Vital Medicines Research Articles

State Pharmacopoeia of the Russian Federation Edition XV: Development Priorities

INTRODUCTION. Regular reviews of the current portfolio of general chapters and monographs are essential to ensure the well-balanced development of the State Pharmacopoeia of the Russian Federation (Ph. Rus.) in line with the priorities of the national healthcare system.AIM. This study aimed to identify the most promising areas for further Ph. Rus. development through an analysis of recent legislative changes in Russia and the current compendial portfolio.DISCUSSION. This article compares Ph. Rus. editions XIV and XV, analyses the key features and structure of edition XV, and reviews amendments to the regulations governing the Ph. Rus. publication. The current compendial portfolio is dominated by monographs on chemical active substances; it also includes a substantial number of monographs on herbal drugs and herbal drug preparations. Noteworthy, edition XV is the first Ph. Rus. edition to include a separate section dedicated to monographs on excipients necessary for the development of pharmacy compounding. Moreover, this article analyses the coverage of active substances that are used for the production of listed vital and essential medicines.CONCLUSIONS. The authors outlined the priority areas for the development of quality standardisation. The Ph. Rus. should continue developing monographs on active substances that are used for the manufacturing and compounding of listed vital and essential medicines. In addition, the coverage of herbal drugs should be expanded. The Ph. Rus. should develop monographs on excipients that are used for the manufacturing and compounding of medicinal products. Finally, the Ph. Rus. should complete the development of requirements for biological medicinal products and relevant test methods.

Mechanism of customs regulation of the import of pharmaceutical products

One of the main features of the Russian pharmaceutical market is that imported pharmaceutical products significantly predominate in its structure according to the criterion of origin. The high share of imports of medicines is due to the need to provide the population with high-quality medicines, including vital medicines, analogues of which are not produced in the Russian Federation. In this regard, consideration of issues related to the customs regulation of imports of pharmaceutical products is particularly relevant. The mechanism of state management of the foreign trade sphere covers a variety of instruments that have a direct or indirect impact on current economic processes, the main of which is customs regulation. The priority area of the customs mechanism is the formation of a favorable economic environment for national production. The customs authorities of Russia are directly involved in regulating the import of pharmaceutical products in order to ensure the economic security of Russia, monitoring compliance with relevant prohibitions and restrictions by participants in foreign economic activity. In the course of the conducted research, it was found that the mechanism of customs regulation of the import of pharmaceutical products is crucial in the formation of foreign trade turnover of goods of the studied commodity group.

СОВРЕМЕННЫЙ ФАРМАЦЕВТИЧЕСКИЙ РЫНОК АНТИБАКТЕРИАЛЬНЫХ ПРЕПАРАТОВ ДЛЯ ЛЕЧЕНИЯ ИНФЕКЦИЙ В АМБУЛАТОРНЫХ УСЛОВИЯХ

The article presents the results of the analysis of systemic antibacterial drugs registered in the State Register of Medicines [4] and available medicines in pharmacy organizations in Voronezh. Antibiotics and synthetic antibacterial agents are one of the most important groups of medicines, since many of them are included in the list of Vital and essential medicines [5]. Despite the overall improvement in the quality of life, infectious diseases have been and remain a serious health problem worldwide. The growth of antibiotic resistance pushes scientists to search and develop new drugs with the necessary spectrum of action and resistance [1]. This, in turn, obliges pharmaceutical and medical professionals to study the ever-expanding range of medicines in pharmacy organizations to prescribe effective treatment [2]. At the same time, specialists need to take into account external and internal factors affecting the pharmaceutical market in the Russian Federation in order to prescribe to patients not only high-quality and effective, but also affordable drugs. Thus, it was revealed that at the time of the study, 38% of all registered antibacterial drugs were located in Voronezh. Some International nonproprietary names (INN), including in the list of Vital and essential medicines, are completely absent in pharmacies (polymyxin b and daptomycin). In general, there is an active growth in the rate of registration of new drugs in the pharmaceutical market of the Russian Federation. In this article, using mathematical analysis methods, the percentage ratio of ATС groups [3,6] in the assortment of antibacterial drugs of systemic action is determined, the most common drugs and dosage forms in pharmacy organizations, as well as their manufacturers, were identified.

