Somatic cell genome-editing systems are the most recent gene therapy technology to treat patients with monogenic hereditary cancer or HIV. Gene editing allows for changing or completely removing a defective gene with regularly interspaced short palindromic repeat (CRISPR), zinc-finger nuclease (ZFN), and transcription activator-like effector nuclease (TALEN) systems.

The aim of the study was to analyse the existing international experience and regulatory requirements relating to the development of medicinal products based on genome editing of postnatal somatic cells.

This article describes the mechanism of action of CRISPR, ZFN, and TALEN systems and compares their advantages and disadvantages. Regulatory and legislative authorities should take a special approach to the development, manufacture, and assessment of medicinal products based on genome editing, as well as to the ethical aspects of their use. Current requirements and recommendations for the development of medicinal products based on genome editing are mostly limited to the need to evaluate the risks of off-target effects and late-onset adverse events and the possibility to adapt clinical trial design to surrogate endpoints, exclude healthy volunteers and comparison groups, and select initial doses for clinical trials based on scientific data. Thus, a regulatory approach should also be developed for the marketing authorisation of medicinal products based on genome-editing systems.

In recent years, glycopeptide antibiotics have been widely used to treat severe bacterial infections. The long-term use of first-generation antibiotics of this group (vancomycin, teicoplanin) has contributed to the emergence of bacteria resistant to them. The problem of resistance has motivated the development of three new glycopeptide antibiotics: dalbavancin, telavancin, and oritavancin. The aim of this study was to consolidate and analyse the data from literature and current quality standards related to glycopeptide antibiotics. The article presents basic information about the discovery of glycopeptide antibiotics of natural origin (vancomycin, teicoplanin) and their derivatives (telavancin, oritavancin, dalbavancin). It briefly characterises the structures of the glycopeptide antibiotics under consideration and describes their main properties, application, and distribution in the pharmaceutical market. The article also gives information on the spectra of antibacterial activity of vancomycin, teicoplanin, and their semi-synthetic derivatives. It considers approaches to vancomycin and teicoplanin standardisation and covers the main requirements of leading pharmacopoeias for the quality of vancomycin, teicoplanin, and the corresponding medicinal products. According to the study results, glycopeptide antibiotics are still widely prescribed because of their high effectiveness in diseases caused by Gram-positive bacteria. However, at present, leading pharmacopoeias have developed and implemented quality standards only for two antibiotics of the group: vancomycin and teicoplanin. According to the results of literature consolidation, further modification of glycopeptide antibiotics is aimed at creating compounds characterised by prolonged action and greater effectiveness against pathogenic microorganisms. Thus, the attention of researchers should be directed to further standardisation of the newest derivatives of glycopeptide antibiotics: telavancin, oritavancin, and dalbavancin.

Chromatographic methods for the analysis of antibiotic degradation products are widely used to evaluate the quality of medicines. Natural multicomponent antibiotics, such as capreomycin, are the most challenging compounds in terms of developing analytical procedures for related substances. Capreomycin sulfate monographs of the leading pharmacopoeias do not contain specifications for related substances. The key requirement concerns the sum of the main components of capreomycin calculated by normalising the peak areas in the test solution chromatogram. Therefore, it is important to develop an analytical procedure for determining not only the main components but also related substances of capreomycin.

The aim of the study was to develop an analytical procedure for determining both the main components (IA, IB, IIA, and IIB) and related substances of capreomycin by ion-pair ultra-high-performance liquid chromatography (UHPLC).

Materials and methods. This study examined capreomycin sulfate powder, an active pharmaceutical ingredient (API). Capreomycin sulfate solutions were analysed after artificial degradation (alkaline or acid hydrolysis) to demonstrate the resolution, selectivity, and efficiency of the experimental chromatographic system. The authors used an Agilent 1100 liquid chromatography instrument (Agilent Technologies) and chromatographic columns: Kinetex C18, YMC-Triart С18, ACQUITY UPLC BEH C18, ACQUITY UPLC BEH C8, ACQUITY UPLC BEH Phenyl, and ACQUITY UPLC CSH C18 (experimental procedure) or Acclaim C18, Zorbax SB-C18, and XBridge BEH130 C18 (The International Pharmacopoeia procedure).

