Introduction. The chlorination reaction in the synthesis of the substance of bendamustine hydrochloride is a complex process. The presence of active adverse reactions makes scaling difficult.

Aim. Improving the performance of the technology for producing bendamustine ethyl ester in a flow microreactor.

Materials and methods. A series of experiments was carried out to carry out the chlorination stage in the synthesis of bendamustine hydrochloride in a flow microreactor with various concentrations in the initial reagent solutions.

Results and discussion. Experimental work was carried out to increase the productivity of the technology for the preparation of bendamustine ethyl ester (4-{[5-[bis(2-chloroethyl)amino]-1-methylbenzimidazol-2-yl}butanoic acid ethyl ester) by increasing the concentration of the starting reagents in the reaction mass. The conditions for conducting the chlorination reaction in the synthesis of bendamustine hydrochloride have been optimized, and possible ways to further increase productivity have been analyzed. The effect of changes in the concentration of reagents in the initial solutions and flow rates of reagent solutions on the final reaction product was studied.

Conclusion. The optimal concentrations of reagents in the initial solutions were selected, allowing to increase the productivity of the flow microreactor with a volume of 137 mL to an equivalent level of a 100 liter capacitive reactor.

Introduction. The creating an effective and safe domestic neuroprotective medicines with a complex of pleiotropic effects realized through specific orphan receptors (SUCNR1, HCA2) of glial cells, is a pressing problem of modern pharmacology and a promising possibility of pharmacotherapy of brain injury and cerebrovascular diseases. Ideally, the medicine should helps restore lost cognitive functions and physical performance after damage to the central nervous system, and its use should improve the quality of life of patients and reduce the risk of complications.

Aim. To develop composition and technology of a new medicine tablets with neuroprotective effect, using fractional factorial design of experiment and the Harrington desirability function.

Materials and methods. The shape and size of particles, physicochemical (solubility, melting point) and technological properties (bulk density, compressibility factor, fractional composition, hygroscopicity) of the pharmaceutical substance of DEAE derivative were studied according to the methods described in the State Pharmacopoeia of the Russian Federation (14^th edition). A three-factor fractional plan based on the 4 × 4 Latin square design for selection a scientifically based composition of solid dosage form was chosen. 16 experiments to test the significance of the factors were carried out. The tablets obtained according to the planning matrix were investigated for disintegration; tablet crush resistance, friability, and hygroscopicity. To optimize the quality of the tablets, the generalized Harrington desirability function was used.

Results and discussion. The study of the physicochemical and technological properties of the DEAE derivative substance showed that it is a highly hygroscopic, amorphous, white or pale yellow, odourless powder, prone to the formation of agglomerates. The powder is very easily soluble in water. Taking into account the values of the general desirability function, the best result was shown by sample № 4 consisting of mannitol, calcium stearate, and partially pregelatinized maize starch.

Conclusion. The physicochemical and technological properties of the DEAE derivative were studied. The DEAE derivative is a highly hygroscopic substance. Via the method of mathematical planning of the experiment the composition of DEAE derivative tablets was selected and scientifically grounded: DEAE derivative 60 mg, mannitol, partially pregelatinized maize starch, calcium stearate. The average tablet weight is 300 mg. The parameters of pressing tablets were selected.

Introduction. Traumatic brain injury is a damage to the brain from an external mechanical force, possibly leading to permanent or temporary impairment of cognitive, physical, and psychosocial functions. It is a leading cause of death and disability among children and young adults. In connection with the above, the objective of developing new, more effective nootropic and antiasthenic drugs in the framework of restorative neurology is considered as one of the priority tasks of medical science in Russia.

Aim. Development the composition and technology of tablets containing a hygroscopic substance using solid dispersions.