АНАЛИЗ РОССИЙСКОГО РЫНКА ЛЕКАРСТВЕННЫХ ПРЕПАРАТОВ, ПРИМЕНЯЕМЫХ ДЛЯ ЛЕЧЕНИЯ ГАСТРОДУОДЕНИТОВ У ПОДРОСТКОВ

The Russian pharmaceutical market (RPhM) has a large assortment portfolio of medicines (MP) used to treat various diseases of the digestive system. But not all of these drugs are approved for use in children and adolescents. Due to their insufficient safety for this age group, it is necessary to be more careful in the selection of suitable medicines that will not be inferior in effectiveness to other drugs used in adults. So, in particular, some medicines used for the treatment of digestive organs are included in the List of vital and essential medicines, according to the decree of the Government of the Russian Federation dated 12.10.2019 No. 2406-r "On approval of the List of VED for 2023, as well as lists of medicines for medical use and the minimum range of medicines necessary for the provision of medical care." The purpose of this study was to analyze the range of drugs on the Russian pharmaceutical market used for the treatment of gastroduodenitis in adolescents. In the course of the study, various official information sources about medicines registered in the territory of the Russian Federation were reviewed and studied: the Register of Medicines of Russia "RADAR" (2023), Internet sources, collections and forms containing statistical data. Research methods: content analysis, ranking, graphic, structural, segmentation, comparative. A marketing study of the product portfolio was conducted, its structure was formed, and a macro-contour of RPhM drugs used for the treatment of gastroduodenitis in adolescents was developed. Research methods: content analysis, ranking, graphic, structural, segmentation, comparative. A marketing study of the product portfolio was conducted, its structure was formed, and a macro-contour of RPhM drugs used for the treatment of gastroduodenitis in adolescents was developed.

Treatment of chronic viral hepatitis c in perm Krai

Objective. To analyze the effectiveness of etiotropic antiviral therapy with direct antiviral drugs against chronic viral hepatitis C in the adult population of the Perm Krai.
 Materials and methods. In the regional register of Perm Krai, 20095 patients with chronic viral hepatitis C were registered. In 2019–2021, antiviral therapy with direct antiviral drugs, registered in the Russian Federation, and included in the list of vital and essential medicines for medical use was prescribed to 282 patients with chronic hepatitis C. There were 137 men (48.6 %), 145 (51.4 %) – women. The age of the patients ranged from 26 to 82 years, the duration of the disease – from 3 to 25 years.
 Results. All the therapy regimes we used showed 100 % effectiveness in the population of patients suffering from chronic hepatitis C associated with mild liver fibrosis regardless of genotype, whereas in the population of patients with grade 3 fibrosis or liver cirrhosis, 100 % effectiveness was achieved only after the use of sofosbuvir-containing schemes. The pangenotypic schemes resulted in 100 % achievement of a stable virological response among patients with genotype 1 regardless of the stage of liver fibrosis and previous therapy experience. In the treatment of patients infected with genotype 3 of hepatitis C virus with severe fibrosis, the effectiveness of 100 % was noted after the use of sofosbuvir-containing regimes.
 Conclusions. Among the adult population of Perm Krai, the overall effectiveness of therapy in patients with chronic hepatitis C, who used direct antiviral drugs, was 97.8 %.

Anti-Inflammatory Effects of Clematis terniflora Leaf on Lipopolysaccharide-Induced Acute Lung Injury.