Results. In contrast to pharmacopoeial procedures, which evaluate only the component composition, the experimental procedure under the selected chromatography conditions can determine both the component composition and related substances of capreomycin. This advantage results from substituting a column packed with 1.7 µm particles for a 5 µm column required for pharmacopoeial procedures. The experimental procedure remains suitable for liquid chromatography instruments with a pressure limit of no more than 400 bar in the gradient elution mode with two mobile phases. According to the efficiency and selectivity evaluation, ACQUITY UPLC BEH C18 columns (150 × 2.1 mm, 1.7 µm) provide optimal peak resolution for capreomycin isoforms and related substances after artificial degradation of capreomycin.

Conclusions. This experimental procedure based on ion-pair UHPLC may be used in the production and stability testing of capreomycin medicines to evaluate the API quality by the content of its main components and related substances.

Gentamicin sulfate is a broad-spectrum bactericidal aminoglycoside antibiotic produced by Micromonospora purpurea and used in clinical practice as an active substance containing a mixture of gentamicins C₁ and C₂. Gentamicin content is a standardised parameter controlled as part of a pharmaceutical product review. Currently, the quality control of the active substance gentamicin sulfate involves the use of high-performance liquid chromatography (HPLC) for the indirect identification of the component composition by comparison with a reference standard and for its quantification by calibration against the reference standard.

The aim of the study was to develop a procedure for identifying and quantifying the components of the active substance gentamicin sulfate using nuclear magnetic resonance (NMR) spectroscopy that would not require reference standards.

Materials and methods. The authors studied a sample of the active substance gentamicin sulfate using an Agilent DD2 NMR spectrometer operating at 600 MHz to record NMR spectra and an Agilent 1200 HPLC system equipped with a multiple wavelength detector (MWD) to obtain chromatograms.

Results. Having determined the spectral properties of the C₁, C_1A, C₂, C_2A and C_2B gentamicins comprising the active substance, the authors observed characteristic signals of the same type that corresponded to each of the gentamicins and did not overlap with other signals in the ¹H and ¹³C spectra. These characteristic signals provided spectral markers indicative of the gentamicins of interest in the sample, with normalised integrated intensities equal to the mole fractions of the analytes. The authors compared NMR and HPLC measurements of the active substance composition.

Conclusions. The authors developed a procedure for identifying and quantifying the constituents of the active substance gentamicin sulfate by ¹H and ¹³C NMR spectroscopy, which requires less effort than HPLC procedures and no reference standards for the intended applications.

In recent years, there has been a tendency to equate the results of insulin testing by physicochemical methods with its biological activity. However, it should be emphasised that the effectiveness of insulin preparations can be judged only by the reaction of the whole organism, i.e. by the hypoglycaemic action, which is a composite indicator. The determination of the biological activity of insulin has become especially relevant with the pharmaceutical market entry of insulin bio similars, which are practically not analogous to the original medicinal products. The effectiveness of insulin products cannot be adequately evaluated using only physicochemical testing. At present, the biological activity of insulin is tested in rabbits. Additionally, the State Pharmacopoeia of the Russian Federation includes an alternative method to determine this parameter using mice. Owing to the physiological characteristics of mice, an adequate test would require special attention to the selection of test concentrations of insulin.

The aim of the study was to offer recommendations for choosing the range of insulin concentrations for determining its biological activity in mice with due consideration of changes in their sensitivity depending on the season.

Materials and methods: the authors analysed the results of testing the biological activity of insulin in female mice, bearing in mind the analytical range of the method specified in the State Pharmacopoeia of the Russian Federation. Test concentrations of insulin were selected taking into account seasonal shifts in insulin sensitivity of the animals.

Results: the study demonstrated significant dose dependence and linearity of the responses of female mice to insulin in the concentration range of 0.03–0.3 IU/mL. Therefore, this range can be recommended as a guideline for determining the biological activity of insulin in female mice. The selection of test concentrations is illustrated with specific examples.

Conclusions: the authors offer a methodological approach to the selection of insulin concentrations and the assessment of the validity of test results during biological activity determination using twin-crossover tests in female mice.

