The article analyses the results of quality evaluation of dextran substances and medicines produced thereof which was carried out by the Institution as part of pre-authorisation testing and involved the analysis of the «molecular mass distribution» parameter. The article gives recommendations on how to present data on determination of dextran molecular mass distribution by size-exclusion chromatography in corresponding sections of product specifications with due consideration for specificity of the tested products and methods of their analysis, as well as on how to interpret the obtained results. It is suggested that particular attention should be paid to the creation of a calibration curve (choice of reference standards, type of experimental curve approximation) and testing of its suitability. The validation/verification (practical testing) of procedures used for determination of dextran molecular mass distribution which was carried out as part of pre-authorisation testing, made it possible to compile a list of documents that have to be submitted to the Institution for evaluation.

The article summarizes the conclusions contained in the authors’ papers on hydrophilic interaction liquid chromatography published in 2010-2016. Chromatographic columns with amine sorbents can perform differently from chromatographic columns with nitrile sorbents in hydrophilic interaction liquid chromatography depending on the products analysed. Chromatographic columns with amine sorbents can be used in the analysis of both hydrophilic compounds and some hydrophobic compounds (nitro compounds, butylhydroxyanisole, parabens). Chromatographic columns with nitrile sorbents can only be used for the analysis of hydrophilic compounds (urea, hydroxyurea) and platinum coordination compounds.

The article summarises the results of a study which assessed the response of the cardiovascular system of cats to intravenous administration of the ansamycin class of antibiotics using commercial samples and investigational samples of rifampicin and rifabutin for injections. It was shown that intravenous administration of ansamycin solutions was accompanied by hypotensive effects of varying severity. The increase in the rate of rifampicin administration at a dose of 2.0 mg/0.5 ml/kg can result in a greater decrease of the cat’s blood pressure as compared to the effect caused by the administration of the same dose at a rate described in the monograph 1.2.4.0008.15 «Test for depressor substances». Based on the results of the study a mechanism underlying the observed effect was suggested.

The 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.

The article discusses various aspects of risk management for quality assurance (QA) of preclinical studies of drugs. The authors analysed risk management methods and approaches, and defined relevant risk management methods to be used in preclinical studies performed according to ISO 9001 and the Good Laboratory Practice principles. The article highlights the need for holistic risk management to ensure the reliability and safety of further preclinical research. The selection of a risk assessment method should be based on the analysis of the preclinical organization’s needs. The risk management activities should result in a system of corrective and preventive actions which aim to reduce risks and to assure regular monitoring.

This paper analyses modern hi-tech methods of diagnosing health problems with the help of X-ray contrast agents used in combination with such technologies as magnetic resonance imaging, single-photon emission computer tomography, etc. The lack of Russian diagnostic drugs is the main hindrance to a wide clinical use of advanced medical diagnostic technologies. The article demonstrates the necessity of developing guidelines which would standardize the scope and nature of preclinical studies for all classes of X-ray contrast agents. The article suggests the main concepts that the guidelines should contain: the definition of the term «diagnostic drug»; the classification of diagnostic drugs by their chemical structure and/or pharmacological action; the required scope of obligatory and additional studies for new drugs and for new indications for already approved drugs; the objectives of experimental pharmacokinetic studies and acceptable methods of obtaining primary data; the list of methods to be used for electronic processing of primary data; evaluation of X-ray contrast agents safety (especially radiopharmaceuticals and PET radiopharmaceuticals), and the standard protocol of test results.

The article summarises the results of a 2015 survey of healthcare professionals and pharmacists that was aimed to reveal their educational needs on the subject of interchangeable medicines. It was discovered that the respondents were not sufficiently informed about interchangeability of medicines, because independent exploration of regulatory framework does not help to get to know this topic well enough. The survey helped to identify a group of specialists who needed training in «interchangeability of medicines» more than others.

Medicinal products evaluation is quite impossible without automation systems. In order to develop and update a large number of information systems, it is necessary either to have considerable resources, or to apply the methodology of adaptive management to projects development. The article analyzes application of Agile and Scrum methods in software development and outlines the key roles of the participants and the actions they perform. It also describes general principles of commitment to communication and control of the scope of proposed requirements. The article illustrates how these methods can reduce the time spent on software development and help manage available resources to harness information systems capacity.

The article reviews scientific literature and regulatory documents on safe and efficacious use of levothyroxine medicines. Levothyroxine has less than a twofold difference between the minimal toxic concentration and minimal effective concentration. The article discusses the issue of switching between levothyroxine medicines that can be therapeutically nonequivalent while having proven bioequivalence. The article reviews results of levothyroxine medicines interchangeability studies in different countries. The authors assert the need for improving the coordination of manufacturing and the clinical use of levothyroxine medicines, which will help achieve the equivalence of generic and innovator medicines in the future.

The article summarises the results of a retrospective study of established acute myocardial infarction in men and women who were hospitalized between 2003 and 2011. Medical records of 1403 patients, 43.98 % of which were women, were analyzed. The analysis showed that myocardial infarction occurred on average 10 years later in women than in men. The women were more likely to have comorbidities including diabetes, obesity, hypertension, dyslipidemia. The analysis revealed an increase in the frequency of reperfusion therapy and coronary angiography. Laboratory test results showed that female patients had higher levels of blood glucose, cholesterol, and arterial pressure and lower hemoglobin levels and glomerular filtration rates than men. The analysis showed a five-fold increase in the frequency of prescribing statins in men and a seven-fold increase in women.

The article reviews literature data on adverse reactions to drugs. The frequency of suspected adverse reactions in indoor patients over 60 years old is 2-3 times higher than that in patients younger than 30 years. This is due to peculiarities of drugs pharmacokinetics (absorption, distribution, metabolism and excretion) in elderly patients. It might be dangerous to combine medicines that cause the QT interval prolongation. A literature review was performed in order to analyse clinically relevant interactions of drugs that are metabolized by CYP3А4 and are associated with a potential or conditional risk of torsade de pointes. It was shown that in order to increase the safety of pharmacotherapy in elderly patients, it is not recommended to prescribe two drugs at a time that cause the QT interval prolongation, nor is it recommended to prescribe combinations of drugs that could potentially lead to the QT interval prolongation due to a change in metabolism of one of the drugs.