For centuries, natural products are regarded as vital medicines for human survival. Clematis terniflora var. mandshurica (Rupr.) Ohwi is an ingredient of the herbal medicine, Wei Ling Xian, which has been used in Chinese medicine to alleviate pain, fever, and inflammation. In particular, C. terniflora leaves have been used to cure various inflammatory diseases, including tonsillitis, cholelithiasis, and conjunctivitis. Based on these properties, this study aimed to scientifically investigate the anti-inflammatory effect of an ethanol extract of leaves of C. terniflora (EELCT) using activated macrophages that play central roles in inflammatory response. In this study, EELCT inhibited the essential inflammatory mediators, such as nitric oxide, cyclooxygenase-2, tumor necrosis factor-α, interleukin- (IL-) 6, IL-1β, and inducible nitric oxide synthase, by suppressing the nuclear factor-κB and mitogen-activated protein kinase activation in macrophages. Acute lung injury (ALI) is a fatal respiratory disease accompanied by serious inflammation. With high mortality rate, the disease has no effective treatments. Therefore, new therapeutic agents must be developed for ALI. We expected that EELCT can be a promising therapeutic agent for ALI by reducing inflammatory responses and evaluated its action in a lipopolysaccharide- (LPS-) induced ALI model. EELCT alleviated histological changes, immune cell infiltration, inflammatory mediator production, and protein-rich pulmonary edema during ALI. Collectively, our results may explain the traditional usage of C. terniflora in inflammatory diseases and suggest the promising potential of EELCT as therapeutic candidate for ALI.

Sorry for the Delay: How FAA Regulations in the U.S. are Stifling Innovation and Hindering the Growth of a Promising New Industry Based on Delivery Drones

From the creation of the transistor radio to robots powered by artificial intelligence, the rapid pace of technological advancements in a multitude of industries has ushered in an innumerable amount of economic, environmental, and social benefits that have collectively produced positive effects around the world. However, in addition to benefits, these rapid advancements in technology have created a particular problem affecting many industries in the United States—antiquated regulations that were promulgated for a particular industry become inefficient and impractical due to rapid technological advancements within that industry. The delivery drone industry, a blossoming new sector of air commerce that has grown exponentially in the past decade, has become the latest victim of regulatory stagnation. The Federal Aviation Administration (FAA) currently regulates commercial delivery drone operations in the U.S. by issuing highly restrictive Part 135 certifications that attach a variety of operating limitations to companies’ delivery drones, such as restricting the traveling distance and airspace location. If companies want to conduct any drone deliveries that fall outside of the strict limitations set by Part 135 certifications, which is the only way to expand their operations to an appropriate commercial scale, those companies must receive exemptions and waivers from the FAA. However, the FAA grants these crucial exemptions and waivers on a case-by-case basis with standards and limitations that vary drastically from company to company. As a result, the FAA has created an unpredictable regulatory minefield that has hindered the expansion of delivery drone operations in the U.S., thus deterring innovation within the drone industry as a whole. Rather than accepting regulatory standards that inhibit the growth of an entire industry, the FAA should adopt a streamlined, standardized certification and approval process for delivery drones that efficiently facilitates the advancement of commercial delivery drone operations in the U.S. This Comment examines the various issues plaguing the current regulatory framework for commercial drone delivery services within the U.S. and seeks to provide a possible solution to these obstructionist regulatory standards through the adoption of a streamlined regulatory scheme for commercial delivery drones. To conduct a full analysis on this topic, this Comment first examines the historical development of the FAA’s current regulations governing commercial drone delivery services, addresses how the current case-by-case exemption process established by the current regulatory regime places an illogical hindrance on the growth of a blossoming industry, and highlights other specific problems plaguing the current regulatory process, echoed by the outcries of various drone industry stakeholders. Additionally, as an alternative solution to the current piecemeal regulatory regime, this Comment argues that Congress, and subsequently the FAA, should adopt the Increasing Competitiveness for American Drones Act of 2023 (American Drones Act) that creates a comprehensive, streamlined regulatory framework for drone delivery services. Finally, this Comment explains how the adoption of the American Drones Act would produce various economic, environmental, and social benefits for millions of individuals across the U.S.—such as the ability to efficiently scale BVLOS drone operations, emissions reduction, and increased consumer access to healthy foods and vital medicines.