Materials and methods. The pharmaceutical substance of a diethylaminoethanol derivative having antihypoxic, neuroprotective, adaptogenic and antioxidant effects is a hygroscopic powder. PEG 6000 was chosen as a matrix for solid dispersion production. Solid dispersions were obtained by high shear mixing and hot-melt extrusion. The technological properties of granulate and the quality indicators of the tablets were determined according to the methods described in the State Pharmacopoeia of the Russian Federation (14^th edition).

Results and discussion. The lactose mixed with the DEAE-PEG composition alloy improve the technological properties of granulate.

Conclusion. A decrease water-absorbing ability of DEAE was achieved using PEG 6000 as a matrix carrier. The increase PEG content did not lead to a significant change in the kinetics of the release of DEAE from tablets.

Introduction. The aim idea of this research article is a development of the quantitative determination of a biologically active substance quinazolin-4(3H)-on derivate with laboratory cypher «VMA-10-182, by UV-spectrophotometry with followed validation. The substance is an effective remedy that combines several pharmacological effects, like an antidepressant, anxiolytic and nootropic. As a result of preclinical trials, the research compound has proven to be an effective remedy in the fight and prevention of acute cerebrovascular accident (stroke). The substance realized pharmacological effects by stimulating the production of nitric oxide by the endothelial cells of the brain. As aresult of stimulating is a vasodilation of the vessels and improvement of blood flow in the ischemic part of the vessels occur. Therefore, for introducing the biologically active substance into medical practice we need to develop ways to control the quality of substance.

Aim. The objective of this research work is to develop a method of the quantitative determination of a biologically active substance, derivative quinazolin-4(3H)-on (laboratory sypher – VMA-10-18), by method of UV spectrophotometry. The results of the research work were validated.

Materials and methods. In this research we used a substance VMA-10-18 wich was previously purified from the initial and intermediate products of the synthesis. This substance is a white crystalline powder, odorless, hygroscopic.

Results and discussion. The quantitative content of the active substance derived quinazolin-4(3H)-on has been determined. The specific absorption rate was calculated, followed by statistical processing of the results. The validation was carried out according to the «Specificity», «Linearity», «Accuracy», «Repeatability». The results indicate the effectiveness of the developed methodology and experimental reproducibility.

Conclusion. Researches of physicochemical properties show al us use 95 % ethanol as a solvent. As a result we developed a method for the quantitative determination of the substance which can be proposed for inclusion in the normative documents. The quantitative determination of the active substance in the test substance was established, and the specific absorption index was calculated. All information are statistically processed and meet the requirements of regulatory documentation.

Introduction. An innovative antifungal agent based on hydrochloride with combination of PEG-400 and PEG-1000 has been developed based at the chairs of Sechenov University. This solution is designated for external application as an antifungal agent. Naftifine hydrochloride has a broad spectrum of action against various fungi capable of causing onychomycosis. PEGs, forming part of the developed dosage form, bring about necessary viscosity of the solution (for retention in application area) and do not prevent drug product performance. Naftifine hydrochloride has an apparent UV absorption band with maximum of 256 ± 2 mn, in connection with this, it is supposed to use the UV spectrophotometry method for further development of quantitation method of naftifine hydrochloride detection in tested oral liquid.

Aim. To evaluate the feasibility of using the UV spectrophotometry method for development of quantitation of naftifine hydrochloride in its solution with a combination of PEG for mycotic infection treatment.

Materials and methods. The substance of naftifine hydrochloride, PEG-400 and PEG-1000, ethyl alcohol 96 %, UV spectrophotometry, «Millipore» filter.

Results and discussion. A set of operations was carried out with UV spectrophotometer, including trials of solutions of initial substance of naftifine hydrochloride, PEG solutions, a solution of developed prolonged antimycotic drug and its placebo. The identity of UV spectra of the actual substance in various media was determined, maximum absorption of actual substance and dependence preservation between specified concentration and optical density of the solution were proved. It was found that auxiliary substances included in liquid dosage form do not affect the main characteristics of the UV spectrum of actual substance.

