The article summarises the main selective and non-selective methods of physical, chemical and physico-chemical analysis which are used in medicines identification testing and which differ in selectivity, sensitivity, informative value, sample preparation, and availability. The article demonstrates that the choice of methods is governed by chemical, physical and physico-chemical properties of medicines and the type of medicine (whether it is a substance or a finished dosage form). The article describes a complex approach based on the use of several analytical methods, the cumulative results of which are used to support medicines identification.

The article analyses foreign and national recommendations on transfer of methods. It substantiates the need to adequately reproduce test methods that introduce a specific analytical procedure in testing laboratories - in order to be able to give a reliable assessment of the quality of substances and dosage forms. The article gives examples of a successful analytical method transfer, describes ways of transferring analytical procedures, cases when the transfer of method is not needed, and validation/verification parameters that are used to check whether the method is suitable for a particular laboratory. It also gives examples of validation parameters that are used in verification of pharmacopoeial methods, which are chosen based on the type of method and the tested parameter.

The article investigates the possibility of using the chromatographic column XBridge Amide 150´4.6 mm (3.5 μm) for separation of hydroxycarbamide (hydroxyurea) and its impurity (urea). The mobile phases used were the mixtures of acetonitrile and water. The separation of analytes on an amide column by hydrophilic interaction liquid chromatography is feasible if the proportion of acetonitrile in the mobile phase accounts for more than 93 %. When performing chromatographic separation on the amide column XBridge Amide, a change in the elution order of hydroxycarbamide and urea was observed, as compared to the elution on nitrile and diol columns. This type of columns can be used for chromatographic separation of a mixture of hydroxycarbamide and urea in order to perform system suitability testing when analyzing urea by HPLC.

The article provides answers to urgent questions relating to the acceptable values of disregard limits for impurities and signal-to-noise ratio ( S / N ) when checking the sensitivity of the chromatographic system. It gives recommendations on the «typical» and maximum acceptable values of disregard limits for impurities. The article also demonstrates that the requirement of S / N ≥ 10 can be unnecessarily rigid in some cases: there could be found convincing arguments justifying a smaller S / N value for the sensitivity solution, for example, in cases when an identified impurity is determined by a specific procedure and the impurity peak appears before the peak of the main substance.

The article substantiates approaches to evaluation of results obtained in preclinical safety pharmacology studies. It describes historical background for the development of regulatory requirements and methodological recommendations for performance of such studies, provides a classification of various types of safety pharmacology studies, lays down general requirements for examination of the main battery of tests as well as subsequent and additional tests, examines the aims and main tasks of such studies, and cites examples of tests. The authors define the main scope of expert evaluation which includes the methodological basis of studies, results of studies, characterisation of a medicine’s safety profile, interpretation of preclinical data, assessment of risk factors and an anticipated clinical safety profile for patients.

The article analyses the regulatory and legal framework for medicines evaluation in the Russian Federation and abroad, as well as guidelines, scientific literature and practical experience to justify criteria for evaluation of efficacy and safety of homeopathic medicines. When selecting appropriate evaluation criteria the authors took into account specificity of homeopathic medicines composition and dosage form formulation, specific characteristics of pharmaceutical substances and therapeutic action, as well as known limitations on the use of standard test methods. The key criteria for homeopathic medicines evaluation are: compliance of the substance quality and the drug production technology with corresponding pharmacopoeial requirements, substantiation of the drug composition safety, and confirmation of the proposed efficacy and safety by the evidence-based pre-clinical and clinical programme.

The article reviews scientific literature on the conduct of in vivo pharmacokinetic studies of drugs that are similar to endogenous compounds. It summarises approaches to pharmacokinetic evaluation of calcium drugs. It was demonstrated that the pharmacokinetic evaluation of drugs containing calcium ions in the form of various salts requires assessment of several parameters: parameters indicative of calcium absorption (C_max and AUC with due regard to baseline concentrations of endogenous calcium), homeostatic mechanisms which regulate the concentration of this endogenous compound (calcium excretion parameters) and hormonal regulation of phosphate and calcium homeostasis (parathyroid hormone).

The article reviews methodological approaches to the assessment of pharmaceutical substances neurotoxicity. It describes the main battery of animal tests that are conducted prior to clinical trials in order to assess drug effects on the functioning of vital body systems. The article addresses the choice of animal species, dosage and duration of pharmaceutical substance administration, as well as the conduct of clinical trials, functional tests and histological studies. It points out that an adequate justification of the study programme may help substantially reduce the number of tests. The authors assert the need to use at least two animal species in neurotoxicity studies, one of which must be a non-rodent species, in order to be able to investigate the drug safety profile during preclinical studies in as much detail as possible and to assure the required safety level for people when moving on to Phase I of clinical trials.

The article reports the results of the study which investigated the pharmacokinetics of mono- and multi-component ibuprofen-containing drugs following single oral administration to healthy volunteers. Plasma concentration of ibuprofen was determined by HPLC with spectrophotometric detection. The main pharmacokinetic parameters - C_max, T_max, AUC_0-t, AUC_0-¥, MRT, K_el, T_Ѕ - were calculated after single oral administration of the tested drugs. The pharmacokinetics of Ibuprofen/mono and Ibuprofen (pitofenone+fenpiverinium bromide) after single administration did not demonstrate any statistically significant differences, while the combination drug Ibuprofen/paracetamol did have statistically significant differences in pharmacokinetics as compared to the monocomponent Ibuprofen drug.

The article analyses international experience of information technology use in pharmaceutical data management. It investigates the possibility of using CALS/PLM-technologies for IT-based management of pharmacy-related activities as exemplified by the introduction of the eCTD format of the registration dossier. The authors provide recommendations that could facilitate the Russian regulatory system’s transition to a similar format and help use this format to create the common medicines market within the Eurasian Economic Union. A brief description of the modules included in the common technical document and their content is provided, as well as general principles of developing an electronic version of the present format. The use of a single electronic format for dossier submission will make it possible to automatically control the completeness of submitted materials and to integrate information systems used by manufactures and regulatory authorities.

The article analyses main quality assurance requirements for organizations that participate in preclinical and clinical trials and pharmacovigilance. It describes the key elements of the quality management system, provides practical advice on their implementation, and reviews the most common mistakes. The author draws attention to the necessity of implementing a holistic, risk-oriented process approach at all stages of drugs development, the importance of improving control over manufacture and circulation of investigational drugs, the need to make trial results available to general public and academic community and to apply the quality by design concept to preclinical and clinical trials in a similar way as it is now applied to drug manufacture.