Infectious diseases in Afghanistan: Strategies for health system improvement.

Afghanistan is grappling with a severe health crisis marked by a high prevalence of infectious diseases, particularly tuberculosis, malaria, HIV, and the added strain of the COVID-19 pandemic. The nation's healthcare system, already fragile, faces formidable challenges. Socioeconomic constraints, including limited resources and financial barriers, hinder healthcare accessibility, leading to delayed or inadequate care. Environmental factors, such as poor sanitation and crowded living conditions, exacerbate the transmission of diseases, especially waterborne illnesses. Governance issues, encompassing transparency, corruption, and political instability, disrupt healthcare efficiency and resource allocation. Addressing these multifaceted issues is vital to enhance Afghanistan's healthcare system and overall well-being. The withdrawal of international support has exacerbated these challenges. The primary research goal is to deeply understand Afghanistan's health system, focusing on the major disease burdens: Tuberculosis, Malaria, AIDS, COVID-19, Measles, Hepatitis, and Cholera. The study aims to assess the feasibility and effectiveness of current approaches, presenting a comprehensive view of challenges and opportunities within the Afghan healthcare system. The research concludes by highlighting policy implications, practical implementation, and offering recommendations for future endeavors. This paper provides a thorough analysis of the literature concerning infectious diseases in Afghanistan and the enhancement of the healthcare system in the nation. A systematic exploration of the literature was conducted through PubMed and Google Scholar databases. The search terms used encompassed "Tuberculosis" OR "TB," "Malaria," "acquired immunodeficiency syndrome" OR "AIDS," "Human immunodeficiency virus" OR "HIV," "COVID-19," "Measles," "Hepatitis virus," "Cholera," "Health system improvement," and "Afghanistan." Additionally, external sources like UNICEF, CDC, and WHO were referenced. In conclusion, while improving access to vital medicines and vaccines is crucial for enhancing health outcomes in Afghanistan, significant challenges must be addressed to ensure the effectiveness and sustainability of such strategies. The Afghan health system's fragile governance, corruption, logistical complexities, and failure to address broader social and economic factors pose significant risks and obstacles to the implementation of proposed health strategies. Therefore, the strategies discussed in this analysis align with key Sustainable Development Goals, particularly SDG 3, and their successful implementation will have implications not only for the health and well-being of Afghanistan but also for global health. Hence, by adopting a comprehensive approach with complementary interventions as discussed, we can address issues in the Afghan health system and reduce transmissible diseases' burden, thereby building a better world for all.

Revisiting the Landscape of Potential Small and Drug Substance Related Nitrosamines in Pharmaceuticals

N-Nitrosamines are a class of indirect acting mutagens, as their metabolic degradation leads to the formation of the DNA-alkylating diazonium ion. Following up on the in-silico identification of thousands of nitrosamines that can potentially be derived from small molecule drugs and their known impurities described in a previous publication, we have now re-analyzed this dataset to apply EMA's Carcinogenic Potency Categorization Approach (CPCA) introduced with the 16th revision of their Q&A document for Marketing Authorization Holders. We find that the majority of potential nitrosamines from secondary amine precursors belongs to potency categories 4 and 5, corresponding to an acceptable daily intake of 1500 ng, whereas nitrosamines from tertiary amine precursors distribute more evenly among all categories, resulting in a substantial number of structures that are assigned the more challenging acceptable intakes of 18 ng/day and 100 ng/day for potency categories 1 and 2, respectively. However, the nitrosative dealkylation pathway for tertiary amine is generally far slower than the direct nitrosation on secondary amines, with a direct nitrosation mechanism suspected only for structures featuring electron-rich (hetero)aromatic substituents. This allows for greater focus towards those structures that require further review, and we demonstrate that their number is not substantial. In addition, we reflect on the nitrosamine risk posed by secondary amine API impurities and demonstrate that based on the ICH Q3A/B identification threshold unknown impurities may exist that could be transformed to relevant amounts of NA. We also demonstrate that the analytical sensitivity required for the quantification of high potency nitrosamines can be problematic especially for high dose APIs. In summary, the regulatory framework rolled out with the latest Q&A document represents a substantial improvement compared with the previous situation, but further refinement through interaction between manufacturers, regulators, not-for-profit and academic institutions will be required to ensure patient access to vital medicines without compromising safety.