Conclusion. The possibility in principle of using the UV spectrophotometry method for quantitative and qualitative analysis of innovative prolonged antimycotic drug – liquid dosage form of naftifine hydrochloride with a combination of PEG has been established.

Introduction. Sea buckthorn (Hippophae rhamnoides), the family Eleagnaceae – a promising source of biologically active substances, the traditional raw materials of which are fruits. The existing regulatory documentation (ND) lacks such an indicator of the authenticity and good quality of the fruit as «microscopy». Despite the available data on the anatomy and histology of the fruits of this type of medicinal plant material (MPM), the scientific literature does not describe the luminescence features of the tissues of sea buckthorn fruit. It is known that the luminescent features of tissues make it possible to identify the localization of biologically active structures, and also, in some cases, to conduct selective diagnosis of MPM.

Aim. The aim of this work was to study the characteristics of the luminescence of the tissues of dried crushed fruits of sea buckthorn, and also to optimize the conditions for analysis.

Materials and methods. The object of the study was the dried, crushed fruits of sea buckthorn of various species. The study of microdiagnostic signs was carried out according to the State Pharmacopoeia of the XIV RF GPA.1.5.3.0003.15 «Technique of microscopic and microchemical studies of medicinal plant materials and herbal medicines». A stereomicroscopic study was carried out on a Biomed-6 microscope. The luminescence of sea buckthorn fruit tissues was examined using a luminescent microscope of the Micromed-3 Lum brand.

Results and discussion. The most pronounced yellow glow is observed for the tissue of the pulp and epidermis of the fetus, which is associated with the highest content of fatty oil in these structures. Groups of phenolic compounds contained along with oil give a greenish tint to objects, while condensed tannins give a brownish tint. The plates that make up the corymbose hairs do not exhibit bright luminescence; a weak glow is characteristic of the joints of the hair platelets. The walls of stellate hairs have a faint greenish glow. Fragments of the actual fruit («sac») are brownish in color, without their own luminescence, as well as the seed peel. The embryo has its own greenish luminescence due to the presence of both a fatty oil and a complex of storage substances.

Conclusion. The luminescent analysis of sea buckthorn fruits was carried out for the first time. The choice of a method for preparing the studied MPM for microscopic examination is experimentally substantiated. The luminescent analysis revealed the peculiarities of the glow of the tissues of the fruits of sea buckthorn. The main microdiagnostic signs of crushed dried sea buckthorn fruits and their biometric characteristics are specified. The analysis of the obtained data will allow us to further develop the section «Microscopic signs» for inclusion in the PA project on MPM, widely cultivated and used by the domestic pharmaceutical industry for the production of herbal medicines.

Introduction. Pantoprazole sodium sesquihydrate is a proton pump inhibitor. This substance is used in the treatment of peptic ulcer of the duodenum or stomach in the acute phase, including those associated with the use of non-steroidal anti-inflammatory drugs.

Text. Pantoprazole is sodium 5-(difluoromethoxy)-2-[(RS)-[(3,4-dimethoxypyridin-2-yl)methyl]sulfinyl]benzimidazol-1-ide sesquihydrate in its structure. The substance is readily soluble in water and ethyl alcohol. The identification of pantoprazole is confirmed by infrared absorption spectrophotometry, as well as by a positive reaction to sodium ion. For the assay of this substance chemical and physico-chemical methods are used. The first group of methods includes titration in a non-aqueous medium with perchloric acid and permanganatometry. Physico-chemical methods used for pantoprazole assay are spectrophotometry and HPLC. The most commonly used method is direct spectrophotometry associated with the measurement of optical density at a wavelength of the maximum absorption of pantoprazole in various solvents. In addition, spectrophotometric methods of assay are known, based on the study of the absorption of colored pantoprazode reaction products. The derivative spectrophotometry is used for the analysis of its preparations. The control of the content of impurities and pantoprazole in the substance and its dosage forms is carried out, as a rule, using HPLC.

