SCIENTIFIC RELEVANCE. The rapid expansion of the range of medicines in the global pharmaceutical market determines the importance of periodically reviewing the range of innovative medicines and products at various stages of development.

AIM. This study aimed to determine the main trends in the development of innovative medicines.

DISCUSSION. This review presents information on the therapeutic effects and value of innovative medicinal products, outlines current approaches to their authorisation, and addresses the increase in their costs. The authors used information search, content analysis, and horizon scanning methods to prepare this narrative review. The review describes the global pharmaceutical pipeline for the second half of 2023, both generally and by specific aspects. The authors determined that over 21,000 pharmaceutical products were in development at the time, with approximately 23% of those in the later stages of development (from phase III clinical trials to the registration stage). The predominant indications for use were cancers. The authors separately reviewed innovations in the treatment of Alzheimer’s disease, as well as gene, cell, and RNA therapies.

CONCLUSIONS. A significant number of innovative pipeline medicines have a high likelihood of changing the landscape of current approaches to disease treatment, prevention, and diagnosis. With the rising costs of innovative medicinal products, the potential for change underscores the importance of introducing predictive tools, such as horizon scanning, into the national healthcare system.

SCIENTIFIC RELEVANCE. Currently, the Russian Federation lacks a comprehensive regulatory framework for the use of gene and cell therapy (GCT) products. There is no standard for conducting clinical trials for purposes other than marketing authorisation in Russia. In contrast, international practice shows that, in addition to marketing authorisation, including approval based on incomplete data with post-approval commitments, there are regulatory mechanisms for the use of unregistered GCT products, such as hospital exemptions, expanded access, or compassionate use in the European Union and the USA. Relatively recently, this framework has been reformed in East Asian countries.

AIM. This study aimed to analyse the regulatory mechanisms for translating GCT products into medical practice in East Asian countries and to assess the possibility of transferring elements of international experience to Russian practice.

DISCUSSION. East Asian countries have adopted legislation on requirements for the manufacturing and medicinal use of GCT products. These requirements include having a mandatory license for production in accordance with Good Manufacturing Practice, consideration of the rationale for the use of GCT products by regulatory authorities or special committees, risk classification of investigational GCT products, approved registries of medical institutions authorised to use GCT products, and necessary monitoring and control of patients after GCT administration. Only cellbased innovative medicines, including genetically modified cells, are used within the framework of medical technologies (Japan, China, and Taiwan) or services (Republic of Korea), and in vivo gene therapy products can be used only in investigator-initiated clinical trials.

CONCLUSIONS. The East Asian experience in translating GСT products into medical practice would be extremely useful for the Russian Federation, especially in terms of GСT use for specific indications based on accumulated clinical experience. The review suggests that it would be appropriate to establish legal provisions for investigator-initiated clinical research in Russian national legislation.

SCIENTIFIC RELEVANCE. Biowaiver is a procedure for establishing the bioequivalence of generic and reference products without in vivo studies. Regulatory requirements for this procedure, as described in a variety of documents, differ in certain features and aspects. These differences need to be analysed.

AIM. The aim was to compare international and Russian regulatory approaches to the Biopharmaceutics Classification System-based biowaivers, provide recommendations on comparative dissolution testing, and outline opportunities for streamlining the regulatory framework of the Eurasian Economic Union (EAEU).

DISCUSSION. In this article, the authors analyse biowaiver requirements and describe procedures for assessing the permeability and pH-dependent solubility of medicines, comparing dissolution profiles in various media that simulate the gastrointestinal environment, and interpreting test results. This paper shows the role of excipients in the solubility and permeability of an active substance.

CONCLUSIONS. The authors recommend a methodological approach to the biowaiver procedure for replacing in vivo bioequivalence studies with in vitro tests under the current EAEU regulatory framework and list the characteristics of medicines that limit the applicability of the procedure. In conclusion, this article provides a rationale for harmonising the existing guidelines and requirements.

SCIENTIFIC RELEVANCE. Russia is pursuing a consistent government policy of import substitution and increasing the localisation of pharmaceutical manufacturing. The Strategy for the Development of the Pharmaceutical Industry until 2030 (Pharma-2030) includes the target share of medicinal products from the List of Strategic Medicines that should be fully localised. Since biotechnological medicinal products have high consumption growth rates and are listed as strategic medicines, it is a priority to study their production localisation process.

AIM. This study aimed to analyse the degree of biopharmaceutical manufacturing localisation in Russia, considering the country of origin of active pharmaceutical ingredients (APIs).

