The article analyses the problem of interchangeability of glibenclamide-containing drugs that sometimes lack therapeutic equivalence even though their bioequivalence has been proven. The authors formulated the key factors affecting interchangeability of glibenclamide drugs and highlighted conditions that compromise interchangeability. Special attention was given to clinical pharmacology of glibenclamide and adverse reactions associated with sulfonylurea products. The article offers a summary of the main groups of glibenclamide drugs. It also substantiates the need for better coordination of production and clinical use of glibenclamide drugs which will help to ensure the comparability of generic and reference glibenclamide drugs in the long run.

The 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.

The article analyses the factors likely leading to the lack of interchangeability of generic drugs for patients with functional gastrointestinal disorders (FGID). It substantiates the need for improvement of the legal basis and regulatory framework underlying drugs circulation in the Russia. Based on the modern classification of FGIDs, laid down in the article, and according to Rome IV criteria the authors formulated major concerns related to the reliability of non-adaptive assessment parameters of generics interchangeability. The article looks into genetically determined differences in the functional activity of the stomach and bowel in healthy people and people with FGIDs that preclude extrapolation of already established interchangeability to the population of patients with FGIDs. The article also highlights potential interaction of drugs that are prescribed to patients with FGIDs either for the treatment of the underlying disease or co-morbidities. It was shown that Rome IV criteria can be used (to a limited extent) in therapeutic equivalence studies of generic drugs used either as primary or concomitant medications in patients with FGIDs.

The authors of the article analysed the terms «measurement uncertainty» and «measurement error» and highlighted the main differences between them. They also analysed approaches to the assessment and expression of the measurement uncertainty that are described in the State Pharmacopoeia of the Russia, XIII edition, and guidelines of the European Directorate for the Quality of Medicines and Healthcare of the Council of Europe. The article reviews basic requirements for reporting assay results as stipulated in the guidelines of the Network of Official Medicines Control Laboratories of the European Directorate for the Quality of Medicines and Healthcare of the Council of Europe.

The article analyses scientific literature on the use of pharmacogenetic testing to optimize sulfonylurea treatment of patients with type 2 diabetes. It describes characteristics of modern sulfonylurea drugs used in the treatment of type 2 diabetes, including their mode of action, and the frequency of associated hypoglycaemia events. The authors analysed the main pharmacokinetic parameters of sulfonylureas (bioavailability, protein binding, metabolites, elimination, etc.), and adverse reactions associated with these drugs. Based on integrated data on Cytochrome P450 isoenzymes role in sulfonylureas metabolism, and determination of the role played by polymorphism of the gene encoding this fragment, the authors demonstrated the usefulness of pharmacogenetic testing combined with phenotypic (losartan) testing in the treatment of patients with type 2 diabetes.

The article analyses international experience in creating analytical databases with information on reference standards. The authors examined and compared publicly available databases, i.e. reference standards catalogues posted on the official websites of the European Directorate for the Quality of Medicines and Healthcare, the United States Pharmacopoeia, the British Pharmacopoeia, the National Institute for Biological Standards and Control. The article summarises features of each of the databases and compares the number of reference standard characteristics that are reflected in the databases. Based on the results of the analysis the authors assessed the existing international approaches to the creation of reference standards databases and determined the main information units to be taken into account while creating a reference standards database. The development of such a database will help improve and coordinate the collection and systematization of data on reference standards and promote the effectiveness of the Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products» of the Ministry of Health of the Russian Federation.

The article proposes a plan of action for assessing effectiveness and reliability of sterility testing in terms of neutralization of antimicrobial activity of residual amounts of antibiotics remaining on the membrane filters during the analysis. It was demonstrated that the proposed plan of action helps to select appropriate test conditions that rule out the possibility of obtaining false negative results for antibiotics with high biological activity that are capable of sticking to membrane filters. The article demonstrates the need for a stepwise experimental selection of test conditions using different test microorganisms in order to determine a combination of several methods for neutralization of residual amounts of antibiotics which helps to reduce costs, given that satisfactory results may be obtained at any stage depending on the nature of an antibiotic drug. The article explicitly substantiates all stages involved in determination of the completeness of membrane filters cleaning from residual amounts of antibiotics using the example of meropenem. Based on results of experiments test conditions were selected for meropenem products that ensured reliable results of sterility testing.

The article describes a newly developed procedure of quantitative determination of fluorine which is present in residual trifluoroacetates in glatiramer acetate pharmaceutical substances by¹⁹F NMR spectroscopy. Test parameters (the relaxation delay and the number of scans) were selected to minimize errors in quantitative measurements. Comparative analysis of available water-soluble fluorine-containing compounds showed that trifluoroethanol could be reasonably used as an internal standard for the determination of the absolute content of trifluoroacetic acid residues in glatiramer acetate. It was demonstrated that the new method could be used for quantitative determination of trifluoroacetates with no need for a series of reference standards and without destruction of glatiramer acetate.