Theoretical and practical approaches to pharmaceutical safety

Over the years the pharmaceutical system of the Republic of Moldova as a component of the healthcare system has faced many problems, such as the reduction of both availability due to the disappearance of vital medicines from the pharmaceutical market, and affordability due to the imperfection of the drug pricing mechanism; the involvement of non-specialists in pharmaceutical activities, which leads to a drastic decrease in the quality of pharmaceutical services; monopolization of some processes and products in the chain of drug supply actions, etc. In recent years, various aspects that directly or indirectly related to pharmaceutical safety (PS) and related health risks have been increasingly discussed in the Republic of Moldova.
 Aim. To substantiate theoretically and scientifically the concepts of PS using the principles of the systematic approach and assess the quality and degree of legislative support for pharmaceutical safety in the Republic of Moldova. 
 Materials and methods. The research was conducted according to the methodology based on the systemic approach, including analysis and synthesis; the study of factors and processes; decomposition and construction of systems; the analysis of legislation; the argumentation and preparation of draft legislative acts, norms, strategies, programs.
 Results. The analysis conducted in the course of the study demonstrates that the concept of “pharmaceutical safety” in different countries by different authors covers several aspects – the quality, safety and effectiveness of medicines, their transportation and storage according to the requirements, availability and import independence, their ethical development and promotion, their rational use, etc. In the course of the study, the definition of factors affecting and characterizing the PS system was proposed – “elements that determine the functionality and characterize the state of the pharmaceutical safety system in the country”. Three groups of factors affecting and characterizing the PS system of the Republic of Moldova were argued. Based on the classification of the factors, the method of analysis using the quantitative and qualitative expertise was developed. The quality of the PS system in the Republic of Moldova was assessed taking into account the current state of the safety level. To assess the quality of this system, the 7-point scale was used, the relative quality coefficient was determined, which was – 1.03; experts rated the quality of the PS system as “low”. To determine the degree of legislative coverage of the PS system, the algorithm was developed; it was used as a methodological tool for determining the degree of legislative and regulatory coverage of the PS system. The results of the studies allowed the elaboration of legislative proposals, which were put forward and adopted.
 Conclusions. The legislative framework of the PS system was created by the adoption of Law No. 312 of 30.11.2018, which amended the Law on pharmaceutical activities, the Law on medicines, the Law on health protection, the Law on state material reserves and mobilization. The advanced training program in the field of pharmaceutical management and legislation to train practicing pharmacists has been supplemented with the topic “Pharmaceutical safety”.

Experience with nusinersen as a pathogenetic therapy in adult patients with spinal muscular atrophy 5q in the Republic of Bashkortostan