MATERIALS AND METHODS. The study used the State Register of Medicines and sales data of the DSM Group marketing agency. The authors used custom software for the Node.js® platform to determine the degree of production localisation.

RESULTS. The analysis showed that the production process was fully localised for 25.6% (in packages) and 26.6% (in roubles) of all biotechnological medicinal products consumed in Russia in 2022. Imported medicinal products dominated the consumption structure, with a share of 33.9% in packages and 31.3% in roubles. Medicinal products with localised secondary packaging accounted for 5.8% in packages and 25.9% in roubles. Finished dosage forms produced using imported APIs had a significant share of 23.7% in packages and 6.2% in roubles. Russian APIs were used to produce 79% of the biotechnological medicinal products listed as strategic medicines, which corresponded to the full localisation of a share of the consumption structure of 10.8% in packages and 32.3% in roubles.

CONCLUSIONS. The Russian biotechnological market remains heavily dependent on imported finished medicinal products and APIs. Although the Pharma-2030 target for the production of strategic biotechnological products has been achieved, the quantitative indicators show the necessity to increase output and localisation.

SCIENTIFIC RELEVANCE. One of the challenges associated with the development of medicines lies in creating a quality management system (QMS) and tools to assess its performance.

AIM. The study aimed to propose a QMS model for the development of biotechnology-derived medicinal products and a performance evaluation tool for this QMS universally applicable in the research centre of the company regardless of the specific activities of its individual divisions.

MATERIALS AND METHODS. The study analysed internal audit outcomes, noncompliance responses, and the document flow of the research centre. Parameter values for quality index (QI) calculations were entered into validated Microsoft Excel spreadsheets. Data analysis and visualisation involved using the Microsoft Power Business Intelligence (BI) business analytics platform (mainly, the Power BI Desktop and Power BI Service components).

RESULTS. The QMS was implemented, and the authors proposed their QMS performance evaluation tool universally applicable to all the divisions of the research centre. CONCLUSIONS. The authors proposed their QMS model for the development of biotechnology-derived medicinal products and the QI tool for collecting digital data, carrying out standardised monitoring, and tracking QMS status changes. The QI tool is universal for all company departments regardless of their requirements, easy to use, and customisable by adding individual company-specific quality parameters. This makes the QI tool applicable not only to drug development departments but also to other research units.

SCIENTIFIC RELEVANCE. The high hygroscopicity and poor flowability of herbal extracts complicate the manufacturing of medicinal products based on these active substances. Microencapsulation of dry herbal extracts reduces their hygroscopicity, improves their flowability, and expands their applicability. Further development of medicinal products based on herbal extracts requires a comparative analysis of the relationships between the quality of microparticles and the selected microencapsulation method.

AIM. This study aimed to conduct a practical evaluation of a previously developed microcapsule production technology and to evaluate the quality of a microencapsulated dry extract of Lycopus europaeus L. herb.

MATERIALS AND METHODS. The study analysed a dry extract of Lycopus europaeus herb with a thyrostatic effect, which was microencapsulated by dispersion. A film-forming agent was used to form the microcapsule shells (gelatine, grade P-11). The microcapsules were characterised by the following pharmacopoeial quality parameters: particle size, moisture content, and flowability. The qualitative and quantitative analysis of the dry extract of Lycopus europaeus herb used thin-layer chromatography and spectrophotometry.

RESULTS. The study identified the optimum ratios for Lycopus europaeus herb dry extract and excipients as well as the procedure for ingredient addition during the microencapsulation process. The resulting microcapsules were homogeneous particles with a diameter of 50–300 µm, a moisture content of 3.21±0.12%, and a good flow. The encapsulation efficiency of the dispersion method reached 95.0±1.3%. In contrast to non-encapsulated dry extract particles, the particles of microencapsulated Lycopus europaeus herb dry extract had a spherical shape, smooth surface, and improved technological properties.

CONCLUSIONS. The authors developed a microencapsulation technology for Lycopus europaeus herb dry extract. The study results confirmed the efficiency of the microencapsulation method in reducing the hygroscopicity of Lycopus europaeus herb dry extract, increasing its stability during storage, and optimising the further development of dosage forms.

SCIENTIFIC RELEVANCE. Owing to specific aspects of their development and use, radiopharmaceuticals require separate rules and regulations for preclinical studies. However, current legislation and regulations on the organisation and conduct of preclinical studies of radiopharmaceuticals contain a number of contradictions and need improvement.