Conclusion. An analysis of the literature has shown that this substance is unstable. Therefore, this feature of pantoprazole must be considered when choosing excipients when developing a dosage form. The preferred method for analyzing pantoprazole preparations is HPLC, since it is possible to determine the substance in the presence of other compounds, which will allow one to control the quantitative content and stability of pantoprazole in the preparation.

Introduction. Digital colorimetry is one of the available and simple methods that can be used for the rapid detection of low-quality drugs. The main limitation of the method is its lack of selectivity. To increase the selectivity, the use of molecular sensors is proposed. Molecular sensors are substances that change color during physicochemical interaction with the analyte. Digital colorimetric analysis using a set of sensors allows one to obtain a large amount of information about the sample, however, such a significant amount of data is rather difficult to interpret and use for rapid assessment of the composition of the drug. In addition, the use of a large set of sensors significantly increases the level of information noise. To reduce the influence of the noise component, as well as to reduce the dimensionality of the data, it is advisable to use chemometric algorithms, in particular, the method of principal components (principal component analysis, PCA). It is shown that the using of PCA will make it possible to replace 24 values of the luminosity of color channels with 2-3 numerical values of the main components without loss of analytical information.

Aim. Aim of our investigation is the development of a new approach to identifying non-steroidal anti-inflammatory drugs using multisensory digital colorimetry by the principal component method.

Materials and methods. The analysis was performed in 96-well transparent polypropylene plates with flat bottom (Thermo Fischer Scientific, USA, № 430341). 100 μl of the correspond-ing sensor and 100 μl of alcohol solutions of non-steroidal anti-inflammatory substance sub-stances were consistently added to the wells of the plate. Sensor solutions were added to a separate row of wells for comparison without adding substance solutions (intact wells). After adding solutions of the substance, the plate was sealed with a film, shaken on a PST-100HL plate shaker (BioSan, Latvia) for 5 minutes and left for 20 minutes to complete the reaction. To obtain raster images an Epson Perfection 1670 office flatbed scanner (CCD matrix) with a removable cover was used. The difference in the lightness of the color channels between the analyte well and the intact well was used as an analytical signal. The obtained digital images of the cells were processed in the ImageJ program using the RGB 24 bit color model (8 bits per channel).

Results and discussion. It is shown that the use of chemometric algorithms for processing the results of multisensor colorimetric analysis allows to use the entire data array in obtaining an-alytical information, and not just the lightness values of individual channels of some sensors. The method of principal components allows you to simultaneously get rid of the noise com-ponent of the colorimetric signal and highlight the most sensitive sensors for this sample. The adequacy of the proposed combined approach is confirmed by the identification of active sub-stances in 5 drugs of the group of non-steroidal anti-inflammatory drugs.

Conclusion. The approach proposed in this work can be successfully applied as an express and available way to assess the authenticity of medications of the group of non-steroidal anti-inflammatory drugs.

Introduction. The article presents the results of the validation of our developed method – stripping voltammetry (SVA) used for mercury impurities determination in protamine sulfate. Procedure was validated in terms of specificity, accuracy, precision (repetability and intermediate precision), and LLOQ. To confirm the results of the SVA method, we choose as comparative analyzes for mercury content determination in protamine sulfate generally accepted methods: atomic absorption spectroscopy (AAS), X-ray fluorescence spectrometry (XRF), and the pharmacopeia method according to the European Pharmacopoeia.

Aim. Validation of method developed for mercury impurities determination in protamine sulphate by stripping voltammetry.

Materials and methods. Protamine sulfate solution for injection 10 mg/mL (Novosibhimpharm», Novosibirsk, Russia) was used as a study object. The method of stripping voltammetry was performed at TA-4 semi-automatic analyzer (Tomanalit, Tomsk) with VALabTx software included. At the A. V. Nikolaev Institute of Inorganic Chemistry (Institute of Inorganic Chemistry SB RAS) atomic absorption spectroscopy was perfomed. At the Pacific State University was carried out X-ray fluorescence spectrometry. We carried out the pharmacopeia method in conjunction with «Novosibhimpharm» factory.

