fixed vegetable oils» and state standards of Russian Federation. The review briefly describes methods for determination of soaps, unsaponifiable components, residual solvents, volatile compounds, foreign fatty oils, aldehydes, moisture, proteins, paraffin, wax, tar and mineral oils, heavy metals, phosphorus-containing substances, cyanides and hydrogen cyanides.

Pharmacoeconomics is an essential component of health technology assessment and the appraisal of medicines for use by patients. As a comparatively young discipline, its methods continue to evolve. Pharmacoeconomic analysis encompass cost-minimization, cost-utility, cost-benefit, and cost-effectiveness studies, providing essential information critical for optimization of pharmacotherapy, optimal healthcare resource allocation and drug development success.

Ever since the first registrations of HIV-infections at the territory of the Russian Federation there was started a great process on arrangement and, subsequently, development of anti-HIV system. It should be noted, that increase of HIV screening and number of patients on antiretroviral treatment are the most important features of the system. Nevertheless, experts note the continuing growth of the size of infected population and, that is more important, the escape of HIV-epidemics from the groups with risk behaviors to the general population, therefore it is necessary to further increase the effectiveness of activities against HIV-spreading. In particular, it is necessary to use more rational (in the context of both the effectiveness, safety and cost) in present settings medical technologies. Pharmacoeconomic analysis is an appropriate instrument for these challenges. However pharmacoeconomic analysis within HIV-infection, like within all other disease areas, has some planning and conducting specialties. We formulated some key aspects of pharmacoeconomic analysis within HIV-infection: need for modelling; use of several criteria (virological, immunological, clinical and epidemiological); consideration of adherence to the therapy; consideration of complications costs; consideration of indirect costs.