Background. Spinal muscular atrophy (SMA) affects 1 in 11,000 people. Until 2016, this was considered an incurable disease, but after the approval of nusinersen, the situation has changed. The efficacy of nusinersen therapy is also known in adult patients, although research is limited due to the majority of studies in infants and children. Nusinersen has been included in the list of “Vital and Essential Medicines” since 2021.Aim. To analyze the experience of using nusinersen as a pathogenetic therapy for patients over 18 years of age with SMA 5q in the Republic of Bashkortostan.Materials and methods. We examined eight patients receiving pathogenetic therapy with nusinersen (SMA type 2 – 34.5 %, SMA type 3 – 65.5 %). The Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM) were used for evaluating the effectiveness of therapy.Results. The median increase on the HFMSE scale was +2 points (7.5, with the initial 5.5) and on the RULM scale – +4.5 points (17 points, with the initial 12.5). Clinically, this was expressed in an increase in muscle strength, an increase in daily activity; a decrease in bulbar, respiratory and vegetative disorders can also be noted. Subjectively, positive dynamics was noted in the increase in working capacity, improvement of the emotional background.Conclusion. The use of the drug nusinersen in adult patients with SMA 5q in some cases provides clinical improvement. The presence of an “overall response” is defined as clinically significant change in one assessed measure of motor function.

Optimal Patent Protection Length for Vital Pharmaceuticals in the Age of COVID-19

The highly unequal access to COVID-19 vaccines observed at a critical moment of the pandemic coupled with the considerable profits cashed by the main vaccine producers have brought the debates on patent protection back into sharp focus. The trade-off between the need to encourage innovation through patent protection and the right of populations across the world to access life-saving pharmaceutical products raises important concerns that go beyond innovation stimulation. This paper leans on the inclusion of non-economic considerations based on social identity theory in optimization strategies to analyze the arguments underlying the patent length in the pharmaceutical industry and questions the measurement of social benefits of innovation in the Nordhaus’s model in its applicability to the case of vital pharmaceuticals. It proposes some new considerations akin to extra welfarism in the microeconomic analysis of the social welfare underlying traditional arguments in support of long patent protection periods. Simplified comparative statics are employed to show that, from the social welfare point of view, an incentive system in which a reward equivalent to the discounted profits is remitted to the innovator yields higher social welfare than monopoly protection without diminishing the incentive to innovate. These results suggest that in the case of vital medicines such as vaccines and antiretroviral drugs for HIV/AIDS treatment, social welfare is maximized by imposing compulsory licensing and making treatment accessible to all (potentially) infected citizens.

МОДЕЛИРОВАНИЕ ОТБОРА ЛЕКАРСТВЕННЫХ ПРЕПАРАТОВ В ПЕРЕЧЕНЬ ЖИЗНЕННО НЕОБХОДИМЫХ И ВАЖНЕЙШИХ ЛЕКАРСТВЕННЫХ ПРЕПАРАТОВ ПО КАЧЕСТВЕННЫМ ПОКАЗАТЕЛЯМ

Abstract. The variety of medicines in circulation on the pharmaceutical market causes the problem of rational choice of medicines for their inclusion in restrictive lists. To form a list of vital and essential medicines (VED), the regulator uses certain rules approved at the legislative level. It should be noted that the determining factor for rational therapy is the evaluation of medicine in terms of the ratio "efficacy / safety". Based on this, the purpose of this study was to develop the process of graphical modeling process when the medicine is included in the VED list in terms of its qualitative characteristics – efficiency and safety. The source was data from Appendix No. 6 "Integral scales of the comprehensive evaluation of a medicinal product" to the " Rules for the formation of lists of medicines for medical use and the minimum range of medicines necessary for the provision of medical care". The developed modeling process eliminates the need to evaluate all indicators in case of obtaining a negative qualifying result in its initial parts, eliminates the need for mathematical operations, and competently ranks the criteria of the selected medicine to the comparison medicine, thus allowing to choose the most preferable option in the case of evaluating several medicines of a single action and significantly speeds up the procedure for a comprehensive assessment of medicine. The model enables the regulator to have a clearer decision-making procedure for the formation of a defining restrictive list of VED in the Russian healthcare system. Thus, the proposed graphical model makes it possible to simplify and, thereby, expedite the process of including medicines in the list of vital and essential medicines of VED.