Results and discussion. We validated the developed method for accuracy and precision. We evaluated the repetability by 10 measurements; the coefficient of variation was 7.8. We tested the intermediate precision for six measurements; the coefficient of variation was 7.9 and 7.4 for analyst № 1 and analyst № 2, respectively. According to our methodology, the mercury impurities content in protamine sulfate is 0.03 ppm. We compared our results with other generally accepted methods for the mercury determination in organic objects. When determining mercury by the AAS method, the result was ≤0.5 ppm, with XRF – 0.1 ppm. Pharmacopeia method results cannot be reliable due to the lack of repeatability.

Conclusion. We validated the previously developed method for mercury impurities determination in protamine sulfate by stripping voltammetry. The results of our method are comparable with the results of other methods, such as AAS and XRF. That Therefore stripping voltammetry can be used in quality control of protamine drug products.

Introduction. Docetaxel is widely used for cancer treatment. Actual issue for newly developed polymer-based Docetaxel formulations is applicability of current quality requirements. The technology of polymeric forms, including gamma-sterilization, are differ from actual Docetaxel injections technology. In this study were used PLGA-based particles with Docetaxel. The main attention was directed to studying qualitative and quantitative content of related impurities in polymeric forms during long-term storage and gamma-sterilization in comparison with pharmacopoeial requirements for Docetaxel injections.

Aim. Studying of possible patterns of Docetaxel-related impurities formation between intact and gamma-irradiated batches.

Materials and methods. Objects of study – lyophilizates of Docetaxel polymeric forms was previously obtained by the authors. Qualitative and quantitative analysis was performed by high pressure liquid chromatography.

Results and discussion. Docetaxel-related impurities was determined and evaluated in the intact and gamma-treated batches. It was cleared, that related substances in the gamma-treated batches was different in comparison with non-treated but after vary storage periods.

Conclusion. Docetaxel-loaded polymeric drugs shown proper stability during long term storage. The influence of gamma-treatment to Docetaxelrelated impurities content was found. Gamma sterilization can be promising method for novel drugs, but it needs individual study in the each case.

Introduction. The strategy of quality control of drugs provides for compliance with the requirements of regulatory documentation methods and critical quality indicators that determine its effectiveness. Special attention should be paid to the properties of the initial pharmaceutical substance (lipophilicity logP, area of the topological polar surface of TPSA, particle size, polymorphism), which determine the solubility and dissolution rate of the active pharmaceutical substance (APS) in terms of their impact on the bioavailability of the finished drug in vivo [1–3]. Since the assessment of pharmacopoeia solubility of APS is reduced to a visual procedure and the use of approximate terms, we have developed an original method for determining the dissolution rate of substances using the laws of chemical kinetics. Validation of the analytical method is carried out at introduction of the new method, and also at change of conditions of analysis of medicines carried out during the life cycle (product lifecycle) of a pharmaceutical product and its manufacturing process [4]. The proposed technique for laser determination of the dissolution rate in water of a medicinal substance of fluoroquinolone group has been tested; elements have been included in validation studies: repeatability, precision, linearity and range.

Aim. Development of the method for determining the dissolution rate of active pharmaceutical substances by laser light diffraction with validation elements.

Materials and methods. Determination of the dissolution rate of moxifloxacin hydrochloride was carried out in water for laboratory analysis of purity level 1 (ultra-pure water) obtained on the Milli-Q^® Integral, the quality of which corresponds to ISO 3696:1987. To achieve this goal, a pharmacopoeia method of research was used – low-angle scattering of laser light (laser diffraction method); instrument equipment – laser dispersion meter Malvern 3600 EC.