In order to obtain valid results when studying the bioavailability of medicinal products containing magnesium salts, it is necessary to take into account endogenous levels of the macroelement in the body. The aim of the study was to conduct a systematic review of the results of clinical studies on the bioavailability of medicinal products containing magnesium, to evaluate the methods used for determining the endogenous level of magnesium, and to establish the necessity for adjusting pharmacokinetic parameters according to the identified endogenous magnesium levels. The review includes data from clinical studies of magnesium bioavailability performed with healthy volunteers and published over the past 5 years. According to the literature review results, the most commonly chosen primary endpoint is urinary magnesium excretion analysis, and the most secondary endpoint is plasma or serum magnesium determination. Data sources for the review included Google’s search engine; PubMed, UpTodate®, ClinicalTrials.gov databases; and official websites of regulatory authorities (EFSA, EMA, and FDA). In most studies, endogenous magnesium levels were taken into account at all blood sampling points, and this provided an opportunity to avoid errors and misinterpretations of the results. Adjustments of pharmacokinetic parameters with regard to endogenous magnesium values were performed differently. Some studies treated endogenous magnesium values as independent variables and compared the values obtained after drug administration with them; other studies treated endogenous magnesium values as a covariate influencing the values obtained and requiring mandatory consideration; two studies involved a classical adjustment of pharmacokinetic parameters, the subtraction of endogenous values from the values obtained after drug administration. The evaluation of endogenous magnesium levels as part of bioavailability studies is necessary to adjust pharmacokinetic parameters and to obtain valid study results. It should be planned beforehand at the time of preparation of the study protocol.

Liposomes are one of the most well-known and promising nanoscale drug delivery systems. Liposomal medicinal products are successfully used in clinical practice for cardiovascular, oncological, dermatological, and other indications. The development of liposomes and their widespread implementation in clinical practice are relevant tasks.

The aim of the study was to summarise and analyse scientific data regarding the structure, composition, and classification of liposomes, as well as specific aspects of liposome production methods.

This review covers up-to-date information on marketed liposomal medicinal products. The authors illustrate how production methods affect the composition and structure of liposomes. The size and lamellarity are important characteristics of liposomes that determine the encapsulation efficiency and biodistribution of active pharmaceutical ingredients (APIs). The choice of excipients depends on the intended use of liposomal medicinal products. The article summarises the main liposome production methods, highlighting specific usage aspects, advantages and disadvantages. Conventional liposome production methods are easy to apply and do not require complex equipment, and their principal disadvantages include the low efficiency of API encapsulation within liposomes and the high complexity of scaling up technological processes. The authors pay special attention to microfluidic techniques for liposome preparation, which are characterised by a highly controlled technological process (in terms of size distribution and lamellarity), high reproducibility, and scalability to the level of industrial production and are applicable to encapsulating different APIs.

Block copolymers of ethylene oxide and propylene oxide (EO/PO block copolymers) are polymeric non-ionic surfactants with a high hydrophilic–lipophilic balance also referred to as pluronics, poloxamers, or proxanols. These compounds are among the most demanded modern excipients for the production of medicines. EO/PO block copolymers are used both in the production of traditional (liquid, semi-solid, and solid) dosage forms and as part of targeted delivery systems. The extensive application of EO/PO block copolymers is due to the diverse array of their properties, including not only solubilising, emulsifying, gelling, and other effects but also thermoreversibility, which is essential for developing in situ delivery systems and 3D printing technologies.

The aim of the study was to evaluate the potential of EO/PO block copolymers for medicinal use and to assess the range of medicinal products approved in the Russian Federation that contain EO/PO block copolymers.

This review presents an analysis of the register of poloxamer-containing medicines approved in the Russian Federation, a list of the largest manufacturers of EO/PO block copolymers in the world, and a study of the possibility to use copolymers for medical purposes. Currently, there are more than 10 chemical manufacturers producing EO/PO block copolymers for the pharmaceutical, biotechnology, and other industries around the world. EO/PO block copolymers are included in more than 60 medicinal products present in the Russian pharmaceutical market; this observation indicates the need to phase out the import of poloxamers.  

Since 2021, the marketing authorisation (MA) of new medicinal products in the Russian Federation has been carried out according to the Rules of Marketing Authorisation and Assessment of Medicinal Products for Human Use that are implemented by Decision No. 78 of the Council of the Eurasian Economic Commission dated 3 November 2016. The Member States of the Eurasian Economic Union (EAEU) must fully transition to the new regulatory framework by 31 December 2025. Therefore, MA holders are required to bring their existing product dossiers into compliance with EAEU requirements and continue submitting new product applications and dossier variations. Under the circumstances, the burden on regulatory authorities has increased significantly, regulatory mechanisms have become more complicated, and applicants have faced the challenge of swift adaptation to the latest requirements. To contribute towards the success of regulatory submissions, this article covers the sequence of regulatory procedures, the scope of work, and recommendations on dividing the procedures into stages, optimising each stage, determining goals and priorities, and assessing timelines and possible risks. To make the approval process more efficient, the authors illustrate the application of different procedures throughout a typical lifecycle of a dossier.