AIM. This review aimed to analyse the rules and regulations governing preclinical studies of radiopharmaceuticals in the Russian Federation and abroad.

DISCUSSION. The regulatory requirements for preclinical studies of radiopharmaceuticals that are conducted by specialised institutions in Russia and abroad have several shortcomings and inconsistencies. Laboratories working with animals and open sources of ionising radiation should prioritise regulations related to radiation safety. Radiation safety requirements should be in line with the sanitary standards and practical guidelines used in preclinical studies. This review covers the specific aspects of conducting preclinical studies of therapeutic and diagnostic radiopharmaceuticals. According to the review results, international guidelines for preclinical studies of radiopharmaceuticals focus on systematising the applicable requirements and aim at providing a consistent approach to preclinical studies to reduce the conduct of studies that are not informative for a specific radiopharmaceutical product.

CONCLUSIONS. Radiation safety requirements should be harmonised with international guidelines. Methodological recommendations and local regulations should be developed and approved to facilitate the resolution of regulatory issues related to the organisation and conduct of preclinical studies of radiopharmaceuticals. Many medical, social, technical, and administrative issues need addressing at the inter-institutional and/or national level.

SCIENTIFIC RELEVANCE. There is a need to move towards an appropriate system of quality assurance in pharmacy compounding. At the same time, the development of a Russian regulatory system for pharmacy compounding requires a broad understanding of international experience.

AIM. This study aimed at analysing the basic principles of pharmacy compounding regulation in the Federal Republic of Germany in order to identify best practices and determine ways to improve the legal and regulatory framework for compounding pharmacies in the Russian Federation.

DISCUSSION. According to German law, pharmacies may dispense compounded medicinal products on an oral request from a patient. The German regulatory framework provides a mechanism delineating medicinal products compounded by pharmacies and those manufactured by pharmaceutical companies. The geographical and quantitative restrictions combined with the neutral pricing policy for pharmacies facilitate the establishment of a highly effective pharmaceutical supply system. In practice, this system helps set uniform prices for medicinal products throughout Germany while preventing pharmacy chains from monopolising the pharmaceutical market. These regulations can be considered regulatory mechanisms operating at the regional (land) level. Moreover, it is of key importance that German legislation divides compounded medicinal products into stock and extemporaneous preparations.

CONCLUSIONS. German pharmaceutical practice features a number of innovations that can be borrowed for Russian pharmaceutical practice. Russian pharmaceutical legislation may benefit from adopting the concept of a “request from an individual” for dispensing compounded medicinal products that do not contain prescription-only active pharmaceutical ingredients (APIs). In order to improve the efficiency of the use of pharmaceutical-quality raw materials, including APIs, it is necessary to identify cases in which regular pharmacies can receive or purchase compounded medicinal products from compounding pharmacies and cases in which compounding pharmacies can purchase APIs from other compounding pharmacies. The authors recommend considering the possibility of defining the role, functions, and powers of self-regulating professional pharmacy organisations at various levels of governance in this social sphere of activity. Furthermore, the authors recommend creating a Russian mechanism to mitigate the risks of stock shortages and/or limited supply of medicinal products that would be similar to the German “standard authorisation” system and would encompass compounding pharmacies and pharmaceutical companies.

SCIENTIFIC RELEVANCE. Studies of the inhalation administration of chemicals are associated with challenges in designing experiments. The parameters to be selected include the experimental animal species, the inhalation chamber, and the mode of inhalation (dynamic or static).

AIM. This study aimed to analyse the practical application of regulatory requirements to non-clinical studies of the inhalation toxicity of chemicals.

DISCUSSION. This review compares international and Russian standards for studying the inhalation toxicity of chemicals, including GOST 32542-2013, GOST 326432020, GOST 32636-2020, GOST 32383-2013, and GOST 2646-2014. The improvement of the legal and regulatory framework correlates with adopting the Good Laboratory Practice and the risk-based approach to categorising test substances into hazard classes. Hazard classes are determined in rodents without dose extrapolation to humans. The authors present the differences between the main guidelines on inhalation exposure in rodent studies of acute, subacute, subchronic, and chronic toxicity. The article describes current approaches to assessing the inhalation toxicity of chemicals, which allow researchers to replace animal studies with in vitro tests.

CONCLUSIONS. According to the current regulatory standards, inhalation toxicity is studied in rats/mice, which have anatomical differences from humans. As an alternative to animal studies, researchers are developing and validating in vitro methods, which yet require regulatory review and approval.