Results and discussion. An additional analytical method for determination of API dissolution rate by laser light diffraction method was developed. Validation studies on parameters: precision (repeatability, intra-laboratory/intermediate), linearity, analytical region. Precision was estimated based on the results of 18 measurements, the coefficient of variation was 8 %, the relative error of average 4 %. Linearity was determined (correlation coefficient R = 0.992). The range of application of the analytical technique depends on its purpose, is determined in the linearity analysis and ranges from 5 · 10^-3 g/ml to 5 · 10^-2 g/ml.

Conclusion. The proposed methodology can be used as an independent test of the properties of pharmaceutical substances both at the stage of their development and preclinical studies, and in the process of quality control in addition to the existing pharmacopoeia test to assess the solubility of pharmaceutical substances, expressed in terms of conditional.

Introduction. Respiratory infections are among the leaders in morbidity and mortality worldwide. The most severe cases of the disease are most often caused by the flu virus. Currently, there are many ways of specific prevention and treatment of influenza infection, but their effectiveness is far from ideal. This is due to the high variability of the influenza virus and the subsequent occurrence of resistance to the drugs used. In this regard, the improvement and development of antiviral drugs is an urgent task.

Text. Influenza virus is an RNA-containing virus that causes massive epidemics and pandemics. Specific influenza prophylaxis includes vaccination. However, antigenic variability of the virus reduces the effectiveness of the vaccine, which requires constant costly development of its more advanced modifications. Specific treatment for influenza infection includes several classes of drugs, such as neuraminidase (NA) inhibitors oseltamivir, zanamivir and M2 protein inhibitors amantadine, rimantadine. At one time, these drugs were quite effective. But the formed resistance of influenza viruses to these drugs requires the creation of new or modifications of existing antiviral agents. Among the new domestic developments of antiviral drugs, histidyl-1-adamantainethylamine, which is a modification of the rimantadine molecule, has shown sufficient antiviral activity at the stage of preclinical studies. A representative of another class of drugs is arbidol (umifenovir), an inhibitor of hemagglutinin (HA) of the influenza virus. According to studies, the drug has high profiles of efficacy and safety, but the recommendation of the World Health Organization is to continue clinical trials. Currently, clinical studies of new classes of drugs are underway – baloxavir marboxil and favipiravir. Baloxavir marboxyl is a prodrug that is converted in vivo to baloxavir, an inhibitor of cap-dependent endonuclease. Favipiravir is an inhibitor of RNA-dependent RNA polymerase. In vitro studies in cell culture and in vivo in laboratory animals have shown higher efficacy of these drugs than the above with minimal toxicity.

Conclusion. The rapid evolution of the influenza virus leads to a gradual decrease in the effectiveness of modern antiviral drugs. New compounds targeting targets important for virus reproduction are in clinical trials. The future of the fight against influenza depends on the outcome of these tests, according to which the compounds can become effective drugs for the prevention and treatment of influenza.

Introduction. The widespread use of immunomodulators in medical practice contributes to the development of their new dosage forms.

Aim. The aim of this work is to develop a transdermal therapeutic system (TTS) Galavit^® and to study a diffusion of the drug from it through the Strat-M membrane in vitro.

Materials and methods. The medicinal substance was Galavit^® in the form of a powder for the preparation of a solution for intramuscular administration («SELVIM», Russia). Saline solution, sodium dodecyl sulfate, apricot kernel oil, Decaglyn PR-20 and others were used as excipients. Heidolph DIAX900 dispersant (Germany) and ultrasonic homogenizer Heilscher UIS250V (Germany) were used to make the emulsion compositions. The delamination time and particle size of emulsion compositions were determined using the LUMiSizer dispersion analyzer (LUM, Germany). Diffusion studies of Galavit^® from TTS through the Strat-M membrane (25 mm in diameter, Merck Millipore) were carried out on the Copley diffusion analyzer (UK). Quantitative determination of Galavit^® was performed by spectrophotometry (UV-2600 Shimadzu, Japan) in the wavelength range 294–298 nm in model media.