ИСПОЛЬЗОВАНИЕ СОВРЕМЕННЫХ ИНФОРМАЦИОННЫХ ТЕХНОЛОГИЙ НА ФАРМАЦЕВТИЧЕКИХ ПРЕДПРИЯТИЯХ

Abstract. The article analyzes the current conditions for the development of the Russian pharmaceutical market and new information technologies, the use of which today is a key factor in the successful development of pharmaceutical enterprises. The risks of information support at domestic pharmaceutical enterprises in the conditions of external sanctions pressure are investigated. As you know, the health sector is not subject to sanctions for humanitarian reasons, so the supply of vital medicines and vaccines to the country continues. However, it is not possible to completely avoid the indirect impact of the most extensive restrictions on the pharmaceutical industry. Many drug manufacturers already are facing disruptions and disruptions in their logistics chains, difficulties are experienced in purchasing raw materials (active pharmaceutical substances and excipients) and packaging materials previously supplied in large quantities from the countries of the European Union and the United States of America. The restrictions imposed against the information technology industry contributed to the indirect impact on the pharmaceutical industry. Therefore, an analysis of possible risks of information support at domestic pharmaceutical enterprises was carried out and proposals were put forward to overcome the imposed restrictions, prospects for further development were considered. In order to achieve this goal, the risks of the information technology sphere were analyzed in general and the main factors affecting the stability of the information support of pharmaceutical organizations were identified. Alternative ways of replacing foreign information platforms with their own domestic developments in the IT field are proposed, allowing businesses, in particular pharmaceutical companies, to automate their internal and external processes, as well as protect their data

Inside Back Cover: Expeditious Access to Morphinans by Chemical Synthesis (Angew. Chem. Int. Ed. 27/2022)

The morphinan alkaloids , especially codeine and morphine, are derived from the opium poppy and have been used for millennia for pain management. They remain vital medicines today, but climate change and geopolitical uncertainties threaten existing supply chains. In their Communication (e202203186), Martin G. Banwell, Ping Lan, and co-workers detail by far the shortest synthesis of (−)-codeine reported to date, which involves a total “in-flask” time of less than 24 hours.

Analysis of adverse reactions of anticancer drugs in the Chuvash Republic

Due to the implementation of the national program “Fight against Oncological Diseases”, a number of anticancer drugs, mainly for targeted therapy and immunotherapy, are annually registered in Russia and included in the list of vital and essential medicines [1]. Purpose: to study the structure of adverse reactions (ADR) when using anticancer drugs based on the analysis of spontaneous reports in the Chuvash Republic for the period 01.09.2008 to 31.12.2021.

Drug shortages in low- and middle-income countries: Colombia as a case study

BackgroundDrug shortages are a global problem. Analyzing shortages worldwide is important to identify possible relationships between drug shortages across countries, determine strategies that reduce drug shortages, and reduce the inequality in access to medicines between countries. In contrast to well-documented shortages in high-income countries, there are few studies that consider low- and middle-income economies. We evaluate drug shortages in one middle-income country, Colombia.MethodsWe collected data from INVIMA, the institution responsible for managing medicine shortage alerts in Colombia. We classified the data using the Anatomical Therapeutic Chemical (ATC) classification system and analyzed them using descriptive statistics. We considered a study period from 2015 to 2021 (vital medicines) and from 2010 to 2020 (non-vital medicines).ResultsIn total, 173 unique ATC codes were in shortage. These included antidotes, alimentary tract and metabolism products, anesthetics, cardiac stimulants and antithrombotic agents. The major causes were manufacturing problems and few suppliers. Drug shortages substantially increased from 2020 to May 2021 due to the COVID-19 pandemic. Among resolved shortages, the average duration was 1.6 years with a standard deviation of 1.9 years. The longest, naloxone tablets, were in shortage for almost 10 years.ConclusionsDrug shortages are a persistent problem in Colombia. Government institutions have made progress in implementing systems and procedures to report them. However, the approaches implemented need to be maintained and refined. This study lays the groundwork for the analysis of drug shortages in other LMICs. We highlight the necessity of addressing drug shortages in their global context and reducing the inequality in access to medicines between countries.