Results and discussion. The characteristic parameters of emulsion compositions were determined during the study: the particle size varied from 0.1 to 2 µm, the delamination time – from 9 to 95 min depending on the composition. The maximum yield of the drug from the TTS was 30 % through the membrane.

Conclusion. The possibility of transdermal transfer of Galavit^® from TTS is shown in model experiments.

Introduction. HIV infection is one of the most relevant diseases from a medical, epidemiological and social point of view. Timely diagnosis, detection and control of the disease, adequate prescription of antiretroviral therapy can sufficiently reduce the viral load on the patient's body, reduce the risk of transmission of infection. Currently, combinations of various antiretroviral drugs are increasingly being prescribed as therapy. One of the most important is combination of atazanavir and ritonavir. The most important stage for the study of pharmacokinetics, studies of comparative pharmacokinetics and bioequivalence is the development of an analytical method that allows you to determine the investigated substances in human plasma. There are currently no published methods for the determination of atazanavir and ritonavir in human plasma using high performance liquid chromatography with mass selective detection using a single quadrupole mass detector. In this article presents the development and validation of a method for the determination of atazanavir and ritonavir in blood plasma after sample preparation by the method of protein precipitation.

Aim. The aim of the study is to develop a method for the quantitative determination of atazanavir and ritonavir in human plasma by HPLC with mass spectrometric detection for performing the analytical part of pharmacokinetic studies.

Materials and methods. Determination of atazanavir and ritonavir in human plasma by HPLC with mass spectrometric detection. A sample was prepared using protein deposition.

Results and discussion. The method was validated of selectivity, matrix effect, calibration curve, accuracy, precision, limit of quantification, carry-over effect and sample stability.

Conclusion. The method of the determination of atazanavir and ritonavir in human plasma was developed and validated by HPLC-MS. The analytical range of the was 50.0–10000.0 ng/mL in plasma for atazanavir and 10.0–2500.0 ng/mL in plasma for ritonavir. Method could be applied to determination of atazanavir and ritonavir in plasma for PK and BE studies.

Introduction. The inevitable of post-registration variations due to the improvement of production processes and quality control related to the integration of the modern technological solutions, replacement of equipment, suppliers of raw, consumables and packaging materials, improvement of form release or composition, administrative changes, as well as obtaining new data on clinical efficacy and safety of immunobiological medicinal products (IMP) during post-marketing studies.

Text. The purpose of this work is to analyze the post-registration changes in the life cycle of IMP «Сholera bivalent chemical Vaccine» produced by Russian State anti-plague Research Institute «Microbe», reflecting the harmonization of the documents of the registration dossier with the innovations of the Russian legislation, the optimization of production and quality control. First of all, the changes made to the registration documentation for IMP concerned the updating of the dossier in accordance with the adopted Federal laws and Resolutions of the government of the Russian Federation. The following changes related to the optimization of methods for controlling the limit content of impurities of substances used at different stages of antigen production. Also, the changes were associated with the improvement of consumer properties of the drug, namely the introduction of modern polymer packaging and several drug’s form release, convenient for use in practical health care institutions. The latest change of Pharmacopoeia enterprise article (PEA) R N001465/01-111119 regulates the application of identification means in the form of a two-dimensional bar code (QR-code) on the packaging of medicines, which is due to compliance with the requirements of article 67 «Information on medicines. The system of monitoring the movement of medicines» Federal law N 61 «Оn medicines circulation».

Conclusion. Maintaining the required level of quality of IMP when changing production technology or control requires a comprehensive analysis of the proposed changes in order to make them in the documents of the registration dossier. At the same time harmonization of documents of the registration dossier with novelties of the Russian legislation is a necessary condition for implementation of production activity within the legal field.