Interchangeability for Biologics is a Legal Distinction in the USA, Not a Clinical One.

Biologics are increasingly vital medicines that significantly reduce morbidity as well as mortality, yet access continues to be an issue even in apparently wealthy countries, such as the USA. While patient access is expected to improve with the introduction of biosimilars, misperceptions in a significant part based on terminology continue to make a sustained contribution by biosimilars difficult. Patients are and will continue to suffer needlessly if biosimilars continue to be impugned. Consequently, it is increasingly urgent that semantics are clarified, and in particular, the implication that interchangeable biologics are better biosimilars dismissed. This paper distinguishes between the real differences between biologics that matter clinically to patients and discusses the actual meaning of a US Food and Drug Administration designation of interchangeability for a biosimilar product. This will help highlight where there is need for further Food and Drug Administration education and which stakeholders likely need that education the most.

Development and Validation of a Method for Determining Deferasirox in Human Blood Plasma by HPLC-UV

Introductio n. Deferasirox is one of the most well-known complexing drugs chelators and is successfully used in chelating therapy for the treatment of excess iron in the human body. Deferasirox is also included in the list of vital and essential medicines, which indicates the importance of this drug for Russian healthcare. In this document, there are drugs only from a foreign manufacturer, therefore, within the framework of the trend towards import substitution, the development of deferasirox preparations of domestic production is a necessary and promising direction. In this connection, there is a need to develop a method that allows quantifying deferasirox in human blood plasma with minimal time and resource costs as part of a pharmacokinetic study. Aim. The aim of this study is to develop a method for quantitative determination of deferasirox in human blood plasma by high performance liquid chromatography coupled with ultraviolet detection (HPLC-UV) for further bioequivalence studies. Materials and methods. Determination of the deferasirox in human blood plasma was carried out by HPLC-UV. The method of proteins precipitation by acetonitrile was used as a sample preparation. Erlotinib solution was used as an internal standard. Mobile phase: 0.3 % solution of orthophosphoric acid in water, brought to pH 3.0 (eluent A) and 0.1 % solution of formic acid in acetonitrile (eluent B). Column was Symmetry®, 75 × 4,6 mm (Waters, США) . Analytical range of the technique for deferasirox was 0.25–70.00 µg/ml in human blood plasma. Detection was carried out using a UV detector at an absorption wavelength of 299 ± 2 nm. Results and discussion. This method was validated by selectivity, calibration curve, accuracy, precision, spike recovery, the lower limit of quantification, carry-over effect and stability. Conclusion. A method of quantitative determination of deferasirox in human blood plasma was developed and validated by HPLC-UV. The analytical range was 0.25–70.00 µg/ml in human blood plasma. This method was used as part of a study of the pharmacokinetics and bioequivalence of deferasirox drugs.

ANALYSIS OF THE MINIMUM RANGE OF MEDICINES REQUIRED FOR MEDICAL APPLICATIONS

Abstract. The article presents the results of the analysis of the minimum range of medicines (MP) required for medical applications. The classification of medicinal products by ATX and dosage forms, as well as the results of a comparative analysis of the minimum assortment of pharmacies, pharmacy points, pharmacy kiosks and individual entrepreneurs. The material for the study was the classification of MP relevant for 2021 by order of the Government of the Russian Federation dated 12.10.2019 N 2406-r (ed. dated December 23, 2021) "On approval of the list of vital and essential medicines, as well as lists of medicines for medical use and the minimum range of medicines necessary for the provision of medical care." Competent maintenance of a minimum assortment in pharmacy organizations has an impact on timely, rational and effective drug provision of the population [2,3,9].